Biomedical subjects

K Mizuguchi

Publications and source records attributed to K Mizuguchi.

At least 73 records · Page 4Linked to original sources

PubMed1996

Effect of carnitine administration on glycine metabolism in patients with isovaleric acidemia: significance of acetylcarnitine determination to estimate the proper carnitine dose.

In isovaleric acidemia (IVA), accumulated isovaleryl-CoA in the mitochondrion induces variable metabolic disturbances. To remove intramitochondrial isovaleryl groups, glycine therapy has been advocated primarily. On the other hand, secondary carnitine deficiency has been documented in this disorder and carnitine supplementation alone has been reported to be effective. In the present study, we administered carnitine and glycine to patients with IVA, and investigated serum carnitine and urinary excretion of total and free carnitine, acylcarnitine profile (i.e., isovalerylcarnitine and acetylcarnitine), and isovalerylglycine. By adding carnitine to glycine supplementation, more isovalerylglycine, not only isovalerylcarnitine, was excreted in the urine. Acetylcarnitine was detected in the urine only when sufficient carnitine was supplemented. We concluded that combined therapy of glycine and carnitine is more effective and safer to eliminate isovaleryl-CoA in IVA than conventional therapy using either glycine or carnitine. Urinary acetylcarnitine concentration might be a good marker indicating the optimal dose of L-carnitine supplementation.

Acetylcarnitine↗

PubMed1996

[Ten-year survival and cardiac event-free rates in Japanese patients with the left anterior descending artery revascularized with internal thoracic artery or saphenous vein graft: a comparative study].

To evaluate the long-term results of surgical patients with coronary artery bypass grafting (CABG), we comparatively analyzed the 10-year survival and cardiac event-free rates between 713 patients group with at least one internal thoracic artery to the left anterior descending artery (LAD), (ITA-CABG) and 241 patients group revascularized with vein grafts alone (SVG-CABG). ITA-CABG patients had more progressed diseases with a higher incidence of risk factors than SVG-CABG patients: number of vessel diseased 2.5 +/- 0.7 vs 2.3 +/- 0.7, LMTD 20.2% vs 14.1%, diabetes mellitus 37.3% vs 27.0% and hyperlipidemia 38.0% vs 30.7%. The 10-year cumulative LAD graft patency and severe disease-free rate was 90.3 and 67.0% for ITAs and vein grafts in this series. The 10-year overall actuarial survival, cardiac death-free and cardiac event-free rates for ITA and SVG groups were 88.8 vs 79.5%, 97.4 vs 92.6% and 84.1 vs 73.1%, all with a statistical significance (generalized Wilcoxon or logrank method). For the patients with reduced ventricular systolic function (EF < or = 0.4), ITA-CABG offered a significantly better 10-year cardiac death free rate. Also, for the diabetic patients, ITA-LAD offered a significantly better 10-year cardiac event-free rate. In conclusion, the use of ITA graft can reduce postoperative cardiac events and enhance the long-term survival in Japanese patients. The ITA should be utilized at least for LAD in all CABG patients whenever feasible.

Coronary Artery Bypass↗

PubMed1995

Seeking significance in three-dimensional protein structure comparisons.

What is the significance of three-dimensional structural similarity? This fundamental question still remains unanswered in spite of advances in automatic structure comparison methods that have been made in the last few years. The answer to this question will give us a much deeper insight into the principles of protein architecture.

Animals↗

PubMed1995

Comparison of spatial arrangements of secondary structural elements in proteins.

We have developed a new method of protein structure comparison based on spatial arrangements of secondary structural elements (SSEs). Each SSE is represented by a single vector, and common spatial arrangements of vectors in a pair of proteins are detected. The method allows not only insertions and deletions of SSEs, but also topological permutations. It has a flexible target function that can be adjusted depending upon particular levels or definitions of structural similarity, and it is fast enough to allow structural comparisons for many pairs of proteins. The parameters for the target function are determined based on distributions of the geometrical variables for the spatial arrangements of the equivalent SSEs in well-known structural motifs. The obtained parameter set is tuned for detecting relatively strong structural similarity. We report several tests on examples including comparisons of known structural similarity and database searches for a target structure, and examine the results when this parameter set is used for the comparison of distantly related structures.

