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Biomedical subjects

K Katayama

Publications and source records attributed to K Katayama.

At least 361 records · Page 20Linked to original sources
PubMed1990

Effect of iodopyracet on renal excretion of sulfamethizole in rabbits.

To predict quantitatively drug interaction kinetics from the single-drug clearance studies, we examined the effect of iodopyracet (IOD) on sulfamethizole (SMZ) excretion in rabbits. Even though the decline of systemic IOD plasma concentration was linear, the renal clearance of SMZ decreased significantly in the presence of IOD. The results could be described by a perfusion model incorporated with the competitive inhibition for tubular secretion. For IOD with a high extraction ratio, it was suggested that a heavy load of the drug was supplied to the sites of secretion and caused the saturation of transport systems, even though the renal excretion kinetics were apparently linear in respect to the systemic circulation. These facts indicated that a linear relationship between the concentrations in the systemic circulation and at the sites of tubular secretion can not always be presumed. Consequently, SMZ-IOD interaction study stressed the importance of the drug concentrations at the sites of interaction for quantitative elucidation of drug-drug interactions.

Animals↗
PubMed1990

Kinetic studies on drug disposition in rabbits. I. Renal excretion of iodopyracet and sulfamethizole.

In order to quantify the renal handling of iodopyracet (IOD) and sulfamethizole (SMZ), single-drug clearance studies in rabbits were performed under quasi-steady state conditions with stepwise increasing the infusion rate of IOD or SMZ. Although concentration dependence of plasma protein binding was observed for both drugs, the urinary excretion rate of IOD was proportional to its total plasma concentration at low total plasma concentrations of 0.05-0.8 mM. On the other hand, the relationship between urinary excretion rate and total plasma concentration of SMZ was a concave-ascending curve at low plasma concentrations and the renal clearance of SMZ was sensitive to changes in plasma protein binding. However, renal clearances referenced to unbound plasma concentration at total plasma concentrations of 0.05 mM for IOD and SMZ were 9.5 and 38 l/h, respectively. Those values were much greater than the effective plasma flow in rabbits. These facts indicated that the intrinsic clearances at the sites of tubular secretion were high and that the rates of secretion were fully or partially limited by the renal plasma flow. Furthermore it was suggested that unbound drug was liberated from plasma protein at the sites of tubular secretion. The data obtained at high plasma concentrations indicated that the tubular secretion of IOD had capacity limited characteristics and that the urinary excretion of SMZ involved tubular reabsorption as well as saturable tubular secretion. From the data obtained, a perfusion-limited pharmacokinetic model was constructed characterizing the excretory processes, namely, glomerular filtration, passive tubular reabsorption, saturable tubular secretion and reequilibrium between bound and unbound drugs in plasma. For both drugs, the estimates for bulk flow rate were reasonable values of effective renal plasma flow and the dissociation constants for tubular secretion agreed well with those for in vitro renal cortex accumulation, suggesting that the kinetic model based on physiological concepts was useful for the understanding of the drug elimination processes.

Animals↗
PubMed1990

Transfer of diclofenac sodium across excised guinea pig skin on high-frequency pulse iontophoresis. I. Equivalent circuit model.

High frequency pulse iontophoresis of diclofenac sodium across excised guinea-pig skin was carried out in vitro. An equivalent circuit model was constructed to simulate the time courses of voltage drop across the donor solution and the skin. Parameter values obtained by the least-squares adaptation of the model to observed data were consistent with expectation and validated the proposed model.

Animals↗
PubMed1990

Transfer of diclofenac sodium across excised guinea pig skin on high-frequency pulse iontophoresis. II. Factors affecting steady-state transport rate.

Some of the factors affecting the steady-state transport rate of diclofenac sodium across excised guinea-pig skin during high-frequency pulse iontophoresis were examined. The same mathematical expression was employed for enhancement ratio as a function of applied voltage as the one derived for direct-current iontophoresis. The effective voltage drop across the skin was only 1.1% of the applied voltage. The steady-state flux value increased with increase of the donor concentration.

