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Biomedical subjects

T Saga

Publications and source records attributed to T Saga.

250 records · Page 14Linked to original sources

Follow-up assessment of the collateral circulation in patients with Kawasaki disease who underwent dipyridamole stress technetium-99m tetrofosmin scintigraphy.

To assess the alteration of myocardial ischemic findings and the role of collateral vessels in patients with Kawasaki disease (KD), we used dipyridamole stress technetium-99m tetrofosmin (Tf) single photon emission computed tomography (SPECT). A comparison study of coronary angiography and dipyridamole stress (0.70 mg/kg) Tf-SPECT was repeated at least twice in 20 patients. The subjects included 7 patients with coronary stenosis, 1 with pre- and post-coronary artery bypass grafting (CABG) due to coronary stenosis, 1 with progression to coronary stenosis, and 11 with persistent coronary aneurysms. In the stenosis group, Tf-SPECT revealed that 6 of the 7 patients had some degree of ischemic findings, and 5 of these 6 did not show any change in their ischemic findings during follow-up. In 1 patient, the ischemic findings changed according to the collateral circulation changes. The patient who underwent CABG had pre-CABG ischemic changes that disappeared after CABG. In the patient whose coronary arteries progressed to stenosis, the ischemic findings progressed as the coronary stenosis progressed. In the persistent aneurysm group, there were no ischemic findings. In the future Tf-SPECT may become one of the most useful methods for monitoring the progressive changes of myocardial ischemia in KD.

Adolescent↗

CT manifestations of a ruptured hepatic tumor after transcatheter arterial embolization.

There are few reports of the radiologic diagnosis of ruptured hepatic tumors. In a patient with right upper abdominal pain and impending shock, angiography demonstrated a hypervascular hepatic tumor, and CT imaged an extrahepatic mass suggestive of a hematoma. Following transcatheter arterial embolization with Lipiodol Ultrafluide and gelatin-sponge, multiple contiguous CT sections revealed numerous lipiodol droplets adjacent to a lipiodol-containing hepatic tumor, clearly outside the liver. These findings were indicative of a ruptured hepatic tumor. After embolization, the patient's condition improved and he was discharged.

Carcinoma, Hepatocellular↗

Renal metabolism of 3'-iodohippuryl N(epsilon)-maleoyl-L-lysine (HML)-conjugated Fab fragments.

Renal localization of radiolabeled antibody fragments constitutes a problem in targeted imaging and radiotherapy. Recently, we reported use of a novel radioiodination reagent, 3'-[131I]iodohippuryl N(epsilon)-maleoyl-L-lysine (HML), that liberates m-iodohippuric acid before antibody fragments are incorporated into renal cells. In mice, HML-conjugated Fab demonstrated low renal radioactivity levels from early postinjection times. In this study, renal metabolism of HML-conjugated Fab fragments prepared by different thiolation chemistries and by direct radioiodination were investigated to determine the mechanisms responsible for the low renal radioactivity levels. Fab fragments were thiolated by 2-iminothiolane modification or by reduction of disulfide bonds in the Fab fragments, followed by conjugation with radioiodinated HML to prepare [131I]HML-IT-Fab and [125I]HML-Fab, respectively. In biodistribution studies in mice, both [131I]HML-IT-Fab and [125I]HML-Fab demonstrated significantly lower renal radioactivity levels than those of [125I]Fab. In subcellular distribution studies, [125I]Fab showed migration of radioactivity from the membrane to the lysosomal fraction of the renal cells from 10 to 30 min postinjection. On the other hand, the majority of the radioactivity was detected only in the membrane fraction at the same time points after injection of both [131I]HML-IT-Fab and [125I]HML-Fab. In metabolic studies, while [125I]Fab remained intact at 10 min postinjection, both HML-conjugated Fab fragments generated m-iodohippuric acid as a radiometabolite at the same postinjection time. [131I]HML-IT-Fab registered two radiometabolites (intact [131I]HML-IT-Fab and m-iodohippuric acid), whereas additional radiometabolites were observed with [125I]HML-Fab. This suggested that metabolism of both HML-conjugated Fab fragments would occur in the membrane fractions of the renal cells. The findings of this study reinforced our previous hypothesis that radiochemical design of antibody fragments that liberate radiometabolites that are excreted into the urine by the action of brush border enzymes would constitute a useful strategy to reduce renal radioactivity levels from early postinjection times.

Animals↗

Comparison of the macromolecular MR contrast agents with ethylenediamine-core versus ammonia-core generation-6 polyamidoamine dendrimer.