Alcohol Dehydrogenase↗

PubMed1995

A thermoconductive and thermoselective leukocyte filter.

Previously, it was reported by our group that the superphysiological temperature of over 43 degrees C affected leukocyte properties. It was speculated that heat treatment might alter the immunological properties of leukocytes. In order to take advantages of this phenomenon, attempts were made to develop a thermoconductive and thermoselective leukocyte filter. A stainless steel fiber was selected for the new material of a leukocyte filter due to its good heat conductance, stability during thermal change, and inertness to any chemicals. Preliminary studies were conducted to evaluate the effect of fiber diameter and temperature on the filtration of blood cells. As a result, more than 99% of white blood cells (WBCs) and platelets were removed utilizing a 4 microns diameter fiber filter. The environmental temperatures of the filtration process were varied to 4, 20, 36, and 50 degrees C for 5 min. Almost 95% of WBCs and platelets were removed at 4, 20, and 36 degrees C. However, the reduction of platelets was remarkably suppressed at 50 degrees C (54%). Additionally, the removal of lymphocytes was significantly lower than that of neutrophils at 50 degrees C (69% vs. 83%; p = 0.0002). These data demonstrate that effective heat treatment and removal of leukocytes are possible with an ultrafine stainless steel fiber filter.

Equipment Design↗

PubMed1995

A fluid dynamic analysis using flow visualization of the Baylor/NASA implantable axial flow blood pump for design improvement.

The Baylor/NASA Axial Blood Flow Pump has been developed for use as an implantable left ventricular assist device (LVAD). The pump is intended as an assist device for either pulmonary or systemic circulatory support for more than 3-months' duration. To date the pump provides acceptable results in terms of thrombus formation and hemolysis (IH of 0.018 g/100 L). A fluid dynamics analysis using flow visualization was performed to investigate the flow fields and to determine areas within the pump that could be improved. These studies focused upon the inflow area in front of the pump. A prototype axial flow pump assembly was constructed to facilitate the flow visualization studies. Particle image tracking velocimetry techniques were used to measure Amberlite particles suspended in a blood analog fluid composed of 63% water and 37% glycerin. This method used a pulsed (612 Hz) laser light to determine flow velocity profiles, shear stress, Reynolds numbers, and stagnant areas within the axial pump. These studies showed that the flow straightener (a vaned assembly in the pump inflow) reduced Reynolds numbers from 4,640 to 2,540 (at 8.5 L/min) and that the flow straightener exacerbates a discontinuity found between it and the impeller. Within the inflow area, a maximum of 80 N/m2 shear stress was measured, which is well below published blood damage thresholds. Design variations were investigated resulting in a smoother flow transition between flow straightener and impeller. These variations must be investigated further to establish a correlation with hemolysis and thrombus formation.

Blood Flow Velocity↗

PubMed1995

Development of an axial flow ventricular assist device: in vitro and in vivo evaluation.

A collaborative effort between Baylor College of Medicine and NASA/Johnson Space Center is underway to develop an axial flow ventricular assist device (VAD). We evaluated inducer/impeller component designs in a series of in vitro hemolysis tests. As a result of computational fluid dynamic analysis, a flow inducer was added to the front of the pump impeller. According to the surface pressure distribution, the flow inducer blades were connected to the impeller long blades. This modification eliminated high negative pressure areas at the leading edge of the impeller. Comparative studies were performed between inducer blade sections that flowed smoothly into the impeller blades (continuous blades) and those that formed discrete separate pumping sections (discontinuous blades). The inducer/impeller with continuous blades showed significantly (p < 0.003) lower hemolysis with a normalized index of hemolysis (NIH) of 0.018 +/- 0.007 g/100 L (n = 3), compared with the discontinuous model, which demonstrated an NIH of 0.050 +/- 0.007 g/100 L (n = 3). The continuous blade model was evaluated in vivo for 2 days with no problems. One of the pumps evaluated ran for 5 days in vivo although thrombus formation was recognized on the flow straightener and the inducer/impeller. As a result of this study, the pump material was changed from polyether polyurethane to polycarbonate. The fabrication method was also changed to a computer numerically controlled (CNC) milling process with a final vapor polish. These changes resulted in an NIH of 0.0029 +/- 0.0009 g/100 L (n = 4), which is a significant (p < .0001) value 6 times less than that of the previous model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

[Effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate on low density lipoprotein in rabbits].

The hypolipidemic effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on cholesterol diet-fed rabbits were studied. EPA-E (300 mg/kg, p.o. x 4 weeks) decreased total cholesterols in the lipoprotein fractions of very low-density lipoprotein and intermediate lipoprotein+low-density lipoprotein (LDL), but not in high-density lipoprotein. Furthermore, the properties of LDL were investigated in rabbits given EPA-E (300 mg/kg, p.o. x 2 weeks). EPA-E had no influence on the lipid composition in LDL, and the cholesterol accumulation into macrophages was not increased by the incubation with EPA-E-treated LDL. However, the omega 3 polyunsaturated fatty acids contents of LDL were increased by the administration of EPA-E. EPA-E-treated LDL was also studied on the binding to the hepatic membranes. The binding of EPA-E-treated LDL to the hepatic membranes was higher than that of ordinary LDL. These results suggest that EPA-E causes a modification of LDL, such that EPA-E has an enhancing effect on the hepatic uptake of LDL. These effects may contribute to the hypolipidemic action of EPA-E.

Animals↗

PubMed1995

Wegener's granulomatosis with multiple cranial nerve involvements as the initial clinical manifestations.

Wegener's granulomatosis (WG) is a disease of unknown origin characterized by necrotizing granulomas of both the upper and lower respiratory tracts and glomerulonephritis. A 62-year-old woman presenting unusual neurological manifestations is reported. The patient suffered from palsies of multiple cranial nerves without manifestation of respiratory tracts in the initial clinical course. Seven years after the onset, pulmonary consolidations appeared on the chest X-ray study. A diagnosis was made by a needle biopsy of the lung. Palsies of cranial nerves suspected to be due to meningeal involvement of WG. During the entire clinical course, no finding of glomerulonephritis was observed.

Cranial Nerve Diseases↗

PubMed1995

[Rest and exercise performance of allografts, Bicer valves and St. Jude Medical valves in the aortic position].

Cardiac catheterization was performed to measure pressure gradients and hemodynamic parameters at rest and during supine bicycle exercise in 37 patients with aortic valve replacements, using allograft valves. Bicer prosthetic valves and SJM prosthetic valves of 19 to 27 mm diameter. Fourteen patients had an allograft valve replacement, 17 a Bicer valve, and 6 a St. Jude Medical valve. Patients were comparable for age, valve size, body surface area and left ventricular systolic function. There were no statistical differences among three groups for body surface area, left ventricular end-systolic and end-diastolic volume indices, exercise cardiac index, exercise heart rate, or workload achieved. In all 37 patients left ventricular and ascending aortic pressures were measured simultaneously according to the Brockenbrough method. In a 21 mm valve size, the mean pressure gradient was higher for Bicer and St. Jude Medical prosthetic valves than for allograft valves, both at rest (8.0 +/- 3.5 mmHg for Bicer, 5.0 +/- 1.4 mmHg for St. Jude Medical versus 0 +/- 0 mmHg for allograft; p < 0.05) and during exercise (11.0 +/- 4.9 mmHg, 10.0 +/- 2.8 mmHg versus 0 +/- 0 mmHg, respectively: p < 0.05). In a 23 mm size, there were no significant differences among three groups for resting mean pressure gradient, but during exercise the mean pressure gradient was higher for Bicer and St. Jude Medical prosthetic valves than for allograft valves (8.4 +/- 9.3 mmHg, 5.5 +/- 4.4 mmHg versus 0 +/- 0 mmHg; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Collective motions in proteins investigated by X-ray diffuse scattering.

