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Biomedical subjects

M Kokubun

Publications and source records attributed to M Kokubun.

At least 37 records · Page 2Linked to original sources

Factors affecting age of walking by children with mental retardation.

The relationship between age of walking and two factors of severity of intellectual disability and clinical types (autism, Down syndrome, epilepsy, and "residual") in children with mental retardation was investigated. Subjects were 118 children whose disabilities ranged from severe to mild. Measures by clinical type were significant, and the differences of any two clinical types except between children with epilepsy and the "residual" group were significant, but severity of intellectual disability was not significant. Most children with autism (27 subjects, 93%) walked by the normal time limit of 18 months. Only 3 children (11%) with Down syndrome began to walk within that limit, and 9 of them (33%) walked after 2 years of age. In the "residual" group (including children with epilepsy), 37 children (60%) walked within the normal limit but 15 (25%) only after 2 years of age.

Activities of Daily Living↗

Developmental trends in pursuit eye movements among preschool children.

The purpose of this study was to investigate the developmental differences in pursuit eye movements among preschool children. The subjects were 28 children aged 3 to 6 years old and 5 adults aged 22 to 37 years. The target was moved sinusoidally on the horizontal plane at 0.3-, 0.5-, and 0.7-Hz stimulus frequency. The power ratio which represented the smoothness of eye movements and the phase difference between eye movements and target movement was calculated. The power ratio decreased with increased stimulus frequency for all subjects, indicating that eye movements became less smooth. At all stimulus frequencies, the power ratio was higher for adults than for children. Among the three age groups of children, there was no statistically significant difference on this parameter. The phase shifted from a small amount of lead for no lag to the lag with faster stimulus frequency in adults, but the gap was not statistically significant. For children, there was a statistically significant difference across age groups on change in the phase difference. These findings may suggest that the developmental differences in pursuit eye movements of children across ages 3 to 6 years were clear in what related to the phase difference.

Adult↗

Effect of ethanol on DNA synthesis and c-met induction in Chang liver cells with long-term culture.

This investigation was performed to determine whether ethanol affects induction on Chang liver cells of the c-met protooncogene product (c-met), a cell-surface receptor for hepatocyte growth factor (HGF). These cells were cultured for 4 weeks with 5, 50, or 100 mmol/L ethanol, or 10, 100, or 200 mumol/L acetaldehyde. Ethanol was found to inhibit [3H]thymidine incorporation by cells in a dose-dependent manner. In addition, acetaldehyde at 100 mumol/L also inhibited [3H]thymidine uptake. Treatment with recombinant HGF led to enhanced [3H]thymidine incorporation by cells treated with ethanol or acetaldehyde as well as by those left untreated, with no significant differences in the rates of increase among these three cell groups. The amount of c-met messenger RNA, however, was unaffected by treatment with ethanol or acetaldehyde. Expression of c-met as measured by cell ELISA was also unchanged by both treatments. These results suggest that ethanol has no effect on c-met induction on Chang liver cells and that HGF may not be involved in the ethanol induced inhibition of DNA synthesis.

Cells, Cultured↗

Metabolic changes in cimetidine treatment for scald injury on the peritoneo-serosal surface in far-advanced gastric cancer patients treated by intraperitoneal hyperthermic perfusion.

Since pretreatment with cimetidine results in the prevention of scald injury on the peritoneo-serosal surface caused by intraperitoneal hyperthermic perfusion (IPHP) for advanced gastric cancer, the diverse influence of IPHP on patients who were either given or not given cimetidine was studied both during and after IPHP treatment. Cimetidine 50 mg/kg was injected intravenously into 12 patients immediately prior to IPHP. There were no statistical background differences between the cimetidine and control groups (those not given cimetidine). The inflow and outflow temperatures of the hyperthermic perfusate in the control and cimetidine groups were 46.1 +/- 0.1 degree C and 44.1 +/- 0.1 degree C and 46.3 +/- 0.1 degree C and 44.2 +/- 0.04 degree C, respectively. Either the pre-IPHP hypothermia or IPHP in the control group resulted in a considerable increase in serum noradrenaline and adrenaline. The intravenous administration of cimetidine led to a stransient but moderate drop in the mean blood pressure as well as a delayed appearance of high concentrations of noradrenaline and adrenaline, induced by high concentrations of circulating histamine released with cimetidine. These results suggest that the sympathetic nervous responses were activated either by hypothermia or hyperthermia. The transient hypotension and delayed increases of both serum catecholamines were attributed to a marked increase in circulating histamine, released with the intravenous cimetidine.

Blood Pressure↗

Effects on tumour microcirculation in mice of misonidazole and tumour necrosis factor plus hyperthermia.

We examined the effects of misonidazole (MISO) and recombinant human tumour necrosis factor (rh-TNF) on tumour blood flow in mice given hyperthermic treatments. MISO (500 mg kg-1) or rh-TNF (6 x 10(4) unit kg-1) was administered intraperitoneally (i.p.) prior to hyperthermia to nude mice bearing a xenoplanted human gastric cancer and tumour blood flow was measured by a hydrogen diffusion method based on polarographic determinations. MISO plus hyperthermia produced a temperature-dependent decrease in blood flow and, at 43.5 degrees C, the flow decreased to 15-30% of control and remained low for up to 24 h. Blood flow following rh-TNF plus hyperthermia was less than that at the same temperatures following MISO plus hyperthermia, and, at 43.5 degrees C, the flow decreased to 10-20% of control and remained low for up to 48 h. Tumour growth delay was closely related to the duration of the decrease in blood flow. Thus, the profound decrease in tumour blood flow following hyperthermia plus MISO or rh-TNF and the consequential tumour regression may well be of potential clinical significance.

Adenocarcinoma↗

[The experimental and clinical study of hyperthermia with thermosensitizer for gastric cancer patients with peritoneal seeding].

We examined experimentally and clinically the effect of misonidazole (MISO), a hypoxic cell radiosensitizer, in combination with hyperthermia. First, tissue blood flow and tumor growth of xenoplanted human gastric cancer in nude mice were measured after treatment with MISO 500 mg/kg ip plus hyperthermia at 40.5, 42.0 and 43.5 degrees C. Also clinically, 17 advanced gastric cancer patients with peritoneal seeding underwent intraperitoneal hyperthermic perfusion (IPHP). They were given MISO 1.45 g/m2 po twice (12 hours and 5 hours before IPHP). And plasma MISO levels were measured. MISO plus hyperthermia produced a more prolonged decrease of the tumor blood flow than hyperthermia alone. At 43.5 degrees C, TbF recovered 2 days after the treatment. MISO plus hyperthermia also made tumor growth delay more marked than hyperthermia alone. In gastric cancer patients treated with MISO plus IPHP, T 1/2 of serum MISO was 7.7 hours and the AUC was 1,087 micrograms.hr/ml. There were no side effects observed which were caused by MISO. Thus MISO can be an effective thermosensitizer when used in combination with hyperthermia.

Animals↗

A clinical pilot study combining surgery with intraoperative pelvic hyperthermochemotherapy to prevent the local recurrence of rectal cancer.

Intraoperative pelvic hyperthermochemotherapy (IOPHC) with mitomycin C (MMC) was prescribed for 14 patients with resectable advanced rectal cancer in an attempt to prevent a postoperative local recurrence. Immediately after rectal amputation and extended lymphadenectomy, IOPHC was performed using physiologic saline containing 40 micrograms/mL of MMC at 45.5 +/- 0.6 C for 90 minutes, with an apparatus devised for IOPHC. At the end of IOPHC, the esophageal temperature was 37.2 +/- 0.8 C and cooling was not required. Antitumor efficacy and complications in the IOPHC group were compared with findings in 12 rectal cancer patients who underwent surgery only within the same period of time. Operation time was not prolonged with IOPHC treatment. In cytologic examinations of the pelvic lavage just before IOPHC treatment, viable cancer cells were detected in 6 of the 14 patients but were never detected in the postoperative exudate drained from the pelvic cavity. Of the 12 patients in the control group, 2 had a local recurrence, while in the IOPHC group there was no local recurrence for 16.9 +/- 9.7 months at this writing. Postoperative complications did not differ between the groups. This IOPHC treatment is a favorable method in eradicating cancer cells for postoperative local recurrence of rectal cancer.

Aged↗

[Prevention of scald injury due to intraperitoneal hyperthermic perfusion for far-advanced gastric cancer].

In an attempt to prevent scald injury on the peritoneo-serosal surface due to intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastric cancer patients, a histamine H2-receptor antagonist, cimetidine, was prescribed for 9 patients. The IPHP treatment was carried out with a closed circuit using a heated perfusate, and intra-abdominal temperature was kept over 44 degrees C throughout IPHP, for 120 minutes. Of 18 patients given IPHP, 9 were administered intravenously cimetidine at a dose of 50 mg/kg just before IPHP (cimetidine group) and the remaining 9 were prescribed IPHP and not given cimetidine (control group). Amounts of exudate and protein from peritoneal cavity and serum histamine were compared between the two groups. The amount of intra-abdominal exudate was 768 +/- 95 ml for 24 hours in the control group, against 408 +/- 75 ml in the cimetidine group. The protein amounts in exudate throughout IPHP were 62.5 +/- 23.5 g in the control group, against 15.9 +/- 5.4 g in teh cimetidine group. Both the exudate and protein amounts were significantly decreased in the cimetidine group, compared with the controls (p = 1.416 x 10(-7), p = 5.358 x 10(-5)). Serum histamine levels in the cimetidine group increased 2.5 to 6.5 fold for over 12 hours after IPHP, compared to those in the control group. These findings suggest that cimetidine suppresses scald injury on the peritoneo-serosal surface by competitive inhibition with histamine. Consequently, histamine originated from the scald region was released into the circulating blood. Thus, cimetidine helped to prevent thermal injury due to the IPHP.

Body Temperature↗

[Clinical evaluation of intra-peritoneal hyperthermic perfusion under hypothermic general anesthesia for advanced gastric cancer].

Right after surgery, intra-peritoneal hyperthermic perfusion (IPHP) was performed under hypothermic general anesthesia for 41 gastric cancer patients with peritoneal dissemination or serosal invasion. The control group consisted of 40 patients given surgery alone. With respect to the direct antitumor efficacy of IPHP, there were no cancer cells in the peritoneal lavage from Douglas' pouch and, ascitic effusion disappeared in all patients with peritoneal dissemination. The 1- and 3-year survival rates for the IPHP group were 68% and 39%, whereas those of the control group were 30% and 0%, respectively. The survival rates for the IPHP group were better than those for the control group, with a statistically significant difference of p = 8.1 x 10(-7). As to prevention of recurrence, the incidence of peritoneal dissemination for the IPHP group was lower at p = 0.002 than the control group.

Anesthesia, General↗

[Clinical evaluation of intra-operative pelvic hyperthermochemotherapy combined with operation for rectal cancer].

In order to prevent local recurrence, intra-operative pelvic hyperthermochemotherapy (IOPHC) combined with surgery for rectal cancer has been performed. In this study, we evaluated the clinical effect of IOPHC in 20 patients who were given IOPHC, compared with 13 patients who underwent curative surgery without IOPHC (control group). The IOPHC procedure was as follows: After rectal amputation, the pelvic cavity was filled with a physiological saline containing 40 micrograms/ml of MMC. Then, the physiological saline was warmed and maintained by the apparatus (heater) we devised at 45 degrees C for 90 minutes. Local recurrence occurred in 2 cases of IOPHC group (2/20:10.0%), and in 3 cases in the control group (3/13:23.1%). On the other hand, distant metastases developed approximately at the same rate in the IOPHC group (4/20:20.0%) and control group (2/13:15.4%). Thus, IOPHC is a feasible approach to reduce local recurrence of rectal cancer.

Combined Modality Therapy↗

Positive results of combined therapy of surgery and intraperitoneal hyperthermic perfusion for far-advanced gastric cancer.

To evaluate the clinical efficacy of intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastric cancer, particularly with peritoneal seeding, we investigated the survival times of 59 patients who underwent distal subtotal gastrectomy, total gastrectomy, or total gastrectomy combined with concomitant resection of some of the remaining intra-abdominal organs. In all the 30 patients given IPHP, no cancer cells were present posthyperthermically in the lavage from the Douglas pouch. The 30 patients given IPHP lived longer than the 29 patients not given IPHP (p = 0.001), with a 1-year survival rate of 80.4% in the former group compared to 34.2% in the latter. With respect to a comparison of survival time of patients with peritoneal seeding, 7 patients not given IPHP had a 6-month survival rate of 57.1% and did not survive more than 9 months, whereas 20 patients given IPHP had 1- and 2-year survival rates of 78.7% and 45.0%, respectively; here the difference was significant (p = 0.001). The IPHP and control groups without peritoneal metastasis included 10 and 22 patients, respectively, and the 1-year survival rates are 85.4% and 45.3%, respectively. The survival rates of the former exceeded those of the latter, with p = 0.015 by the generalized Wilcoxon test. Thus this combined therapy offers the promise of extended survival for patients with far-advanced gastric cancer.

Combined Modality Therapy↗

[Clinical results of intraperitoneal hyperthermic perfusion combined with surgery in patients with peritoneal recurrence from gastric cancer].

Six patients with peritoneal recurrence after radical operation for gastric cancer were treated by an intraperitoneal hyperthermic perfusion (IPHP) combined with surgery (IPHP group). Immediately after surgery, a 2-hour IPHP was performed, using a perfusate containing 10 micrograms/ml of MMC, warmed at the inflow temperature of 46.5 +/- 1.1 degree C. Within the same period of time, 5 patients with intra-abdominal recurrent gastric cancer (control group) were treated by an intraperitoneal administration of MMC 10 mg combined with surgery. These 11 patients had malignant peritoneal effusion and, although in 3 of the control group, ascitic effusion did re-accumulate rapidly soon after surgery, the 6 patients of IPHP group did not re-accumulate post-hyperthermically. The average survival duration of IPHP group is 13.6 +/- 10. 6 months, whereas that for controls is 3.0 +/- 2.1 months. Again, the survival rate for IPHP group surpassed that for controls at p = 0.012 and p = 0.008, in a generalized Wilcoxon method and Logrank method, respectively. Post-hyperthermically, hypoproteinemia and thrombocytopenia occurred transitorily. These results show that IPHP using MMC combined with surgery is a safe, reliable treatment for patients with peritoneal recurrence due to gastric cancer.

Combined Modality Therapy↗

[Clinical evaluation of recurrent patterns of gastric cancer after intraperitoneal hyperthermic perfusion].

The patterns of recurrence and the prognosis of 24 gastric cancer patients with peritoneal seeding and/or serosal invasion, who underwent gastrectomy followed by intraperitoneal hyperthermic perfusion (IPHP), were studied in comparison with 23 gastric cancer patients given surgery alone (controls). With respect to 22 patients with peritoneal seeding, all of 8 patients in the control group died of re-accumulation of ascitic effusion, whereas of 14 patients in the IPHP group, 3 died of peritoneal recurrence, 2 of intraperitoneal tumors, 1 from pleural metastasis, and 1 of liver metastasis. The remaining 7 cases are alive without a sign of recurrence. Again, with respect to 25 patients with large serosal penetration of cancer, 7 of 15 patients in the controls died of peritoneal recurrence, whereas this was never observed in the IPHP group. As to the relation of histology and prognosis, while the poorly differentiated adenocarcinoma and signet ring cell carcinoma had poor prognosis in the controls, the same patterns in the IPHP group proved not to be so unfavorable. Since a few given IPHP resulted in hepatic metastasis and/or nodal involvement, adjuvant treatment will be required. The survival rate for the IPHP group was significantly better at p = 3.43 x 10(-2) than in controls.

Aged↗

[Clinical effect of intraperitoneal hyperthermochemotherapy on the survival rate for advanced gastric cancer patients].

Intraperitoneal hyperthermic perfusion (IPHP) was performed right after surgery for 31 advanced gastric cancer patients with serosal invasion and/or peritoneal dissemination. The survival rate in the IPHP group, was compared with that in the control group, 30 patients who underwent surgery alone within the same period of time. The 1-year survival rates for IPHP group and control group were 81.9% and 40.3%, respectively. The 2-year survival rates were 52.1% and 11.8%, and the 3-year survival rates were 26.1% and 0%, respectively. The survival rate for IPHP group was better than that for control group, with p = 1.46 x 10(-4). IPHP and control group with peritoneal dissemination included 21 and 9 patients respectively, and 50% survival rates were 18 months and 4.2 months, respectively. IPHP and control group with serosal invasion included 10 and 21 patients, respectively, and 8 out of 10 patients survived in the IPHP group, while 17 out of 21 patients died in the control group. These results suggest that IPHP is effective for gastric cancer patients with peritoneal dissemination and/or serosal invasion.

Aged↗

[Eosinophilia in primary biliary cirrhosis].

The numbers and the percent of eosinophils in peripheral blood of thirty patients with primary biliary cirrhosis were serially measured and were compared with their clinical data. eosinophils of 22 patients at non icteric stage (total bilirubin less than 2.0 mg/dl) were significantly higher (P less than 0.05) than those of 8 patients at icteric stage (total bilirubin more than 2.0 mg/dl). Seven patients (23.3%) showed eosinophilia with value of 6% or more and in which four patients (13.3%) showed eosinophilia more than 8%. These eosinophilia was found in non icteric patients alone but not in icteric. In two patients who have shown eosinophilia at their non icteric stage, numbers of their eosinophils decreased gradually following the increment of their total bilirubin levels. These results would indicate that eosinophils in the peripheral bloods of PBC patients could reflect some clinical conditions at their non icteric stage.

Adult↗

Clinical trial with surgery and intraperitoneal hyperthermic perfusion for peritoneal recurrence of gastrointestinal cancer.

To treat six patients with peritoneal recurrence after radical operation for gastrointestinal cancer, an intraperitoneal hyperthermic perfusion (IPHP), combined with surgical resection of recurrent tumors, intestinal by-pass anastomosis, or both, was carried out. Immediately after complete resection of the intraperitoneal recurrent tumors, a 2- to 3-hour IPHP was performed under hypothermic general anesthesia at about 32 degrees C, using a perfusate containing 10 micrograms/ml or 20 micrograms/ml of mitomycin C (MMC) warmed at the inflow temperature of 46.6 degrees C to 46.9 degrees C. The apparatus used for IPHP was designed for intraperitoneal perfusion as a closed circuit. Although five of the six patients had a malignant peritoneal effusion at the time of admission, the effusion disappeared soon after IPHP, and no cancer cell was present in the lavage from Douglas' pouch. The other patient had a recurrent tumor at the anastomotic region after low anterior resection for rectal cancer and complete resection of the recurrent tumor, combined with IPHP, was carried out. One patient with a recurrent gastric cancer died of hepatic metastasis and cancerous pleuritis 5 months after this treatment, and the other five are in good health 12.8 +/- 5.1 months after IPHP. On the other hand, five patients with intra-abdominal recurrent gastric cancer, who received only surgical treatment within the same period of time, died 3.0 +/- 2.1 months after the surgery. Postoperatively, in the six patients with IPHP, transitory hepatic dysfunction, hypoproteinemia, and thrombocytopenia occurred. These results show that IPHP using MMC combined with surgery is a safe, reliable treatment for patients with peritoneal recurrence of gastrointestinal cancer.

Adult↗

Thermotolerance of xenografted human gastric cancer.

To compare the thermotolerance in vivo of two human gastric cancers with different doubling times, the xenografted tumors were warmed twice at 43.5 +/- 0.1 degree C in a water bath for 20 minutes at a predetermined interval. In the tumors with doubling times of 5.2 and 10.9 days, a 7-day interval heat treatment resulted in a prolongation in tumor tripling times by 156 per cent and 132 per cent, respectively, compared with a single heat treatment for 40 minutes. On the contrary, two heat treatments given at intervals of 3 to 5 days had a short tumor tripling time, compared to that of the 40-minute single treatment. Thus, the thermotolerance of these human gastric cancers gradually increased to a maximum within a 3- to 4-day interval and disappeared completely after a 7-day interval. These results indicate that the times required to reach maximal thermotolerance in these human gastric cancers were longer than those previously demonstrated for human and rodent cancer cell lines in vitro. The development and decay of thermotolerance in these human gastric cancers need to be considered in the design of multiple-fractionated regimens.

Adenocarcinoma↗