Randomised clinical trial: prevention of recurrence of peptic ulcers by rabeprazole in patients taking low-dose aspirin.

BACKGROUND: Few studies have evaluated the effects of rabeprazole on low-dose aspirin (LDA)-induced gastroduodenal injuries. AIM: To conduct a randomised, double-blind, triple-dummy, active-controlled, multicentre trial, named the PLANETARIUM study, to assess the efficacy, dose-response relationship and safety of rabeprazole for peptic ulcer recurrence in Japanese patients on long-term LDA therapy. METHODS: Eligible patients had a history of endoscopically confirmed peptic ulcers and were receiving long-term LDA (81 or 100 mg/day) therapy for cardiovascular or cerebrovascular protection. Subjects were randomly segregated into three groups receiving rabeprazole 10 mg once daily (standard dose in Japan), rabeprazole 5 mg once daily, or teprenone (geranylgeranylacetone; mucosal protective agent commercially available in Japan) 50 mg three times per day as an active control. The primary endpoint was recurrence of peptic ulcers over 24 weeks. RESULTS: Among 472 randomised subjects, 452 subjects (n = 151, 150, 151, respectively) constituted the full analysis set. The cumulative recurrence rates of peptic ulcers over 24 weeks in the 10- and 5-mg rabeprazole groups were 1.4% and 2.8%, respectively, both of which were significantly lower than that in the teprenone group (21.7%). The cumulative occurrence rate of bleeding ulcers over 24 weeks in the teprenone group was 4.6%, while bleeding ulcers were not observed in the 10- or 5-mg rabeprazole groups. Rabeprazole was well tolerated at both doses. CONCLUSION: Rabeprazole prevents the recurrence of peptic ulcers with no evidence of a major dose-response effect in subjects on low-dose aspirin therapy.

Positional cues that are strictly localized in the telencephalon induce preferential growth of mitral cell axons.

In mice, mitral cells are the major efferent neurons of the main olfactory bulb and elongate axons into a very narrow part of the telencephalon to form a fiber bundle referred to as the lateral olfactory tract (LOT). To clarify the mechanisms responsible for guidance of mitral cell axons along this particular pathway, we co-cultured mouse embryo main olfactory bulbs with the telencephalons, and analyzed the pathways taken by mitral cell axons. Ingrowth of mitral cell axons into the telencephalon was observed in those co-cultures in which the olfactory bulbs had been exactly combined to their normal pathway (the LOT position) of the telencephalon. The axons grew preferentially along the LOT position, and formed a LOT-like fiber bundle. When the olfactory bulbs were grafted at positions apart from their normal pathway, however, no mitral cell axons grew into the telencephalon. Neocortical fragments combined with the telencephalon projected fibers into the telencephalon in random directions. These results suggest that the LOT position of the telencephalon offers a guiding pathway for mitral cell axons and that guiding cues for mitral cell axons are extremely localized.

[Evaluation of plasma prothrombin fragment 1+2 in healthy donors and thrombotic diseases].

We have evaluated plasma F1+2 values by enzyme immunoassay (Enzygnost F1+2; Behringwerke) in 80 healthy blood donors in various ages and compared to that from patients with DIC, thrombosis and oral anticoagulant therapy. The reference range of F1+2 from 35 donors with 20 to 29 age-group, was found 0.82 +/- 0.39 nM, whereas the range from 20 donors with 30 to 39 age-group showed higher F1+2 levels with 1.46 +/- 0.56nM (p < 0.001). F1+2 values from 15 donors with 40 to 49 age-group revealed similar with 30 to 39 age-group, while the range from 10 donors with 50 to 59 age-group was found much higher F1+2 levels with 2.16 +/- 0.80nM (p < 0.001). In patients with DIC, F1+2 levels were significantly higher than those in all healthy subjects (p < 0.01). In patients under stable oral anticoagulant therapy, F1+2 values were significantly lower than in healthy donors with any age-group (p < 0.001). On the contrary, in patients with thrombosis including 9 AMI and 4 DVT, the determination of F1+2 values appeared controversial. They were significantly higher than those in 20 age-group donors (p < 0.001), however, when compared with those in all healthy donors, it showed no statistical significance. These results suggest that evaluation of reference range of plasma F1+2 values is very important from the viewpoint of aging. In addition, F1+2 determination is clinically useful for monitoring of DIC and anticoagulant therapy.

[Study on platelet satellitism].

The platelet leukocyte adherence phenomenon, so-called 'Platelet Satellitism (PS)', was recognized on peripheral blood smear from ethylenediaminetetraacetic acid (EDTA)-anticoagulated blood in two patients. The present study was undertaken to elucidate both inducing and inhibitory factors for PS by utilizing two patients' blood. Both heparin and sodium citrate could not induce PS in these patients. This phenomenon was inhibited by anti-platelet membrane glycoprotein (GP) IIb/IIIa complex antibody (AP-2), but not by antibodies against platelet membrane glycoprotein (GP) Ib/IX complex, fibrinogen and von Willeb and factor. Patients' sera were subjected to column chromatography of Sephacryl S-300 to obtain immunoglobulin (Ig) G, IgA and IgM fractions. In one patient, IgG fraction, but neither IgA nor IgM fractions could induce PS phenomenon in normal whole blood, while IgA but neither IgG nor IgM could induce PS in another patient. Furthermore, when purified IgG from the first patient was treated with 2U/ml of plasmin to digest Fc portion, PS phenomenon disappeared. The F(ab')2 portion was prepared from whole IgG treated with pepsin, then added to normal whole blood. Purified F(ab')2 fragment by itself could not induce PS phenomenon, whereas the preincubation of F(ab')2 in normal whole blood could inhibit the PS caused by the patient's whole IgG. These results indicate that platelet membrane glycoprotein (GP) IIb/IIIa complex and both Fab and Fc portions of immunoglobulin might be necessary to induce PS phenomenon in EDTA-anticoagulated whole blood.

The effect of 1alpha-hydroxyvitamin D3 and cortisone on the development of chick duodenal alkaline phosphatase in organ culture.

The development of alkaline phosphatase influenced by 1 alpha-OH-D3 (a synthetic active form of vitamin D3) and cortisone was studied in chick duodenal organ cultures. The administration of cortisone to the embryo in ovo on the 14th day of incubation resulted in a precocious increase in alkaline phosphatase after six days (20-day embryo). When duodena from 14-, 18- and 20-day embryos were cultured in the presence of cortisone, there was no significant enhancement of alkaline phosphatase activity except for a marginal effect observed in the 18-day duodenum. On the other hand, the alkaline phosphatase activity in cultured duodena from 20-day chick embryos was significantly stimulated by the addition of 1 alpha-OH-D3. The effects of cortisone and 1 alpha-OHD-3 were not additive. The activity of maltase, another intestinal enzyme, was not influenced by 1 alpha-OH-D3. Studies on inactivation of alkaline phosphatase by EDTA suggest that the observed increase in alkaline phosphatase activity induced by the administration of 1 alpha-OH-D in vitro may be related to the qualitative changes in the enzyme that take place during development in vivo.