Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis.

BACKGROUND: Vonoprazan is a novel potassium-competitive acid blocker which may provide clinical benefit in acid-related disorders. AIM: To verify the non-inferiority of vonoprazan vs. lansoprazole in patients with erosive oesophagitis (EE), and to establish its long-term safety and efficacy as maintenance therapy. METHODS: In this multicentre, randomised, double-blind, parallel-group comparison study, patients with endoscopically confirmed EE (LA Classification Grades A-D) were randomly allocated to receive vonoprazan 20 mg or lansoprazole 30 mg once daily after breakfast. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 8. In addition, subjects who achieved healed EE in the comparison study were re-randomised into a long-term study to investigate the safety and efficacy of vonoprazan 10 or 20 mg as maintenance therapy for 52 weeks. RESULTS: Of the 409 eligible subjects randomised, 401 completed the comparison study, and 305 entered the long-term maintenance study. The proportion of patients with healed EE up to week 8 was 99.0% for vonoprazan (203/205) and 95.5% for lansoprazole (190/199), thus verifying the non-inferiority of vonoprazan (P < 0.0001). Vonoprazan was also effective in patients with more severe EE (LA Classification Grades C/D) and CYP2C19 extensive metabolisers. In the long-term maintenance study, there were few recurrences (<10%) of EE in patients treated with vonoprazan 10 or 20 mg. Overall, vonoprazan was well-tolerated. CONCLUSIONS: The non-inferiority of vonoprazan to lansoprazole in EE was verified in the comparison study, and vonoprazan was well-tolerated and effective during the long-term maintenance study.

Randomised clinical trial: a dose-ranging study of vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis.

BACKGROUND: The potassium-competitive acid blocker vonoprazan (VPZ) has potent acid-inhibitory effects and may offer clinical advantages over conventional therapy for acid-related disorders. AIM: To investigate the efficacy and safety of VPZ in patients with erosive oesophagitis (EO). METHODS: In this multicentre, randomised, double-blind, parallel-group, dose-ranging study, patients ≥20 years with endoscopically confirmed EO [Los Angeles (LA) grades A-D] received VPZ 5, 10, 20 or 40 mg, or lansoprazole (LPZ) 30 mg once daily for 8 weeks. The primary endpoint was the proportion of healed EO subjects as shown by endoscopy at week 4. RESULTS: A total of 732 subjects received VPZ or LPZ. The proportion of healed EO subjects at week 4 was 92.3%, 92.5%, 94.4%, 97.0% and 93.2%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. All VPZ doses were non-inferior to LPZ when adjusted for baseline LA grades A/B and C/D. Among those with LA grades C/D, the proportions of healed EO subjects were 87.3%, 86.4%, 100%, 96.0% and 87.0%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. The incidence of adverse events was similar across the groups. CONCLUSIONS: Vonoprazan was effective and non-inferior to LPZ in healing EO. VPZ 20 mg or higher was highly efficacious for severe EO (LA grades C/D). VPZ was associated with no safety concern during this 8-week study, while there was a dose-dependent increase in serum gastrin. Once-daily VPZ 20 mg is the recommended clinical dose for treating EO.

[Experimental study on directional asymmetry of vertical OKN and OKAN].

We studied the directional asymmetry of human vertical optokinetic nystagmus (OKN) and optokinetic after nystagmus (OKAN) based on two experiments conducted in 22 normal subjects. The results of the first experiment indicated that, during upward optokinetic stimulation OKN is produced by the pursuit system and the velocity storage system while during downward optokinetic stimulation the velocity storage system plays no significant role. Up-down asymmetry in vertical OKN seemed to be caused mainly by directional asymmetry of the velocity storage system. Furthermore, as the velocity storage function is very important for producing OKN at a higher stimulation velocity, domination of upward slow phase velocity becomes more apparent with a high stimulation velocity. In our second experiment the subjects were exposed to optokinetic stimulation with or without a stable fixation point. When subjects were exposed to optokinetic stimulation with fixation, they felt a rotating sensation within themselves or a moving sensation of the fixation point. When the stimulation disappeared, most experienced an illusion of small dots moving in the direction opposite the stimulation. In this condition some of the subjects showed after-nystagmus the slow phase of which was in the opposite direction. Subsequently the after-nystagmus became more distinct, with pursuit of the moving dot illusion. This result shows the existence of a mechanism which produces reverse after-nystagmus by mean of a retinal error input. We speculate that these phenomena play causative roles in reverse after-nystagmus (RAN), pursuit reverse after nystagmus (pRAN), and the RAN system.

[Recording characteristics of the eye mark recorder in measurements of vertical eye movements].

