[Evaluation of the effects of pre-operative hyperthermia, chemotherapy, and radiotherapy (HCR) on malignant esophageal cancer].
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Aged↗
Biomedical subjects
M Kitamura
Publications and source records attributed to M Kitamura.
[Selection of surgical procedures in heart valve diseases based on follow-up results: comparative evaluation of valve replacement and valvoplasty].
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Adolescent↗
[Evaluation of clinical trials on adjuvant chemotherapy for curatively resected gastric cancer].
Reports of the results of clinical trials on adjuvant chemotherapy for curatively resected gastric cancer in Japan and other countries were reviewed. The efficacy of adjuvant chemotherapy outside Japan was not recognized except in two trials. Japanese trials did not reveal a significant survival benefit compared with surgery alone. However, a consensus was achieved in Japan on its efficacy by understanding some results of subset analysis as definite proof. Recently, it has been recognized that the re-evaluation of adjuvant chemotherapy should be carried out with the control group of surgery alone. The results of the trials of JCOG and N.SAS-GC, comparing adjuvant chemotherapy versus surgery alone, are much awaited. At the present time, carefully designed randomized controlled trials with sufficient sample size, which include surgery alone for control arm, are the only way to establish the efficacy of adjuvant chemotherapy.
Antineoplastic Combined Chemotherapy Protocols↗
Gene transfer into the kidney: promises and limitations.
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Animals↗
[Implantation of the Novacor left ventricular assist device in a patient with dilated cardiomyopathy].
The Novacor left ventricular assist device has been widely applied as a bridge to heart transplantation. The patient, a 29-year-old, male had severe left ventricular failure due to dilated cardiomyopathy. The heart failure had progressively worsened and showed severely reduced wall motion of the left ventricle with fraction shortening of 0.03. His cardiac catheterization data with 7 r of dopamine infusion was as follows; RA(12), RV46/9EDP(12), PA(w)(31), cardiac Index 1.73 l/min/cm2. Novacor implantation was performed on March 11th, 1996. After the implantation the patient was extubated on day 3 and recovered rapidly. No complications, such as bleeding or thromboembolic episodes were seen. The patient was flown to the USA for cardiac transplantation on 24th, September, 1996. During the 11-hour flight from Narita to Los Angeles, he experienced no adverse effects. The patient underwent a successful cardiac transplant at UCLA Medical Center. His post-operative course was uneventful. We believe that either chronic circulatory support or the bridge to transplant using Novacor LVAS will be a significant breakthrough for the treatment of Japanese patients with severely deteriorated cardiomyopathy.
Adult↗
Gastric hyperemic response during vagally mediated acid secretion by TRH analog in rats.
The mechanisms of gastric hyperemic response during vagally mediated acid secretion induced by YM-14673, an analog of thyrotropin-releasing hormone, were investigated in urethane-anesthetized rats. The stomach was mounted on an ex vivo chamber and perfused with saline, and gastric mucosal blood flow (GMBF) was measured using a laser Doppler flowmeter, simultaneously with acid secretion. The i.v. injection of YM-14673 (0.1 approximately 1 mg/kg) increased both GMBF and acid secretion in a dose-dependent manner, and these responses persisted during a 90-min test period. The increases in GMBF and acid secretion induced by YM-14673 (0.3 mg/kg) were totally abolished by either bilateral vagotomy or atropine. Sensory ablation by capsaicin also significantly attenuated GMBF response without affecting acid secretion. On the other hand, N(G)-nitro-L-arginine methyl ester (L-NAME), but not D-NAME, significantly attenuated the increase in GMBF in an L-arginine-sensitive manner, although acid secretion was slightly augmented; in particular, gastric hyperemic response during the first 30 min (early period) was almost totally abolished. In contrast, omeprazole significantly attenuated GMBF response only in the late period, although it completely inhibited acid secretion in response to YM-14673. Combined treatment of omeprazole and L-NAME totally abolished hyperemic responses induced by YM-14673 during the test period. YM-14673 significantly elevated the release of nitrite and nitrate into the gastric lumen, and this response was inhibited by either atropine or L-NAME. These results suggest that YM-14673 increases GMBF as well as acid secretion, mediated by vagal-cholinergic pathways, and that gastric hyperemia is further regulated by two distinct mechanisms. The response in the early period is independent of acid secretion and mediated mainly by nitric oxide, whereas that in the later period occurs in association with acid secretion and may be mediated by nitric oxide and sensory neurons.
Animals↗
Acute hemorrhagic gastritis associated with acetazolamide intoxication in a patient with chronic renal failure.
Acetazolamide (Diamox) is a carbonic anhydrase inhibitor commonly used in patients with glaucoma in order to reduce intraocular pressure. Acetazolamide (AZ) is mostly excreted in the urine, therefore, the blood levels of AZ often tend to increase in patients with chronic renal failure. We experienced a case of chronic renal failure in a patient suffering from acute hemorrhagic gastritis associated with AZ intoxication. A 66-year-old female with chronic renal failure was referred to our hospital because of drowsiness and an acute deterioration of renal function. She had been treated with AZ, 500 mg per every day for eleven days for the treatment of glaucoma. Laboratory studies showed leukocyturia, thrombocytopenia, severe anemia, and tarry stools. The serum concentration of AZ was elevated to a maximum of 76.5 mg/ml. She was thus diagnosed as having AZ intoxication. On further examination, acute extensive hemorrhagic gastritis was also found by gastroscopy. Despite of the administration of intensive therapies, she died of disseminated intravascular coagulation (DIC) and septic shock due to bone marrow depression 6 days after admission. It is generally known that excessive blood levels of AZ inhibit not only the gastric juices but also prostaglandin levels and HCO3- excretion in the gastric mucosal barrier. We thus concluded that an excessive dose of AZ had probably destroyed the gastric mucosal barrier or thrombocytopenia due to bone marrow disorder and thus eventually led to the development of hemorrhagic gastritis. As far as we know, this is the first case report of acute hemorrhagic gastritis associated with AZ intoxication. Even though AZ tends to strongly bind to plasma protein and its clearance is generally poor by hemodialysis (HD), in our patient, HD was observed to be rather effective since the clearance of AZ was 45.8 ml/min on HD and 66 ml/min on direct hemoperfusion (DHP). DHP often reduces the number of platelets, also DHP needs a lot of heparin, therefore, we should have performed HD alone instead of DHP. In patients with an impaired renal function, AZ should therefore be administered very carefully in order to avoid an accumulation of the drug. In addition, HD alone should be used to remove any excessive amounts of AZ from the blood.
Acetazolamide↗
[Evaluation of intraperitoneal chemotherapy using CDDP/MMC or CDDP for gastric carcinomatous peritonitis].
The prognosis of positive cytology case (cy (+)) without peritoneal dissemination (P0) and P (+) cases were poor. In this study, the efficacy of intraperitoneal chemotherapy (i.p. therapy) for these patients was evaluated in 26 gastric cancer patients. Intraperitoneal repeated administration of MMC 10 mg/body and CDDP 40-50 mg/body (15 cases) or CDDP 40-50 mg/body (11 cases) alone was performed once a month via the drug delivery system. Negative change of cytology was observed in 13 out of 19 patients, and the prognosis of these patients was better than that of the unchanged cytology group. The prognosis of P0/cy(+) was better than that of P(+) patients. Two year survival rate of P0/cy(+) with i.p. therapy was better than that of P0/cy(+) without i.p. therapy (58.3% vs 22.5%). Adverse drug reaction such as severe gastro-intestinal symptoms and bone marrow toxicities were not recognized. In conclusion, this report suggests that i.p. therapy is more useful for P0/cy(+) cases than that of P(+) cases in gastric cancer. Randomized controlled trials should be done to confirm the efficacy of the intraperitoneal chemotherapy regarding the prolongation of life.
Antineoplastic Combined Chemotherapy Protocols↗
[Extra-arterial dislocation of indwelling catheter in hepatic arterial infusion chemotherapy--special reference to tissue destruction by 5-fluorouracil].
The causes of extra-arterial dislocation of indwelling catheter (EAD), which was one of the serious complications in arterial infusion chemotherapy, were examined. Subjects were six cases of EAD among the 45 cases of gastric cancer with liver metastases treated with hepatic arterial infusion chemotherapy. According to the route of cannulation, EAD occurred more frequently in the cases of cannulation via gastroduodenal artery (18.5%) than in those via subclavian artery (5.5%). Concerning the drugs and their administration, all cases of EAD were treated by continuous injection of 5-fluorouracil (5-FU). Main symptoms of EAD were high fever, abdominal pain and anemia, which developed after administration of total doses from 4.0 g to 30.5 g of 5-FU. In conclusion, it was strongly suggested that arterial destruction due to the toxicity of 5-FU caused EAD in hepatic arterial infusion chemotherapy, especially in cases of cannulation via gastroduodenal artery due to the high concentration of 5-FU in a limited part of the arterial wall.
Aged↗
[Correlation between anti-tumor effects and serum hepatocyte growth factor level in patients with liver metastases from gastric cancer treated by induced hypertensive chemotherapy with angiotensin II].
To clarify the clinical significance of serum hepatocyte growth factor (HGF), the possible correlation between anti-tumor effect and serum HGF level was examined in six patients with liver metastases from gastric cancer. These patients were treated by induced hypertensive chemotherapy with angiotensin II (IHC). We measured the serum concentration of HGF and compared them with the anti-tumor effect and conventional tumor makers (CEA, CA 19-9). The cut-off level of serum HGF was prescribed at 0.4 ng/ml from healthy volunteer's samples. As the result, anti-tumor effects were one case of CR, two of PR, one of NC and two of PD. Serum HGF levels before IHC were positive in all cases (0.44 to 1.35 ng/ml), whereas the levels were not related to the extent of liver metastases. With regard to the anti-tumor effect, the serum HGF level after IHC was more sensitively reflected compared with conventional tumor markers. In conclusion, it is considered that the serum HGF level might be a useful indicator for the treatment effect in gastric cancer.
Aged↗
Gene transfer of interleukin-1 receptor antagonist into the renal glomerulus via a mesangial cell vector.
Towards gene transfer-based therapies of renal glomerulonephritis, this study examines the feasibility of using a mesangial cell vector (J. Clin. Invest. 94, 497-505, 1994) engineered to secrete interleukin-1 receptor antagonist (IL-1ra). IL-1ra cDNA was introduced into cultured rat mesangial cells, and stably transfected vector cells were established. Compared to mock transfectants, the vector cells showed blunted expression of gelatinase B, stromelysin and monocyte chemoattractant protein-1 in response to IL-1 beta. The attenuated responses were transferable to untransfected cells by cross-feeding with vector cell-conditioned media. The vector cells were then delivered into the glomeruli of rats via the renal circulation. Compared to either unmodified or mock cell-containing glomeruli, the glomeruli transferred with vector cells showed repressed expression of gelatinase B in response to IL-1 beta. Transfer of vector cells thus conferred insensitivity to IL-1 on the glomerulus. This result indicates the feasibility of modifying glomerular microenvironment against certain pathogenic mediators via the ex vivo transfer of therapeutically-relevant genes to the glomerulus.
Animals↗
Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour.
The goal of this study was to determine whether the dopamine D3 receptor in limbic structures plays a role in the shell-specific and dopamine-dependent display of turning behaviour in rats. When combined with the dopamine D1 receptor agonist (+/-)-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7,8-diol (SKF-38393, 5 micrograms), the putative dopamine D3 receptor agonist (+/-)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT, 1, 5 and 10 micrograms) elicited contralateral turning in a dose-dependent manner following unilateral injection into the shell, but not the core, of the nucleus accumbens. The turning pattern displayed was identical to that reported previously after intra-accumbens administration of the cocktail of SKF-38393 and the dopamine D2 receptor agonist quinpirole. The behaviour under study was dose-dependently attenuated by local administration of the dopamine D1 receptor antagonist R(+)-7-chloro-8-hydroxy-3- methyl-I-phroyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390: 10 and 100 ng), the dopamine D2 receptor antagonist domperidone (25 and 50 ng) or the dopamine D2/3 receptor antagonist l-sulpiride (5 and 25 ng). Combined blockade of both dopamine D1 and D2 receptors in the shell with a dose of either antagonist alone that produced just a moderate reduction (10 ng SCH 23390 and 50 ng domperidone) completely antagonized the turning behaviour elicited by the cocktail of SKF-38393 and 7-OH-DPAT. Replacing 7-OH-DPAT by another putative dopamine D3 receptor agonist,S(+)-(4aR, 10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4, 3-b]-1, 4-oxazin-9-ol (PD 128,907, 10 micrograms), in the cocktail did produce no turning behaviour at all. It is concluded that mesolimbic dopamine D3 receptors play no role in the dopamine-dependent and shell-specific turning behaviour: the contribution of 7-OH-DPAT in the cocktail of SKF-38393 and 7-OH-DPAT to the display of turning behaviour is solely due to its ability to activate dopamine D2 receptors.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Creation of a reversible on/off system for site-specific in vivo control of exogenous gene activity in the renal glomerulus.
Using genetically engineered glomerular mesangial cells, an in vivo gene transfer approach was developed that specifically targets the renal glomerulus. By combining this system with a tetracycline (Tc)-responsive promoter, the present study aimed to create a reversible on/off system for site-specific in vivo control of exogenous gene activity within the glomerulus. In the Tc regulatory system, a Tc-controlled transactivator (tTA) encoded by a regulator plasmid induces target gene transcription by binding to a tTA-responsive promoter located in a response plasmid. Tc inhibits this tTA-dependent transactivation via its affinity for tTA. In double-transfected cells, therefore, the activity of a transgene can be controlled by Tc. Cultured rat mesangial cells were cotransfected with a regulator plasmid and a response plasmid that introduces a beta-galactosidase gene. In vitro, stable double-transfectant MtTAG cells exhibited no beta-galactosidase activity in the presence of Tc. However, following withdrawal of Tc from culture media, expression of beta-galactosidase was induced within 24 h. When Tc was again added, the expression was rapidly resuppressed. Low concentrations of Tc were sufficient to maintain the silent state of tTA-dependent promoter. MtTAG cells were then transferred into the rat glomeruli via renal artery injection. In the isolated chimeric glomeruli, expression of beta-galactosidase was induced ex vivo in the absence of Tc, whereas it was repressed in its presence. When Tc-pretreated MtTAG cells were transferred into the glomeruli of untreated rats, beta-galactosidase expression was induced in vivo within 3 days. Oral administration of Tc dramatically suppressed this induction. These data demonstrate the feasibility of using mesangial cell vectors combined with the Tc regulatory system for site-specific in vivo control of exogenous gene expression in the glomerulus.
Animals↗
Stimulation of acetylcholine or dopamine receptors in the nucleus accumbens differentially alters dopamine release in the striatum of freely moving rats.
The present study examined whether unilateral stimulation of acetylcholine or dopamine receptors in the nucleus accumbens induces an asymmetry in dopamine transmission in the ventrolateral striatum. For this purpose, a microdialysis technique was used to measure dopamine release in both sides of the ventrolateral striatum following unilateral injections of carbachol (5 micrograms/0.5 microliter) or a mixture of dopamine D1 and dopamine D2 receptor agonists (1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7,8-diol 5 micrograms + quinpirole 10 micrograms/0.5 microliter) into the nucleus accumbens. The results show that carbachol injection increased dopamine release in the ipsilateral striatum without changing dopamine release in the contralateral striatum, whereas the dopamine D1/D2 receptor agonist mixture injected unilaterally into the nucleus accumbens produced an increase followed by a decrease in dopamine release in the ipsilateral striatum, but only a decrease in dopamine release in the contralateral striatum. The biochemical effects of the cholinergic treatment greatly outlasted the drug-induced contralateral turning, whereas the biochemical effects of the dopaminergic treatment showed a good correlation with the drug-induced contralateral turning. The present study provides biochemical evidence that unilateral stimulation of acetylcholine or dopamine receptors in the nucleus accumbens elicits an asymmetry in dopaminergic activity in the ventrolateral striatum. The present study also provides biochemical evidence that two distinct neural substrates are involved in the effects of cholinergic and dopaminergic manipulation of the nucleus accumbens.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
What is the earliest malignant lesion in the esophagus?
BACKGROUND: The incidence of early esophageal cancer is definitely increasing due to recent advances in diagnostics. When we discuss early carcinoma of the esophagus, however, there is still controversy as to whether dysplasia is either benign or the earliest malignant lesion. METHODS: Nineteen resected esophaguses with both cancer and dysplasia (including 19 cancers concomitant with 26 dysplastic lesions) were studied for expression of p53 protein. RESULTS: Immunohistochemical overexpression of p53 protein in esophageal dysplasia is almost the same as that in cancer. CONCLUSIONS: Esophageal dysplasia should be recognized as the earliest malignant lesion which already demonstrates cancerous features although it is not immediately critical. A routine endoscopic Lugol's solution test is very useful for both detection and following-up of the early nests in the esophagus. These lesions are good candidates for endoscopic mucosal resection for the purpose of accurate diagnosis or curative treatment.
Esophageal Neoplasms↗
Transforming growth factor-beta 1 is the predominant paracrine inhibitor of macrophage cytokine synthesis produced by glomerular mesangial cells .
Cross-communication between glomerular cells and infiltrating mononuclear cells plays an important role in the generation of or recovery from glomerular diseases. We found that cultured mesangial cells secrete a factor that inhibits production of proinflammatory cytokines by activated macrophages. Treatment of J774.2 macrophages with conditioned media from rat mesangial cells blunted the transcriptional induction of IL-1 beta, IL-6, and TNF-alpha by LPS. None of the media conditioned by other fibroblastic, epithelial, or endothelial cell lines exhibited the inhibitory effect. Media conditioned by normal rat glomeruli contained a similar inhibitory activity, which was enhanced in an acute model of mesangial proliferative glomerulonephritis. To identify the active component involved, we examined the expression of known macrophage deactivators IL-10, IL-13, and TGF-beta 1 in mesangial cells. Under the basal culture conditions, strong expression of TGF-beta 1 mRNA was observed, whereas expression of neither IL-10 nor IL-13 was detected. Immunoblot analysis and a specific bioassay detected the active form of TGF-beta 1 exclusively in the mesangial cell conditioned media. The inhibitory activity was enhanced by heat treatment, consistent with the known property of TGF-beta. A specific anti-TGF-beta 1 neutralizing Ab abolished the inhibitory effect exerted by the mesangial cell media, and exogenously added TGF-beta1 suppressed macrophage cytokine expression in a dose-dependent manner. These findings demonstrate that mesangial cells and isolated glomeruli secrete a factor which suppresses cytokine expression by activated macrophages, the active entity being identified as TGF-beta 1.
Animals↗
Development of postoperative delirium in relation to a room change in the general surgical unit.
To analyze the relationship between the development of postoperative delirium and a change of the patient's room, 1,006 cases of patients who had undergone surgery with general anesthesia were reviewed. Postoperative delirium developed in 84 (8.3%) cases. On the basis of symptomatic features, postoperative delirium was divided into four types: (1) excitement type, (2) excitement-hallucination type, (3) hallucination type, and (4) disorientation type. Of the 31 excitement-type cases, 21 developed within the 2nd postoperative day (POD) while 27 of 29 hallucination types developed after POD 2. Of 29 hallucination types, 22 developed after a room change while 20 of these 22 cases were transferred to a single room before POD 2. A quiet, dark, and isolated environment in a single room is suggest to contribute to the development of hallucinations. The development of postoperative delirium with hallucinations alone should thus be taken into consideration whenever a room change is decided.
Adult↗
Analysis of results of surgery performed over a 20-year period on 500 patients with cancer of the thoracic esophagus.
This study was conducted to examine the long-term outcome of 500 patients who underwent surgery for cancer of the thoracic esophagus during the past 20 years. Favorable results were obtained with postoperative adjuvant radiation and chemotherapy and there were no surgical deaths in the last 5 years. The mortality rate decreased from 17% prior to 1980 to 5% between 1981 and 1993, this being most probably attributable to the decreased incidence of suture leakage. With respect to changes in surgical techniques, during the initial years we performed intrathoracic anastomosis, after which sternal manubrium resection with anterior mediastinal esophagogastrostomy was carried out. Subsequently, we invented a technique for performing esophagogastrostomy via the posterior mediastinum. The posterior mediastinum was selected as the most physiologic route, based on measurement of tissue oxygen tension. Using blood flow determinations obtained by laser-Doppler velocimetry, we concluded that the effectiveness of thicker gastric tubes was superior to that of thin tubes. Esophagogastrostomy was performed in a shallow field in the cervical region, with the anastomosis ultimately positioned in the superior mediastinum and covered with mediastinal pleura.
Anastomosis, Surgical↗