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Biomedical subjects

K Kusakabe

Publications and source records attributed to K Kusakabe.

At least 37 records · Page 2Linked to original sources

Sympathetic denervation and reinnervation after arterial switch operation for complete transposition.

BACKGROUND: Sympathetic cardiopulmonary nerves arise from the cervical sympathetic trunks and the stellate ganglia and subsequently course along the origin of the great arteries and the coronary arteries to innervate the ventricles. Therefore, the sympathetic nerves may be obligatorily interrupted by the arterial switch operation (ASO) for complete transposition of the great arteries. METHODS AND RESULTS: To demonstrate and characterize the possible sympathetic denervation, 51 patients after ASO, 4.8 years old (range, 1 month to 10.1 years), underwent [123I]metaiodobenzylguanidine (MIBG) imaging of the sympathetic nerve terminal. MIBG uptake to the heart was graded by quantitative analysis using the heart-to-mediastinum (H/M) ratio of MIBG uptake. A quantitative criterion for absent uptake of MIBG was set to 1.48 in the H/M ratio. Four patients < 1 month after ASO showed complete absence of MIBG uptake, which had been observed preoperatively. In contrast, 47 patients late after ASO (range, 15 months to 10.1 years) showed various degrees of uptake of MIBG. Patients operated on at < or =55 days of age showed positive MIBG uptake much more frequently than those operated on at later ages. Heart rate and rate-pressure product at peak exercise on a treadmill exercise test were significantly greater in patients with positive uptake than in those with absent uptake of MIBG. CONCLUSIONS: Cardiac sympathetic nerves were denervated early after and reinnervated late after ASO. Neonatal ASO may be favorable to facilitate sympathetic reinnervation, which may affect exercise tolerance late after surgery.

3-Iodobenzylguanidine↗

Evaluation of regional cardiac sympathetic innervation in congenital long QT syndrome using 123I-MIBG scintigraphy.

The aim of this study was to determine whether sympathetic imbalance in congenital long QT syndrome (LQTS) can be identified by cardiac sympathetic neuronal dysinnervation. 123I-metaiodobenzylguanidine (MIBG) is a tracer of the norepinephrine analogue which reflects the regional innervation and norepinephrine kinetics in cardiac sympathetic nerves. Sixteen patients with LQTS, who were members of 12 families, and 7 normal controls underwent MIBG scintigraphy. Myocardial SPET and planar images were obtained 15 min and 4 h after the injection of MIBG in each patient. The relative regional uptake (RRU) and regional washout rate (rWR) of MIBG at 4 h in each of nine regions were compared with those in the control group. The heat-to-mediastinum ratio (H/M) and global washout rate (GWR) were also calculated. The RRU, rWR, H/M and GWR showed no significant difference between LQTS patients and normal controls. Furthermore, the RRU in 96% of all regions in LQTS was within the mean +/- 2 standard deviations of that in the control group. Patients with LQTS have normal cardiac sympathetic innervation, as assessed by MIBG. The sympathetic imbalance hypothesis is unlikely to be attributed to an abnormal distribution and different regional norepinephrine kinetics of cardiac sympathetic nerves.

3-Iodobenzylguanidine↗

Establishment of a 24-hour electrocardiogram recording system using a Holter recorder for miniature swine.

A Holter recording system was established for the Göttingen miniature swine. For this purpose, we first developed a jacket to hold a Holter recording set, and subsequently determined a bipolar lead suitable for obtaining stable electrocardiogram (ECG) recording without artifacts. To make the jacket, we measured the lengths of eight sites of the body of 14 miniature swine. Several types of jackets were made and tested. We observed the behaviour of animals with these jackets by videotape recorder (VTR) recording. These observations permitted development of a jacket suitable for Holter recording. The jacket permits easy placement of the recorder, and long-term ECG recording can be performed without difficulty. In order to determine a suitable lead for long-term recording, we recorded ECGs from six adult miniature swine using three types of leads, the M-X, R-L and A-B leads. The R-L lead frequently exhibited baseline drift, and QRS complexes often disappeared in this lead due to low amplitude. ECG recording with the M-X and A-B leads was of sufficient quality to permit analysis. This system is expected to be useful for further cardiovascular research in miniature swine.

Anesthesia↗

Cardiac malignant pheochromocytoma with bone metastases.

