PubMed Health⌕ Search

Biomedical subjects

T Fukuyama

Publications and source records attributed to T Fukuyama.

At least 19 recordsLinked to original sources
PubMed1996

Myocardial adrenergic nervous activity is intensified in patients with heart failure without left ventricular volume or pressure overload.

OBJECTIVES: To clarify whether myocardial adrenergic activity is different in patients with heart failure without left ventricular volume or pressure overload, we used iodine-123 metaiodobenzylguanidine (MIBG) imaging to study patients with mitral stenosis. BACKGROUND: In patients with heart failure due to cardiomyopathy or to valve diseases with volume or pressure overload, or both, myocardial adrenergic nerve activity is accelerated independent of underlying cause. However, it is not clear whether this change in myocardial adrenergic nerve activity is present in patients without left ventricular volume or pressure overload. METHODS: The study patients were 20 men and women with normal left ventricular function and heart failure due to mitral stenosis. Planar MIBG images obtained from these patients were compared with images from nine age-matched healthy subjects (control group). Myocardial uptake of MIBG was calculated as the heart/mediastinal activity ratio. Storage and release of MIBG were calculated as percent myocardial MIBG washout from 15 min to 4 h after isotope injection. All 20 study patients underwent echocardiography, and 16 underwent right heart catheterization. RESULTS: The heart/mediastinal activity ratio in the immediate images (15 min) did not show any significant difference between the patient and control groups. Myocardial washout was increased in patients with severe heart failure. The level of myocardial washout correlated with left atrial diameter (r = 0.51, p = 0.02) and mitral valve area calculated with Doppler echocardiography (r = -0.61, p < 0.01) and mitral valve area calculated with cardiac catheterization (r = -0.62, p = 0.02). The closest correlation existed between myocardial washout and cardiac output (r = -0.80, p < 0.01). CONCLUSIONS: In heart failure due to mitral stenosis, myocardial adrenergic nerve activity is intensified. A decrease in cardiac output associated with mitral stenosis acts as a potent stimulus for this intensification.

3-Iodobenzylguanidine↗
PubMed1996

Case report: mucin-producing cystic neoplasm of the pancreas with onset in childhood.

Mucin-producing tumours of the pancreas have been recently reported with increasing frequency and most cases have occurred in middle-aged and elderly people. In the present report, a case of a 21-year-old man with mucinous cystadenoma of the pancreas is reported. He had a long history of recurrent pancreatitis from the age of 8. When he was aged 10, the first branch of the main pancreatic duct was shown to be enlarged on endoscopic retrograde pancreaticography (ERP). A series of ERP studies and computed tomography scans performed over a period of 11 years demonstrated continuing growth of this enlargement of the pancreatic duct. Pancreaticoduodenectomy was performed and the patient has been well without further episodes of acute pancreatitis and has been free of recurrent tumour for 1 year.

Adult↗
PubMed1996

Inhibitory effect of pentobarbital on biliary excretion of diclofenac in a rat liver perfusion system.

The effect of pentobarbital on the biliary excretion of diclofenac was investigated in a rat liver perfusion system following a pulse input of the drug. Without albumin in the perfusate, a trace amount of diclofenac was detected in the outflow from the liver (< 0.1%). The total biliary excretion of diclofenac (intact diclofenac plus its glucuronide) decreased from 23.8% (diclofenac 6.01, glucuronide 17.8%) to 16.3% (diclofenac 5.09, glucuronide 11.2%) with an increase in the perfusate concentration of pentobarbital from 0 to 2.5 micrograms mL-1. At pentobarbital concentrations exceeding 2.5 micrograms mL-1, the biliary excretion of diclofenac and its glucuronide (14% total diclofenac) was not reduced further. The mean local excretion times of both diclofenac and its glucuronide were approximately 17 min and were unchanged at all pentobarbital concentrations tested. The ratios of biliary excreted diclofenac and its glucuronide to total diclofenac were 22 and 78%, respectively, and these values were virtually constant at all concentrations of pentobarbital in the perfusate. These results suggest that the glucuronidation of diclofenac and the biliary excretion of its glucuronide are rapid processes and that pentobarbital blocks a step before glucuronidation.