We have developed theoretical models for analysis of X-ray diffuse scattering from protein crystals. A series of models are proposed to be used for experimental data with different degrees of precision. First, we propose the normal mode model, where conformational dynamics of a protein is assumed to occur mostly in a limited conformational subspace spanned by a small number of low-frequency normal modes in the protein. When high precision data are available, variances and covariances of the normal mode variables can be determined from experimental data using this model. For experimental data with lower degrees of precision, we introduce a series of simpler models. These models express the covariance matrix using relatively simple empirical correlation functions by assuming the correlation between a pair of atoms to be isotropic. As an application of these simpler models, we calculate diffuse-scattering patterns from a human lysozyme crystal to examine how each adjustable parameter in the models affects general features of the resulting patterns. The results of the calculation are summarized as follows. (1) The higher order scattering makes a significant contribution at high resolutions. (2) The resulting simulated patterns are sensitive to changes in correlation lengths of about 1 A, as well as to changes of the functional form of the correlation function. (3) But only the "average" value of the intra- and intermolecular correlation lengths seems to determine the gross features of the pattern. (4) The effect of the atom-dependent amplitude of fluctuations is difficult to observe.

Computer Simulation↗

PubMed1994

The need for standardizing the index of hemolysis.

Hemolysis is one of the most important performance parameters of blood pumps. However, comparative in vitro evaluation of the reported hemolysis effect is difficult owing to the lack of uniformity in the test methods used. Currently, three types of formulas are generally accepted and widely used for the index of hemolysis: the traditionally used index of hemolysis (defined as grams of plasma free hemoglobin released per 100 L of blood pumped); the normalized index of hemolysis (normalized by hematocrit); and the modified index of hemolysis (taking into account not only hematocrit but also hemoglobin). In addition, the tested blood conditions are often not indicated in the reports. To address this confusing situation, all three indices of hemolysis were routinely derived in our laboratory. To avoid further confusion, the tested blood conditions and test loop were defined in each study in our laboratory. If we limit the acceptable range of hemoglobin in human blood, the normalized index of hemolysis is sufficient. Furthermore, using milligrams as the unit of expression would be easier and reasonable for comparing the less hemolytic blood pumps, such as the centrifugal pumps that are currently available clinically. We would like to propose this value of a normalized index of hemolysis in milligrams as the most useful formula for the index of hemolysis in the assessment of various types of rotary blood pumps.

Assisted Circulation↗

PubMed1994

An ultimate, compact, seal-less centrifugal ventricular assist device: Baylor C-Gyro pump.

We have developed a compact, seal-less, all-purpose centrifugal pump, the Baylor C-Gyro pump, which is intended as a long-term ventricular assist device (VAD) as well as a cardiopulmonary bypass pump. In attaining this goal, we began with eliminating the shaft seals by adopting a pivot bearing system at the impeller shaft. In addition, a ring magnet encased in the bottom of the impeller was coupled magnetically to a driver magnet placed outside the pump housing (C1 Prototype). This first model yielded satisfactory performance in vitro with a flow rate of 8 L/min against 250 mm Hg at 2,400 rpm, and an index of hemolysis (IH) of 0.0083 g/100 L using bovine blood. In the second model, the C1 Eccentric Inlet Port Model, the inlet bearing support bar in the prototype were eliminated without reducing the prototype's performance. These designs for antithrombogenicity are being tested by the first in vivo experiment, which has lasted for more than 2 weeks.

Animals↗

PubMed1994

Internal hydraulic loss in a seal-less centrifugal Gyro pump.

A new index "loss factor Z" defined by Eq. 1 was introduced as the absolute expression of the mock loop resistance for testing a nonpulsatile pump. [formula: see text] where gamma is specific gravity of the fluid, g is the acceleration of gravity, delta P is total pressure head, and Q is flow. Z is expected to be constant, regardless of the pumping parameters. Z values obtained in the same mock loop but with different rotary blood pumps were almost identical and were defined as Z0. New methods of analysis of the flow-restrictive conditions of various rotary blood pumps are proposed in this paper: namely, differential loss factor delta Z, and loss factor sensitivity delta Z/delta A. The proposed Z-Q curves demonstrated better performance mapping than the conventional delta P-Q curves. Delta Z is the difference between the Z-Q curves of two different pumps. A is a design parameter of the pump; therefore delta Z/delta A is a quantitative expression of the effect of the design change on the hydraulic performance. These various indices were used to analyze the internal hydraulic loss of a centrifugal pump (Gyro pump). The relationship between its gap size (rotor casing) and hydraulic performance was assessed quantitatively by these indices. In this paper, the derivation processes and above-mentioned indices are described.

