Evaluating benign and malignant musculoskeletal lesions with radionuclide angiography and SPECT using Tc-99m MIBI

PURPOSE: The purpose of this study was to evaluate the use of radionuclide angiography and single photon emission computed tomography (SPECT) using Tc-99m hexakis-2-methoxyisobutylisonitrile (Tc-99m MIBI) for analyzing musculoskeletal lesions. MATERIALS AND METHODS: Radionuclide angiography and SPECT using Tc-99m MIBI were performed in 36 patients with various soft tissue and bone pathologies (18 benign and 18 malignant lesions). The ratio of the counts of the lesion to that of the contralateral normal area was calculated from the region of interest drawn on the MIBI scan. The MIBI-uptake ratio was calculated using SPECT and the MIBI-perfusion index was calculated using radionuclide angiography. RESULTS: The MIBI-uptake ratio in malignant lesions (4.80 +/- 4.43) was significantly higher (P < 0.05) than that in benign lesions (1.83+/-2.48). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the MIBI-uptake ratio for malignant lesions were 72%, 83%, 78%, 81%, and 75%, respectively. The MIBI-perfusion index in malignant lesions (17.68 +/- 21.19) was significantly higher (P < 0.05) than that in benign lesions (2.25 +/- 2.56). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the MIBI-perfusion index for malignant lesions were 87%, 75%, 81%, 77%, and 86%, respectively. CONCLUSIONS: The MIBI-uptake ratio and MIBI-perfusion index using Tc-99m MIBI can yield important additional information with which to differentiate musculoskeletal lesions.     

Three-dimensional surface anatomical scanning with 3D-FSPGR: anatomical conformity with surgical findings

Three-dimensional imaging with MRI is a useful method for neurosurgical simulations. As in our previous study, we have constructed three-dimensional surface anatomical scanning (3D-SAS) from the data of contrast enhanced 3D fast spoiled gradient recalled acquisition in the steady state (3D-FSPGR) sequence. Using this technique, it is possible to generate 3D images from the data of only one acquisition, without using the fusion function. In our previous study, we did not compare the 3D images with the operative views at surgery. In the present study, two radiologists and one neurosurgeon assessed the 3D images in comparison with the operative views. There were problems in some cases, including unclear cortical sulci owing to brain swelling, lack of depiction of the cortical veins owing to meningeal enhancement, inadequate distinction between pial veins and meningeal veins, and so forth. However, in the majority of cases, 3D-SAS with 3D-FSPGR was able to demonstrate good anatomical conformity with the operative views, indicating the clinical usefulness of this technique.     

Free radical scavenger, edaravone, in stroke with internal carotid artery occlusion

BACKGROUND: Edaravone has potent free radical quenching and antioxidant actions. The agent has been recently in commercial use for acute ischemic stroke patients. In this study, we investigated the therapeutic effect of edaravone on severe carotid-territorial stroke. METHODS: Stroke patients with internal carotid artery occlusion and baseline NIH Stroke Scale Score > or =15 were treated for 14 days with drip intravenous infusion of edaravone (n=30) and were compared with a historical control cohort of similar patients (n=31). Glycerol was also administered to all patients in both groups. RESULTS: Infarct volume (P<0.02) and midline shift (P<0.02) on CT performed on day 2 of the patients treated with edaravone were smaller than those without edaravone. For patients with edaravone, infarct volume (P<0.0001) and midline shift (P<0.0001) on days 5-7 were greater than those on day 2. Hemorrhagic transformation of infarcts on day 2 was less severe in patients with than without edaravone (P<0.03). Within 14 days after the onset of stroke, 6 patients with edaravone (20%) and 14 without edaravone (45%) died directly of stroke (P<0.03). Among all patients, only two treated with edaravone were independent without any assistance 8 weeks after the onset. CONCLUSIONS: Edaravone was associated with delayed evolution of infarcts and edema in patients with severe carotid-territorial stroke and decreased mortality during the acute stage. The agent, however, failed to prevent evolution of infarcts and edema on later days, and did not significantly improve functional outcome among the surviving patients.     