Adjuvants, Anesthesia↗
PubMed1996

Influence of pentobarbitone on in-vivo local disposition of diclofenac in rat liver.

Because the liver is the main organ eliminating many drugs from the body and because pentobarbitone and other analogues can inhibit biliary secretion, the influence of pentobarbitone on hepatic local disposition of diclofenac has been investigated. Diclofenac was infused into the portal and femoral veins of non-anaesthetized rats (group A) and rats anaesthetized with pentobarbitone (group B) and the plasma concentration of diclofenac and the total amount of diclofenac excreted in the bile (in both cases intact diclofenac plus its glucuronide) were simultaneously monitored by HPLC at appropriate time intervals. The time-courses of plasma concentration and amount excreted in the bile were evaluated by moment analysis with trapezoidal integration. The hepatic recovery ratio (FH) was calculated by comparing the area under the curve (AUC) of plasma concentration after intravenous infusion with that after intraportal infusion. The mean biliary transit time (tb) was estimated by subtracting the mean residence time (MRT) of the plasma data from the mean biliary residence time (MRTb) of the biliary excretion data. The FH values of diclofenac were 0.664 in group A and 0.643 in group B. The biliary excretion ratio (Fb) of total diclofenac after intravenous administration was 27.0% in group A and 14.1% in group B. The tb values for total diclofenac were estimated to be 0.192 h (intravenous) and 0.159 h (intraportal) in group A, and 0.174 h and 0.238 in group B. Analysis of variance showed that differences among these four tb values were insignificant at the 5% level. The differences in the mean residence time (MRT), total clearance (CL) and distribution volume at steady state (Vss) were insignificant between groups A and B. Whereas total and the hepatic clearance of diclofenac were not affected by pentobarbitone, biliary clearance was extensively reduced. It took a relatively long time for diclofenac to move from the sinusoid into the bile and the time was not affected by pentobarbitone.

Adjuvants, Anesthesia↗
PubMed1996

Local absorption kinetics into the portal system using the portal-venous concentration difference after an oral dose of diclofenac in the awakening rat. Accelerative effect of bile on intestinal absorption of diclofenac.

The local absorption kinetics from the intestinal tract into the portal system was evaluated using the portal-venous concentration difference (P-V difference) after oral administration of diclofenac in conscious rats. The local absorption ratio (Fa), mean local absorption time (ta), and relative variance (sigma 2/ta2) from the intestinal tract into the portal system were estimated by simultaneously measuring the portal and venous concentrations, using diclofenac as a model drug. The effect of bile on diclofenac intestinal absorption was also investigated. The awakening rats simultaneously cannulated into the jugular and portal veins were divided into group A with intact enterohepatic circulation (EHC) and into another group with bile-duct cannulation to block EHC. The rats in the latter group were further divided into group B without the bile supply to the intestinal tract and into group C with the bile supply from the other rat. After oral administration of diclofenac to rats in groups A, B, and C, the portal and venous concentrations of diclofenac in each rat were simultaneously monitored by HPLC method at proper time intervals. The absorption time profile of diclofenac into the portal system was directly predicted from P-V difference. Plasma concentrations of diclofenac in the portal vein were constantly higher than those in the jugular vein after the oral administration. It was demonstrated that P-V difference was caused by absorption from the intestinal tract into the portal system. Fa in groups A, B, and C were estimated to be 91.5% for 8 hr, 33.8% for 3 hr, and 57.8% for 3 hr, respectively. ta in groups A, B, and C were estimated to be 2.26 hr, 0.65 hr, and 0.96 hr, respectively. sigma 2/ta2 in groups A, B, and C were 1.31, 0.48, and 0.55, respectively. Fa and ta of diclofenac extensively increased in the presence of the bile in the intestinal tract, whereas sigma 2/ta2 was unaffected by the bile. The mean absorption time (MAT) almost agreed with ta, which demonstrates that the mean transit time through the liver (tH) is negligible in MAT(= ta+tH).

Administration, Oral↗
PubMed1996

Influence of downscatter in simultaneously acquired thallium-201/technetium-99m-PYP SPECT.