Two novel macromolecular MRI contrast agents based upon generation-6 polyamidoamine dendrimers (G6) of presumed similar molecular size, but of different molecular weight, were compared in terms of their blood retention, tissue distribution, and renal excretion. Two G6s with either ammonia core (G6A) or with ethylenediamine core (G6E), which possessed 192 and 256 exterior primary amino groups, respectively, were used. These dendrimers were reacted with 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M). The G6--1B4M conjugates were reacted with (153)Gd for studying biodistribution and blood clearance or Gd(III) for the MRI study. 3D-micro-MR angiography of the mice were taken with injection of 0.033 mmol of Gd/kg of G6A--(1B4M-Gd)(192) or G6E--(1B4M-Gd)(256) using a 1.5-T superconductive MRI unit. Although numerous fine vessels of approximately 100 microm diameter were visualized on subtracted 3D-MR-angiography with both G6A--(1B4M-Gd)(192) and G6E--(1B4M-Gd)(256), (153)Gd-labeled saturated G6E-(1B4M)(256) remained in the blood significantly more than (153)Gd-labeled saturated G6A--(1B4M)(192) at later than 15 min postinjection (p < 0.01). In addition, G6E--(1B4M-Gd)(256) visualized these finer vessels longer than G6A--(1B4M-Gd)(192). The G6A--(1B4M-Gd)(192) showed higher signal intensity in the kidney on the dynamic MR images and brighter kidney images than G6E--(1B4M-Gd)(256). In conclusion, the G6A--(1B4M-Gd)(192) was observed to go through glomerular filtration more efficiently than G6E--(1B4M-Gd)(256) resulting faster clearance from the blood and higher renal accumulation, even though both of G6--1B4M conjugates have almost similar molecular size and same chemical structure. In terms of the ability of intravascular contrast agents, G6E--(1B4M-Gd)(256) was better due to more Gd(III) atoms per molecule and longer retention in the circulation than G6A--(1B4M-Gd)(192).

Ammonia↗

Avidin-dendrimer-(1B4M-Gd)(254): a tumor-targeting therapeutic agent for gadolinium neutron capture therapy of intraperitoneal disseminated tumor which can be monitored by MRI.

Peritoneal carcinomatosis is a late stage in cancer progress, for which no effective therapeutic modality exists. Targeting therapeutic agents to disseminated lesions may be a promising modality for treating peritoneal carcinomatosis. Gadolinium ((157,155)Gd) is known to generate Auger and internal conversion electrons efficiently by irradiation with a neutron beam. Auger electrons from neutron-activated Gd(III) are strongly cytotoxic, but only when Gd(III) atoms have been internalized into the cells. In the present investigation, we have developed a quickly internalizing tumor-targeting system to deliver large quantities of Gd(III) atoms into tumor cells to generate the Auger emission with an external neutron beam. Simultaneously, one would be able to image its biodistribution by MRI with a shortened T1 relaxation time. Avidin-G6-(1B4M-Gd)(254) (Av-G6Gd) was synthesized from generation-6 polyamidoamine dendrimer, biotin, avidin, and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M). The Av-G6Gd was radiolabeled with Gd(III) doped with (153)Gd. All of the 1B4M's on the conjugate were fully saturated with Gd(III) atoms. An in vitro internalization study showed that Av-G6Gd accumulated and was internalized into SHIN3 cells (a human ovarian cancer) 50- and 3.5-fold greater than Gd-DTPA (Magnevist) and G6-(1B4M-Gd)(256) (G6Gd). In addition, accumulation of Gd(III) in the cells was detected by the increased signal on T1-weighted MRI. A biodistribution study was performed in nude mice bearing intraperitoneally disseminated SHIN3 tumors. Av-G6Gd showed specific accumulation in the SHIN3 tumor (103% ID/g) 366- and 3.4-fold greater than Gd-DTPA (0.28% ID/g, p < 0.001) and G6Gd (30% ID/g, p < 0.001) 1 day after i.p. injection. Seventy-eight percent of the tumor-related radioactivity of Av-G6Gd in the SHIN3 tumor was located inside the cells. The SHIN3 tumor-to-normal tissue ratio was greater than 17:1 in all organs and increased up to 638:1 at 1 day after i.p. injection. In conclusion, a sufficient amount (162 ppm) of Av-G6Gd was accumulated and internalized into the SHIN3 cells both in vitro and in vivo to kill the cell using (157/155)Gd with external irradiation with an appropriate neutron beam while monitoring with MRI. Thus, Av-G6Gd may be a promising agent for Gd neutron capture therapy of peritoneal carcinomatosis. This reagent also has the potential to permit monitoring of its pharmacokinetic progress with MRI.