A patient with malignant cardiac pheochromocytoma with bone metastases is described. The primary tumor was located between the pulmonary trunk and the left atrium, while metastatic lesions were found in the iliac bones. Treatments with antihypertensive agents, alpha-methylparatyrosine, and combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine partially improved the patient's symptoms, catecholamine levels, and the metastatic lesion of the iliac bones. However, the primary tumor in the heart progressively increased in size and the patient died of disseminated intravascular coagulation and other various complications about 4 years after the diagnosis of the disease.

Antineoplastic Combined Chemotherapy Protocols↗

[Cardiac sympathetic denervation after aortic surgery in a patient with thoracic dissecting aneurysm: a case report].

We experienced a case of a 60 year-old man with cardiac sympathetic denervation after aortic graft replacement of ascending aorta for a dissecting aneurysm (Debakey type II). Fourteen years after pheochromocytomectomy (paraganglioma), the patient developed a severe chest pain, and admitted to the hospital for the diagnosis of dissecting aneurysm. CT scan with contrast enhancement revealed thrombosed dissecting aneurysm in the region of ascending aorta to aortic arch. Graft replacement was undergone on the same day. 123I-MIBG imaging 20 days after the operation showed severely attenuated myocardial uptake (heart to mediastinum ratio 1.19), although the MIBG imaging before the operation showed normal myocardial uptake (heart to mediastinum ratio 1.55). Heart rate variability analysis in Holter ECG showed that the power of the low frequency (LF), that of the high frequency (HF) and L/H ratio were severely decreased. MIBG and heart rate variability analysis indicated that cardiac sympathetic and parasympathetic nerve were denervated. This is the first report of cardiac sympathetic denervation after aortic vascular surgery. Clinical significance of cardiac sympathetic denervation after aortic vascular surgery is uncertain, and further investigation will be required.

3-Iodobenzylguanidine↗

[Clinical utility of pulmonary 99mTc-Tetrofosmin uptake measurement by the exercise myocardial scintigraphy in patients with ischemic heart disease].

Increased pulmonary 201TlCl (Tl) uptake during exercise has been used as a marker of multivessel critical stenosis. We studied whether pulmonary 99mTc-Tetrofosmin (TF) uptake measurement during exercise is useful as an additional indicator for the detection of coronary artery disease. Pulmonary to myocardial uptake ratio (P/M) measured by TF scintigraphy during exercise were compared with findings of coronary angiography in eighty one patients with ischemic heart disease and also P/M measured with Tl in twenty one cases. TF P/M level in the patients with triple vessel disease was higher than that in the patients with no coronary stenosis, single vessel disease and double vessel disease. However, there was no significant correlation between TF P/M and the severity of coronary artery stenosis. Inverse correlation was observed between TF P/M and left ventricular ejection fraction (LVEF) (r = 0.29, p < 0.01). TF P/M in the patients less than 50% of LVEF was significantly higher than that in the patients over 50% of LVEF (p = 0.05). TF P/M was well correlated with Tl P/M (r = 0.86). In conclusion, quantitative TF P/M during exercise was thought to be useful indicator for the evaluation of coronary artery disease.

Aged↗

Evaluation of myocardial perfusion and fatty acid uptake using a single injection of iodine-123-BMIPP in patients with acute coronary syndromes.

UNLABELLED: The purpose of this study was to clarify the possibility of simultaneous evaluation of myocardial perfusion and fatty acid metabolism using a single injection of 123I-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) in patients with acute coronary syndromes. METHODS: Thirty patients with unstable angina pectoris (UAP group) and 15 patients with acute myocardial infarction (MI group) were studied. BMIPP dynamic SPECT was performed 2 min after the injection of BMIPP (185 MBq), and images were obtained every 3 min for 15 min with a three-head gamma camera. Conventional BMIPP SPECT was also performed 30 min after the injection. Serial BMIPP and resting 201TI images were compared. RESULTS: A 201TI-BMIPP mismatch between 30-min BMIPP and resting 201TI images was observed in 27 of 30 patients in the UAP group and 8 of 15 patients in the MI group, respectively. However, a 201TI-BMIPP mismatch between early (2-5-min) BMIPP and resting 201TI images was observed in only 2 of 30 patients in the UAP group and in only 2 of 15 patients in the MI group, respectively. The kappa statistics of tracer uptake between early BMIPP and resting 201TI images showed good concordance in UAP (kappa = 0.823) and MI (kappa = 0.765) groups, respectively. These results indicated that initial distribution of BMIPP reflects myocardial perfusion in patients with acute coronary syndromes. CONCLUSION: Myocardial perfusion and fatty acid metabolism can be evaluated simultaneously using a single injection of BMIPP, when images are taken soon (2-5 min) and long after the injection in patients with acute coronary syndromes.