Isolation and characterization of the stage-specific cytochrome b small subunit (CybS) of Ascaris suum complex II from the aerobic respiratory chain of larval mitochondria

We recently reported that Ascaris suum mitochondria express stage-specific isoforms of complex II: the flavoprotein subunit and the small subunit of cytochrome b (CybS) of the larval complex II differ from those of adult enzyme, while two complex IIs share a common iron-sulfur cluster subunit (Ip). In the present study, A. suum larval complex II was highly purified to characterize the larval cytochrome b subunits in more detail. Peptide mass fingerprinting and N-terminal amino acid sequencing showed that the larval and adult cytochrome b (CybL) proteins are identical. In contrast, cDNA sequences revealed that the small subunit of larval cytochrome b (CybS(L)) is distinct from the adult CybS (CybS(A)). Furthermore, Northern analysis and immunoblotting showed stage-specific expression of CybS(L) and CybS(A) in larval and adult mitochondria, respectively. Enzymatic assays revealed that the ratio of rhodoquinol-fumarate reductase (RQFR) to succinate-ubiquinone reductase (SQR) activities and the K(m) values for quinones are almost identical for the adult and larval complex IIs, but that the fumarate reductase (FRD) activity is higher for the adult form than for the larval form. These results indicate that the adult and larval A. suum complex IIs have different properties than the complex II of the mammalian host and that the larval complex II is able to function as a RQFR. Such RQFR activity of the larval complex II would be essential for rapid adaptation to the dramatic change of oxygen availability during infection of the host.     

Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors

Lysophosphatidic acid (LPA) exerts a variety of biological responses through specific receptors: three subtypes of the EDG-family receptors, LPA1, LPA2, and LPA3 (formerly known as EDG-2, EDG-4, and EDG-7, respectively), and LPA4/GPR23, structurally distinct from the EDG-family receptors, have so far been identified. In the present study, we characterized the action mechanisms of 3-(4-[4-([1-(2-chlorophenyl)ethoxy]carbonyl amino)-3-methyl-5-isoxazolyl] benzylsulfanyl) propanoic acid (Ki16425) on the EDG-family LPA receptors. Ki16425 inhibited several responses specific to LPA, depending on the cell types, without any appreciable effect on the responses to other related lipid receptor agonists, including sphingosine 1-phosphate. With the cells overexpressing LPA1, LPA2, or LPA3, we examined the selectivity and mode of inhibition by Ki16425 against the LPA-induced actions and compared them with those of dioctyl glycerol pyrophosphate (DGPP 8:0), a recently identified antagonist for LPA receptors. Ki16425 inhibited the LPA-induced response in the decreasing order of LPA1 >/= LPA3 > LPA2, whereas DGPP 8:0 preferentially inhibited the LPA3-induced actions. Ki16425 inhibited LPA-induced guanosine 5'-O-(3-thio)triphosphate binding as well as LPA receptor binding to membrane fractions with a same pharmacological specificity as in intact cells. The difference in the inhibition profile of Ki16425 and DGPP 8:0 was exploited for the evaluation of receptor subtypes involved in responses to LPA in A431 cells. Finally, Ki16425 also inhibited LPA-induced long-term responses, including DNA synthesis and cell migration. In conclusion, Ki16425 selectively inhibits LPA receptor-mediated actions, especially through LPA1 and LPA3; therefore, it may be useful in evaluating the role of LPA and its receptor subtypes involved in biological actions.     

Intracaval endovascular ultrasonography for large adrenal and retroperitoneal tumors

