Complement Activation During Low-Density Lipoprotein Apheresis

Complement system activation was investigated in two girls with familial homozygous hypercholesterolemia undergoing two monthly sessions on LA15 or LA40 (Kaneka liposorber). We determined blood levels of C3c and C3a, leukocyte counts, and plasma levels of C3c and C3a in the extracorporeal circulation device at the start of the sessions and 15 and either 60 or 120 min into them. Sequential eluates were collected from LA40 at the end of the sessions (0.5M NaCl, 1M hydroxylamine). Anaphylatoxin C3a increased throughout, especially with LA40. As previously reported, C3a was trapped in the dextran column but was noticeably present in efferent plasma. Besides many proteins, nonnative complement fragments bearing C3a and C3d antigens were detected in almost all the eluates, suggesting possible in situ complement activation. Practically, complement activation induced by the first filter is a risk; long-term side effects may arise from this extracorporeal circulation device.     

Analgesic plasma concentrations of morphine in children with terminal malignancy receiving a continuous subcutaneous infusion of morphine sulfate to control severe pain

Three children with terminal malignancy received a continuous subcutaneous infusion of morphine sulfate for the control of severe pain, the morphine dose being adjusted until the patient and/or parent reported complete freedom from pain. Analgesic plasma morphine concentrations at the steady state in these patients ranged from 12.9 to 57 ng/ml (median 19.6 ng/ml) while receiving morphine doses of 0.45-2.0 mg/h (0.034-0.06 mg/kg/h). One patient, who received 2 mg morphine per hour for 12 days demonstrated a 2-fold variation in steady-state plasma concentration during this period.     

Abolition by dextran sulfate of the heparin-accelerated antithrombin III/thrombin reaction

Dextran sulfate did not inhibit the amidolytic activity of thrombin on Boc-Val-Pro-Arg-4-methylcoumaryl-7-amide, but abolished inhibition of the enzyme with antithrombin III (AT III) in the presence of heparin.

Dextran sulfate did not bind to AT III and had less affinity than immobilized heparin for the protein. Dextran sulfate bound strongly to thrombin and had higher affinity than immobilized heparin for the enzyme.

These findings indicate that binding of dextran sulfate to a site other than the active site of thrombin to prevent the approach of AT III in the presence of heparin.     

Evidence for an accelerated adaptation to starvation in chronic uremia

During a 72-hr period of starvation plasma levels of glucose and immunoreactive insulin fell to a greater extent, and alanine, free fatty acid, and glycerol concentrations were higher in fasted chronically uremic rats than in nonuremic controls. These changes, in conjunction with a significant increase in the uremic group's activity of phosphoenolypyruvate-carboxykinase, the rate-limiting enzyme in hepatic gluconeogenesis, after only 12 hr of fasting suggest that alterations in glucose metabolism in uremia may contribute to an exaggeration and acceleration of the metabolic consequences of starvation.     

Similarity between the effect of experimental congestion of the isolated perfused rat liver and the action of cytochalasin B

Summary Livers of rats were perfused with dextran solutions, containing no red cells. Changes in the dextran concentration due to water shifts between the intra- and extracellular space of the liver were recorded continuously by polarimetric measurement. Cytochalasin B causes an uptake of potassium and water, followed by a release of water and a spontaneously reversible release of potassium, while the liver weight increases. From these effects an uptake of dextran, probably by an endocytotic process, is concluded.     

Treatment of unipolar depression following electroconvulsive therapy. Relapse rate comparisons between lithium and tricyclics therapies following ECT.

A restrospective chart study and follow-up telephone interviews were used to compare the relapse rates of unipolar depressives who had received either lithium or tricyclics following ECT. The results showed no difference between the two treatment groups. The literature on ECT was reviewed in the light of the results from the present study. We concluded that ECT followed by either lithium or a tricyclic antidepressant is a more effective treatment for unipolar depression than ECT alone.     

Efficacy and tolerance of fluocortin butyl administered twice daily in adult patients with perennial rhinitis

Fluocortin butyl (FCB) is a newly developed corticosteroid drug with no detectable systemic corticosteroid activity when it is used topically. Previous studies have demonstrated the therapeutic efficacy of FCB applied topically to the nasal mucosa three to four times a day for perennial rhinitis. The therapeutic efficacy of FCB used only twice daily, with total daily dosages similar to those previously found to be effective when these were applied more frequently, was studied in a multicenter, double-blind, placebo-controlled trial. This was a 4-week study with a 1-week observation (baseline) period and a 3-week period during which the response to three dosage regimens (2 mg per day, 4 mg per day, and 8 mg per day) of FCB and placebo were compared to baseline observations of rhinitis. Two hundred thirty-five patients from six centers were studied. Patients had perennial rhinitis of allergic, nonallergic, or combined etiology. Patients who received FCB exhibited significant amelioration of signs and symptoms of rhinitis as assessed by patients and physicians and had a greater reduction in the use of concomitant antihistamine and/or decongestant therapy compared to placebo-treated patients. Relief tended to occur early and was progressive during the 3 wk of therapy. There were no significant differences in response between the various dosages of FCB used. Side effects were minimal and insignificant and did not differ between FCB-treated and placebo-treated patients. FCB appears to be an effective well-tolerated topical steroid useful in the treatment of perennial rhinitis.