Angina, Unstable↗

[Evaluation of clinical utility of 99mTc-MIBI scintigraphy in the localization of hyperfunctioning parathyroid lesions in patients with hyperparathyroidism--a report of multicenter phase III clinical trials].

Phase III clinical study in 78 patients with hyperparathyroidism was performed to determine clinical utility of 99mTc-MIBI in the localization of hyperfunctioning parathyroid lesions. Except slight tremor in one patient, no adverse events were reported. No abnormal changes in clinical laboratories or vital signs were noted. The clinical utility of the agent was evaluated in 70 patients. Out of 108 hyperfunctioning glands, 93 (86%) were detected with 99mTc-MIBI regardless of their histology, numbers, or location. Specifically, single or ectopic lesions were detected with high sensitivity (97% and 100%, respectively). Sensitivity in 53 glands with weight data was 79%, while 94% in 36 glands above 200 mg, which is extremely high compared to the 201T1-99mTc subtraction method. Specificity in a group of PHP patients with single adenoma who underwent surgery was 100% (63/63), though in case of coexistent thyroid disease obviously interfered parathyroid images. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the localization of hyperfunctioning parathyroid tissues. Especially, the fact that 99mTc-MIBI detected ectopic glands with high specificity is a great advantage over the ultrasound or 201Tl-99mTc subtraction method.

Female↗

[Evaluation of clinical utility of 99mTc-MIBI scintigraphy in the localization of thyroid, breast and lung/mediastinum tumors--a report of multicenter phase III clinical trials].

Phase III clinical study in 136 patients diagnosed or strongly suspected of thyroid, lung/mediastinum or breast cancer was performed to determine clinical utility of 99mTc-MIBI in the localization of tumors, and the results in 135 were evaluated. Except taste peculiar in 43 patients and nausea in one, no adverse events were reported. Seven abnormal changes in vital signs and 27 in clinical laboratories were noted, which were all judged as having no or unlikely relationship to the agent. Out of 177 malignant lesions, 156 (88%) were detected with 99mTc-MIBI regardless of their histology or location. Of 6 benign tumors, 3 were detected. Fifteen sites of false positive in 11 malignant tumor patients and 5 sites in 6 patients with non-tumor disease were observed. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the localization of tumors. Especially, the fact that 99mTc-MIBI detected remote metastatic lesions with high sensitivity is a great advantage over the other conventional imaging modalities.

Adult↗

[Evaluation of the safety and clinical feasibility of exercise 99mTc-MIBI SPECT using one day protocol--multicenter phase III clinical trial report].

We evaluated the safety and clinical usefulness of the same day protocol of exercise 99mTc-MIBI SPECT in 107 patients with heart diseases. No adverse event was observed except for one case of transient hypotension caused by the exercise. More than 95% of stress images and all of the rest images were judged as "Excellent" or "Good" in image quality. Overall sensitivity was 84.3% in detecting coronary artery disease, and no statistical difference was observed between the results obtained with Re-Ex and Ex-Re protocols. The examination was "Quite Effective" or "Effective" in diagnostic efficacy in 96.2% of the cases. We concluded that the same day protocol is a safe and useful method for diagnosing myocardial ischemia, which provides high image quality and valuable information.

Adult↗

Characterization of the cells that migrate from metrial glands of the pregnant mouse uterus during explant culture.

