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Biomedical subjects

M Hashizume

Publications and source records attributed to M Hashizume.

At least 127 records · Page 7Linked to original sources

[Measurement of platelet thromboxane A2/prostaglandin H2 receptor in asthmatic patients].

To evaluate the characteristics of platelet TXA2/PGH2 receptors in patients with bronchial asthma, we performed radiobinding assay of gel-filtrated washed platelets obtained from 15 asthmatic patients and 8 normal adults using [3H]-labeled S-145, a TXA2/PGH2 receptor antagonist, as a radiolinged. Data were evaluated by Schatchard's analysis, and the dissociation constant (Kd), an index of the binding characteristic of receptors, and the maximum number of binding sites (Bmax) were calculated. Venous blood was simultaneously collected and was centrifuged, and platelet-rich plasma was prepared. The platelet aggregation rates induced by various concentrations of U-46619, a TXA2 analogue, were measured by Born's method (nephelometry), and the concentration that induced 50% of the maximum platelet aggregation (EC50) was calculated using a concentration-response curve. The Kd value did not differ between the asthmatic patients and normal controls. Some of the asthmatic patients showed a low EC50 and a high Bmax. EC50 was inversely correlated with Bmax. The number of platelet TXA2/PGH2 receptors was shown to be increased in some asthmatic patients.

Adult↗

[Oculopharyngeal myopathy with autoimmune disease].

A 34-year-old woman had suffered from systemic lupus erythematosus (SLE) and autoimmune hemolytic anemia (AIHA) in the teen age. She developed progressive ptosis of the eyelids, and difficulty in swallowing and speaking for several years. Endocrinological studies showed primary hypothyroidism. A serum IgG level was elevated (1,973 mg/dl), and antinuclear antibody, thyroid test and microsome test were positive. A muscle biopsy showed massive inflammatory cell infiltrates in the perivascular area in addition to some myopathic change; some variation in fiber size. Immunological staining demonstrated most of these inflammatory cell infiltrates were CD3+ cells and CD4+ cells were counted more than CD8+ cells (CD4/CD8 = 2.3). The diagnoses were confirmed as oculopharyngeal myopathy and Hashimoto's disease. In addition, she had suffered from SLE and AIHA. Therefore we conclude that manifestation of this myopathy may be associated with some autoimmune process.

Adult↗

Laparoscopic ligation of splenic artery aneurysm.

Efforts should be made to avoid splenectomy because host resistance is maintained by the spleen. We describe here a 50-year-old woman in whom laparoscopic ligation of a splenic artery aneurysm 3.0 cm in diameter was successfully performed, without major complications. Computed tomography performed 5 months later revealed no infarction in the spleen. For this patient with liver cirrhosis and cholelithiasis, laparoscopic cholecystectomy was performed at the same operation. Laparoscopic surgery is most feasible when the splenic artery is markedly tortuous and protrudes from the pancreas.

Aneurysm↗

[Study on the inhibitory effect of AA-2414 on platelet aggregation and its clinical effect in asthmatic patients].

We previously reported that AA-2414, an eicosanoid receptor antagonist, inhibits platelet aggregation mediated by TXA2/PGH2 receptors in patients with bronchial asthma, but that the inhibitory effects differ among individuals. In this study, we measured the in vitro inhibition rate of platelet aggregation by AA-2414 using U-46619 as an aggregating agent in 22 asthmatic patients and classified them into Group A (showing an inhibition rate of 60% or more) and Group B (showing a rate of less than 60%). Subsequently, AA-2414 tablets (40 mg/day) were orally administered to both groups for 6 weeks, and the clinical effects were compared. A positive correlation was observed between the in vitro U-46619-induced platelet aggregation rate and the inhibition rate of aggregation by AA-2414. At the end of administration, marked inhibition of U-46619-induced platelet aggregation was observed in all patients. However, Group A showed a higher improvement rate of symptoms than Group B. Asthmatic patients can be classified into the groups showing good or poor platelet responses. The response may reflect reactivity to TXA2 in the local airway.

Adult↗

Albumin inhibits hemolysis of erythrocytes induced by ethanolamine oleate during endoscopic injection sclerotherapy.

