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Biomedical subjects

A Yoshikawa

Publications and source records attributed to A Yoshikawa.

At least 19 recordsLinked to original sources

Stomach-partitioning gastrojejunostomy for unresectable gastric carcinoma.

OBJECTIVES: To analyze the results of a new type of bypass procedure, stomach-partitioning gastrojejunostomy (SPGJ), for unresectable gastric carcinoma and to compare these results with those of conventional gastrojejunostomy (GJ). DESIGN: Retrospective review. SETTING: A university hospital in Japan. PATIENTS: Eight patients underwent SPGJ in 1 group, and 13 underwent conventional GJ in the other group. Staging was determined using preoperative diagnostic imagings and intraoperative findings. MAIN OUTCOME MEASURES: Assessment of food intake and mean survival rates. RESULTS: There were no significant differences between the 2 groups regarding male-female ratio, mean age, and histological type of carcinoma. All patients had stage IV cancers according to the classification of the Union Internationale Contre le Cancer. The rates of taking a regular meal at 2 weeks after an operation were 88% in the SPGJ group and 31% in the GJ group (P < .05). The mean 1-year survival rates for SPGJ and GJ groups were 42.9% and 7.7%, respectively (P < .05). The mean survival times were 13.4 months in the SPGJ group and 5.8 months in the GJ group (P < .05). CONCLUSIONS: Stomach-partitioning gastrojejunostomy achieved an improved quality of life and a better prognosis for patients, and it is the preferred bypass procedure for unresectable gastric carcinoma.

Aged

Infection with hepatitis G virus and its strain variant, the GB agent (GBV-C), among blood donors in Japan.

BACKGROUND: The purpose of the study was to survey the epidemiology of recently reported non-A through -E hepatitis virus designated hepatitis G virus (HGV) and its strain variant, the GB agent (GBV-C). STUDY DESIGN AND METHODS: Pilot samples from 2461 blood donors in Japan, randomly selected to form cohorts with different levels of alanine aminotransferase (ALT) and markers of hepatitis B virus or hepatitis C virus (HCV) infection, were tested for RNA of HGV/GBV-C by reverse transcription-polymerase chain reaction with nested primers deduced from the 5'-noncoding region. RESULTS: HGV/GBV-C RNA was detected in 23 (7.4%) of the 361 donors with anti-HCV and HCV RNA. This detection is more frequent than that in donors without elevated ALT levels (< or = 45 U/L) or markers of HCV or hepatitis B virus infection (15/1303; 1.2%) (p < 0.001), donors with ALT values between 46 and 99 U per L (0/108) (p < 0.002), donors with ALT values > or = 100 U per L (5/361; 1.4%), and donors with anti-HCV but without detectable HCV RNA (1/93; 1.1%) (p < 0.05). CONCLUSION: More than 1 percent of Japanese blood donors were infected with HGV/GBV-C, and the prevalence was much higher in those with HCV RNA. Should persistent infection with HGV/GBV-C induce any hepatotoxic sequelae, either alone or in concert with the other hepatitis viruses, screening of blood units for HGV/GBV-C would deserve consideration.

Adult

Factors associated with survival exceeding 5 years after transcatheter arterial embolization for hepatocellular carcinoma.

During the period between April 1981 and March 1988, 232 consecutive patients underwent transcatheter arterial embolization (TAE) for hepatocellular carcinoma at the Department of Radiology, Wakayama Medical College. A > or = 5-year course calculated from the time of the initial TAE was able to be confirmed in 216 patients, who became the subjects of this study. Five-year survival rates were calculated by the direct method, while the clinical features existing at the time of the initial therapy and the clinical course of patients surviving > or = 5 years were studied. The 5-year survival rate was 6.0%. Comparison of the patients dying within 1 year and the patients surviving for > or = 5 years revealed differences in the severity of liver cirrhosis and the tumor type. The long-term survivors tended to have low serum alpha-fetoprotein values. The clinical picture of the patients surviving > or = 5 years after TAE was characterized by relatively mild liver cirrhosis (Child's class A or B), a serum alpha-fetoprotein value of < or = 1,500 ng/dL, relatively small nodular-type tumors with a maximum main tumor diameter of < or = 5.5 cm, a tumor-occupying rate of less than 20%, and absence of portal vein involvement by the tumor. There were patients in whom a relatively small number of TAE sessions was effective in controlling the tumor for a prolonged period, with the patients then dying of causes unrelated to the tumor, as well as patients in whom proliferation of the tumor was controlled by numerous applications of transcatheter therapy, resulting in > or = 5-year survival but with eventual death due to the tumor. Transcatheter arterial embolization makes a major contribution to achieving long-term survival of > or = 5 years in patients with hepatocellular carcinoma.