Animals↗

Induction of vascular endothelial growth factor (VEGF) by hyperthermia and/or an angiogenesis inhibitor.

Intratumoral localization of vascular endothelial growth factor (VEGF) following administration of hyperthermia (HT) and/or anti-angiogenic drugs (TNP-470) was evaluated using SCC VII tumours in C3H/He mice. Hyperthermia at 44.0 degrees C for 30 min was given with a water bath on day 0. TNP-470 (100 mg/kg) was administered alone or after HT on day 0 and day 3. Histological changes on day 4 were evaluated by haematoxylin-eosin (HE) staining and immunohistochemical staining for VEGF. The percentage of the necrotic area relative to the entire tumour area (the % necrotic area) was measured on HE stains. The average % necrotic area of the untreated SCC VII tumours was 7%, while those of tumours treated with TNP-470 alone and HT alone were 27 or 65%, respectively. When HT and TNP-470 were combined, the % necrotic area was 82%, which was significantly higher than that caused by HT alone (p < 0.05). Immunohistochemical staining for VEGF in untreated SCC VII tumours was weak, although strong staining for VEGF was noted in untreated EMT-6 tumours of BALB/c mice, which have spontaneous central necrosis. After administration of HT and/or TNP-470, layer-shaped staining by VEGF was observed in the residual SCC VII tumour cells adjacent to the necrotic area. In conclusion, the expression of VEGF increased in response to administration of HT and/or TNP-470. Hypoxia caused by heat-induced vascular damage may be attributable to increased expression of VEGF in SCC VII tumours.

Animals↗

Gadolinium-phthalein complexone as a contrast agent for hepatobiliary MR imaging.

Gadolinium-phthalein complexone (Gd-PC) was developed as a hepatobiliary magnetic resonance (MR) contrast agent. Phthalein complexone is one of the iminodiacetic acid derivatives and a structural analogue of bromosulfophthalein. Gadolinium-PC substantially enhanced signal intensity of normal functioning livers on T1-weighted MR images. Contrast enhancement of rabbit liver and gradual accumulation of high intensity bile in the gallbladder were observed after intravenous injection of 0.05 and 0.1 mmol/kg Gd-PC. However, 0.1 mmol/kg of Gd-DTPA caused little effect on liver MR.

Animals↗

Positron emission tomography application for gynecologic tumors.

Positron emission tomography (PET) using fluorine-18-fluoro-2-deoxy-d-glucose (FDG), which originated as a research tool to evaluate glucose metabolism in cancer tissues, has now become an essential imaging modality for determining the appropriate therapeutic management of various cancer patients. The clinical role of FDG-PET for gynecologic tumors has not been established yet, but FDG-PET has come to be considered one of the important imaging modalities for evaluating patients with gynecological cancers. The objective was to review the literature regarding the utility of FDG-PET in the clinical setting of gynecological malignancies. Many articles reported that FDG-PET could be used for staging and restaging in patients with uterine cervical cancer. Although there is limited data about the feasibility of FDG-PET for endometrial cancer, preliminary results for detecting recurrence were promising. Furthermore, FDG-PET has been reported as a useful imaging modality, especially for restaging, in ovarian cancer, although the prognostic value needs to be fully investigated. Currently, a combined PET/computed tomography scanner is available, and its clinical application has begun. It is expected that this modality will contribute to the management of gynecological cancers, as has been reported recently for other malignancies.

Animals↗

Total extracardiac right heart bypass using a polytetrafluoroethylene graft.

BACKGROUND: With regard to hemodynamics and late arrhythmias, total cavopulmonary connection has been accepted as a superior technique as compared to Fontan type procedures. However, intra-atrial baffles for lateral tunnel or conduit remain construction retain some similar disadvantages. PATIENTS AND METHODS: As an alternative to total cavopulmonary connection, total extracardiac right heart bypass using a polytetrafluoroethylene tube for the inferior vena cava to pulmonary artery connection may obviate some problems. Five patients with complex heart disease necessitating one ventricle repair underwent this procedure successfully. RESULTS: Aortic cross-clamp time ranged from 0 to 24 minutes (mean = 15.8 min). No case required takedown or an additional step. Although the follow-up periods have been relatively short (mean = 19 months), all patients are well and no arrhythmic event or thromboembolic episode has occurred. CONCLUSIONS: As a simple, safe, and reproducible procedure, total extracardiac right heart bypass is an alternative to Fontan or total cavopulmonary connection procedure.

Blood Vessel Prosthesis↗

A case of hyperLp(a)aemia, associated with systemic lupus erythematosus, suffering from myocardial infarction and cerebral infarction.

