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Biomedical subjects

K Toda

Publications and source records attributed to K Toda.

390 records · Page 22Linked to original sources

Development of an integrated artificial heart-lung device for long-term cardiopulmonary support.

An integrated artificial heart-lung device has been developed as a long-term cardiopulmonary support system. The device is composed of gas exchange and pumping units. The gas exchange unit consists of a special hollow fiber membrane that can prevent serum leakage. The entire blood contacting surface of the gas exchange unit is treated with covalent heparin bonding. The pumping unit consists of two pusher-plate artificial hearts joined to each end of the artificial lung unit. The core size and priming volume of the device are 11 x 14 x 17 cm and 400 ml, respectively. In in vitro evaluation, the device exhibited a maximum output of 7.0 L/ min, with a pressure gradient of 10 mmHg per 1 L/min flow rate. In acute in vivo evaluation with adult goats, the device satisfactorily replaced the animals' circulation and respiration for 6 hr. Pumping output ranged from 5.5 to 6.0 L/min, whereas PaO2 and PaCO2 were kept above 500 mmHg and below 30 mmHg, respectively. The device demonstrated prominent thrombus resistant properties in nonheparin animal use trials. These results indicate that the integrated artificial heart-lung device has a potential to be a long-term cardiopulmonary support system that can be used with minimal anticoagulant therapy.

Animals↗

Development of a membrane oxygenator for long-term respiratory support and its experimental evaluation in prolonged ECMO.

The authors developed a new membrane oxygenator (MO) for long-term respiratory support and evaluated its performance in animal experiments for as long as 336 hr. The MO, with a membrane area of 1.2 m2 and priming volume of 140 ml, is compact and designed to be interposed in a ventricular assist system (VAS) conduit. It is made with a novel hollow fiber membrane, in which micropores are blind-ended so that serum leakage can be prevented during prolonged use. The blood contacting surface of the MO is heparinized with a newly developed covalent bonding technique that ensures good thrombus resistance. In vivo evaluation with five adult goats was performed by installing the MO into a venoarterial or venovenous bypass circuit. No systemic anticoagulant therapy was used, except for a heparin-added fluid infusion to keep the pressure monitoring lines open (2-3 U/kg/hr). Throughout the experiments, no plasma leakage was observed, and gas transfer rates were maintained in a satisfactory range. Platelet counts did not decrease to less than 60% of levels before bypass, and hemolysis was negligible. The levels of coagulation parameters including fibrinogen, fibrin degradation products (FDP), antithrombin III (AT III), antiplasmin, prothrombin time (PT) and activated partial thromboplastic time (APTT) remained within physiologic ranges and relatively constant. At the end of the evaluation, no thrombus formation was noted in three of five MOs. These results suggest that this MO is a promising device for long-term respiratory support.

Animals↗

Altered oxygen metabolic conditions associated with increased norepinephrine levels in a nonpulsatile systemic circulation.

Change in oxygen metabolic conditions accompanying the conversion of systemic flow from pulsatile to nonpulsatile (from P-mode to N-mode) was investigated in association with blood norepinephrine levels. Total left heart bypass was instituted through a left thoracotomy under general anesthesia in 10 adult goats. Pulsatile and nonpulsatile pumps were incorporated in the circuit in parallel, and the flow character was rapidly converted from the P-mode to the N-mode. Norepinephrine levels increased significantly after the conversion, from 222 +/- 54 pg/ml to 285 +/- 65 pg/ml. While oxygen delivery (DO2) was kept constant, the oxygen extraction ratio significantly decreased, from 21 +/- 3% to 16 +/- 3%, and venous oxygen saturation (SvO2) significantly increased, from 77 +/- 6% to 84 +/- 6% after depulsation. The serum lactate level was significantly higher in the N-mode than the P-mode (P-mode: 35 +/- 2 mg/dl, N-mode: 45 +/- 5 mg/dl). Strong positive and negative correlations of norepinephrine levels were observed with oxygen extraction ratio and SvO2, respectively, whereas norepinephrine levels did not correlated with DO2. Regression lines in these correlations unveiled higher oxygen uptake in the P-mode than the N-mode at the same norepinephrine level. These results indicate that, in the setting of an acute animal experiment, oxygen uptake is less efficient with the absence of pulsatility, and the higher norepinephrine concentration functioned to tune the oxygen metabolism in the initial stage of nonpulsatile systemic circulation.

Animals↗

Immunoglobulin G subclass distribution of human anticolon antibodies in ulcerative colitis.

Immunoglobulin G (IgG) subclasses of anticolon antibodies were studied in patients with ulcerative colitis (UC) using enzyme-linked immunosorbent assay (ELISA). The concentrations of total serum IgG subclasses were also measured by ELISA. The values for total serum IgG subclasses in patients with UC were not significantly different from those in normal controls, while the ratio of IgG1 to IgG2 in the patients was significantly higher than that in normal controls. All four IgG subclasses of autoantibodies were demonstrated in the sera of the patients. IgG4 anticolon antibodies were detected most frequently (15 out of 18 patients, 83%). IgG2 was the next most prevalent (9 of 18 patients, 50%). The activity of anticolon antibodies in each subclass did not correlate with the concentration of the corresponding serum IgG subclass. Seven cell lines producing anticolon antibodies were obtained from the colonic mucosa of the patients by Epstein-Barr virus (EBV) transformation. IgG subclasses of anticolon antibodies secreted by these cell lines were also varied. IgG4 subclass was secreted by three EBV transformed cell lines, all of which produced IgG4 anticolon antibodies. These results suggest that all four different IgG subclasses could respond to the colon antigens and that various antigens in colonic mucosa or lumen may contribute to the induction of those autoantibodies. In addition, the prominence of IgG4 anticolon antibodies may support the pathogenic role of this subclass in UC as in other autoimmune diseases.

Adult↗

P300 and reaction time in Parkinson's disease.

The event-related potential and motor reaction time were simultaneously recorded in 35 patients with Parkinson's disease (26 nondemented and nine demented) and 15 age-matched neurologically normal control subjects during the performance of visual discrimination tasks. There were no significant differences in either the latency or amplitude of the P300 component between the nondemented patients and the control subjects, but the patients with nondemented Parkinson's disease had a significantly prolonged reaction time compared with the controls. In patients with demented Parkinson's disease, both P300 latency and reaction time were significantly prolonged compared with the normal controls. These results suggest that response selection and execution are impaired in patients with nondemented Parkinson's disease, although the stimulus evaluation process is largely preserved, whereas patients with demented Parkinson's disease have impairment of stimulus evaluation, go/no-go response selection, and execution.

Aged↗

Effects of local hyperthermia on natural killer activity in mice.

The effect of local hyperthermia on natural killer (NK) activity in C3H mice was investigated, because there have been reports on both the enhancing and suppressing effects of hyperthermia on NK activity. When right hind legs of mice were treated at 43 degrees C for 45 min, NK activity was first suppressed. It reached its lowest level 2 days after the treatment, then recovered, and was significantly enhanced on the 7th day. When mice were treated at a lower temperature (41 degrees C), NK activity was enhanced even 2 days after the treatment. In addition, the suppression of NK activity, which was observed 2 days after the treatment at 43 degrees C, was diminished to some extent by i.p. injection of liposomal recombinant human superoxide dismutase (L-r-hSOD). From these results it is suggested that local hyperthermia had an enhancing effect on NK activity, which plays an important role in the anti-tumour mechanism of hyperthermia, and that transient suppression of NK activity after hyperthermia at 43 degrees C was partially cancelled by the administration of L-r-hSOD.

Animals↗

Neoadjuvant intra-arterial infusion chemotherapy combined with hormonal therapy for locally advanced breast cancer.

To determine the efficacy of combined neoadjuvant intra-arterial infusion chemotherapy and hormonal therapy for treating locally advanced breast cancer, we compared the outcomes of patients with or without this therapy, and also assessed histologic response. Ninety-four patients with locally advanced breast cancer (stage IIIa, 56; stage IIIb, 38). Nineteen stage IIIa and 17 stage IIIb patients received intra-arterial plus hormonal therapy while 37 stage IIIa and 21 stage IIIb patients with similar ages and follow-up durations did not. Treated patients received intra-arterial epirubicin plus oral medroxy-progesterone. Five-year disease-free survival rates were 77.5% for intra-arterially treated and 33.0% for other patients in stage IIIa, and 70.5% for intra-arterially treated and 38.1% for other patients in stage IIIb. Five-year overall survival rates were 94.4% for intra-arterially treated and 61.7% for other patients in stage IIIa, and 90.9% for intra-arterially treated and 56.3% for other patients in stage IIIb. Ten-year overall survival rates in stage IIIb were 90.9% for treated and 22.5% for other group patents. All differences were statistically significant (p<0.05). Good histologic response to intra-arterial therapy was seen in 75% of the primary tumors and 71% of involved lymph nodes. Neoadjuvant intra-arterial therapy with hormonal therapy yielded better survival rates than no intra-arterial therapy or our previous intra-arterial regimen.

Administration, Oral↗

Long-term local hyperthermia in the treatment of advanced breast cancer (case report).

BACKGROUND: It is difficult to control non-resectable locally advanced primary and recurrent breast cancer by conventional modalities. Recently, hyperthermia (HT) has been recognized as an effective adjuvant to radiotherapy (RT) and chemotherapy (CT) in treatment of various malignancies, including breast cancer. PATIENT AND METHODS: The patient was a 58-year-old female Japanese, with breast cancer, T4N2M0, stage IIIb (papillo-tubular carcinoma). Previous treatment included RT and neoadjuvant CT Local HT was performed with a total number of 87 sessions given over 12 months. The mean time of each session was 40 minutes. Elevation of temperature to a tumoricidal level of 43 degrees C was confirmed. The patient received cyclophosphamide (50 mg p.o./day) and tamoxifen (20 mg p.o./day) during the whole period of HT. Due to the decreased amount of WBC, further CT was not possible, except for one course of CMF performed 3 months after the start of HT. RESULTS: The patient had a decrease in the intensity of pain even after the first 3 sessions. In one month, movement in the right shoulder became possible in an anterio-posterior direction. By 5 months, the healing of ulceration became evident. At present, the patient is in continuous CR for 15 months after HT. The movement in the shoulder joint is markedly improved in all directions. In addition, HT did not cause any notable complications. CONCLUSION: Long-term HT may be useful in the management of locally advanced breast cancer and these results should encourage further clinical study.

Breast Neoplasms↗

[Towards eradication of poliomyelitis in Vietnam and the western Pacific region, 1993].

In 1988, the World Health Assembly established the goal of global eradication of poliomyelitis by the year 2000, and the Western Pacific Region (WPR) of WHO established the goal of regional eradication by 1995. Countries in the WPR with endemic poliomyelitis include China, Viet Nam, Cambodia, Laos, and the Philippines. Each country has a national plan of action for eradication, based on three main strategies: maintenance of high coverage with three doses of OPV through routine immunization; supplemental immunization with OPV, including annual National Immunization Days (NIDs); and surveillance of acute flaccid paralysis cases, including isolation of polioviruses in stool specimens. The number of confirmed poliomyelitis cases reported to WHO decreased from 2,635 cases in 1991 to 1,226 cases in 1993, mostly reflecting the decrease in China where supplemental immunization started in 1990 in high-incidence provinces. In six provinces in Viet Nam where immunization days took place in 1992, confirmed cases dropped from 168 in 1992 to 42 in 1993. China, the Philippines, Viet Nam and Laos have conducted NIDs in 1993-1994, with two doses of OPV administered to more than 100 millions children under 5 years of age. NIDs will be repeated in 1994 and 1995, and are planned in Cambodia in January-February 1995. NIDs receive strong support from national governments, and financial assistance from Rotary International, Unicef, the governments of Australia, Japan and Canada, and the US CDC. The apparent elimination of wild polioviruses from the Americas, and the substantial progress already made in the WPR, demonstrate the feasibility of eradicating polio in the WPR and other regions of the world.

Child, Preschool↗

Effect of propentofylline and pentoxifylline on cerebral blood flow using 123I-IMP SPECT in patients with cerebral arteriosclerosis.

Propentofylline and pentoxifylline were administered to patients age 65 years or older who were suffering from chronic cerebrocirculatory insufficiency. Changes in clinical symptoms and the level of cerebral blood flow before and after drug administration were compared. 123I-IMP single photon emission computed tomography was used to compare cerebral blood flow before treatment with that 3 months after initiation of therapy. Focal regions of interest were established in the cerebellum, the frontal, temporal, parietal, and occipital lobes, and the thalamus. Comparisons were made between patients age 75 years or older (very old age group) (n = 5) and those age 65 to 74 years (old age group) (n = 7). Complaints of dizziness and slight headache disappeared by the eighth week after the start of therapy in both age groups. Two of the five patients in the very old age group showed elimination of memory disturbance symptoms at the 12th week of treatment. Six of the seven patients in the old age group had no memory disturbance symptoms by the eighth week of treatment, which indicates a high therapeutic effect in this group. In the cerebral blood flow studies, no increases in blood flow after drug administration were observed in the very old age group. This finding is probably related to the poor level of recovery achieved in disturbances in memory in this group. In contrast, improvements in blood flow were observed for all regions of the brain monitored in the old age group, which is consistent with the amelioration of clinical symptoms observed in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

A two stage axial flow pump. New approach to reduction of hemolysis.

From an engineering point of view, the suitable revolution number for high efficiency operation of an axial flow pump is known. A multistage axial flow pump is a useful tool for reducing revolution number with a high efficiency axial flow pump. A two stage (25) axial flow pump designed at a 5 L/min flow rate and a 100 mmHg pressure head was evaluated in three kinds of in vitro hemolysis tests. Each stage design point of the 2s pump was tested at a 5 L/min flow rate and a 50 mmHg pressure head. Specific speed and revolution number of the 2S pump were 1400 rpm, m3/min, m, and 15500 rpm, respectively. In the first test the 2S pump was compared with two single stage axial flow pumps (1S-A and 1S-B100) designed by the same method. The specific speed of the 1A was the same as that of the 2S pump, which was driven at 26000 rpm. The impeller of the 1S-B100 was the same as that of the 2S pump, which was driven at a 22000 rpm RN and a 1100 specific speed. The 2S pump was separated into two single stage axial flow pumps and the effect of series operation on hemolysis was evaluated in the second test. In the third test the 2S pump was compared with the 1S-B100 by using diluted goat blood samples with three different hematocrit values. The results showed that the hemolysis index of the 2S pump, regarded as a total hemolysis index of both stage axial flow pumps, was less than those of the single stage axial flow pumps at all hematocrit values.

Animals↗