Animals↗
PubMed1990

Global and regional diastolic filling dynamics in compensated dilated cardiomyopathy.

To assess the left ventricular (LV) global and regional (anterior, apical, inferior) diastolic filling dynamics in compensated dilated cardiomyopathy (DCM), we measured left ventricular pressure and instantaneous volume from angiography in 7 normal controls (CTL) and 6 DCM patients with sinus rhythm. Global and regional peak filling rate (PER), time constant of LV pressure decline (T; Weiss's method) and LV chamber stiffness (k; Gaasch's method) were calculated. In DCM, left ventricular end-diastolic volume (ml/m2) was larger than in CTL (137 +/- 29 vs. 74 +/- 6, p less than 0.001), and stroke index (ml/m2) was not different from CTL (46 +/- 14 vs. 46 +/- 8, NS), indicating a compensated state of LV. Mitral valve opening pressure (mmHg) tended to increase in DCM compared with CTL (12 +/- 6 vs. 8 +/- 4). Global PFR (ml/sec/m2) (CTL = 216 +/- 47 vs. DCM = 201 +/- 36) and k (CTL = 0.044 +/- 0.023 vs. DCM = 0.029 +/- 0.016) were not different between 2 groups. However, T (msec) was markedly prolonged in DCM compared with CTL (61 +/- 10 vs. 35 +/- 5, p less than 0.001). In CTL, regional PFR (1/sec) showed almost the same values in each region, but in DCM, apical region showed higher PFR than in other regions. Thus, early diastolic filling might play an important role in maintaining the total transmitral flow in DCM despite severe impairment of LV relaxation. This compensation could be related mainly to accelerated regional lengthening of the LV apical region.

Adaptation, Physiological↗
PubMed1990

Factors affecting prognosis of intrauterine hydrocephalus diagnosed in the third trimester--computerized data analysis on controversies in fetal surgery.

Twenty hydrocephalic patients diagnosed in the third trimester of fetal life were evaluated and followed during a 7-year period. The factors affecting the prognosis, including the type of hydrocephalus, underlying conditions, associated anomalies, time of diagnosis and delivery, fetal period after diagnosis, head circumference and degree of ventriculomegaly at birth, and age at treatment, were comprehensively analyzed. The difference between final outcomes as assessed by developmental quotient (DQ) or intelligence quotient (IQ) were statistically tested with computation by means of STAX packages in an NEC 9801 VX. Hydrocephalus as an isolated defect occurred in six cases (30%), was associated with other central nervous system anomalies in nine (45%), and was secondary to intrauterine intraventricular hemorrhage or brain tumor in five (25%). The average age at the time of diagnosis was 33.9 weeks of gestation (range, 27-40 weeks). One fetus was treated by transabdominal cephalocentesis, but the majority of patients underwent ventriculoperitoneal shunt postnatally. The final IQ or DQ scores ranged from 20 to 120 (mean score, 50.6). The data analyses revealed that the only significant factor affecting outcome was the fetal period after diagnosis of hydrocephalus (r = -0.5076, p less than 0.01). Our data supports the fact that the results of an on-going hydrocephalic state may become irreversible during fetal life. It is emphasized that establishment of a more precise pathophysiological evaluation, and a less invasive but more reliable decompressive technique for fetal hydrocephalus, is urgent.

Chi-Square Distribution↗
PubMed1990

Antagonistic effects of interleukin 6 and G-CSF in the later stage of human granulopoiesis in vitro.