We describe a case of systemic lupus erythematosus (SLE) with nephrotic syndrome who suffered from myocardial infarction and cerebral infarction associated with hyperLp(a)aemia. The proband was an 18-year-old Japanese male who was found to have hypercholesterolemia and hyperLp(a)aemia, with a serum total cholesterol level of 361 mg/dl and a serum Lp(a) level of 197 mg/dl. His father and mother showed higher Lp(a)levels (26 and 56 mg/dl, respectively) than those in normals (18 +/- 0.6 mg/dl, mean +/- SE). Lp(a)glycoprotein phenotypes were examined. The proband had the phenotype S2/4, which is associated with high Lp(a) concentration. His parents had the phenotype S3/4 and S2/4. No cardiovascular diseases were noted in other members of his family. After treatment with CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Lp(a) levels decreased from 197 to 121 mg/dl, but still remained abnormally high. LDL apheresis using a Liposorber system was attempted in this patient. Total and LDL cholesterol levels decreased by 57 and 62%, respectively. Lp(a) levels decreased by 68%. These results suggest that LDL apheresis may be an alternative therapy in drug resistant hyperLp(a)aemia.

Adolescent↗

An asymptomatic, normotensive sipple syndrome patient with glucose intolerance and hypercholesterolemia, and her kindred.

The proband, a 42-year-old woman without any symptoms or hypertension, was admitted for examination of accidentally discovered bilateral adrenal masses. Physical examination disclosed bilateral nodular goiter and mild sinus tachycardia. Pheochromocytomas and medullary thyroid carcinomas were revealed by biochemical and histopathological examinations. Hypercholesterolemia and abnormal glucose metabolism returned to normal after bilateral total adrenalectomy and thyroidectomy. Screening examination showed four affected family members. Three of them were also asymptomatic and normotensive. In pheochromocytoma patients, normotension, hypercholesterolemia, and impaired glucose metabolism might be signs of excess secretion of epinephrine rather than norepinephrine.

Adrenal Gland Neoplasms↗

A study of the clinical significance of lipoprotein (a) in nephrotic syndrome.

Lipoprotein (Lp)(a) concentrations were measured in eight patients with nephrotic syndrome in the age range of 8 to 69 yrs. Mean (+/- SE) levels of serum Lp(a) were elevated in the nephrotic patients compared to controls (76.5 +/- 19.7 vs 18.6 +/- 0.9 mg/dl, p less than 0.001). After treatment with prednisolone, Lp(a) concentrations were decreased from 85.2 +/- 21.6 to 42.2 +/- 14.0 mg/dl. During the treatment, serum total cholesterol showed a negative correlation with serum albumin concentration. However, no correlation was noted between Lp(a) and serum albumin concentration. There were no significant correlations between Lp(a) and other lipoprotein lipid and apolipoprotein levels. It was concluded that hyperLp(a)aemia may be an independent risk factor in the development of premature atherosclerosis in patients with nephrotic syndrome.

Adolescent↗

Value of low-dose gallium-67 imaging in detection of non-Hodgkin's lymphoma recurrence.

We evaluated the usefulness of low-dose Ga-67 scintigraphy as a diagnostic tool for the detection of non-Hodgkin's lymphoma recurrence. Forty-six patients were included in this retrospective study. Anterior and posterior whole body images were obtained two or three days after the injection of 74 MBq of Ga-67. Inter- and intraobserver variability in scintigraphic imaging interpretation was analyzed using the kappa (kappa) statistics. Ga-67 scintigraphy allowed correct detection of recurrence in 18 of 22 events (sensitivity, 82%), and excluded relapse in 34 of 39 events (specificity, 87%). The positive predictive value was 0.78 and negative predictive value 0.89. All cases involving superficial lymph nodes (10/ 10) could be detected by Ga-67. Chest lesions were diagnosed with a sensitivity of 86% (6/7), bone and soft tissue 83% (5/6), and abdomen 80% (8/10). The sensitivity and specificity of CT were 91% (22/24) and 67% (8/12), respectively. In abdominal lesions, ultrasonography had sensitivity and specificity of 93% (14/15) and 94% (15/16), respectively. Kappa (kappa) statistics demonstrated good to strong inter- and intraobserver agreement in the interpretation of Ga-67 scintigraphy. The diagnostic results of low-dose Ga-67 scans, currently applied in Japan, were similar to those reported by the authors using high doses of 296 MBq to 370 MBq. Ga-67 scintigraphy, even at low dose, is useful in the detection of non-Hodgkin's lymphoma recurrence.

Adult↗