UNLABELLED: Simultaneously acquired dual-isotope imaging is a unique and useful approach in SPECT. Photon spillover, however, is a potential limitation of this technique. METHODS: To investigate the degree of 99mTc downscatter into the 201Tl window in patients, simultaneously acquired dual-isotope 201Tl/99mTc-pyrophosphate imaging was performed in 17 patients with acute myocardial infarction (MI). Thallium-201 SPECT imaging was performed first, with a 201Tl photopeak window after the 201Tl injection (early 201Tl images), followed by 99mTc injection and SPECT acquisition using dual-isotope windows (dual 201Tl images). Twenty-four hours after the 99mTc injection, a third set of 201Tl images was obtained (24-hr 201Tl images). Thallium defect size (extent score) and defect severity (severity score) were calculated from these three sets of 201Tl images to quantify the MI. RESULTS: Technetium-99m accumulation of varying intensity was recognized in all patients. Extent scores and severity scores were identical in early 201Tl images and 24-hr 201Tl images. Both scores, however, in the dual 201Tl images were decreased by 36% and 53%, respectively. CONCLUSION: There in a considerable 99mTc downscatter into the 201Tl window, which prevents precise quantification of MI in simultaneously acquired dual-isotope 201Tl/99mTc-pyrophosphate imaging.

Female↗
PubMed1995

Iodine-123 metaiodobenzylguanidine images reflect intense myocardial adrenergic nervous activity in congestive heart failure independent of underlying cause.

OBJECTIVES: This study was undertaken to assess myocardial adrenergic activity using iodine-123 metaiodobenzylguanidine (MIBG) imaging in patients with heart failure. BACKGROUND: In patients with congestive heart failure, adrenergic nerve activity is accelerated. However, whether myocardial adrenergic nerve activity reflects the severity of heart failure and its relation to the underlying cause have not yet been elucidated. METHODS: Planar MIBG images were obtained from 96 patients with heart failure and compared with images from 9 age-matched healthy subjects. Groups 1 and 2 included 65 patients with heart failure related to impaired myocardial function and whose left ventricular ejection fraction was < 40% (group 1 = 40 patients with dilated cardiomyopathy; group 2 = 25 patients with ischemic cardiomyopathy). Group 3 included 31 patients with heart failure related to a mechanical abnormality and whose left ventricular ejection fraction was > 40% (mitral regurgitation in 16, aortic regurgitation in 9, aortic and mitral regurgitation in 4, ruptured aneurysm of Valsalva in 2). Myocardial uptake of MIBG was calculated as the heart/mediastinal activity ratio. Storage and release of MIBG were calculated as percent myocardial MIBG washout from 15 min to 4 h after isotope injection. RESULTS: The heart/mediastinal activity ratio in the immediate images (15 min) showed a significant decrease only in patients with severe heart failure (groups 1 and 2). The myocardial washout was accelerated in all three heart failure groups. The level of myocardial washout was related to severity of heart failure and correlated well with New York Heart Association functional classification. CONCLUSIONS: In severe heart failure associated with cardiomyopathy, norepinephrine uptake is reduced. In addition, myocardial adrenergic nerve activity is accelerated in proportion to severity of heart failure, independent of the underlying cause.

3-Iodobenzylguanidine↗
PubMed1995

Evaluation of intestinal absorption into the portal system in enterohepatic circulation by measuring the difference in portal-venous blood concentrations of diclofenac.