Granulated metrial gland (GMG) cells are estrogen-receptor and Interleukin 2 (IL-2) receptor positive lymphocytes of the Natural Killer cell lineage found in the murine uterus during pregnancy. Functional studies of these cells, which are now more frequently called uterine NK (uNK) cells, have been limited due to technical difficulties. The cells are difficult to isolate and their proliferation and differentiation have not been achieved in culture. In 1988, Mukhtar and Stewart (Cell Tiss. Res., 253, 413-417) reported a method for explant culture of metrial glands isolated from pregnant rodents that yielded an almost pure population of uNK cells. This major technical advance has supported most of the subsequent functional and molecular studies of rodent uNK cells. However, the quality of the cells isolated by the explant culture procedure has not been established. A cytochemical approach was used to identify and quantify the cells migrating from metrial glands. At midpregnancy, almost all (> 90%) migrating nucleated cells were NK cells. Earlier in gestation, a significant proportion (25%) of cells having lymphoid morphology could not be assigned to the lineage. The viability of cells migrating from explants was assessed by DNA isolation and electrophoresis on days 6-16 of gestation. At all times evidence for apoptosis was found, even after culture intervals as brief as 4 h. Parallel analyses of histological sections of the metrial gland, using terminal deoxytransferase labelling to detect nuclear fragmentation, did not support significant levels of uNK cell death in situ prior to day 12 of gestation. Supplementation of the explant culture medium with estrogen, IL-2, various extracellular matrices, decidual cells or combinations of these did not lead to in vitro proliferation of uNK cells and usually did not extend the short term viability of these cells in serum supplemented or serum free media. Thus, the optimal culture conditions for uNK cells remain undefined.

Animals↗

A study of granulated metrial gland cells in the pregnant, alymphoplasia (aly/aly) mice.

During pregnancy, a population of uterine NK cells, commonly called granulated metrial gland (GMG) cells, differentiates in the uterus of both immune competent and various immunodeficient mice. Regulatory mechanisms controlling the differentiation of GMG cells are not fully known. It has been proven that GMG cells are derived from bone marrow, appear under the influences of progesterone and estrogen, do not require the presence of an embryo, and are associated in rodents with decidualization of the uterine stroma. Mice of genotype aly/aly are genetically deficient in lymph nodes and Peyer's patches due to a lymphoid-associated mesenchymal disorder. They are considered to be a useful model for the study of interactions between lymphocytes and stromal components. This immunodeficient animal is completely different from nu/nu and scid/scid mice who differentiate GMG cells during pregnancy. To determine whether the differentiation of GMG cells depends on mesenchymal interactions in the uterus, aly/aly mice were studied histologically between days 10 and 14 of pregnancy for differentiation of GMG cells and development of the metrial gland. Metrial gland tissue was present and appeared normal in aly/aly mice. There were no significant differences in the distribution of GMG cells in comparison to control pregnant aly/+ mice. Fewer GMG cells were present in aly/aly mice than aly/+ mice on days 12 and 14 of pregnancy. The features of individual GMG cells were different on days 10 and 12 of pregnancy. GMG cells in aly/aly mice were small in size and the granules were poorly developed. By day 14, however, GMG cells acquired a mature size and the granules appeared mature. It is likely that GMG cell differentiation was delayed in pregnant aly/aly mice, due to a mesenchymal disorder affecting metrial gland development in this animal.

Animals↗

Class-switching of the IgM type anti-adenocarcinoma human antibody HB4C5 into an IgG1 type resulted in the loss of the antigen binding ability.

The heavy and light chain genes (mu and lambda) of the human anti-adenocarcinoma monoclonal antibody HB4C5 (MAb-C5) were cloned from the human-human hybridoma cell line HB4C5 and co-expressed in Chinese hamster ovary (CHO) and COS-7 cells. ELISA assay and the RI imaging of the cancer tissue xenografted into nude mice showed that the recombinant MAb-C5 retained the original antigen binding activity. We then replaced the IgM constant region of the MAb-C5 heavy chain gene with the human IgG1 constant region gene and co-expressed it with the light chain gene. This recombination was confirmed by a complete DNA sequencing and Western-blot analysis. Despite the fact that the DNA sequence, the expressed protein size, and the assembly of heavy and light chains were indicated to be normal, the IgG1 type MAb-C5 could not bind to the original antigen. This result suggest that this antibody alters its antigen binding property upon class-switching.

Adenocarcinoma↗

[A case of dilated cardiomyopathy with early back-diffusion of 123I-BMIPP].

A 28-year-old woman was pointed out cardiomegaly and diffuse hypokinesis of left ventricle by ultrasonography in community hospital. Coronary angiography showed normal coronary artery and, left ventriculography revealed diffuse hypokinesis (LVEF 40%). She was diagnosed idiopathic dilated cardiomyopathy by myocardial biopsy and other clinical information. Myocardial scintigraphy with 201Tl. revealed dilatation of left ventricle and diffuse inhomogeneous accumulation of 201 Tl. Dynamic 123I-BMIPP SPECT image 2 minutes after injection showed BMIPP accumulation in all segment, though, static image 15 minutes after injection indicated reduced BMIPP accumulation. These findings suggested existence of the early back-diffusion in inferior segment. Early back-diffusion of BMIPP may become a marker of abnormal fatty acid metabolism in patient with dilated cardiomyopathy.