In attempts to avoid hemolytic nephropathy following injection of 5% ethanolamine oleate during endoscopic injection sclerotherapy for esophageal varices, the relationship between serum levels of albumin and hemolysis induced by ethanolamine oleate was investigated. The rate of hemolysis at various concentrations of ethanolamine oleate and albumin was examined using a spectrophotometer in ten cirrhotic patients and five healthy volunteers (controls). Hemolysis induced by ethanol-amine oleate increased in an ethanolamine oleate concentration-dependent fashion (p < 0.01) but was dose-dependently inhibited by albumin (p < 0.05). The state of liver function was unrelated to the rate of hemolysis. The relationship between hemoglobinuria and serum albumin levels in seventy-nine cirrhotic patients with esophageal varices treated by endoscopic injection sclerotherapy with ethanolamine oleate was also examined. Hemoglobinuria was evident in 20 out of 24 patients (83.8%) in whom the serum albumin level was less than 3.0 g/dl, and in 24 out of 55 (43.6%) in whom it exceeded 3.0 g/dl, the difference being statistically significant (p < 0.01). On the day after endoscopic injection sclerotherapy, creatinine clearance fell from 81.6 +/- 33.8 m/l min to 60.1 +/- 31.4 ml/min in the hemoglobinuria-positive patients (p > 0.01) and two went into acute renal failure. The creatinine clearance ranged from 79.5 +/- 27.9 ml/min to 83.0 +/- 39.9 ml/min in the hemoglobinuria-negative patients (p < 0.1). In the light of this evidence we correct the serum albumin level cut off point to 3.0 g/dl prior to endoscopic injection sclerotherapy in order to maintain renal function.

Aged↗

Sclerotherapy vs. esophageal transection vs. distal splenorenal shunt for the clinical management of esophageal varices in patients with child class A and B liver function: a prospective randomized trial.

Ninety-six patients with good liver function (Child class A or B) and esophageal varices were randomly assigned to one of three groups given different treatments: endoscopic injection sclerotherapy (n = 32), esophageal transection (n = 32) or distal splenorenal shunt (n = 32). Five patients (5.2%) had to be excluded from this study because severe chronic pancreatitis made separation of the distal splenic vein from the pancreatic bed difficult. Esophageal transection was performed for these patients. No deaths occurred during the 30 days of treatment. The 5-yr cumulative bleeding rates were 0%, 5.9% and 12.9% in the endoscopic injection sclerotherapy, esophageal transection and distal splenorenal shunt groups, respectively (no statistical significance). In no case in the three groups did death occur because of variceal bleeding. Sixteen patients died, mainly because of underlying liver disease; four were in the endoscopic injection sclerotherapy group, five were in the esophageal transection group and seven were in the distal splenorenal shunt group. No statistically significant difference in survival rate among the three groups was found. These results show that endoscopic injection sclerotherapy is a satisfactory alternative to esophageal transection or distal splenorenal shunt for the clinical management of patients with esophageal varices.

Esophageal and Gastric Varices↗

Endoscopic injection sclerotherapy for 1,000 patients with esophageal varices: a nine-year prospective study.

We report here the results of endoscopic injection sclerotherapy performed in 1,000 consecutively treated Japanese patients with esophageal varices. This prospective study covered the period from 1982 to 1990. Variceal bleeding was controlled in 215 (97.7%) of 220 patients. Esophageal varices were completely eradicated in 778 patients (77.8%); the mean number of sessions was 4.2. In only 3 of the 778 patients did esophageal varices of the same size recur. Small, dilated, venous vessels that required additional sclerotherapy in follow-up endoscopy at 3-mo intervals appeared in 171 (22.2%) of 778 patients. The cumulative nonbleeding rate at 5 yr was 94.5% in patients in whom the varices had been eradicated. Deaths caused by upper gastrointestinal bleeding accounted for 2.6% of cases, whereas the rates of liver failure and hepatoma were 4.6% and 47.3%, respectively. The 5-yr cumulative survival rate was 54.1% in patients without concomitant hepatoma; it was 12.0% in patients with hepatomas. Multivariate analysis showed that hepatoma, Child classification, indication (acute, elective or prophylactic) and eradication were independent factors that significantly influenced survival time. This study clearly shows that close follow-up with endoscopy and complete eradication lead to significant reduction in bleeding from esophageal varices and reduction of mortality related to this bleeding.

Endoscopy↗

Improvement of large intestinal absorption of insulin by chemical modification with palmitic acid in rats.

The intestinal absorption of 125I-labelled palmitoyl insulin was examined following administration into in-situ closed large intestinal loops of rats. When mono- and dipalmitoyl insulins (Palins-1 and Palins-2, respectively) were administered in polyoxyethylene hydrogenated castor oil (HCO 60) micellar system into intestinal loops, a marked increase in plasma radioactivity and a corresponding disappearance of residual radioactivity in the intestinal lumen were observed in the following rank order: Palins-2 greater than Palins-1 greater than native insulin. In addition, the derivatives were more stable than native insulin in the mucosal tissue homogenates of the large intestine. These results suggest that chemical modification of insulin with palmitic acid may not only increase the lipophilicity of insulin but also reduce its degradation, resulting in the increased transfer of insulin across the large intestinal mucous membrane. The linoleic acid-HCO 60 mixed micelles system did not have a significant effect on the large intestinal absorption of radioactivity associated with the lipophilic insulin analogues.