The effect of recombinant human interleukin 6 (rhIL-6) on the in vitro growth of human bone marrow myeloid progenitors (granulocyte-macrophage colony-forming units, CFU-GM) was investigated. Recombinant human IL-6 by itself did not induce colony formation. When rhIL-6 at various concentrations was added to the CFU-GM colony cultures containing recombinant human granulocyte colony-stimulating factor (rhG-CSF) or recombinant human granulocyte-monocyte/macrophage colony-stimulating factor (rhGM-CSF), rhIL-6 significantly suppressed the colony formation induced by rhG-CSF, but not by rhGM-CSF. This suppressive effect of rhIL-6 on rhG-CSF-induced, but not rhGM-CSF-induced colony formation was confirmed by using an MY10(+)-cell-enriched population. Neither interleukin 3 nor interleukin 1 alpha suppressed the growth of myeloid progenitors. The preincubation of bone marrow cells with rhIL-6 for a short time (30 min) resulted in a reduction of colonies induced by rhG-CSF, but not by rhGM-CSF. The suppressive effect of rhIL-6 on rhG-CSF-induced colony formation was not observed when the cells were preincubated together with rhG-CSF at a high ratio of rhG-CSF to rhIL-6. The rhIL-6-mediated suppressive effect was further confirmed by blocking the effect by the anti-IL-6 antibody. These results suggest antagonistic interaction between IL-6 and G-CSF in the later differentiation of myeloid progenitors.

Adult↗
PubMed1990

[Multivariate analysis of gastric cancer patients with liver metastases].

In 93 cases of stomach cancer with liver metastasis, the influence of surgery and chemotherapy on the patients' prognosis was examined. Chemotherapy comprised systemic administration of mitomycin C (MMC) (39 cases), intra-hepatoarterial administration of MMC (19 cases) and intra-hepatoarterial infusion of cisplatin (CDDP) + MMC (PM intra-arterial chemotherapy) (24 cases) in the first 1-2 postoperative weeks. MMC and CDDP were given by 1-4 courses every 1-3 weeks. Examination of the prognosis factors by generalized Wilcoxon test revealed significant differences in the extent of lymph node metastasis (N0-2 vs N3,4), possible resection of primary lesion, and chemotherapeutic regimen (PM intra-arterial chemotherapy and other chemotherapeutic regimens). The response rate was 4.3% (1/23), 29.4% (5/17) and 73.8% (17/23) for MMC systemic administration, MMC intra-arterial chemotherapy and PM intra-arterial chemotherapy, respectively, with a significantly high response rate for the latter. Also for the 50% survival period, the latter showed 11.8 months compared with 2.7 months for other chemotherapeutic treatments, indicating its good prognosis regardless of possible resection of the primary lesion. Cox proportional hazard model revealed the latter alone to be a significant independent factor. The above results suggest that the PM intra-arterial chemotherapy is an effective approach to stomach cancer with liver metastasis.

Adult↗
PubMed1990

[Comparison of myocardial perfusion assessments by digital subtraction angiography with those of left ventricular wall dynamics].

In clinical and experimental studies we assessed images of digital subtraction coronary angiography (DSA) for evaluating regional myocardial perfusion. Myocardial perfusion was assessed by injecting contrast medium into the coronary artery, and by imaging the regional myocardium using DSA. On the time-density curve obtained from the myocardial region of interest, we calculated the time to peak concentration (TPC) and the exponential washout rate (T). TPC and T were measured in five patients with stable effort angina pectoris (AP) and left anterior descending (LAD) lesions before and after percutaneous transluminal coronary angioplasty (PTCA). The values of 1/T increased significantly from 0.09 +/- 0.02 l/sec to 0.21 +/- 0.04 l/sec (p less than 0.01) after PTCA, but l/TPC did not change. No significant difference in ejection fractions was observed between the patients with AP and the normal subjects (n = 7), while the regional percent area shrinkage in the anterolateral and apical regions supplied by the LAD was significantly decreased in the patients with AP compared with those of normal subjects (anterolateral: 39.8 +/- 8.8% vs 51.3 +/- 6.8%, apical: 36.6 +/- 8.4% vs 52.4 +/- 13.4%, both p less than 0.01). In 10 anesthetized dogs with varying degrees of reduction in the left circumflex coronary artery (LCX) blood flow (CBF: categories of stenosis (S1-S5), we compared 1/TPC and 1/T with regional myocardial function (systolic wall thickening: %WTh). With varying LCX stenosis, there were no significant changes in heart rate and mean aortic pressure and significant linear correlations were observed between %WTh and 1/TPC (r = 0.51), between %WTh and 1/T (r = 0.55). At S1 (CBF: 100-90% of the control), neither %WTh nor 1/TPC differed from that of the controls, but 1/T was significantly decreased (80% of the controls, p less than 0.01). From S3 (CBF: 79-60%) to S5 (CBF: 39-0%), %WTh, 1/TPC and 1/T were significantly decreased from those of the control levels (all p less than 0.01). However, at S5 (CBF: 39-0%) the values of 1/TPC (71% of controls) and 1/T (33%) did not differ from those at S4; whereas, %WTh was markedly reduced and the systolic thinning of the ventricular wall occurred at S5. Therefore, in critical coronary stenosis, 1/T was more sensitive than 1/TPC or wall dynamics for assessing myocardial ischemia. Both 1/TPC and 1/T, as well as %WTh, were useful for assessing moderate myocardial ischemia; however, these DSA indices had considerable limitations for evaluating the severity of myocardial ischemia when CBF was markedly reduced.

