Development of Duodenal Ulcers due to the Discontinuation of Proton Pump Inhibitors After the Induction of Sofosbuvir Plus Ledipasvir Therapy: A Report of Two Cases.

Sofosbuvir plus ledipasvir (SOF-LDV) combination therapy is a promising therapy for post-transplant hepatitis C virus (HCV) reinfection. It is known that gastric pH elevation induces lower absorption of ledipasvir; therefore, the use of proton pump inhibitors (PPIs) should be considered regarding dose reduction after SOF-LDV therapy induction. Here, we report two patients who developed duodenal ulcers due to the discontinuation of PPIs after the induction of SOF-LDV therapy for post-transplant HCV reinfection. The first patient was a 71-year-old man who had undergone living donor liver transplantation due to HCV-related liver cirrhosis. Lansoprazole, 30 mg daily, was discontinued upon SOF-LDV therapy induction. Seven days after SOF-LDV therapy induction, gastrointestinal endoscopy revealed the presence of a duodenal ulcer. The second patient was a 54-year-old man who had undergone living donor liver transplantation due to HCV-related end-stage liver disease. Similar to the first patient, rabeprazole sodium was discontinued upon the induction of SOF-LDV therapy. Eighteen days after SOF-LDV therapy induction, gastrointestinal endoscopy revealed the presence of a duodenal ulcer. In both cases, these duodenal ulcers improved after the resumption of the administration of PPIs, and a sustained virologic response at 12 weeks was achieved by SOF-LDV therapy with PPI use. Thus, PPI use should be continued consistently during SOF-LDV therapy for post-transplant HCV reinfection.

Flow visualization study to improve hemocompatibility of a centrifugal blood pump.

A correlation study was conducted among quantitative flow visualization analysis, computational fluid dynamic analysis, and hemolysis tests regarding the flow in a centrifugal blood pump to prevent hemolysis. Particular attention was paid to the effect of the impeller/casing gap widths on the flow in the volute and in the outlet. Flow vector maps were obtained for 250% scaled-up models with various geometries, using an argon ion laser light sheet, a high speed video camera, and particle tracking velocimetry. In terms of the results, in the small radial gap model, high shear occurred near the inside wall of the outlet and stagnation near the outside wall of the outlet whereas the standard model maintained smooth flow and low shear. The small radial gap model showed a lower head and greater hemolysis than the standard model. This head decrease could be partly restored by relocating the outlet position; however, the hemolysis level hardly decreased. From these results, it was found that the small radial gap itself is important. It was also confirmed by detailed flow visualization and simple laminar shear analysis near the wall that the small radial gap caused a wider high shear layer (110-120 microm) than the standard model (approximately 80 microm). In the small radial gap model, the high shear layer in the outlet (approximately 50 microm) is much narrower than that in the volute. Flow visualization together with the aid of computational fluid dynamic analysis would be useful to eliminate the causes of hemolysis.

Development of design methods for a centrifugal blood pump with a fluid dynamic approach: results in hemolysis tests.

The purpose of this study was to examine the relationship between local flow conditions and the hemolysis level by integrating hemolysis tests, flow visualization, and computational fluid dynamics to establish practical design criteria for centrifugal blood pumps with lower levels of hemolysis. The Nikkiso centrifugal blood pump was used as a standard model, and pumps with different values of 3 geometrical parameters were tested. The studied parameters were the radial gap between the outer edge of the impeller vane and the casing wall, the position of the outlet port, and the discharge angle of the impeller vane. The effect of a narrow radial gap on hemolysis was consistent with no evidence that the outlet port position or the vane discharge angle affected blood trauma in so far as the Nikkiso centrifugal blood pump was concerned. The radial gap should be considered as a design parameter of a centrifugal blood pump to reduce blood trauma.

Computational fluid dynamics analysis to establish the design process of a centrifugal blood pump: second report.

To establish an efficient design process for centrifugal blood pumps, the results of computational fluid dynamics (CFD) analysis were compared to the results of flow visualization tests and hemolysis tests, using the Nikkiso centrifugal blood pump. CFD analysis revealed that the radial gap greatly affected the shear stress in the outlet diffuser. The hemolysis study also indicated a similar tendency. To see the flow behind the impeller, we conducted a comparative study between models with and without washout holes using the CFD technique. CFD analysis indicated that flow and pressure distributions behind the impeller were different between both models, and a particle was observed to remain longer behind the impeller in the model without washout holes. In the future, CFD analysis could be a useful tool for developing blood pumps in comparison to flow visualization tests and hemolysis tests.

Development of the small caliber centrifugal blood pump.

Regarding the development of a centrifugal blood pump to be connected directly with small diameter tubings for pediatric use while minimizing hemolysis, we have studied the inlet port side configurations of a pump using both a hemolysis test and computational fluid dynamics (CFD) analysis. We have conducted a hemolysis test on 2 models. The tapered shape inlet has proven to be lower in the index of hemolysis (IH) than the straight shape. CFD analyses utilizing expanded flow paths indicated that the flow velocity decreased as the fluid path became larger within the tapered nozzle. When entering the pump chamber, the flow rushed in at a greater velocity through the straight nozzle due to its small diameter. The straight shape showed an abrupt change in pressure around the entrance of the pump chamber while the tapered shape did not. The flow inlet angle of the straight model was observed to be larger than that of the tapered model because of its smaller turning radius.