Animals↗

[Surgical versus non-surgical treatment in patients with esophageal varices--a prospective randomized study].

In Japan, non-shunting procedures and selective shunt such as esophageal transection (ET), and distal splenorenal shunt (DSRS) have been widely performed. A prospective randomized trial was done to assess the effects of EIS and DSRS for treating patients with esophageal varices. Ninety-six Japanese with good liver function (Child A or B) and large esophageal varices were randomly assigned to one of three groups given different treatments; (EIS, n = 32), (ET, n = 32) and (DSRS, n = 32). Five patients (15.6%) of the DSRS group has to be excluded from this study, because of severe chronic pancreatitis. No patient died within 30 days of the treatments. The 5-year cumulative bleeding rates were 0%, 4.3% and 12.1% in the EIS, ET and DSRS groups, respectively, with no statistical significances. In no case in the three groups did the death occur because of variceal bleeding. Nineteen patients died mainly due to the underlying liver disease; 5 in the EIS, 5 in the ET and 9 in the DSRS group. There was no statistically significant difference in the survival rates among the three groups. We conclude that EIS is a satisfactory alternative to ET or DSRS for the management of patients with large esophageal varices.

Adult↗

Splenic hyperkinetic state and splenic artery aneurysm in portal hypertension.

Forty-eight out of six hundred and thirty patients with portal hypertension undergoing a celiac angiography series were diagnosed as cases of splenic artery aneurysm during the period 1977-1988. The case-control study of patients with portal hypertension with splenic artery aneurysms and those without was designed to characterize the angiological features. The splenic arterial flow was assessed by measuring the radii of the splenic arteries on celiac arteriograms. In the portal hypertensive patients with splenic artery aneurysms, the splenic artery was larger (p < 0.05) and the splenic arterial flow greater (p < 0.05), and these patients were in a more hyperkinetic state, than were those with no splenic artery aneurysm. The study suggests that splenic artery aneurysms in cases of portal hypertension may be the consequence of a hyperkinetic state in the spleen.

Adolescent↗

Comparative effects of 5% ethanolamine oleate versus 5% ethanolamine oleate plus 1% polidocanol for sclerosing esophageal varices.

Sixty-six patients with portal hypertension and esophageal varices due to liver cirrhosis were randomized to receive either 5% ethanolamine oleate (EO) or 5% EO plus 1% polidocanol (EOP) as a sclerosant for endoscopic injection sclerotherapy (EIS). The two groups were well matched with regard to age, sex and the severity of liver disease. In no patient in the two groups was there any major complication, such as esophageal perforation or esophageal bleeding. Eradication of esophageal varices was attained with an average of 4.7 and 4.3 sessions of endoscopic injection sclerotherapy in the ethanolamine oleate and polidocanol groups, respectively. Data on one patient in the ethanolamine oleate group had to be excluded because he left the hospital after 2 sessions of endoscopic injection sclerotherapy. Esophageal ulcers occurred earlier in the polidocanol group (after an average of 2.8 weeks) than in the ethanolamine oleate group (3.8 weeks), the difference being statistically significant (P < 0.01). The rate of occurrence of esophageal stricture requiring more than 2 sessions of bougienage was significantly (P < 0.01) higher in the polidocanol group (16/33, 48%) than in the ethanolamine oleate group (4/32, 12%). This study suggests that the two sclerosants have equal efficacy for treating patients with esophageal varices. With polidocanol there was ulceration and stricture in the distal esophagus.

Drug Combinations↗

[Clinical studies of panipenem/betamipron in pediatrics].

We conducted clinical studies on panipenem/betamipron (PAPM/BP), a newly developed parenteral carbapenem antibiotic, for its clinical application in the field of pediatrics. 1. A clinical study was performed on 13 children with infections, including 6 with acute bronchopneumonia, 1 each with acute pharyngitis, acute bronchitis, sepsis, staphylococcal scalded skin syndrome, urinary tract infection, subcutaneous abscess and furuncle. PAPM/BP was administered by intravenous drip infusion. Doses varied from 12 to 27 mg/kg body weight were given t.i.d. or q.i.d. Lengths of treatment ranged from 4 to 25 days. Clinical efficacies were excellent in 3 and good in 9 cases, with an efficacy rate of 92%. 2. No adverse reactions were observed. In laboratory tests, elevations of GOT, GPT and urobilinogen were observed in 3 cases. It was concluded that PAPM/BP was a promising drug for the treatment of bacterial infections in children.

Adolescent↗

[alpha-Interferon in the treatment of essential thrombocythemia].