Adult

[Evaluation of hepatic encephalopathy and portal hemodynamics by Doppler ultrasonography after a transjugular intrahepatic portosystemic shunt].

TIPS (transjugular intrahepatic portosystemic shunt) is an efficacious treatment for esophagogastric varices, ascites and hypertensive gastrointestinal vasculopathy associated with portal hypertension. The main complication after the procedure is hepatic encephalopathy. We tried to elucidate the correlation between hepatic encephalopathy and changes in portal hemodynamics after TIPS, based on observation by Doppler ultrasonography. We carried out Doppler ultrasonography in 28 cases of TIPS to assess hepatopetal and hepatofugal blood flow in the right and left portal branches. Hepatic encephalopathy occurred after TIPS in 9 cases out of 28 (32%), and new onset of disease was observed in 6 of 9. Doppler ultrasonography revealed hepatofugal blood flow in both right and left portal branches in 6 cases, 5 of which showed encephalopathy. Hepatopetal blood flow of the right and left portal branches was observed in 17 of 28 cases after TIPS. Hepatic encephalopathy occurred in only 2 of 17 cases. The changes in portal vein hemodynamics after TIPS were investigated by color Doppler ultrasonography, which were considered to be very useful for prediction of hepatic encephalopathy and indication of medical treatment to prevent the occurrence of this disease.

Adult

Point mutations of the topoisomerase IIalpha gene in patients with small cell lung cancer treated with etoposide.

Reverse transcription-PCR-single-strand conformation polymorphism analysis was performed to detect topoisomerase IIalpha mutations using total RNA from 19 bronchial biopsy specimens obtained from 13 patients with small cell lung cancer. An abnormally migrating single-strand conformation polymorphism band was observed in one tumor sample from a patient treated with etoposide-containing chemotherapy. DNA sequence analysis of this tumor showed two transversions at codons 486 (G to A) and 494 (A to G), resulting in two missense mutations (Arg to Lys and Glu to Gly, respectively). The codon 486 mutation was identical to that previously found in two cell lines selected for amsacrine resistance. These results demonstrate that mutations of topoisomerase IIalpha occur in patients with small cell lung cancer. The significance of these mutations in the development of resistance to etoposide needs further investigation.

Aged

Technology and staffing in Japanese university hospitals. Government versus private.

We examined staffing levels, acquisition of medical technologies, and utilization of those technologies in private and government teaching hospitals in Japan. Adjusting for size and case mix, we found that government hospitals acquire more technology, use that technology less, and employ a more highly skilled staff than do private hospitals.

Diffusion of Innovation

Buffering of plasmalemmal Ca2+ current by sarcoplasmic reticulum of guinea pig urinary bladder myocytes.

The effects of cyclopiazonic acid (CPA), an inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), on cytosolic Ca2+ concentration ([Ca2+]c) and membrane currents were studied in isolated urinary bladder myocytes to test the hypothesis that the sarcoplasmic reticulum (SR) buffers Ca2+, which enters the myocyte at a slow to moderate rate. Inhibition of SERCA by CPA was demonstrated by the following modifications of the caffeine-induced [Ca2+]c transients: 1) CPA prolonged the 90% decay time from peak to resting [Ca2+]c from 2.2 +/- 0.3 to 8.3 +/- 0.92 s (n = 5), 2) CPA abolished the "undershoot" of the [Ca2+]c transient that follows the washout of caffeine, and 3) CPA prevented caffeine from inducing a second [Ca2+]c transient. CPA reversibly increased resting [Ca2+]c. Starting from a control [Ca2+]c of 137 +/- 10 nM, 19 of 24 cells responded with a monotonic increase in [Ca2+]c to a steady [Ca2+]c of 238 +/- 10 nM, whereas 5 of 24 cells responded with a transient rise of [Ca2+]c to 472 nM (within 2.8 +/- 0.5 s) followed by a decay to a steady [Ca2+]c of 161 +/- 10 nM. The CPA-mediated rise in [Ca2+]c was augmented by increasing extracellular Ca2+ concentration ([Ca2+]o), suggesting a "leakage pathway" for Ca2+ influx that is unmasked by SERCA blockade. CPA reduced [Ca2+]c transients and Ca(2+)-activated K+ currents (IK,Ca), induced by depolarizing clamp steps from -60 to 0 mV, compatible with suppression of SR Ca2+ release on depletion of SR Ca2+. To reduce the contribution due to Ca(2+)-induced Ca2+ release, the cells were depolarized with a slow ramplike command (-60 to 0 mV, 15 mV/s). In 12 of these 40 cells, CPA increased [Ca2+]c and IK,Ca signals. If spontaneous transient outward currents were present, they were suppressed by CPA. CPA reduced the peak L-type Ca2+ channel current apparently through increased Ca2+ inactivation of voltage-gated Ca2+ channels. The current could be restored to control by elevating [Ca2+]o from 2.5 to 5 mM. Under these conditions, CPA increased the ramp-induced [Ca2+]c transients from 105.1 +/- 22 to 162.0 +/- 31 nM (n = 9, P < 0.05). These results suggest that Ca2+ sequestration by the SR can buffer part of the Ca2+ influx during slow depolarizations.

Animals

[Treatment of advanced gastric carcinoma based on histologic type].

It is well known that clinicopathological characteristics in gastric carcinoma are different according to its histologic type, intestinal type or diffuse type. Multivariate analysis of advanced gastric carcinoma revealed that the histologic type significantly related to the type of recurrence, hematogenous metastasis or peritoneal dissemination. Therefore, we introduced a prospective randomized trial for treatment of advanced gastric carcinoma based on histologic type of carcinoma. Intraoperatively, 10 mg of mitomycin C was given via portal system in the intestinal type and given in peritoneal cavity in the diffuse type. As results, in the intestinal type, survival rate in patients with the chemotherapy was longer than that without the chemotherapy, but this did not reach to a significant difference. On the contrary, in the diffuse type, patients with the chemotherapy showed a significant longer survival rate compared to those without the chemotherapy. These results suggests the availability of treatment based on histologic type of carcinoma. Much more selective and effective improvements in this type of treatment will be required.

Antineoplastic Combined Chemotherapy Protocols

Evaluation of the pharyngeal airway in obstructive sleep apnea: study by ultrafast MR imaging.

To evaluate dynamic morphologic changes of the respiratory tract in patients with obstructive sleep apnea syndrome (OSAS), the cross section and the midline sagittal section of the upper respiratory tract of OSAS were examined using ultrafast MR imaging technique. In 10 men and 2 women diagnosed with OSAS, 30 images obtained in 30-90 s at each location of sagittal and multilevel transverse sections were observed with cineloop display in awake and sleeping status. No patients had complete pharyngeal obstruction while awake. On the other hand, 9 patients had at least one occluded site, and 3 patients had wider obstructed sites during sleep. We are convinced that ultrafast MR imaging is very useful in determining the indication and the method for surgical treatment for OSAS.

Adult

Distinct signal transduction through the tyrosine-containing domains of the granulocyte colony-stimulating factor receptor.

The receptor for granulocyte colony-stimulating factor (G-CSFR) is a hemopoietic growth factor receptor, which mediates proliferation and differentiation signals. The cytoplasmic region of G-CSFR carries four tyrosine residues in its C-terminal half. We constructed mutant receptors in which each tyrosine residue of G-CSFR was mutated to phenylalanine. Two mutant receptors (Tyr703 and Tyr728) neither transduced the growth-inhibitory signal nor induced the neutrophil-specific myeloperoxidase (MPO) gene. The Tyr703 mutant did not induce morphological changes in cells, whereas transformants expressing the Tyr728 mutant adhered to plates with a macrophage-like morphology upon G-CSF stimulation. Mutation of the most distal tyrosine residue (Tyr763) abolished the ability of G-CSFR to stimulate the tyrosine phosphorylation of a cellular protein with an M(r) of 54 kDa. These results indicated that the regions around the three tyrosine residues of G-CSFR play essential and distinct roles in signal transduction.

Animals

Relationship between the pharmacokinetics of irinotecan and diarrhea during combination chemotherapy with cisplatin.

Two phase I trials of irinotecan (CPT-11) in combination with cisplatin were conducted. In both cases, the dose-limiting toxicities were leukopenia and/or diarrhea. During these trials the pharmacokinetics of CPT-11 and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), were investigated to evaluate the relationship between pharmacokinetic parameters and diarrhea, since this is an unpredictable and severe toxicity of combination chemotherapy using CPT-11 and cisplatin. Twenty-three previously untreated patients with advanced lung cancer were evaluated in the pharmacokinetic study. Ten patients received CPT-11 at 80 or 90 mg/m2 plus cisplatin at 60 mg/m2. The other 13 patients received CPT-11 at 80 or 90 mg/m2 plus cisplatin at 80 mg/m2 with the granulocyte colony-stimulating factor support (2 micrograms/kg x 16 days). CPT-11 was given as a 90-min intravenous infusion on days 1, 8, and 15. Cisplatin was given on day 1. The pharmacokinetics of CPT-11 and SN-38 were analyzed on day 8 during the first course of treatment. The maximum tolerated dose of CPT-11 was 90 mg/m2 in both phase I trials. The severity of diarrhea was best correlated with the peak plasma concentration of SN-38 among the pharmacokinetic parameters tested. In addition, patients with a plasma SN-38 level > 12.4 ng/ml at 1.75 h after the start of CPT-11 infusion had a higher incidence of Eastern Cooperative Oncology Group grade 3-4 diarrhea than those with a lower SN-38 level (P = 0.0003). Stepwise logistic regression analysis identified the SN-38 concentration as a significant contributor to the development of diarrhea (P = 0.0021). We conclude that there is a clear relationship between the SN-38 concentration and diarrhea during chemotherapy with CPT-11 plus cisplatin.

Adult

Acetylcholine-sensitive intracellular Ca2+ store in fresh endothelial cells and evidence for ryanodine receptors.

In a freshly isolated endothelial cell preparation from rabbit aorta, the regulation of the acetylcholine (ACh)-sensitive intracellular Ca2+ store and the effects of the Ca(2+)-induced Ca2+ release agonists ryanodine and caffeine were studied using fura 2 imaging fluorescence microscopy. ACh (10 mumol/L) caused a transient release of Ca2+ from an intracellular store, presumably via an inositol tris-phosphate-sensitive mechanism. This ACh response could be repeated in the presence of extracellular Ca2+ but was obtained only once in Ca(2+)-free bathing solution, which shows that a depleted intracellular Ca2+ store can be rapidly refilled from the extracellular space. Refilling can be prevented by the endoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid (10 mumol/L), implying that Ca2+ enters the cytoplasm before accumulation in the endoplasmic reticulum. Ionomycin (10 mumol/L) caused a large Ca2+ release even after the ACh-releasable store had been emptied, indicating the existence of other ACh-insensitive stores, perhaps including the mitochondria. In one third of the cells studied, ACh induced oscillations in [Ca2+]i that were dependent on extracellular Ca2+. Also investigated were the effects of caffeine and ryanodine. In this cell preparation neither caffeine nor ryanodine induced a Ca2+ transient but instead slowly increased [Ca2+]i. It was observed that both caffeine and ryanodine were able to slowly deplete the ACh-sensitive store. These results indicate the presence of functional ryanodine receptors in native endothelial cells and demonstrate overlap between the caffeine and agonist-sensitive Ca2+ stores. We also found that caffeine was able to directly inhibit the process of ACh-induced Ca2+ release.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Linear transverse forehead incision for patients with alopecia praematura--technical note.

A method for craniotomy via a transverse linear scalp incision on the forehead wrinkle line with cosmetic reconstruction is described. The method requires minimal knowledge of plastic surgical techniques. Operative scars are inconspicuous and the normal appearance of the forehead can be retained, which is especially valuable for patients with alopecia praematura.

Adult

The effect of copayments and income on the utilization of medical care by subscribers to Japan's National Health Insurance System.

This study uses cross-sectional data from Japan's 47 prefectures covering subscribers to Japan's National Health Insurance system to analyze the effects of income and copayment levels on the utilization of medical care. Multivariate regression models were run for the years 1984 and 1989, with the utilization ratio (number of health insurance claims per 100 insurance subscribers) for total, inpatient, outpatient, and dental services as the dependent variable. Independent variables included copayment per patient day, deflated per capita income, population density, percentage of subscribers over age 65, number of beds and clinics per 1,000 persons, and number of doctors and dentists per 1,000 persons. The data were then stratified according to per capita income and percentage of insurance subscribers over the age of 65 in each prefecture. The copayment amount exhibited a small, but significant negative effect on the utilization of all medical services. Utilization of outpatient care was most sensitive to the copayment rate. The per capita income stratification models revealed the greatest copayment effect on inpatient care for the lowest income group. The results of the age stratification models support popular notions about the use of hospitals by the elderly as substitutes for elderly care facilities. The effects of copayments and income vary not only among the type of medical care (inpatient, outpatient, and dental) but also among the income and age stratifications of groups in the National Health Insurance system.

Age Factors

[Therapeutic strategy for advanced non-small cell lung cancer].

This paper describes the recent progress in the treatment of advanced non-small cell lung cancer (NS CLC) as follows: 1) The results of single agent chemotherapy in NSCLC, particularly development of new drugs, are summarized. CPT-11, taxol, taxotere, vinorelbine and gemcitabine have appeared to have a response rate of more than 20%. In addition results of phase I and II trials that involved these agents as part of combination regimens are presented. 2) We summarize 8 randomized trials of combination chemotherapy compared with best supportive care. These studies have provided that combination chemotherapy modestly improves survival of patients with advanced NSCLC. 3) Although several randomized trials with adjuvant or neoadjuvant chemotherapy have reported in the patients with locally advanced NSCLC, we have still not confirmative results. 4) Cisplatin based combination chemotherapy followed by chest irradiation improves outcomes of the patients with stage IIIA or IIIB unresectable NSCLC as compared with chemotherapy alone or radiation therapy alone. In spite of these advances further investigations are necessary to improve the treatment results of patients with advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols