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Biomedical subjects

T Iwai

Publications and source records attributed to T Iwai.

At least 127 records · Page 7Linked to original sources
PubMed1998

[The effects of YM26818: 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea and derivatives on pulmonary surfactant secretion and lung compliance].

To discover a novel compound which has an effect on pulmonary surfactant (PS) secretion, we studied the effects of various compounds on PS secretion by measuring the contents of PS in the bronchoalveolar lavage (BAL) fluid in guinea pigs. In the chemical modification study of ambroxol, which is known as a PS secretagogue, and a compound we discovered from our compounds library, 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea: YM-26818 (the increasing effect on PS in BALF, 34.7% at 50 mg/kg, i.p.). In the surfactant deficient model induced by BAL in guinea pigs, YM-26818 (5 and 10 mg/kg, p.o.) significantly increased the contents of PS in the BAL fluid compared with that of control animals (5 mg/kg: 60.3 +/- 8.0, 10 mg/kg: 59.4 +/- 4.3% increase). Concomitantly by these effects, the recovery of lung compliance was observed in this model (AUC of lung volume, control: 560 +/- 15, YM-26818 5 mg/kg: 898 +/- 51, YM-2681 10 mg/kg: 956 +/- 11 ml.min). These results may indicate that YM-26818 is useful for the therapy of adult respiratory distress syndrome (ARDS) and obstructive pulmonary diseases.

Animals↗
PubMed1998

[Management of invasive carcinoma of bladder and abdominal aortic aneurysm (AAA); technique of radical total cystectomy and simultaneous AAA repair].

BACKGROUND: There is no consensus on the optimal surgical treatment for patients with concomitant invasive carcinoma of bladder and abdominal aortic aneurysm (AAA). We experienced two patients who were treated successfully with simultaneous radical cystectomy and AAA repair. The techniques required for the combined procedure and case reports are discussed. PROCEDURE: The goal of the one-stage operation was to minimize the risk of graft infection without compromising postoperative morbidity and mortality secondary to carcinoma of bladder. Initially pelvic lymph node dissection and radical cystectomy were performed. We preferred retrograde cyctoprostatectomy because most of the cystectomy procedure can be performed without opening the peritoneal cavity and the extent of the retroperitoneal dissection can be minimal. A single-stoma ureterocutaneostomy was preferable urinary diversion. Urinary diversions which utilize intestine such as ileal conduit or ileal urinary reservoir may cause contamination of a graft with bowel content and should be avoided. Before or after urinary diversion, aneurysmal resection and a bifurcated graft replacement were performed. The replaced graft was wrapped with the aneurysmal wall. The major omentum was mobilized and fixed in front of the graft, thereby serving as a protective barrier of the graft. A Dacron graft which was sealed with rifampicin-bonding gelatin was used to further reduce the risk of graft infection. RESULT: Two male patients were treated with the one stage radical cystectomy and AAA repair. Single-stoma ureterocutaneostomy and bilateral ureterocutaneostomy were selected as a urinary diversion. No major postoperative complications, except for paralytic ileus in one case, were observed. CONCLUSION: Our experience and reports of others indicate that radical cystectomy and simultaneous AAA repair can be safely performed with less morbidity than staged operations for the management of concomitant invasive carcinoma of bladder and AAA.

Aged↗
PubMed1998

[Thoracoscopic repair of diaphragmatic eventration sustained at knife injury: a case report].

A 46-year-old male taxi driver was stabbed onto the left chest while on duty. On arrival soon after, he was hemodynamically stable. Computed tomography showed omental prolapse into the left thorax through the diaphragm. On the 11th day, he underwent thoracoscopy revealing omental prolapse via a 3-cm rent in the left diaphragm, which was reduced manually. The diaphragmatic orifice was lifted and debrided with suturing using a stapling cutter. The post-operative course was uneventful. Finger palpation through the orifice enabled safe suturing of the left diaphragm facing the omentum, the colon, and the stomach, all of which may suffer iatrogenic injury.

Endoscopy↗
PubMed1998

[Clinical study on the inhibitory effect of a 5-HT3 antagonist, granisetron, for nausea and vomiting induced by chemotherapy (CHOP, VEPA, high-dose ETP) for non-Hodgkin's lymphoma].

The antiemetic effect of granisetron on nausea and vomiting induced by cancer chemotherapy (CHOP, VEPA, VEPA-B, massive dose of ETP) was studied in fifty patients with non-Hodgkin's lymphoma. There was almost no difference in the inhibitory effect by regimen, with the rates of perfect inhibition of nausea and vomiting standing at 55.6% to 60%. Nausea and vomiting was perfectly controlled in 60% of 35 patients receiving CHOP therapy. As a part of this study, a comparison was made of perfect inhibitory effect on nausea and vomiting by potency of chemotherapy under the potency scale of 750 mg/m2 of CPA as 1, revealing no significant difference in the rates of complete inhibition as 71.4% for a drug potency of less than 0.8 vs 52.4% for 0.8 or above (p = 0.26). However, it was clear that the higher the dose of chemotherapy, the lower the rate of complete inhibition. The results confirmed the high efficacy and safety of granisetron in the treatment of nausea and vomiting induced by cancer chemotherapy.

Adult↗
PubMed1998

[p53 expression and response to hepatic intraarterial infusion chemotherapy in patients with colorectal cancer metastasis to liver].

We have reported that hepatic artery infusion (HAI) chemotherapy with 5-fluorouracil for unresectable colorectal liver metastasis may lead to improved overall survival for some patients compared with controls. The aim of this work is to determine whether p53 nuclear protein expression examined by immunohistochemical technique could predict the outcome of patients treated with HAI chemotherapy. No significant difference was found in the response rate (p > .99, Fisher's exact method.) and median survival time (12 months in patients with p53-positive tumors and 11 months with negative tumors). Our results indicate that HAI chemotherapy is an effective treatment for liver metastasis regardless of p53 nuclear protein expression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Clinical evaluation of cefozopran for infections associated with hematological malignancies].

Cefozopran (CZOP) was used as an initial antibacterial therapy for infections in patients with hematological malignancies. CZOP was given at a daily dose of 4 g by drip intravenously to patients who were febrile over 38 degrees C and were suspected as having bacterial infections. As underlying diseases, 8 patients had acute lymphoblastic leukemia (ALL), 9 acute myeloblastic leukemia (AML), 2 aplastic anemia (AA), 2 adult T cell leukemia/lymphoma (ATLL), 28 non Hodgkin lymphoma (NHL), and 2 multiple myeloma (MM). Bacterial infections diagnosed were sepsis in 7 patients, suspected sepsis in 32, bronchitis in 6, pneumonia in 5 and acute peritonitis in 1. Clinical responses among 51 evaluable cases were excellent in 14, good in 15, fair in 3, poor in 19 and the overall response rate was 57%. The overall response rates for AML, ALL, AA, ATLL, NHL and MM were 56%, 63%, 100%, 50%, 50%, and 100%, respectively. Those for sepsis, suspected sepsis, bronchitis, pneumonia and acute peritonitis were 14%, 63%, 100%, 40%, and 0%, respectively. This therapy was effective in 53% (9/17) of patients whose granulocyte count remained below 500/microliter throughout the course of CZOP therapy. Six bacterial and one fungal strains were isolated from blood and sputum of six patients including five sepsis cases; two bacteria were eradicated and bacterial change was observed in one case. As side adverse effects, 10 patients had liver dysfunction, 1 anemia, 2 proteinemia, 1 indirect bilirubinemia, 2 thrombocytopenia, and 1 eosinophilia. We tried to establish a scoring system for the severities of patients with their infections, underlying diseases, treatments for the underlying disease, and granulocyte counts in order to evaluate the efficacy of CZOP more precisely. This scoring system was consisted of three grades; severe, moderate, and mild. CZOP was effective on mild and moderate grades. These results indicate that the initial antibacterial therapy by CZOP is useful for the treatment of mild and moderate grade infections complicated with hematological malignancies.

Acute Disease↗
PubMed1998

[Clinical evaluation of panipenem/betamipron as a second line chemotherapy in severe infections associated with hematological disorders].

Thirty three patients with severe infections associated with hematological disorders were treated with panipenem/betamipron as a second line chemotherapy. Of these, 30 patients were evaluated for effectiveness. An excellent response was obtained in 14 patients (46.7%) and a good response in 5 (16.7%), and the overall efficacy rate was 63.3%. Efficacy rates were 3/6 in patients with sepsis, 68.4% (13/19) in patients with fever of undetermined origin, 2/4 in patients with pneumonia. In patients whose peripheral granulocyte count was below 100/microliter at the start of chemotherapy, the efficacy rate was 3/7. Side effects were observed in 5 of 33 patients (15.2%). These results show that PAPM/BP is useful as a second line chemotherapy for the treatment of severe infections in patients with hematological disorders.

Adult↗
PubMed1998

[Endoscopic diagnosis of early cancer in the esophagogastric junctional region].

The endoscopic diagnosis of early esophageal and gastric cancers located within 2 cm above and below the esophagogastric junction (EGJ) is discussed. We reviewed 25 cases (10 mucosal cancers and 15 submucosal cancers). Histologically, early cancers frequently appeared as type IIc lesions (16/25: 64%). There was no relationship between tumor size and the depth of invasion of cancer lesions, and most of the lesions were well or moderately differentiated carcinomas. Endoscopically, homogenous redness with a thin white coating, some granular appearance, and easy bleeding were very important factors for the diagnosis of early gastric cancer. For superficial esophageal cancer, differential diagnosis from reflux esophagitis is correctly performed with the endoscopic dye (lugol)-staining method and biopsy. In order not to overlook early cancer at the EGJ, this area should be observed with sufficient air inflation by the U-turn or J-turn method using a frontal-view panendoscope.

Adult↗
PubMed1998

[Clinical efficacy of MRCP for diagnosis of patients with pancreatic neoplasm].

We examined the usefulness of MRCP in pancreatic cancer compared with ERCP. Moreover, it examined in the same way in focal pancreatitis, too. We compare three findings of 1) main pancreatic duct, 2) branches of the stricture part, 3) side of tail main pancreatic duct about ERCP and MRCP. As for the branches of the stricture part, MRCP was poor compared with ERCP but as for the property of the side of the tail main pancreatic duct, MRCP excelled. The study of mass forming chronic pancreatitis was a similar result and was not the one, which excels ERCP in case of qualitative diagnosis. However, we thought that it was not invasively, suitable behind the digestive operation and digestive passage fault, in case of elapse observation and moreover that MRCP is suitable for pick up the pancreatic cancer in our clinic.

Adenocarcinoma↗
PubMed1997

Effects of angiotensin II receptor blockade on hypoxia-induced right ventricular hypertrophy in rats.

It was the aim of the present study to characterize the hemodynamic, biochemical and morphologic effect of angiotensin II receptor blockade on hypoxia-induced right ventricular hypertrophy in rats. Isolated right ventricular hypertrophy was induced in female Sprague-Dawley rats by intermittent hypoxia (IH; 10% O2, 8 h/day, 5 days/week, 20 days of exposition, n=15). After completion of IH, left- (LV) and right-ventricular (RV) hemodynamic parameters were measured under room air conditions in the intact, thiopental-anesthetized animals with special Millar ultraminiature tipcatheter-manometers. Cardiac output was determined using the thermodilution method. Cell volume (CV) of isolated cardiomyocytes was measured with a Coulter Channellyzer after collagenase cell isolation. The specific activities of the myocardial pentose phosphate pathway enzymes glucose-6-phosphate-dehydrogenase (G-6-PD) and 6-phosphogluconate-dehydrogenase (6-PGD) were determined using a spectrophotometric assay. IH caused a rise in right ventricular systolic pressure (RVSP) from 38.1+/-0.83 to 58.1+/-1.42 mmHg and an increase in the RV weight/body weight ratio (RVW/BW) from 0.884+/-0. 053 to 1.166+/-0.049 mg/g. The activities of G-6-PD and 6-PGD were significantly increased after IH in the RV, but not in the LV. CV was increased from 24 248+/-1193 to 29 541+/-1765 micrometer 3, myocardial cell length was unchanged. IH had no influence on the LV parameters or cardiac output. Co-infusion of the angiotensin II receptor antagonist losartan (LO; 12 mg/kg/d i.p., n=14) during the IH period reduced the rises in RVSP (49.4+/-2.06 mmHg), RVW/BW (0. 99+/-0.072 mg/g), G-6-PD and 6-PGD significantly, but not completely. The increase in CV, however, was prevented (24 524+/-2370 micrometer 3) entirely. We conclude from these data that the IH-induced RV-hypertrophy was primarily of the concentric type. LO attenuated the hypoxia-induced isolated RV hypertrophy and significantly reduced the metabolic response of the RV. The LO effect was most potent with regard to the increase in cardiomyocyte volume.

Angiotensin Receptor Antagonists↗
PubMed1997

One-point measurement of the peak-to-peak pulsatility index as an indicator for evaluation of infrainguinal bypass procedures.

While duplex scanning has been advocated as the most accurate modality for postoperative graft surveillance, it is time-consuming for evaluating the entire graft. The aim of the present study was to determine which parameter predicts graft failure most simply and precisely, by examining 62 men and 1 woman who collectively underwent 71 infrainguinal arterial bypasses. A total of 212 scannings were obtained using a duplex scanner, and the peak systolic velocity (PSV), PSV ratio, and peak-to-peak pulsatility index (PPI) were analyzed. This analysis revealed 7 occlusions, 9 stenoses, and 1 arteriovenous fistula. When a PSV < 45 cm/s and/or a PSV ratio > 2.0 was defined as graft failure the sensitivity was 84.0% and the specificity was 81.8%: however, a PPI < 7.0 at the midgraft, indicating graft failure, showed a sensitivity of 100% and a specificity of 83.3%. The PPI exhibited better sensitivity and specificity than the PSV, even though the PPI needs only to be measured at the midgraft whereas the PSV should be measured at at least two points. Thus, we believe that the PPI could be the most useful and simple parameter to assess infrainguinal bypass grafts.

Adult↗
PubMed1997

Clinicohistological study of oligodendroglioma and oligoastrocytoma.

The clinical and histological characteristics of oligodendroglioma and oligoastrocytoma were investigated in patients, mainly adults with supratentorial tumors, who were treated with surgery and radiotherapy, and with chemotherapy for recurrent, anaplastic tumors, or both. The median survival time was 13.2 years for oligodendroglioma (four patients), 12.7 years for anaplastic oligodendroglioma (five patients), 13.5 years for oligoastrocytoma (seven patients), and 4.8 years for anaplastic oligoastrocytoma (four patients). Two of three recurrent oligodendrogliomas and two of two recurrent oligoastrocytomas showed malignant transformation. Minigemistocytes were sometimes recognized in recurrent tumors and had a sinister prognosis. Oligodendroglioma and oligoastrocytoma may transform into each other at recurrence.

Adolescent↗
PubMed1997

Changes of response to caffeine in Ca(2+)-deficient medium in guinea-pig tenia coli.

1. After the washing out of the first caffeine, the second 25 mM caffeine-induced tension was about 50% of the first response in tenia coli. Cyclopiazonic acid (CPA), a specific sarcoplasmic reticulum Ca(2+)-ATPase blocker, almost inhibited the contraction to the next application of caffeine after the washing out caffeine in the presence of CPA. The peak tension to caffeine increased after the pretreatment with 10 mM K+ for 1 min. After pretreatment with K+ in the presence of 10(-7) M nifedipine (only phasic response), the tension to caffeine also increased. 2. The response to caffeine was rapidly reduced after incubation in a Ca(2+)-free medium and was abolished after 6 min of incubation. However, the response to caffeine in Ca(2+)-free medium 30 sec. after pretreatment with 10 mM K+ in normal Ca medium was larger. 3. These results suggest that, when the cell membrane is in the resting state, Ca2+ enters the cytoplasm by a leaky pathway and enters storage sites through Ca(2+)-ATPase. Furthermore, when the cell membrane is depolarized for a short period (less than 1 min), Ca2+ entry occurs, leading to refilling of the Ca2+ storage sites utilized by caffeine. The retention of Ca2+ in the storage sites in the Ca(2+)-free condition in tenia coli was less relative to the position in vascular smooth muscle.

Animals↗
PubMed1997

Determining variations in colonic circulation during aortic surgery.

The aim of this study was to compare transanal Doppler examination, intraoperative angiography via the inferior mesenteric artery, and the inferior mesenteric artery stump pressure measurement during abdominal aortic surgery to assess the collateral circulation to the inferior mesenteric artery bed. Transanal Doppler examination revealed that the collateral circulation depended on the superior mesenteric artery in 25 patients (superior mesenteric artery-dominant group), the inferior mesenteric artery in two patients (inferior mesenteric artery-dominant group), and the internal iliac artery in one patient (internal iliac artery-dominant group). The mean (+/-S.D.) inferior mesenteric artery stump pressure index was 0.65 (+/-0.12) in the superior mesenteric artery-dominant group, which was significantly different from 0.43 (+/-0.00) in the inferior mesenteric artery- and internal iliac artery-dominant groups. The Intraoperative angiography showed the meandering mesenteric artery clearly in the superior mesenteric artery-dominant group. The Transanal Doppler examination as well as inferior mesenteric artery stump pressure measurement were useful methods to assess a dominant artery to the inferior mesenteric artery bed and colonic viability.

Aged↗
PubMed1997

Tandem duplications of the FLT3 receptor gene are associated with leukemic transformation of myelodysplasia.

We recently reported an internal tandem duplication of the human flt3 receptor gene (FLT3) as a somatic mutation in 17% of acute myelogenous leukemia (AML). The present study revealed the duplication at the juxtamembrane and the first tyrosine kinase domains of FLT3 in seven of 92 (8%) patients with myelodysplastic syndrome (MDS) and AML with trilineage myelodysplasia (AML/TMDS), the diseases which may represent neoplastic changes of pluripotent stem cells. A tandem duplication of exon 11 of FLT3 was harbored by two of 58 (3%) patients with MDS and five of 34 (15%) with overt leukemia, including MDS-derived leukemia, AML/TMDS and therapy-related leukemia. Although the duplicated regions varied within exon 11 in each case, they occurred in-frame, and altered mRNA expressions were demonstrated by reverse-transcription polymerase chain reaction. Two cases of MDS with a FLT3 duplication transformed to overt leukemia within a few months. Longitudinal analyses in two other patients with leukemia revealed that the duplication was a late genetic event during the disease course; one of whom showed two independent duplications of FLT3 at the terminal therapy-resistant phase. Of seven patients with the FLT3 duplication, six had abnormal karyotypes, and four harbored a point mutation of the N-RAS and/or TP53 genes. Patients with FLT3 mutations have poor prognoses. This study uncovered the fact that the accumulation of genetic events, including FLT3 duplication, correlates with leukemic transformation from antecedent myelodysplasia and with subsequent disease progression.

Aged↗
PubMed1997

Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines.

In this study, we examined a large number of patients to clarify the distribution and frequency of a recently described FLT3 tandem duplication among hematopoietic malignancies, including 112 acute myelocytic leukemia (AML), 55 acute lymphoblastic leukemia (ALL), 37 myelodysplastic syndrome (MDS), 20 chronic myelogenous leukemia (CML), 30 non-Hodgkin's lymphoma (NHL), 14 adult T cell leukemia, 15 chronic lymphocytic leukemia (CLL) and 38 multiple myeloma (MM). We also evaluated 71 cell lines derived from 11 AML, 31 ALL, two hairy cell leukemia, three acute unclassified leukemia, 10 CML, 12 NHL including six Burkitt's lymphoma, and two MM. Using genomic PCR of exon 11 coding for the juxtamembrane (JM) domain and first amino acids of the 5'-tyrosine kinase (TK) domain, this length mutation was found only in AML (22/112, 20%) and MDS (1/37). According to the FAB subclassification, they were 5/18 (28%) of M1, 4/29 (14%) of M2, 3/17 (18%) of M3, 6/24 (25%) of M4, 4/20 (20%) of M5 and 1/9 of refractory anemia with excess of blast in transformation. In the various cell lines examined, this abnormality was determined in only one derived from AML and never found in other hematological malignancies. The sequence analysis of the abnormal PCR products revealed that 23 of 24 showed internal tandem duplication with or without insertion of nucleotides. In one AML, insertion and deletion without duplication was determined. All 24 lengthened sequences were in-frame. Duplication takes place in the sequence coding for the JM domain and leaves the TK domain intact. In conclusion, we emphasize that the length mutation of FLT3 at JM/TK-I domains were restricted to AML and MDS. Since all these mutations resulted in in-frame, this abnormality might function for the proliferation of leukemic cells.

Acute Disease↗
PubMed1997

Expression of Bax and Bcl-2 protein in the gerbil hippocampus following transient forebrain ischemia and its modification by phencyclidine.

To determine the effect of phencyclidine (a noncompetitive NMDA receptor antagonist) on expression of Bax and Bcl-2 (apoptosis-regulating proteins) in gerbil hippocampus after transient forebrain ischemia, brain sections were immunohistochemically evaluated 48, 72, 96 h and 7 days following ischemia. In ischemic control animals, the expression of Bax in CA1 neurons was increased with time and peaked at 72 h, then disappeared at 96 h. In the phencyclidine (5 mg kg-1, intraperitoneally)-treated animals, the intensity of Bax expression at 72 h was weaker than that of ischemic control animals. Furthermore, at 96 h, Bax expression was still observed in CA1 neurons. No expression of Bcl-2 in the CA1 neurons was detected in either control or phencyclidine-treated animals. From these results, it is possible that NMDA receptor antagonists exert their preventive effect against delayed neuronal death through inhibition of Bax protein expression, although the precise relationship between the function of Bax protein and delayed neuronal death is still unclear.

Animals↗