Two patients with essential thrombocythemia were successfully treated by administering native alpha-interferon (alpha-IFN). One patient was a 38-year-old man in whom thrombocytosis was found accidentally. His platelet count on admission was 880,000/microliters and megakaryocytes increased. Three million units of alpha-IFN was administered subcutaneously everyday, and the platelet count decreased gradually to about 500,000/microliters within 2 weeks. The other patient was a 66-year-old woman who visited our hospital complaining of tenderness and swelling of the fingertips. Her platelet count was 1,610,000/microliters, and megakaryocytes increased and showed abnormal morphology. Six million units of alpha-IFN was administered subcutaneously every other day. The tenderness and swelling of the fingertips disappeared soon after the beginning of alpha-IFN administration. The platelet count decreased to about 500,000/microliters within 10 days, but she developed itching of the skin over the entire body. Therefore, alpha-IFN treatment was discontinued. It was suggested that alpha-IFN suppresses not only the maturation and proliferation of the progenitors of megakaryocytes but also the production of platelets from megakaryocytes. Administration of alpha-IFN should be considered in treating patients with essential thrombocythemia, because effects appear soon and alpha-IFN does not induce a second malignancy.

Adult↗

ATP diphosphohydrolase is responsible for ecto-ATPase and ecto-ADPase activities in bovine aorta endothelial and smooth muscle cells.

An ATP diphosphohydrolase (EC 3.6.1.5) is an enzyme hydrolyzing pyrophosphate bonds in nucleoside di- and triphosphates with broad substrate specificity in the presence of divalent cations. The ATPase and ADPase activities in the enzyme purified to homogeneity from bovine aortic vessel wall were insensitive to oligomycin, ouabain, and various protease treatments, and sensitive to azide and Ap5A. Bovine aorta endothelial and smooth muscle cells were cultured separately to characterize the ectonucleotidase activities. The activities were dependent on the addition of divalent cations and had broad substrate specificity. The ecto-ATPase and -ADPase activities were insensitive to oligomycin, ouabain, and protease treatments, and sensitive to azide and Ap5A. No enzyme degrading only ADP was found in the aortic vessel wall. Moreover, antiserum raised against purified ATP diphosphohydrolase inhibited the ecto-ATPase and -ADPase activities. These results indicated that ecto-ATPase and ecto-ADPase are not separate enzymes but are expressed by one enzyme, ATP diphosphohydrolase.

Adenine Nucleotides↗

High rate of portal thrombosis after splenectomy in patients with esophageal varices and idiopathic portal hypertension.

Data on 126 consecutive patients who were admitted to our clinics from January 1979 to May 1989 were scrutinized to assess changes in portal hemodynamics following splenectomy. Two groups were classified: (1) a group of 106 patients with cirrhosis of the liver and (2) a group of 20 patients with idiopathic portal hypertension (IPH). Portal thrombosis was present in five (25.0%) of the 20 patients with IPH and in two (1.8%) of the 106 patients with cirrhosis of the liver. As seen on celiac arteriography, the mean (+/- SD) diameter of the trunk of the splenic artery and vein was 8.99 +/- 1.55 and 16.2 +/- 3.6 mm, respectively, in patients with IPH, while it was 7.94 +/- 1.28 and 14.2 +/- 3.1 mm, respectively, in patients with cirrhosis of the liver. Changes in portal venous pressure were 78.4 +/- 59.4 mm H2O in patients with IPH and 43.5 +/- 38.7 mm H2O in patients with cirrhosis of the liver. There were no significant differences in the maximum level of thrombocytes in patients with IPH or in those patients with cirrhosis of the liver. These events suggest that portal thrombosis can occur with a significantly higher incidence in patients with IPH than in those patients with cirrhosis of the liver after splenectomy, and a decrease in blood flow in the portal vein may be closely linked to the formation of portal thrombosis after splenectomy in patients with IPH. Preoperative examination of portal hemodynamics must be thorough.

Esophageal and Gastric Varices↗

Platelet aggregability and prostacyclin/thromboxane A2 ratio after endoscopic injection sclerotherapy with different sclerosants.

Platelet aggregability and coagulative and fibrinolytic systems were analyzed with regard to positive effects and for side effects of 5% ethanolamine oleate (EO) versus 5% sodium morrhuate (SM) used for endoscopic injection sclerotherapy (EIS). Twelve patients each were treated with each sclerosant. There was a temporary activation of coagulative and fibrinolytic systems within 1 h in both groups. Platelet aggregability was significantly suppressed to 78.6 +/- 8.9% of that before EIS in the EO group, but was activated to 110.0 +/- 10.5% in the SM group at 1 h after EIS. The ratio of concentrations of prostacyclin (PGI2) to thromboxane A2 (TXA2) increased in the EO group and decreased in the SM group after EIS. The clinical effect in the SM group after the initial session was weaker than that in the EO group with regard to endoscopic findings at the second session. As change in platelet aggregability after EIS is apparently induced by alterations in the ratio of PGI2/TXA2, there would be related effects concerning the sclerosants.

Adult↗