PURPOSE: We evaluated the first-pass effects in vivo by the intestine and liver during enterophepatic circulation (EHC) by simultaneously measuring the portal and venous plasma concentrations of the rat. METHODS: The venous and upper portal blood vessels were cannulated through the jugular and the pyloric veins, respectively, to obtain simultaneously blood samples from both sites. After diclofenac was injected as a bolus through the jugular vein, the concentrations of diclofenac in the portal and jugular veins were measured at time intervals. The absorption rate from the intestinal tract into the portal system was determined using the portal-venous difference in plasma concentrations of diclofenac, considering 40% partitioning of diclofenac into erythrocytes. RESULTS: After one hour, the plasma concentration in the portal vein was always higher than that in the jugular vein in awakening rats with intact EHC (portal-venous blood concentration difference). No portal-venous difference was observed in awakening rats with bile-duct cannulation. Therefore, it was concluded that this portal-venous concentration difference was not due to the hepatic clearance but to diclofenac reabsorption from the intestinal tract. CONCLUSIONS: Approximately 40% of the dose of diclofenac was reabsorbed over 8 hours from the intestinal tract into the portal system. By comparing the reabsorbed amounts in the portal system and in the systemic circulation, the hepatic extraction ratio in vivo (FH) of diclofenac was estimated to be 63%.

Animals↗
PubMed1995

Influence of laparotomy on disposition kinetics of diclofenac in CCl4-intoxicated rats.

The effect of the acute hepatic failure induced by CCl4 on the pharmacokinetics of diclofenac, which is definitely subject to enterohepatic circulation (EHC) in normal rats, was evaluated. This hepatic failure extinguished the secondary peak on the plasma time course which is usually observed in normal rats due to EHC. In the group without EHC by means of bile cannulation, the total clearance (CL) markedly decreased by CCl4-intoxication from 0.7 l/h/kg down to 0.1 l/h/kg, and mean residence time (MRT) increased from 0.29 h up to 2.8 h. The plasma time curves of the rats with laparotomy and with bile duct-cannulation were almost the same in the CCl4-intoxicated group. The bile excretion ratio of diclofenac markedly decreased by CCl4-intoxication from 43% down to 13%. In both groups, 92% of the total diclofenac excreted into the bile was glucuronide. While EHC made area under the curve (AUC) and MRT obviously increase in the CCl4-free rats, the effect of EHC on these moments was negligible in the CCl4-intoxicated rats. In the CCl4-intoxicated condition, the elimination of diclofenac in the rats with laparotomy was considerably slower than that in the rats without laparotomy. The plasma time courses were obviously monoexponential in the former group, while those were almost biexponential in the latter group.

Animals↗
PubMed1995

Effect of liver intoxication by carbon tetrachloride on hepatic local disposition of oxacillin using moment characteristics as index.

The effect of liver intoxication by carbon tetrachloride (CCl4) on the hepatic local disposition using oxacillin as a test drug and bovine serum albumin (BSA) as a reference substance was evaluated by single-pass bolus input method in the isolated perfused rat liver. Oxacillin and BSA were introduced into the liver from the portal vein, and the outflow concentration-time profiles of oxacillin and BSA from the rat liver into the hepatic vein were kinetically assessed by moment analysis. Liver damage was monitored by plasma SGOT, plasma SGPT, and bile flow rate. Hepatic recovery ratio FH of oxacillin increased from 50% to 80%, with an increase in liver intoxication by CCl4; whereas FH of BSA was naturally 100%. Mean transit time tH of oxacillin increased from 6 to 12 sec, with an increase in liver intoxication; whereas tH of BSA increased from 7 to 10 sec. The relative variance sigma 2/tH2 of oxacillin increased from 0.2 to 0.7, with an increase in liver intoxication; whereas sigma 2/tH2 of BSA took the value of approximately 0.4, independent of liver damage. In the relationship between the dispersion model and moments, it was shown that the blood space VB increased from 15 to 20%, the index for distribution (1 + k') of oxacillin from 1.0 to 1.5, the efficiency number RN of oxacillin decreased from 0.7 to 0.3 with the increase in liver damage, and the extent of eddy mixing was predicted to be unaffected by liver damage. The intensive increases in tH and sigma 2/tH2 of oxacillin with the liver intoxication by CCl4 were explained by increases in the extent of distribution and nonequilibrium distribution, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

Shorter interval between cycles of cyclophosphamide, doxorubicin, cisplatin using recombinant human granulocyte colony-stimulating factor for urothelial cancer--phase I/II study.

BACKGROUND: Despite improvement in the response rate and protraction of the progression-free period of urothelial cancer produced by chemotherapy, severe bone marrow suppression often results in delays in the initiation of treatment cycles and/or decreases in drug dosages. Reduction of leukopenia during chemotherapy has been demonstrated by the combined administration of granulocyte colony-stimulating factor (G-CSF) in various malignancies. METHODS: A phase I/II study was conducted to assess whether the interval between cycles of CISCA (cyclophosphamide, doxorubicin, cisplatin) chemotherapy could be shortened under support of recombinant human granulocyte colony-stimulating factor (rhG-CSF) for urothelial cancer. Three or more patients with transitional cell carcinoma of the urinary tract were allocated to each of four different treatment intervals (step 1: 28 days, step 2: 21 days, step 3: 17 days, and step 4: 14 days) by reducing the interval in a step-wise manner. Two mg/kg/day of a rhG-CSF, lenograstim, was injected subcutaneously on days 3 to 16 (until day 14 for the 14-day interval group). RESULTS: Sixteen patients were enrolled, four patients were treated with the step 1 protocol, five with step 2, four with step 3, and three with step 4. Leukopenia/neutropenia was the most severe toxic reaction, but none of the patients at any step manifested neutropenia of WHO grade 4 for more than four days. There were no significant differences in the hematological and nonhematological toxicities among the 4 steps. Seven of eight patients with measurable diseases were treated with CISCA on shortened schedules (steps 2-4), and one complete remission (CR) and four partial responses (PR) were demonstrated. CONCLUSIONS: CISCA chemotherapy supported by rhG-CSF was safely shortened to a 14-day interval in the pilot study. The potential role of rhG-CSF in shortening the interval of CISCA, as well as the benefit of the intensified schedule, remains to be clarified.

Adolescent↗
PubMed1993

Origin of laryngeal sensory-evoked potentials (LSEPs) in the cat.

Sensory-evoked potentials elicited by electrical stimulation of the superior laryngeal nerve were recorded at the dural surface on the cortex and the caudal medulla in anesthetized cats as a reflection of activities in the central afferent systems. These evoked potentials were named laryngeal sensory evoked potentials (LSEPs). LSEP was mainly composed of five components, N1, N2, N4, N12, and large biphasic potential (LBP). The peak latencies of these components were as follows: N1, 1.09 +/- 0.18 ms; N2, 1.93 +/- 0.19 ms; N4, 3.97 +/- 0.19 ms; and N12, 12.48 +/- 1.01 ms. LBP was a large component lasting from approximately 6 ms to 18 ms. The generator sources of these components were identified as follows: N1, nodose ganglion; N2, presynaptic potentials of the nucleus tractus of solitarius (NTS); N4, NTS complex including the postsynaptic potentials; and N12, activities of the frontal part of the orbital gyrus. The LBP was speculated to be generated from certain subcortical structures, such as the amygdala, the thalamus, the hypothalamus, and the basal ganglia.

Animals↗
PubMed1993

Adenocarcinoma of the urachus associated with stromal osseous metaplasia.

Urachal adenocarcinoma is a rare bladder tumor, occasionally associated with calcification. We report a case of urachal adenocarcinoma with remarkable stromal osseous metaplasia and review the literature on this rare condition. This is the first complete case report in English of this uncommon entity.

Adenocarcinoma, Mucinous↗
PubMed1993

Detection of largyneal sensory-evoked potentials (LSEPs) in the cat.

We previously reported on evoked potentials elicited by electrical stimulation of the superior laryngeal nerve at an appropriate site on the dural surface as a reflection of activities in the brain stem and cortex in anesthetized cats. This evoked potential was called the laryngeal sensory evoked potential (LSEP). In this study we attempted to establish a less invasive procedure for measuring LSEP. The procedures were recording on the scalp using chloride-coated silver disk electrodes and stimulation by insertion of a bipolar platinum hooked wire electrode into the laryngeal mucosa. Evoked potentials could be detected using these less invasive procedures. The response morphologies and relative timing of LSEP components were quite similar for each method in a given cat. However, the amplitudes were slightly lower and the latencies were slightly prolonged with the less invasive techniques. These results suggest that this LSEP method might be applicable to human beings as a noninvasive method for evaluating the function of the laryngeal sensory pathway.

Animals↗