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Biomedical subjects

M Sakaki

Publications and source records attributed to M Sakaki.

At least 19 recordsLinked to original sources

Prognostic factors in cirrhotic patients receiving long-term sclerotherapy for the first bleeding from oesophageal varices.

OBJECTIVE AND DESIGN: The aim of this study was to identify prognostic factors in cirrhotic patients receiving long-term sclerotherapy for their first bleeding from oesophageal varices. METHODS: Ninety-eight patients with acute bleeding from oesophageal varices receiving long-term endoscopic injection sclerotherapy were retrospectively investigated. Thirteen variables (five qualitative and eight quantitative) related to clinical, biological, and radiographic features were collected at admission. The qualitative variables were: gender, hepatocellular carcinoma, cause of cirrhosis, ascites and degree of encephalopathy. The quantitative variables were age, bilirubin, albumin, prothrombin index, number of sessions of sclerotherapy, volume of ethanolamine oleate, time taken to reach the hospital and shock index. These variables were examined with a multivariate analysis using stepwise logistic regression procedures and a prognostic index was calculated from the Cox equation. The predictive power of the final Cox model was prospectively tested in 43 patients with cirrhosis receiving long-term sclerotherapy for their first variceal bleeding. RESULTS: Of the 13 variables studied in a multivariate analysis using a logistic regression model, four had an independent prognostic value: the presence of hepatocellular carcinoma, bilirubin, albumin and time taken to reach the hospital. When the Cox model was examined in an independent set of 43 patients, there were no statistically significant differences between the observed and expected survival. CONCLUSION: Prognosis of patients with bleeding from oesophageal varices is related to residual liver function and time taken to reach the hospital. Furthermore, the presence of hepatocellular carcinoma is an additional risk factor.

Esophageal and Gastric Varices

HLA-DR8 subtyping by polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis: a simple and practical genotyping method.

Two hundred Japanese panels were serologically typed for human leukocyte antigen (HLA) - DR to assign 65 HLA-DR8 haplotypes, which were then subdivided into two genotypes, i.e., DRB1*0802 and DRB1*0803, by a polymerase chain reaction (PCR)--based, simple, and practical method. The panels possessing DR8 specificity were firstly subjected to PCR with a couple of primers specifically to amplify their DR52 associated group--DRB1 genes. PCR products were then denatured in the presence of formamide, electrophoresed in a non-denaturing polyacrylamide gel, and visualized by silver staining. The same DRB1 products of these samples were also mixed with the DRB1*1302, and simultaneously analyzed by the same procedure. Electrophoretic mobilities of the samples were compared with those of the typing standards to genotype their DR8--DRB1 alleles by using the characteristic polymorphism in the single-stranded DNAs and the heteroduplexes. This method, designated PCR--DNA conformation polymorphism (DCP) analysis, allowed for genotyping of the DR8-DRB1 alleles without using sequence-specific oligonucleotide probes (SSOP) or restriction endonucleases. The entire process after PCR was completed within a few hours. The tested panels were also genotyped for DRB1 gene by the PCR-SSOP method for comparison with results obtained by the PCR-DCP method. Satisfactory coincidence was achieved and it represented how accurately the new system genotyped DRB1*0802 and DRB1*0803. PCR-DCP analysis was thus shown to be practical and useful for subtyping of serologically defined DR8 specificities.

Base Sequence

Effects of exercise-induced sympathoadrenergic activation on portal blood flow.

We examined the relationship between portal venous blood flow and sympathoadrenergic activation after muscle exercise. For this purpose, we used echo Doppler and measured plasma noradrenaline concentration before and after mild (7 metabolic units, N = 8) and maximal exercise (14 metabolic units, N = 8) in 16 patients without significant disease. Portal venous flow did not change after mild exercise. In contrast, a significant reduction in portal venous flow was observed after maximal exercise (P < 0.01). This was due to reductions in both cross-sectional area of the portal vein (P < 0.01) and portal venous velocity (P < 0.01). Overall, there were significant inverse relationships between the change in plasma noradrenaline concentration and that in cross-sectional area of the portal vein [r = -0.44, P < 0.01 (absolute change); r = -0.47, P < 0.01 (relative change)], that in portal venous velocity (r = -0.63, P < 0.01; r = -0.61, P < 0.01), and that in portal venous flow (r = -0.54, P < 0.01; r = -0.59, P < 0.01). These results suggest that the reduction in portal venous flow after exercise is related to the degree of sympathoadrenergic activation. This reduction may be due mainly to splanchnic vasoconstriction.

Adult

A field isolate of Sendai virus: its high virulence to mice and genetic divergence form prototype strains.

A field isolate of Sendai virus, the Hamamatsu strain, was far more virulent in mice than the prototype Z strain. The Hamamatsu strain replicated more efficiently in the mouse lung than the Z strain, causing deteriorating lung lesions. Nucleotide sequence analysis of the HN, F and M genes revealed that the Hamamatsu strain was divergent from the prototype Z, Harris and Fushimi strains.

Animals

Wedged hepatic venous pressure reflects portal venous pressure during vasoactive drug administration in nonalcoholic cirrhosis.

Hepatic venous catheterization is widely used to assess portal pressure. However, it remains unclear whether wedged hepatic venous pressure is a close indicator of portal venous pressure during vasoactive drug administration in nonalcoholic cirrhosis. To address this issue, we analyzed the data from our previous published studies. Forty patients with nonalcoholic cirrhosis (HBV infection in five, HCV infection in 28, and cryptogenic in seven) were available in this analysis. A vasoconstrictor (N = 14), vasodilator (N = 10), or combination (N = 16) was administered. The agreement of the changes between portal and wedged hepatic venous pressures during pharmacological manipulation was assessed by an intraclass correlation coefficient. The intraclass correlation coefficient in each subgroup was more than 0.60 (0.62 in vasoconstrictor group, 0.87 in vasodilator group, and 0.73 in combination group). When the analysis was performed according to the cause of liver disease, the values were 0.67 in HBV infection, 0.73 in HCV infection, and 0.74 in cryptogenic cirrhosis. These results suggest that wedged hepatic venous pressure reflects portal venous pressure during vasoactive drug administration in patients with nonalcoholic cirrhosis.

Female

Portal pressure after prophylactic sclerotherapy in patients with high-risk varices.

Portal hemodynamics and transhepatic portal venographic findings were studied before and after prophylactic sclerotherapy (mean duration = 40 +/- 14 days) in 16 patients with high-risk esophageal varices. Portal pressure, evaluated by the portal venous pressure gradient, increased by a mean of 21% in eight patients (50%) and decreased by a mean of 20% in eight patients (50%) with no statistically significant change overall. The two groups were further analyzed separately to identify the mechanism of the change in portal pressure. Intrahepatic vascular resistance did not change significantly in either group. However, the prevalence of extravariceal portosystemic shunts was greater in patients with decreased portal pressure than in those with increased portal pressure (88% vs. 25%, p < 0.05). Further, the enlargement of extravariceal portosystemic shunts was more marked in patients with decreased portal pressure than in those with increased portal pressure (88% vs. 0%, p < 0.01). In addition, liver function, assessed by intrinsic clearance, was not modified in the two groups. We conclude that prophylactic sclerotherapy increases or decreases portal pressure without modifying liver function. Although the mechanism of these portal pressure changes is not clear, intrahepatic vascular resistance does not play an important role and the presence of extravariceal portosystemic shunts may prevent further increases in portal pressure.

Esophageal and Gastric Varices

Portal vein hemodynamics in cirrhotic patients with portal hypertensive gastropathy: an echo-Doppler study.

Portal hypertensive gastropathy is a major complication of cirrhosis. The aims of this study were to characterize portal vein hemodynamics and sympathetic nervous activity in cirrhotic patients with gastropathy. Forty-seven cirrhotics (mild gastropathy in 7) and 25 controls were included in this study. Portal vein hemodynamics was assessed by echo-Doppler, and sympathetic nervous activity by plasma adrenaline and noradrenaline concentrations. Portal blood flow was similar in cirrhotics and controls. However, the congestion index of the portal vein (calculated as the ratio of cross-sectional area and blood velocity) was significantly higher in the former than in the latter. Furthermore, the congestion index of the portal vein paralleled the severity of the gastropathy (ANOVA, p < 0.05). Plasma adrenaline and noradrenaline concentrations were higher in cirrhotics than in controls. However, there was no linear relationship between plasma adrenaline (ANOVA, NS) and noradrenaline (ANOVA, NS) concentrations and the severity of gastropathy. These results suggest a relative contribution of "passive congestion" in the pathogenesis of gastropathy.

Aged

Cardiovascular responsiveness after isotonic exercise in cirrhotic patients: study on sympathoadrenergic and renin-angiotensin systems.

OBJECTIVES: The aim of this study was to evaluate cardiovascular responsiveness after isotonic exercise in cirrhotic patients. METHODS: Included were 11 cirrhotic patients and 10 age-matched normal subjects, who served as controls. Hemodynamic data were obtained on each subject before and after muscle exercise on a treadmill (7 metabolic units). Plasma noradrenaline concentration and plasma renin activity also were determined. RESULTS: In both groups, isotonic exercise increased heart rate and systolic arterial pressure, whereas diastolic arterial pressure was not modified. The increase in heart rate and systolic arterial pressure did not differ significantly between the two groups. Plasma noradrenaline concentration and plasma renin activity also were increased. The changes in plasma noradrenaline concentration and plasma renin activity was higher in cirrhotic patients than in controls (p < 0.05, p < 0.05), although the differences were not significant when calculated as a percentage. CONCLUSIONS: Cardiovascular responsiveness to isotonic exercise is almost intact in cirrhotic patients. However, supernormal activation of the sympathoadrenergic and renin-angiotensin systems is required to maintain cardiovascular homeostasis in these patients.

Adult

Influences of nonpulsatile pulmonary flow on pulmonary function. Evaluation in a chronic animal model.

To clarify the influences of nonpulsatile blood flow on the physiologic function of the lung, we established nonpulsatile pulmonary circulation with a centrifugal pump in a chronic animal model (adult goats, n = 6). As the initial phase, a pulsatile right ventricular assist device was implanted to bypass the whole blood supply from both the right atrium and right ventricle to the pulmonary artery. After 2 weeks of pumping, the pulsatile pump was replaced with a centrifugal pump without anesthesia, and nonpulsatile pulmonary circulation was instituted. In this experimental model, no significant change was observed in either mean pulmonary arterial pressure or pulmonary vascular resistance index during the pulsatile pumping compared with that on the fourteenth day of nonpulsatile pumping. Blood gas data, extravascular lung water content, and serum level of angiotensin-converting enzyme were maintained within normal ranges. There was also no significant change in the ventral to dorsal blood perfusion ratio of the lower lobe of the right lung. These results indicate that pulmonary functions are not affected by nonpulsatile pulmonary circulation for a period of 14 days in this animal model.

Animals

Reduced portosystemic hemodynamic responsiveness after orthostasis in patients with cirrhosis.

We studied portosystemic hemodynamic responsiveness after 1 min orthostasis in nine patients with cirrhosis and nine age-matched normal subjects. Orthostasis increased diastolic arterial pressure, which is a close indicator of arterial tone, in normal subjects (+17%, P < 0.01). In contrast, no significant change in diastolic arterial pressure was observed in patients with cirrhosis (-3%, NS). The increase in heart rate was less in patients with cirrhosis than in normal subjects (+15% vs +28%, P < 0.05). Orthostasis also decreased portal blood flow, which was assessed by an echo-Doppler flowmetry, in normal subjects (-27%, P < 0.01), but in patients with cirrhosis it was not modified (-3%, NS). Plasma noradrenaline concentration showed similar increase in both groups (normal vs cirrhosis; +61% vs +55%, NS). Although the change in plasma noradrenaline concentration was related with that in diastolic arterial pressure (r = 0.71, P < 0.05) and inversely with that in portal blood flow (r = -0.69, P < 0.05) in normal subjects, no such significant correlation was found in patients with cirrhosis. We conclude that (1) a reduced hemodynamic responsiveness to sympathetic stimulation exists on both systemic and portohepatic vascular beds and (2) such a blunted baroreflex function is probably located at the receptor or effector level in patients with cirrhosis.

Adult

Effects of vasopressin and nicardipine on hemodynamics and liver function in patients with cirrhosis: comparison with vasopressin alone.

The effects of a combination of vasopressin and a calcium channel blocker (nicardipine) on portohepatic hemodynamics and liver function were compared with the effects of vasopressin alone in 18 patients with portal hypertension. Nine patients received 0.4 units/min of vasopressin and 9 patients received the same dose of vasopressin plus 0.3 mg/min of nicardipine for 40 min. Vasopressin plus nicardipine induced a significant reduction in both free portal venous pressure and the portal venous pressure gradient. These effects were similar to the changes with vasopressin alone (-14% vs. -16% in free portal venous pressure; -29% vs. -31% in portal venous pressure gradient). Vasopressin decreased both hepatic blood flow (-34%, P < 0.01) and intrinsic clearance of indocyanine green (-22%, P < 0.05). In contrast, these two parameters did not significantly change after vasopressin plus nicardipine (-8% and -3%, respectively). These results suggest that the addition of nicardipine improves hepatic impairment induced by vasopressin but causes no further reduction on portal pressure.

Aged

Observer agreement and variability in measuring gastric mucosal blood flow by laser Doppler flowmetry in humans.

We evaluated the reliability (i.e. reproducibility and variability) in measuring regional gastric mucosal blood flow by laser Doppler flowmetry in a total of 32 subjects (12 normal subjects and 20 patients with cirrhosis). The measurements were performed in quadruplicate within 10 min by observer A (A1, A2) and B (B1, B2) using blind techniques. The intraclass correlation coefficient (Ri) was used to assess observer agreement. Overall, the level of intra- (Ri, 0.87 for A1 vs. A2 and 0.87 for B1 vs. B2) and interobserver agreement (0.86 for A vs. B) was excellent. In contrast, there was a higher observer variability assessed by coefficient of variation. Overall, the mean value of coefficient of variation was 12% (max. 35%) for A1 vs. A2, 12% (max. 35%) for B1 vs. B2, and 13% (max. 33%) for A vs. B. These results suggest that laser Doppler flowmetry, although the reproducibility may be clinically acceptable, seems to still be a subjective method for quantitation of gastric mucosal blood flow in humans. Therefore, studies using this method can only be acceptable when the changes that investigators intend to measure are significantly higher than the variability.

Adult

A flow visualization study of centrifugal blood pumps developed for long-term usage.

We have developed centrifugal pumps for long-term circulatory assistance, with the final goal of a completely implantable ventricular assist device or total artificial heart. The previous model, NCVC-0, was characterized by a nonseal design and few flow-stagnating parts and acquired high durability and antithrombogenicity. To improve its pumping performance, NCVC-0 was modified. In the new model, NCVC-1, the profile shape of the impeller was changed from flat to conical, the number of vanes from 4 to 6, and the vane entrance angle from 30 degrees to 60 degrees. A flow visualization study performed by means of a combination of the polystyrene tracer method and the light-cutting method indicated decreased flow turbulence between vanes in NCVC-1, which corresponded well with the increased pumping performance. Flow visualization is a useful method to evaluate the design elements that are closely related to the pumping performance of a centrifugal blood pump.

Equipment Design

Reduced gastric mucosal blood flow in patients with portal-hypertensive gastropathy.

Although congestive gastric mucosal circulation has been suggested in patients with portal-hypertensive gastropathy, whether it is due to "active" (overflow) or "passive" (stasis) congestion is not known. To answer this question, we assessed regional gastric mucosal blood flow with laser Doppler flowmetry in 57 patients with portal hypertension and 30 controls. Twelve patients had portal-hypertensive gastropathy of the antrum: in eight it was mild and in four it was severe. Portal-hypertensive gastropathy of the corpus was seen in 32 patients: it was mild in 24 and severe in 8. Thus prevalence of portal-hypertensive gastropathy was higher in the corpus than in the antrum (p < 0.01). In the antrum, gastric mucosal blood flow was significantly lower (p < 0.05) in patients with severe portal-hypertensive gastropathy (0.54 +/- 0.27 V) than in controls (1.12 +/- 0.44 V), whereas the values in patients without portal-hypertensive gastropathy (0.90 +/- 0.35 V) and with mild portal-hypertensive gastropathy (0.91 +/- 0.31 V) were not significantly different from the values in controls (p < 0.05 on one-way analysis of variance). In the corpus, gastric mucosal blood flow was significantly lower in patients with mild (0.75 +/- 0.25 V) or severe portal-hypertensive gastropathy (0.42 +/- 0.22 V) than in controls (1.16 +/- 0.37 V) (p < 0.01 and p < 0.01, respectively) whereas the value in patients without portal-hypertensive gastropathy (0.99 +/- 0.37 V) was not significantly different from values in controls (p < 0.01 on one-way analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Nicardipine infusion improved hepatic function but failed to reduce hepatic venous pressure gradient in patients with cirrhosis.

We investigated the effects of nicardipine on systemic and splanchnic hemodynamics and on liver function in 16 patients with cirrhosis and portal hypertension. Patients received a continuous infusion of 0.3 mg/min of nicardipine (n = 10) and a control infusion (n = 6). No significant changes were observed after a control infusion. In contrast, systemic vasodilatation, evidenced by a significant fall in mean arterial pressure (-14%, p less than 0.01) and systemic vascular resistance (-30%, p less than 0.01), increased heart rate (+8%, p less than 0.01) and cardiac output (+21%, p less than 0.01), and increased hepatic blood flow (+43%, p less than 0.01) were observed at 60 min after a continuous infusion of nicardipine. Although nicardipine improved hepatic function (intrinsic clearance from 0.29 +/- 0.13 to 0.33 +/- 0.15 L/min, p less than 0.05), portal pressure evaluated by hepatic venous pressure gradient was not reduced significantly (from 16.3 +/- 4.9 to 15.1 +/- 5.7 mm Hg; NS). We conclude that a continuous infusion of nicardipine improves liver function but has no beneficial effect on portal pressure in patients with cirrhosis.

Adult

Portohepatic pressures, hepatic function, and blood gases in the combination of nitroglycerin and vasopressin: search for additive effects in cirrhotic portal hypertension.

We studied the effects of the combination of nitroglycerin and vasopressin on portohepatic hemodynamics, hepatic function, and blood gases in nine patients with cirrhosis and portal hypertension. Vasopressin infusion at a dose of 0.4 U/min caused a significant fall in portal pressure, which is evaluated by portal venous pressure gradient (-34%, p less than 0.01), associated with a decrease in hepatic perfusion (-33%, p less than 0.01) and intrinsic clearance (-20%, p less than 0.01) after 30 min. The arterial oxygenation, however, was not modified (paO2; from 73 +/- 8 to 72 +/- 7 mm Hg, NS). Nitroglycerin infusion at a dose of 100 micrograms/min was then administered for 20 min. The addition of nitroglycerin produced a further reduction in free portal venous pressure (-12%, p less than 0.01), but this was not associated with a significant improvement in both hepatic perfusion (+16%, NS) and intrinsic clearance (-7%, NS). In addition, there was a significant fall in arterial oxygenation (paO2; from 72 +/- 7 to 59 +/- 5 mm Hg, p less than 0.01). We conclude that the addition of nitroglycerin to vasopressin has a beneficial effect on free portal venous pressure, but does not have hepatic benefit. Moreover, sufficient care must be taken, when treating portal hypertension with this combination, to avoid arterial hypoxemia.

Aged

[Serotypes and antibiotic sensitivity of hemolytic streptococci isolated from clinical specimens in Hiroshima Prefecture, 1987-1989].

The grouping, the typing and the drug-sensibility of hemolytic streptococci isolated from the clinical specimens taken from 4 medical centers in Hiroshima Prefecture have been examined and reviewed during the past 3 years 1987-1989. The results were summarized in this report. 1. Of 1572 strains of hemolytic streptococci, 844 strains (53.7%) were group A; 539 strains (34.3%), group B; 14 strains (0.9%), group C; 82 strains (5.2%), group G; and 93 strains (5.9%), the others. We found that group A and group B were predominant, and the incidence rate of group B was higher than it used to be. 2. The prevalent types were T-4 (37.9%), T-1 (13.6%), T-12 (12.0%), and T-28 (10.7%) in group A, while Ia (26.2%), M9 (provisional type 18.4%), and III (14.5%) in group B. 3. As far as the detection data of each month is concluded, during the summer season we could hardly detect group A which peak of occurrence during the winter season. These findings were really consistent with the occurrence pattern of those patients who suffered from streptococcal infectious disease. But this occurrence pattern couldn't be found in group B. 4. In our study, the positive frequency was throat swab greater than urine greater than sputum greater than vaginal swab greater than pus greater than ear secretion in order. Group A was mainly isolated from throat swab, while group B, from several specimens including urine. 5. We found that there was a high drug-sensibility to the beta-lactam drugs in all strains except for 3 strains of group B which were resistant to CEX.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents