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Biomedical subjects

T Nakatsu

Publications and source records attributed to T Nakatsu.

At least 55 records · Page 3Linked to original sources
PubMed1990

[Clinical reevaluation of continuous intravenous infusion of 5-fluorouracil--plasma concentrations and clinical dose by continuous intravenous and 60-min infusions].

Daily and intermittent continuous intravenous infusions [by gravity drip, (IVG) or infusion pump, (IVP)] and intermittent short-time intravenous drip infusion of 5-FU were carried out on advanced cancer patients. The MTD and dose-limiting toxicity were investigated in relation to the plasma concentrations of 5-FU determined by HPLC. Responses in eleven patients receiving IVG administration daily at 8-21 mg/kg/day were NC, but those given 5-FU alone showed no adverse reactions. Plasma concentrations were too low to be determined. In 9 patients receiving IVG or IVP administration weekly at 60 mg/kg for 24 hr, 1 of the 5 evaluable patients showed reduced hepatic metastatic lesions. One of 4 patients receiving IVP administration weekly at 120 mg/kg for 48 hr showed a disappearance of metastatic lesions in the skeletal muscle, but bone marrow suppression was observed as dose-limiting toxicity. Pharmacokinetics were more stable in IVP than in IVG with less individual difference in the plasma concentrations. Among the outpatients receiving short-time iv, IVG administration once or twice a week, 2 patients given weekly administrations at 20 mg/kg for 60 min showed slight adverse reactions. In 6 patients given high-dose administrations, bone marrow suppression was observed. When pharmacokinetics in the patients given 5-FU for 60 min were compared between the IVG and IVP groups, there were individual differences in plasma concentrations, but the differences were not significant. It was concluded from above results that the following practical dose schedules would be recommendable: 60 mg/kg for 24hr/week by IVP for inpatients and 20 mg/kg for 60 min/week by IVG for outpatients.

Adult↗
PubMed1987

The effect of cardiac sympathetic nerve stimulation on the right ventricle in canine heart.

The change in coronary hemodynamics during right or left cardiac sympathetic nerve stimulation was studied in anesthetized open chest dogs. No difference in the increasing rate of mean coronary blood flow between right coronary artery (RCA) and left anterior descending coronary artery (LAD) was observed. However the increasing rate of right ventricular systolic pressure X heart rate (RVSP X HR) was greater than that of left ventricle (LV). With phentolamine injection, cardiac sympathetic nerve stimulation showed similar changes as the controls. Beta-stimulation by isoproterenol infusion did not cause different effects on the increasing rate of coronary blood flow between RCA and LAD. These results showed that cardiac sympathetic nerve stimulation increased the double product of the right ventricle (RV) more than that of the LV and the increase was not affected by phentolamine. Moreover, cardiac sympathetic nerve stimulation, either the right or the left, caused the greater effects on the RV compared to the LV mainly through beta-adrenoceptors, and that the response of the RV to increase in oxygen demand was possibly, in part, different from that of the LV.

Animals↗
PubMed1987

Effects of dichloroacetate on the mechanical function of the isolated ischemic heart.

The effects of sodium dichloroacetate (DCA) on the activity of the pyruvate dehydrogenase complex (PDH) and the mechanical function of the isolated ischemic rat heart were investigated. Ischemia was induced by restriction of coronary flow. Perfusion with DCA caused a decrease in the tension developed (DT) and the maximal rate of tension development (+ dT/dt max), and an increase in the resting tension (RT) at low flow rates (0.6 and 0.15 ml/min). However, it did not affect the DT or +dT/dt max of normoxic hearts (3 ml/min) or hearts at zero flow rate. DCA increased PDH activity in hearts at all flow rates. It was concluded that this effect of DCA was associated with a decrease in lactate production, rather than an increase in the lactate/pyruvate ratio.

Acetates↗
PubMed1987

Clinical features and cardiopulmonary function of patients with atrophic heart in Duchenne muscular dystrophy.

The clinical features and cardiopulmonary function of 5 patients with atrophic heart in Duchenne muscular dystrophy (DMD) were studied by echocardiography and spirometry. Atrophic heart was defined as a state where the left ventricular end-diastolic volume decreased markedly during long-term follow-up (over 5 years). The patients with atrophic heart were more emaciated and showed more severe motor disability than the controls (18 DMD patients with a normal left ventricular cavity size). The pre-ejection period/ejection time ratio was significantly higher in patients with atrophic heart than in controls, and the maximal diastolic posterior wall velocity was reduced. The forced vital capacity was lower in patients with atrophic heart than in controls, but the one-second forced expiratory volume rate was similar in the 2 groups. Three patients with atrophic heart died. Examination at autopsy showed that their hearts were small and of low weight, and showed not only fibrosis, but also brown atrophy and waxy degeneration. These findings indicate that cardiopulmonary function is significantly reduced in DMD patients with atrophic heart.

Adolescent↗
PubMed1987

[An autopsy case of dentatorubropallidoluysian atrophy showing marked atrophy of the brain stem].

An autopsy case of a 66 year-old woman is reported. She developed personality change and psychotic symptoms at the age of 58. She began to show gait disturbance and forgetfullness at the age of 60. She was admitted to Okayama University Hospital at the age of 61, when she showed personality change, dementia, cerebellar sings and chorea like involuntary movement. The illness progressed slowly and she died of septicemia at the age of 66. At autopsy brain weighed 990 g. Macroscopically, the atrophy of the brain stem was severe, and the cerebellum was slightly atrophic. Microscopically, the globus pallidus was almost intact, but the degeneration involved dentate nuclei, their projections, red nucleus and the subthalamic nuclei, so this case was considered to be a case of pseudo-Huntington form of dentatorubropallidoluysian atrophy, proposed by Hirayama. The most striking feature of this case was marked atrophy of the brain stem and her intense familial history. Investigation of her familial history revealed that there were 18 affected cases in 5 successive generations. Their onset of the disease varied from the age of 10 to 60 years old. Cases of juvenile onset showed myoclonus and convulsion as the initial symptoms, and convulsion as the initial symptoms, and those of presenile onset showed dementia, cerebellar ataxia and chorea like involuntary movement. And in some of these cases it was proved by NMR-CT that their brain stem were small. We discussed the meaning of the atrophy of the brain stem in these cases and the difference of the symptoms between the cases of juvenile onset and the cases of presenile onset.

Age Factors↗
PubMed1987

[Phase II study of 590-S (1-phthalidyl-5-fluorouracil) in patients with gastrointestinal cancer. Tokyo Cancer Chemotherapy Cooperative Group].

590-S is a new masked compound of 5-fluorouracil, the antimetabolic antitumor agent of the fluorinated pyrimidine group. The safe dose for the phase II study was determined during the phase I study to be 600 mg/m2/day, equivalent to 900 mg/body/day. The phase II study involving 24 institutions was performed for the treatment of gastro-intestinal cancer. A daily dose of 900 mg was given 3 times a day after meals for more than 4 weeks. The number of registered cases was 32 with stomach cancer, 17 with colo-rectal cancer and 8 with others. 4 of the 23 completed cases with stomach cancer were judged as PR, and the response rate was 19.0%. No response was found in the cases with colo-rectal cancer. Slight side effects were observed in 14 of the 44 evaluable cases. Most of these were gastro-intestinal disorders.

Administration, Oral↗
PubMed1986

Effects of interventricular shunt on indices of left ventricular function.

The accuracies of indices of left ventricle function were examined in an open-chest model in dogs with and without a ventricular septal defect, in which the ventricular shunt was opened and reclosed by a specially designed flowmeter probe with a cap. The systolic time interval, the maximal rate of pressure development in the left ventricle (+LV dP/dt), +LV dP/dt corrected for the isometric pressure (+LV dP/dt/Pd), and the time to +LV dP/dt (t-dP/dt) were determined by recording the aortic flow, ventricular shunt flow, aortic pressure, pulmonary arterial pressure, and left ventricular pressure. The isometric contraction time, the preejectional period, and the ejection time shortened with decrease of the mean aortic pressure and aortic flow, and the mean pulmonary arterial pressure increased after opening the ventricular shunt. When the pulse was varied by atrial pacing, the systolic time interval was affected in dogs both with and without a ventricular septal defect, but "isometric contraction time" was not affected in animals with a ventricular septal defect. Dopamine and methoxamine were used to evaluate the effects of the inotropic state and afterload on these indices. The extents of the changes in the systolic time interval and +LV dP/dt were different in animals with and without a ventricular septal defect, but the changes in preejectional period/ejection time, +LV dP/dt/Pd and t-dP/dt were similar in the two conditions. These results suggest that the systolic time interval and the indices of left ventricular pressure are useful in assessment of cardiac function only in certain conditions.

Animals↗
PubMed1986

Effect of proximal and distal coronary pressure change on the resistance of stenotic coronary segment.

While dynamic changes in the resistance of stenotic coronary segments were recently proposed by several investigators, the mechanisms of these changes are obscure. This study was conducted to correlate changes in coronary pressure distal to the stenosis to dynamic changes in the stenosis resistance in the canine heart. Coronary pressure distal to the stenosis was raised by either proximal aortic pressure elevation or intracoronary blood infusion distal to the stenosis. The pressure rise resulted in a significant fall in the stenosis resistance. Distal coronary pressure drop induced by phlebotomy or removal of blood from the distal coronary bed caused the reverse effects on resistance. Linear regression analysis revealed a close relationship between changes in distal coronary pressure (delta DCP) and those in resistance of the stenotic coronary segment (delta RL) represented by the following equation; delta RL (dyne X cm-5 X sec X 10(-3)) = 0.50 X [delta DCP (mmHg)]-6.0 X 10(-2), r = 0.86, p less than 0.01. The results suggest that dynamic changes in stenosis resistance appear largely to be a function of the pressure changes distal to the stenosis.

Animals↗
PubMed1986

Change in pulmonary and systemic circulation in acute ventricular septal defect.

The correlation between left to right ventricular (L-R) shunt flow and other hemodynamic changes was studied in 16 dogs with an acute ventricular septal defect (VSD) and normal pulmonary vascular bed. The interventricular shunt flow was measured directly with a specially designed electromagnetic flowmeter probe, where the area of the VSD was constant. The sudden presentation of VSD increased pulmonary arterial pressure, pulmonary flow and left ventricular end-diastolic pressure. L-R shunt flow was not changed significantly by atrial pacing except when the rate was increased to over 200/min. Dogs with a VSD were treated with isoproterenol and dextran to vary the shunt flow and hemodynamic parameters. L-R shunt flow was decreased by isoproterenol and increased by dextran loading. The percentage changes of L-R shunt flow from pre-drug values correlated well with the change in left ventricular end-diastolic pressure (r = 0.75) and the ratio of pulmonary to systemic vascular resistance (r = -0.73). Change in total pulmonary vascular resistance had a greater effect on L-R shunt flow than did a change in systemic vascular resistance, whereas a change in aortic flow had less effect (r = 0.35) on L-R shunt flow than did a change in preload and afterload. The time to peak LV dP/dt, as an index of cardiac contractility, and heart rate were not correlated with the relative change in L-R shunt flow. These results indicate that L-R shunt flow induced by the sudden presentation of a VSD varied with changes in the pulmonary and systemic circulation.

Animals↗
PubMed1985

Remarkable improvement of clinical status in a patient with multiple lymphomatous polyposis of the gastrointestinal tract after repetitive chemotherapy.

The effect of repeated courses of chemotherapy on gastrointestinal tumors seen in a 43 year-old male patient with multiple lymphomatous polyposis involving the entire gastrointestinal tract was presented. Numerous polypoid lesions from the stomach to the rectum were the characteristic finding in this case. The biopsied specimens from polyps either of the stomach or large intestine showed diffuse lymphocytic accumulation in the submucosa, which is consistent with multiple lymphomatous polyposis of the gastrointestinal tract. Remarkable regression of the large masses in the gastrointestinal tract was obtained by two courses of VEMP therapy, along with improvement of hypoalbuminemia and a positive CRP. Recurrence of gastrointestinal masses in the cecum and rectum was also eliminated by six courses of CHOP therapy, and a total of nine courses of CHOP therapy led to complete disappearance of masses in the gastrointestinal tract. The present case is different from the others in terms of the following viewpoints that first the ensuing large masses favorably responded to repetitive chemotherapy, secondly the histopathological findings remained benign despite the fact that large nodular masses had recurred in the cecum and rectum, and thirdly the pathological changes were still confined to the gastrointestinal tract without developing systemic malignant manifestations.

Adult↗
PubMed1985

Effect of adenosine deaminase inhibitors on myocardial reactive hyperaemia following brief coronary occlusions.

Effect of two agents of adenosine deaminase inhibitor, 8-azaguanine and adenine, on myocardial reactive hyperaemia was tested in the anaesthetised open-chest dog. Reactive hyperaemic flow response of the circumflex coronary artery was observed following 5, 10, 15, 20 and 30 s coronary occlusions before, during and after infusion of 8-azaguanine and adenine, which are known as adenosine deaminase inhibitors. Intracoronary infusion of 8-azaguanine and adenine caused the minimum increase in the baseline coronary flow. Both the nucleic acids shifted the dose response curve of adenosine to the left. 8-azaguanine enhanced volume response of flow at all occlusion intervals tested. The infused dose of adenine also intensified volume response of flow after 5, 15, 20 and 30 s occlusions. Fifteen minutes after termination of the nucleic acid infusions, the reactive hyperaemia returned towards control levels. The results suggest that 8-azaguanine and adenine enhance myocardial reactive hyperaemia possibly by inhibiting adenosine deaminase to degradate myocardial interstitial adenosine to inosine.

Adenine↗
PubMed1985

Intracoronary adenosine enhances myocardial reactive hyperemia after brief coronary occlusion.

Adenosine is a prime candidate for the role of mediator between myocardial metabolic state and coronary blood flow. However, there are few reports concerning the direct effects of exogenously added adenosine on coronary autoregulation. The present investigation in the open-chest dog studied the effects of a threshold dose of intracoronary adenosine infusion on reactive hyperemia following brief coronary occlusions. The infused dose did not increase nonocclusive flow by greater than 10%. Adenosine enhanced total hyperemic flow at all occlusions tested (5, 10, 15, 20, and 30 s). Aminophylline pretreatment reduced reactive hyperemia below the control level even in the presence of an intracoronary infusion of adenosine. Adenosine injected into the left atrium and intracoronarily infused papaverine did not affect hyperemic response to 5- and 15-s coronary occlusions. The results suggest that a minimum dose of exogenously added adenosine enhances myocardial reactive hyperemia, possibly by potentiating the effects of endogenous adenosine released during ischemia.

Adenosine↗
PubMed1985

Effect of respiratory acidosis on ventricular shunt flow and hemodynamics in dogs with ventricular septal defect.

The effects of respiratory acidosis on ventricular shunt flow and hemodynamics were studied in 20 anesthetized dogs with a ventricular septal defect and a normal pulmonary vascular bed. The interventricular shunt flow was measured directly by using a specially designed electromagnetic flow probe. Respiratory acidosis was produced by hypoventilation and tachypnea with constant minute volume. Hypoxemia was also induced by hypoventilation, but not by tachypnea with constant minute volume. Systemic vascular resistance was increased in severe hypoventilation at 100 and 50 ml of tidal volume, and tachypnea at 100 ml of tidal volume. However the increase of pulmonary vascular resistance was observed in only severe hypoventilation: arterial pH 6.9, PaO2 24 mmHg, and PaCO2 88 mmHg. Left to right ventricular shunt flow and pulmonary blood flow were increased significantly with no change of systemic blood flow in both conditions of respiratory acidosis. The diastolic fraction of shunt flow was increased significantly. These findings indicate that the increase of left to right shunt flow in respiratory acidosis might be one of the risk factors of congestive heart failure for the patients with ventricular septal defect.

Acidosis, Respiratory↗