Effect of superparamagnetic particles as oral contrast medium at magnetic resonance imaging. A phase I clinical study.

Non-biodegradable superparamagnetic particles were used as an oral contrast medium in different concentrations, and evaluated in 25 human volunteers. The aim of the study was to determine the most appropriate concentration of the contrast medium, and to evaluate the effect, distribution, safety and tolerance. With the concentration of 1.0 g/l a substantial reduction of the signal intensity in the bowel was achieved in both T1 and T2 weighted images. The intraabdominal structures were well differentiated from the bowels containing contrast medium. 'Metal' artifacts and blurring of adjacent structures, probably due to an increased local concentration, were observed at higher dosages. The distribution of the preparation in the gastrointestinal tract varied between individuals. As a rule a good contrast effect was achieved in the small bowel with the exception of the duodenum. The contrast medium was well accepted and did not cause any side effects of clinical importance. The results suggest that the preparation is well tolerated by humans and may be a useful contrast medium for abdominal MR imaging.

Clinical trial program for iopentol. A new nonionic ratio 3.0 contrast medium with emphasis on clinical phases I and II.

Iopentol is a new nonionic, water-soluble ratio 3.0 roentgen contrast medium (CM) for vascular use. The aim is to present the vascular clinical trial program for iopentol and to report the findings from the clinical phases I and II. The clinical program started with an intravenous (IV) safety and pharmacokinetic phase I trial (24 volunteers) and continued with six open, noncomparative phase II trials (61 patients) for studying cardiovascular and arterial tolerance (two trials in cardioangiography), venous tolerance (two trials in IV computed tomography [CT] enhancement), and cerebral and arterial tolerance (2 trials in cerebral arteriography). One volunteer in the phase I trial was excluded because of a vasovagal reaction following saline injection, and four patients were protocol deviators in cardioangiography. Mainly renal glomerular filtration of unmetabolized iopentol, close to 100% recovered after 24 hours in the urine, was found in the phase I study. No unexpected or severe contrast-induced reactions were encountered in phases I and II. Good diagnostic efficiency was obtained in phase II. As also expected, iopentol seemed to be well-tolerated. However, its relative efficiency and tolerance profile can only be documented from the ongoing comparative phase III trials.

High-dose versus low-dose metoclopramide in the prevention of cisplatin-induced emesis. A randomized crossover study in patients with ovarian carcinoma.

Forty-six patients with ovarian carcinoma who received single drug cisplatin chemotherapy were evaluated for the antiemetic efficacy of two different doses of metoclopramide. Each patient received during the first two courses a 4-hour continuous infusion of either 8 or 0.8 mg/kg in a random order. Total protection from emesis was achieved in 12 (26%) of the high-dose courses and in three (7%) of the low-dose courses of metoclopramide. Major control (one or two emetic episodes) was achieved in seven (16%) and in four (9%) of the courses, respectively. The higher dose of metoclopramide significantly reduced the degree of nausea as recorded on a visual analogue scale. A significant difference between courses 1 and 2 could only be seen when the high-dose treatment was followed by low-dose metoclopramide. The duration of anorexia after the courses was not influenced by the metoclopramide dosage. Side effects were mild. It is concluded that there is a dose-response relationship for the antiemetic effect of metoclopramide.

Relative bioavailability of oral low dose methotrexate. A comparison of 2 different formulations.

In 39 patients the bioavailability of methotrexate from the two tablets Emthexat 2.5 mg and Methotrexate 2.5 mg was assessed in a double-blind study after a single oral dose of 30 mg/m2 Methotrexate. There was a considerable inter-individual variation of the serum pharmacokinetics in regard to Cmax and tmax, independent on the MTX formulation. Emthexat 2.5 mg tablets and Methotrexate 2.5 mg tablets were bioequivalent according to the definition (AUCE greater than or equal to AUCM X 80%).

A new, purified Dermatophagoides farinae allergen preparation. Evaluation with SPT and RAST techniques.

A purified, standardized and characterized allergen preparation of the house dust mite Dermatophagoides farinae (Df) was evaluated by skin prick test (SPT) and radioallergosorbent test (RAST) in 88 subjects. Skin reactions to the purified Df preparation and a corresponding crude Df preparation were compared. SPT was also performed with a crude Dermatophagoides pteronyssinus (Dpt) preparation to compare reactions obtained with the two mite preparations. By SPT the purified Df allergen preparation was representative of the crude Df preparation (r = 0.78) and the correlation between skin reactions to Df and Dpt was high (r = 0.78). The concordance between results obtained with RAST and SPT techniques with the purified Df preparation was high (84%). The purified D. farinae preparation was well tolerated and is well suited for SPT.

Clinical effects of hyposensitization using a purified allergen preparation from Timothy pollen as compared to crude aqueous extracts from Timothy pollen and a four-grass pollen mixture respectively.

Most extracts used in hyposensitization are complex and ill-defined mixtures of a large number of antigenic components. A highly refined (purified) and well-characterized allergen preparation from Timothy pollen (Phleum pratense) is now available. This paper describes the results of hyposensitization for 3 years comparing the purified preparation Timothy N, the crude extract Timothy O and a four-grass mix in sixty patients with allergic rhinitis due to grass pollen. The sixty patients were randomized into three groups and compared with a control group not hyposensitized. All three groups showed a significant decrease in clinical symptoms compared with the control group. The Timothy N group had a significantly higher nasal tolerance shown by nasal challenge test after 3 years' treatment than the group treated with the crude extract (P = 0.05). In addition, the Timothy-N-treated patients needed significantly less antihistaminic medication than the patients having received the crude extract or the four-grass mix (P = 0.02 and P = 0.01, respectively).