Assisted Circulation↗

PubMed1994

Development of the Baylor/NASA axial flow ventricular assist device: in vitro performance and systematic hemolysis test results.

Our newly developed axial flow pump consists of a flow tube, an internal rotating impeller, and a fixed flow stator (we call the stator) behind the impeller. This pump produces a flow of 3 to 8 L/min against 50 to 150 mm Hg pressure difference, respectively, in the range of 10,000 to 16,000 rpm. An axial flow pump that will be used as a ventricular assist device (VAD) has to have low hemolytic and good antithrombogenic characteristics. This paper will show how to decrease the hemolytic properties of this axial flow pump systematically using a test matrix. The test variables evaluated were impeller blade tip geometry, impeller flow tube clearance (radial clearance), impeller stator clearance (axial clearance), impeller blade number, stator blade number, and impeller length. All in vitro hemolysis tests were performed at 5.0 L/min against 100 mm Hg pressure difference using a total of 83 bags of fresh bovine blood. The results were as follows: the impeller blade tip geometry did not significantly effect hemolysis, a 0.005-inch and a 0.009-inch radial clearance were significantly (p < 0.01 or 0.001) less hemolytic than the other clearances, a 0.075-inch axial clearance was significantly (p < 0.05) more hemolytic than the other clearances, two- and six-bladed impellers were significantly (p < 0.01 and 0.02, respectively) less hemolytic than a four-bladed impeller, a five-bladed stator was significantly (p < 0.05 or 0.01) less hemolytic than the other stators, and the impeller length did not make a significant difference. Currently, the best index of hemolysis is 0.031 +/- 0.018 g/100 L, and using parameters from these results, implantable devices are being fabricated.

Animals↗

PubMed1994

Axial flow ventricular assist device: system performance considerations.

A cooperative effort between Baylor College of Medicine and NASA/Johnson Space Center is under way to develop an implantable left ventricular assist device for either pulmonary or systemic circulatory support for more than 3 months' duration. Using methodical evaluation and testing, an implantable axial pump has been systematically improved. These improvements include the addition of an inducer as a pumping element in front of the impeller and the construction of an efficient brushless direct current motor. To date, less than 10 W of power is required to generate 5 L/min flow against 100 mm Hg. An index of hemolysis of 0.021 g/100 L has been achieved. Two-day in vivo feasibility studies in calves are under way to evaluate the antithrombogenic nature of the pump. Further improvements in system efficiency, hemolytic performance, and the antithrombogenic nature of the pump are expected with the use of empirical studies, computer flow modeling, and in vivo testing in calves.

Animals↗

PubMed1994

Successful thermal management of a totally implantable ventricular assist system.

Thermal management of the implantable ventricular assist system (VAS) is important not only from the pathophysiological point of view but also from the standpoint of system endurance. The heat distribution within the Baylor VAS was measured using different motor housing materials and environmental conditions. The temperature of the circulating water in the mock loop was set at 37 degrees and 42 degrees C. A polycarbonate motor housing was not a suitable material because of the high temperature development in the actuation system. An anodized aluminum housing demonstrated excellent heat conductivity. The surface temperature of this motor housing was 41.6 degrees C when immersed in circulating water at 42 degrees C. Heat conduction from the motor to the circulating blood revealed an effective thermal path. In the worst case, the heat flux of the motor to the circulating blood revealed an effective thermal path. In the worst case, the heat flux of the motor housing was calculated to be less than 0.062 W/cm2--an acceptable level for the surrounding tissues.

Equipment Design↗

PubMed1994

In vitro and in vivo validation tests for total artificial heart.

Properly planned in vitro and in vivo studies are mandatory to validate blood pump performance. However, standard procedures for in vitro and in vivo tests of total artificial heart (TAH) performance still do not exist. At Baylor College of Medicine, standard tests procedures for performance validation of the totally implantable TAH have been established. In this paper, these in vitro tests protocols (performance mapping tests, accelerated endurance test, hemolysis test, flow visualization tests, etc.) are described as well as in vivo test procedures (TAH implantation procedure, including surgical technique, postoperative management and tests, etc.). In addition, pathological protocols are presented. In our experience, these procedures are very simple, easy to perform, and inexpensive. These protocols are proposed as standard in vitro and in vivo tests for a TAH.

Animals↗