BACKGROUND: An accurate diagnosis of inferior vena cava (IVC) invasion is important in deciding the surgical strategy for a large adrenal tumor. We investigated the diagnostic value of intracaval endovascular ultrasonography (ICEUS) for invasion of the IVC by a large adrenal tumor. METHODS: Nine of 163 patients with adrenal and retroperitoneal tumors underwent ICEUS between 1993 and 2002. Intravascular ultrasonography was performed through the right femoral vein with the use of an 8Fr, 20-MHz transducer. The diagnostic criterion for detecting IVC invasion with ICEUS was identification of destruction of a single echogenic layer of the IVC wall or identification of an intracaval tumor mass. The ICEUS finding was confirmed by pathologic examination. RESULTS: The mean diameter of the tumors in 9 patients undergoing ICEUS and resection was 12.6 cm (range, 8.6-16 cm). Pathologic diagnosis varied: adrenocortical carcinoma, 4; malignant pheochromocytoma, 1; leiomyosarcoma, 1; metastatic lung cancer, 1; paraganglioma, 1; and neurilemmoma, 1. Vascular invasion was identified in 2 patients by ICEUS and confirmed by examination of resected specimens. The sensitivity, specificity, and positive predictive values of ICEUS for the diagnosis of the IVC invasion were 100%, 100%, and 100%, respectively. However, these values for computed tomography were 100%, 14%, and 25%, respectively; and for cavography, 100%, 57%, and 40%, respectively. CONCLUSIONS: ICEUS provides confirmatory information regarding tumor invasion of the IVC. This modality also can assist in formulating an operative strategy for large adrenal or retroperitoneal tumors.     

Genetic and environmental factors affecting peak bone mass in premenopausal Japanese women

The purpose of this study was to examine the relationships between peak bone mass and genetic and environmental factors. We measured whole-body bone mineral density (BMD), lumbar spine BMD, and radius BMD with dual-energy X-ray absorptiometry (DXA) and analyzed eight genetic factors: vitamin D receptor (VDR)-3′, VDR-5′, estrogen receptor (ER), calcitonin receptor (CTR), parathyroid hormone (PTH), osteocalcin (OC), apolipoprotein E (ApoE), and fatty acid binding protein 2 (FABP2) allelic polymorphisms using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs). We also surveyed menstrual history, food intake, and history of physical activity using questionnaires. After adjusting for age, body mass index (BMI), current smoking status, current Ca intake, alcohol intake, menoxenia, and physical activity, the mean BMD in subjects with the HH/Hh genotype was significantly higher than that of subjects with the hh genotype for whole-body BMD (mean±SD, 1.20±0.10 vs. 1.18±0.09 g/cm²; HH/Hh vs. hh, p=0.04) and at lumbar spine BMD (mean±SD, 1.18±0.14 vs. 1.14±0.12 g/cm²; HH/Hh vs. hh, p=0.02) in OC allelic polymorphism. Furthermore, the results of multiple regression analyses taking the 8 genetic factors plus the 7 environmental factors listed above into account showed that the strongest factor contributing to BMD was BMI at any site (whole-body and lumbar BMD p<0.0001, radius BMD p=0.0029). In addition, OC polymorphism (p=0.0099), physical activity (p=0.0245), menoxenia (p=0.0384), and PTH polymorphism (p=0.0425) were independent determinants for whole-body BMD, and OC polymorphism (p=0.0137) and physical activity (p=0.0421) were independent determinants for lumbar BMD and radius BMD, respectively.     

Effect of physical activity during teenage years,based on type of sport and duration of exercise,on bone mineral density of young,premenopausal Japanese women

In this cross-sectional study, 91 healthy premenopausal women aged 20-39 years were investigated to determine the effect of physical activities during their teenage years on their current bone mineral densities (BMD). We measured whole-body BMD (WBMD), lumbar BMD (LBMD), and radial BMD (RBMD) with dual energy X-ray absorptiometry (DXA). Using a questionnaire, we asked the women about their physical activities during junior and senior high school and at present. We also asked about their current nutritional status and past and current milk intake. After adjusting for age, body mass index (BMI), current total calorie and calcium (Ca) intake, and milk intake when they were teenagers and at present, we determined that subjects who exercised during extracurricular activities at each of the three periods (during junior and senior high school and at present) had significantly higher WBMD and LBMD (P <0.01, respectively) than did those who did not exercise at those times. Subjects who played high-impact sports at each period had significantly higher WBMD and LBMD than did subjects who played low-impact sports (P <0.05, respectively). Subjects who had exercised regularly from their teenage years to the present had significantly higher BMD at all sites than BMD in other subjects after adjusting for the potential confounders described above (P <0.05, respectively). Our data suggest that continuous exercise beginning in junior high school, especially high-impact sports, may be associated with greater current bone mass. It is important to incorporate adequate exercise beginning in the teenage years to lower one's future risk for osteoporosis.