Electronystagmography (ENG) has been widely used in physiological studies of eye movements. It is generally known that ENG is at a disadvantage in recording the vertical component of eye movements, and thus there has been a great deal of difficulty in physiological studies of vertical eye movements using ENG. The eye mark recorder is an instrument which has already been used in the study of visual point movement in various situations. We tried to apply the eye mark recorder to the recording of eye movements in normal volunteers, and then compared its recording characteristics with those of ENG. When recording vertical eye movements with the eye mark recorder there is little baseline drift and no confusing waves caused by blinking, which is sometimes misinterpreted as nystagmus. The result is easy calibration of the device and more accurate measurement of the slow-phase velocity of nystagmus than ENG. Recording with the eye mark recorder is atraumatic and allows binocular visual stimulation. There are certain other techniques, such as search coil or video oculography, which allow more accurate recording of vertical eye movements than ENG. The search coil techniques, however, requires the attachment of a measuring contact lens during the examination and video oculography is still in development process, so both of them are difficult to use widely. Thus, we found that the eye mark recorder has a great advantage in recording the slow-phase eye velocity of vertical nystagmus and the vertical component of smooth eye movements in humans. We think that eye mark recorder can serve as a powerful new tool to investigate vertical OKN and OKAN.

[Determinants of homologous blood utilization in addition to autologous blood transfusion--a multivariate study].

Since April 1989, we have been using autologous blood donation in order to avoid homologous blood transfusion as much as possible. To determine the factors which influence the necessity for homologous blood transfusion as well as autologous blood donation. Of them 77.6% (group 1) required autologous blood only, but others needed homologous blood transfusion as well as autologous blood. Using an invert analysis, preoperative factors that showed significant differences were age, body weight, number of autologous blood donations, amount of donated autologous blood, preoperative Hb and Ht. Among operative factors, aortic cross clamping time, cardiopulmonary bypass time, amount of concentrated blood from CPB circuit, amount of transfused autologous blood and amount of drainage demonstrated significant differences between groups. Univariately significant factors were studied by multivariate discriminant analysis. Total amount of drainage proved to be the best contributor of non-homologous blood transfusion surgery, followed by preoperative Hb, body weight, amount of concentrated blood from CPB circuit and amount of donated autologous blood in order of contribution Understanding these factors, homologous blood transfusion requirement may be greatly reduced. This is thought to be the largest series of autologous blood donation in Japan.

[A case of pigeon breeder's lung].

A 34 year-old male pigeon breeder developed a sudden fever, cough, and dyspnea with diffuse nodular shadows on the chest X-ray film and computer tomogram. His symptoms and diffuse nodular shadows on the chest X-ray film improved and gallium (Ga) scintigram showed no accumulation of 67Ga-citrate in his lungs when examined after corticosteroid therapy. Serum precipitin against pigeon serum and pigeon dropping extracts could be detected. In his bronchoalveolar lavage (BAL) fluid, total cell count, mainly lymphocytes, were increased. OKT8(+)-HLA-DR+T cells were dominant in the lymphocyte subpopulation of the BAL fluid. Pathological examination of transbronchial lung biopsy specimen showed interstitial pneumonia. Blastogenic response of peripheral blood mononuclear cells when cultured with pigeon serum could not be observed, which suggested suppressive effects of lymphocyte blastogenesis by corticosteroid therapy. An inhalation provocation test with pigeon serum was performed. The patient developed fever, leucocytosis, hypoxemia and decreased vital capacity after the inhalation provocation test. Consequently, the case was diagnosed as a pigeon breeder's lung.

Comparison of immunoreactive renin and plasma renin activity in human plasma.

Measurement of immunoreactive plasma renin concentration (PRC) using direct radioimmunoassay (RIA) was compared with the common procedure, measurement of plasma renin activity (PRA). The sensitivity of the PRC assay was 5 pg/ml. In 67 normal subjects aged 45.2 +/- 1.2 year, the mean PRC value was 17.0 +/- 0.9 pg/ml in the recumbent position and 38.0 +/- 5.4 pg/ml in the upright position. In patients with high renin essential hypertension and renovascular hypertension, discrepancies were observed between changes in PRA and PRC at 60 min after the administration of captopril. In a patient with Bartter's syndrome PRC was markedly elevated (393 pg/ml) and the changes in PRA and in PRC after captopril were very different (452% vs. 1249%). In all 10 cases of primary hyperaldosteronism PRC was less than 5 pg/ml. The correlation coefficient between PRC and PRA was 0.85 (n = 227, p less than 0.01). The slope of the regression line between PRA and PRC decreased in proportion to PRC values. Direct RIA for PRC is likely to be useful for the determination of plasma active renin when renin levels are high or substrate concentrations are abnormal. Moreover, the combined use of PRA and PRC measurements might be useful in assessing abnormalities in renin substrate concentration as well as in PRC.