Effects on complement activation of a new continuous autotransfusion system.

Allogeneic blood transfusions may subject patients to risks of infection and allergic reactions. Various techniques for transfusion of shed blood have been developed. The aim of this study was to evaluate a new continuous autotransfusion system (Fresenius CATS) as regards its impact on the complement system, and on erythrocytes and leucocytes. Eighteen consecutive patients undergoing hip replacement surgery were studied. Complement variables (C4d, factor Bb, C3a and terminal complement complex, SC5b-9) and free haemoglobin, haemoglobin, leucocytes, platelets, albumin and protein were determined in the patient's blood preoperatively, 1 min before the start of transfusion, 15 and 60 min after transfusion; and in the reservoir, in the waste bag and in the retransfusion blood. Increased concentrations of C3a and SC5b-9 were found in the collected reservoir blood (P < 0.05). The washing and centrifugation procedure reduced these concentrations (< 0.001). High levels of free haemoglobin were found in the collected blood as well as in the processed product. The median haemoglobin level in the processed blood was 260gL-1 (range 104-289gL-1). Inflammatory mediators from the complement cascade are removed by continuous autotransfusion technique. The processed blood contains high levels of free haemoglobin.

Sulfadiazine versus sulfafurazole excretion in urine and risk of crystallization in children with conventional dosage regimen.

The excretion of sulfadiazine (Adiazin) (n = 8) and sulfafurazole (n = 8) in urine and the risk of crystallization were compared in children, 3-14 years of age. They suffered from acute urinary tract infection and were treated with conventional dosage regimen of either of the sulfonamides. Sulfadiazine (4 mg/kg twice daily, the initial dose 8 mg/kg) produced active serum drug levels which in relation to antimicrobial activity of sulphonamides corresponded to 25-30% of those obtained with sulfafurazole (50 mg/kg four times a day). In urine the corresponding sulfadiazine levels were 21-61% of those of sulfafurazole. In none of the urine fractions sulfadiazine concentrations exceeded the theoretical drug solubility but sulfafurazole exceeded this risk limit altogether in 4 urine fractions (2 patients). Urine sediment showed, however, sulfonamide crystals in only one urine fraction of the sulfafurazole group. The results suggest that with conventional dosage regimen sulfafurazole produces higher effective serum and urine drug concentrations in children than sulfadiazine but shows a higher risk to crystallize in urine.

Disopyramide pharmacokinetics in patients with acute myocardial infarction.

To study the effects of acute myocardial infarction on the pharmacokinetics of disopyramide a single oral dose of disopyramide base (200 mg) was administered to 6 patients with myocardial infarction both in the acute (Study I) and recovery (Study II) phases. An intravenous tracer dose of 14C-disopyramide (2.5 micrograms/0.3 mg) was given simultaneously with the oral dose. On the basis of the intravenous tracer data, the volume of distribution, binding to plasma proteins, total plasma clearance, renal clearance and elimination half-life of disopyramide and mono-N-dealkyl disopyramide were the same in Studies I and II. The peak serum concentrations of disopyramide after oral dosing in Studies I and II were 2.6 +/- 1.2 (SEM) and 6.4 +/- 1.9 microgram/ml, respectively (p less than 0.05), the peak times 3.29 +/- 1.22 and 1.21 +/- 0.39 h (N.S.) and the AUCINF 38.0 +/- 7.7 and 60.7 +/- 9.9 micrograms . h . ml-1 (p less than 0.05). The recovery of disopyramide in urine over 3 days averaged 46% and 47% of dose, and that of mono-N-dealkyl disopyramide 22% and 16% of the dose, respectively. Thus, the gastrointestinal absorption of disopyramide was disturbed, resulting in low plasma concentrations after oral dosing, whereas the elimination of disopyramide was unaltered in the acute phase of myocardial infarction.

Quantitative determination of methoxsalen in human serum, suction blister fluid and epidermis by gas chromatography mass spectrometry.

A selected ion-monitoring gas chromatographic mass spectrometric method is described for the determination of methoxsalen employing trioxsalen as internal standard. Methoxsalen in the serum and skin of 5 psoriatic patients after PUVA bath therapy was determined. Quantitative gas chromatographic mass spectrometric analysis was performed in the election impact mode by monitoring the ratio of ions m/z 216/228. The methoxsalen level in human serum varied between 3-15 ng/ml, in suction blister fluid between 2-9 ng/ml and in suction blister roof (epidermis) between 6-242 ng/g during the first 30 min after the methoxsalen bath.

Variations in skin photosensitization during repeated oral 8-methoxypsoralen medication.

Nine adult volunteer dermatological patients were subjected to five repeated oral exposures of 0.6 mg/kg of 8-methoxypsoralen at near-fasting conditions. In the individual volunteer, the plasma 2-h drug level varied by a factor of 1.3 to 7.1, mean 3.5. The simultaneously measured skin minimal UVA sensitivity varied in the individual subjects by a factor of 1.3 to 3.8, mean 2.2. When all serum level and skin photosensitivity data of the study were tabulated, a negative correlation factor of 0.5758 was obtained, which is statistically highly significant (P less than 0.001). It is concluded that both serum drug levels and degree of skin photosensitivity may fluctuate considerably in a single subject during repeated exposures to a standard oral 8-methoxsalen dose. Attempts should be made to minimize such undesirable variation by improvements of drug formulations and better consideration of the influence of dietary factors on drug absorption.

Ocular kinetics of 8-methoxypsoralen. An experimental study with pigmented and albino rabbits without UVA-stimulation.

Tritiated 8-methoxypsoralen (8-MOP), with radioactivity in the ring system, was injected into both pigmented rabbits and albino rabbits; at 0.5, 1, 2, 4, 6, and 24 h after 8-MOP injection the animals' plasma and ocular radioactivities were determined by liquid scintillation counting. The experiment was done without photostimulation but in incomplete darkness. The plasma radioactivity declined rapidly during the first hour, peak radioactivity occurring in the first samples of vascularized ocular structures taken 0.5 h after the injection. The radioactivity of these tissues generally declined rapidly and similarly in both animal groups. The 1, 2, and 4 h samples of pigmented animals formed an exception; in these the radioactivities in the iris-ciliary body and the retina-choroid of the pigmented animals showed increased activities that were statistically significant, and the plasma radioactivity was exceeded by two to three times. The radioactivities in the internal parts of the eye were lower than in the vascular parts. The radioactivity in the lens reached a peak in the specimens taken 1-2 h after injection and remained at the level of the plasma radioactivity for the rest of the 24 h.

Pharmacokinetics of low dose sulfadiazine in patients with renal failure.

The pharmacokinetics of sulfadiazine (SD) in a lower dose (500 mg once a day, loading dose 1000 mg) than generally used was studied in patients with normal, moderately (creatinine 154--360 mumol/l) and severely (creatinine 753--1600 mumol/l) impaired renal function. In all groups SD concentrations in serum and urine were high enough for the treatment of urinary tract infections (UTI). The serum concentration of SD and metabolites showed a clear increase in severely uremic patients within 5 days. The patients showed, on the other hand, no signs of side-effects. In moderate uremia hardly any tendency towards an accumulation of SD and its metabolites was detectable during the same period of investigation. SD can thus evidently be used for the treatment of UTI with a low dose of 500 mg daily (loading dose 1000 mg), but caution should be taken in cases of impaired renal function. In moderate uremia treatment can be continued for more than one week provided that the drug concentrations in serum can be monitored. In severe uremia treatment should be limited to a period of one week.