Aged↗
PubMed1990

[Two cases of ataxic sensory neuropathy associated with silicosis].

Two patients of ataxic sensory neuropathy associated with silicosis were studied. Case 1 is a 53-year-old (in 1979) man who was a stonecutter for 40 years and diagnosed as silicosis in 1973. Case 2 is a 64-year-old (in 1984) man who was a glasscutter for 30 years and had been treated for silicosis from 1980 to 1982. Both patients developed dysesthesias in the hands, feet and face asymmetrically and gait ataxia over a few months. Vibratory and joint position senses were profoundly diminished but were accompanied by only mildly decreased pain and temperature sensations. Their muscle power was almost unchanged. Both had absent muscle power was almost unchanged. Both had absent muscle stretch reflexes. Sensory nerve conduction velocities were absent and motor nerve studies were almost normal. Nerve biopsy in case 2 showed a severe loss of large myelinaed fibers, and no inflammatory infiltrates and onion bulb formations. Although these findings suggested the carcinomatous neuropathy, we could not find any malignancy. Both patients had elevated polyclonal gamma-globulin levels and rheumatoid factors and, in case 2 an increase of IgG in serum. Cerebrospinal fluid showed an albumino-cytogenic dissociation and steroid therapy was successful in both patients. Case 1 died of pneumonia in 1989. Though an autopsy was not performed, his condition had continued to improve without signs of malignancy during 10 years. The condition of case 2 has also continued to improve, although ataxias remain.(ABSTRACT TRUNCATED AT 250 WORDS)

Ataxia↗
PubMed1990

[Expression of hepatitis B virus (HBV) markers in chronic liver disease positive for antibody to hepatitis C virus (HCV)].

We investigated expression of HBV markers in chronic liver disease positive for antibody to HCV (anti-HCV). Sera from 107 patients with chronic non-A, non-B liver disease, 65 HBs antigen carriers with chronic liver disease and 14 asymptomatic HBV carriers were tested for the presence of anti-HCV. Anti-HCV was detected in 83 (78%) patients with chronic non-A, non-B liver disease, irrespective of the past history of blood transfusion, and anti-HCV prevalence was similar in each category of chronic liver disease. Fifty-three (64%) out of these 83 sera positive for anti-HCV has also antibodies to HBV. Anti-HBc antibody was detected frequently in liver cirrhotics with hepatocellular carcinoma than in chronic persistent hepatitis, chronic active hepatitis and cirrhotics without hepatocellular carcinoma. In addition, titers of anti-HBc antibody were significantly higher in cirrhotics with hepatocellular carcinoma than in the other groups. On the other hand, anti-HCV was detected in 7 out of 65 patients with HBV-related liver disease. Four out of these 7 were patients with HBV-related hepatocellular carcinoma. Anti-HCV was detected in none of asymptomatic HBV carriers. These findings suggest that infection with both HBV and HCV is likely to cause more serious liver disease than infection with a single agent.

Adult↗
PubMed1989

[Continuous hyperthermic peritoneal perfusion with cisplatin and mitomycin C for peritoneal dissemination in gastric cancer].

Thirty-four patients with advanced gastric cancers had received continuous hyperthermic peritoneal perfusion (CHPP) for prevention or treatment of peritoneal dissemination (PD). These patients received intra-abdominal perfusion 30-40 minutes by about 10-liter saline heated to 50-52 degrees C dissolving 200-300 mg cisplatin (CDDP) and 20-30 mg mitomycin C (MMC). The perfusate was infused in the peritoneal cavity through the peritoneal cavity expander (PCE Nihon Kayaku Co. Ltd.) newly developed for sufficient irrigation in our clinic. Eleven patients with macroscopic serosal invasion without PD (P0) or with mild PD (P1) underwent prophylactic CHPP for prevention of peritoneal recurrence. (Pn means degree of PD according to The General Rules for the Gastric Cancer Study.) Twenty-three patients with moderate PD (P2) or severe PD (P3) underwent therapeutic CHPP. The prognosis of patients having undergone prophylactic or therapeutic CHPP (CHPP (+) group) was compared with those not having done CHPP (CHPP (-) group) in the historical control study. In the prophylactic study two-year-survival rates of CHPP (+) group was 90% significantly higher than 63% in CHPP (-) group. There was no significant difference between two-year-survival rates of CHPP (+) (11%) and CHPP (-) (0%) in the therapeutic CHPP. But ascites was observed to disappear in five of twelve (41.7%). Surprisingly second look operation disclosed macroscopic and microscopic disappearance of PD in three of nine (33.3%). The side-effects in those patients had consisted of leakage, bone marrow suppression, perforation of small bowel and so on. But there was no mortality after introduction of PCE. About laboratory data, rises in WBC, BUN, creatinine and LDH and drops in total lymphocytes counts and platelets were all normalized within four weeks. The maximal concentrations of total and free, which emerged at five minutes after CHPP, were 2.19 and 1.29 micrograms/ml. These results suggested that CHPP with CDDP and MMC was well tolerated and effective for prevention of peritoneal recurrence and treatment of peritoneal dissemination in the gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[The effect of RU486 and progesterone on luteal function during pregnancy].

In order to investigate the role of progesterone in the maintenance of pregnancy, an anti-progesterone agent, RU486 (RU) was injected subcutaneously into pregnant rats on day 12 (D12), and morphological changes of the uterus as well as endocrinological changes were observed. In all rats injected with RU, abortion occurred with macroscopic and microscopic intrauterine hemorrhage and degeneration or delivery of conceptuses. Endocrinologically, the levels of progesterone decreased rapidly 48 hours after the injection, while the levels of estradiol showed a tendency to increase. As progesterone is mainly produced by the corpus luteum but not by the placenta in rats, the decrease in progesterone is suspected to be due to luteolysis. Then in order to clarify the mechanism of luteolysis induced by RU and the effects of progesterone on this phenomenon, the dynamics of the luteotrophic factors (estradiol, LH, PRL) and specific binding capacity of the ovaries to LH/hCG were investigated in D7 pregnant rats treated with RU 1 mg/kg alone (RU group) or with both RU 1 mg/kg and progesterone 50mg/kg (RU + P group). The serum levels of progesterone in the RU group decreased significantly after 72 hours of administration, while those in the RU + P group remained within the levels of the control group. However, serum levels of luteotrophic factors in the RU group did not decrease, and some of them were even higher than those in the control group. In the RU + P group, luteotrophic factors remained within control levels. On the other hand, the specific bindings of LH/hCG to ovarian homogenates decreased significantly after 72 hours in the RU group. But in the RU + P group, the specific bindings were kept at the same levels as the controls. Scatchard analysis of these results disclosed that in the RU group, both affinity and numbers of receptors decreased compared to the controls, and that in the RU + P group only affinity decreased transiently and afterwards recovered quickly. From these results, it is concluded that deterioration of affinity and numbers of ovarian LH/hCG receptors seems to be one of the factors which induce luteolysis in pregnant rats treated with RU, and that progesterone can spare the effect of RU on the corpus luteum during pregnancy.

Animals↗