Flow visualization as a complementary tool to hemolysis testing in the development of centrifugal blood pumps.

With a 250% scaled-up pump model, high speed video camera, and argon ion laser light sheet, flow patterns related to hemolysis were visualized and analyzed with 4 frame particle tracking software. Different flow patterns and shear distributions were clarified by flow visualization for pumps modified to have different hemolysis levels. A combination of in vitro hemolysis tests, flow visualization, and CFD analysis suggested a close relationship between hemolysis and high shear caused by small impeller/casing gaps. Because arbitrary cross sections can be illuminated by laser light sheet, flow visualization is a useful tool in finding locations related to hemolysis in the design process of rotary blood pumps.

Computational fluid dynamic analyses to establish design process of centrifugal blood pumps.

To establish quantitative, efficient design theories for centrifugal blood pumps, computational fluid dynamics (CFD) analyses were compared to the results of flow visualization tests and hemolysis tests, mainly on the Nikkiso centrifugal blood pump. The results turned out to coincide in the velocity vector plots. CFD analysis revealed that the smaller the gap is, the greater the shear stress becomes. This tendency becomes even greater with a radial gap change. Hemolysis study also indicated that the smaller the gap is, the greater the hemolysis. CFD analysis in comparison with hemolysis tests could be a useful index for developing blood pumps in the future.

Development of design methods of a centrifugal blood pump with in vitro tests, flow visualization, and computational fluid dynamics: results in hemolysis tests.

There are few established engineering guidelines aimed at reducing hemolysis for the design of centrifugal blood pumps. In this study, a fluid dynamic approach was applied to investigate hemolysis in centrifugal pumps. Three different strategies were integrated to examine the relationship between hemolysis and flow patterns. Hemolytic performances were evaluated in in vitro tests and compared with the flow patterns analyzed by flow visualization and computational fluid dynamic (CFD). Then our group tried to establish engineering guidelines to reduce hemolysis in the development of centrifugal blood pumps. The commercially available Nikkiso centrifugal blood pump (HPM-15) was used as a standard, and the dimensions of 2 types of gaps between the impeller and the casing, the axial and the radial gap, were varied. Four impellers with different vane outlet angles were also prepared and tested. Representative results of the hemolysis tests were as follows: The axial gaps of 0.5, 1.0, and 1.5 mm resulted in normalized index of hemolysis (NIH) values of 0.0028, 0.0013 and 0.0008 g/100 L, respectively. The radial gaps of 0.5 and 1.5 mm resulted in NIH values of 0.0012 and 0.0008 g/100 L, respectively. The backward type vane and the standard one resulted in NIH values of 0.0013 and 0.0002 g/100 L, respectively. These results revealed that small gaps led to more hemolysis and that the backward type vane caused more hemolysis. Therefore, the design parameters of centrifugal blood pumps could affect their hemolytic performances. In flow visualization tests, vortices around the impeller outer tip and tongue region were observed, and their patterns varied with the dimensions of the gaps. CFD analysis also predicted high shear stress consistent with the results of the hemolysis tests. Further investigation of the regional flow patterns is needed to discuss the cause of the hemolysis in centrifugal blood pumps.

Development of the Baylor-Nikkiso centrifugal pump with a purging system for circulatory support.

The Baylor-Nikkiso centrifugal pump is a magnetically coupled system with a V-ring seal separating the pump and the actuator chamber. To prevent thrombus formation behind the impeller and to extend the life of the pump to 2 weeks of continuous operation, we incorporated a purging chamber behind the V-ring seal. An external pump connected to this purging chamber infused fluid at a constant rate to wash the shaft-seal area. To evaluate the effectiveness of the purging system, we have carried out biventricular bypass experiments using calves. The purging system was successful in reducing the level of thrombus formation after 2 weeks of operation. The results of these studies confirmed that the Baylor-Nikkiso centrifugal pump with this purging system is suitable for at least 2 weeks of continuous operation as a circulatory support system.

Differential-absorption-lidar measurement of tropospheric ozone with excimer-Raman hybrid laser.

The vertical distribution of tropospheric ozone was measured by a two-wavelength differential absorption lidar based on excimer lasers. Emission of a XeCl laser (308 nm) and stimulated Raman scattering of methane (290.4 nm) pumped by a KrF laser were used. Ozone concentrations in an altitude range of 4-12 km were determined with a resolution of 750 m. The proposed method can be used to measure the ozone distribution over a wide altitude range (2-28 km) with high reliability because the excimer-Raman hybrid laser is simple and has high average power and a high repetition rate, in comparison with frequency-doubled two-wavelength dye lasers.

Quantitative detection of atomic absorption by intracavity dye-laser quenching.

A new technique for quantitative detection of atomic absorption by intracavity dye-laser quenching is studied. For the sodium D(2) line, a sensitivity of 7 x 10(4) atoms/cm(3) x 1% quenching is obtained; and the sensitivity in single-pass detection is 4 x 10(8) atoms/cm(3) x 1% absorption for a 15-cm cell. Use of a cw dye laser improves the sensitivity and the stability. The dependence of the sensitivity on the bandwidth of laser action is measured, and a simple theoretical consideration is given for single-pass absorption.