Adult↗

[Detection of angina-related coronary artery in patients with unstable angina pectoris by using 123I-BMIPP myocardial scintigraphy].

To evaluate the diagnostic accuracy of detection of angina-related coronary arteries in patients with unstable angina pectoris. Twenty patients with unstable angina pectoris underwent 123I-BMIPP scintigraphy at rest. A mean duration from last anginal attack to 123I-BMIPP scintigraphy was 408 +/- 3.2 days. Seventeen of 20 angina-related coronary territories were detected by reduced 123I-BMIPP uptake. The sensitivity and specificity for detection of angina-related coronary arteries were 85% and 95%, respectively. The decrease in myocardial uptake of 123I-BMIPP agreed with the decrease in regional wall motion by using ultrasonic echocardiography. 123I-BMIPP scintigraphy may be useful for detection of angina-related coronary artery in a routine clinical examination in patients with unstable angina pectoris.

Aged↗

[Effect of reconstruction arc in myocardial SPECT imaging--comparison between 180 degrees and 360 degrees arc--].

A series of thallium-201 (201Tl) and technetium-99m (99mTc) myocardial perfusion images with or without perfusion defects were acquired by 360 degrees arc using a triple-head camera. The vertical long, horizontal long, and short axis images of 201Tl and 99mTc with 360 degrees, 180 degrees, and opposite 180 degrees were identically reconstructed and reoriented without attenuation correction. In order to detect the detailed differences between 360 degrees (30 degrees - 390 degrees) and 180 degrees (30 degrees - 210 degrees) images, the opposite 180 degrees (210 degrees - 30 degrees) images were utilized. Opposite 180 degrees images revealed the contribution of those to the 360 degrees images. In the normal perfusion images, the CV (coefficient of variation) of the counts in 360 degrees images with 201Tl by the segments was larger than 180 degrees images. On the contrary, the CV of the counts in 360 degrees images with 99mTc was smaller than 180 degrees images. This difference, caused by the difference of photon energy, were detected mainly as the extent of counts decreasing in the deep segments in the opposite 180 degrees images. Lesion contrasts of the opposite 180 degrees images were lower than those of 180 degrees images due to distance related collimator response (the detector response of the collimated gamma camera varies with source-to-detector distance) and scatter. Therefore, lesion contrasts were more decreased in the 360 degrees images compared with those of 180 degrees images, especially in the segments of lateral and anterior walls. The differences in lesion contrasts between 201Tl and 99mTc images were mainly in the segments of inferior and posterior walls (p < 0.05). Lesion contrast was dependent on the location of the perfusion defects, reconstruction arc, and photon energy.

Aged↗

[Exposure to the technologists from radioactive patients during nuclear medicine studies].

In order to evaluate the exposure to the nuclear medicine technologists from patients who had been administrated with radiopharmaceuticals, we measured the exposure in 5 common diagnostic procedures (bone, lung, tumor scan, and brain, myocardial SPECT, n = 8 to 52) using a silicon semiconductor pocket dosimeter. We also measured the spatial dose rates at 5 cm, 50 cm, and 100 cm from skin surface of the patients (n = 10 to 21) using an ionization chamber, both 5 min after injection and right before the studies with the same procedures above. We further measured the spatial dose rate distributions around the patients in the 4 procedures (bone, renal, blood pool scan, and brain SPECT, n = 2 to 3). In results, the exposure to the technologists in each procedure was small (0.5, 0.5, 0.7, 1.6, and 0.3 muSv in each bone, lung, tumor scan, and brain, myocardial SPECT, respectively), compared with the dose limits of the medical workers. However, the dose-response relationships in cancer and hereditary effects, referred to as the stochastic effects, have been assumed linear and no threshold models; therefore, the exposure should be minimized. For this purpose, the measurements of spatial dose rates and spatial dose rate distributions were thought to be useful. The differences of these results among procedures were caused by the differences of dose distributions and physical and biological half lives of the radiopharmaceuticals. The results of the measurements in 7 consecutive weeks suggested that the direct measurement of the exposure using a high sensitive digital pocket dosimeter might result a reduced exposure to the technologists.

Adult↗