Comparison of load responsiveness of cartilage T1rho and T2 in porcine knee joints: an experimental loading MRI study.

OBJECTIVE: To compare changes in T1rho and T2 values of the femoral cartilage in porcine knee joints under staged loading and unloading conditions. DESIGN: Sixteen porcine knee joints with intact capsules and surrounding muscle were imaged using a custom-made pressure device and 3.0 T magnetic resonance imaging. Sagittal T1rho and T2 images were obtained for the lateral and medial condyles under the following compression loads: none (Load 0), 140 N (Load 140), 300 N (Load 300), and no compression after decompression (Post-load). The percentage changes of cartilage T1rho and T2 values under each loading condition from those at Load 0 were calculated for weight-bearing overall and eight subdivided regions of interest (ROIs) in both femoral condyles. The actual contact pressure under Load 140 and Load 300 was measured using pressure-sensitive film. RESULTS: For the overall ROI, the mean decreases of T1rho and T2 values were 4.4% and 5.1% under Load 140% and 10.9% and 10.6% under Load 300 in the medial condyle and were 5.2% and 4.0% under Load 140% and 10.6% and 6.0% under Load 300 in the lateral condyle. In the medial condyle, the actual contact pressure correlated highly with percentage changes in T1rho (r = -0.84, P < 0.01) and T2 (r = -0.79, P < 0.01), but those correlations were relatively low in the lateral condyle. CONCLUSION: Although there were side-dependent variations in the correlations with actual pressure, cartilage T1rho and T2 showed similarly sensitive responses to applied load.

A c-Met inhibitor increases the chemosensitivity of cancer stem cells to the irinotecan in gastric carcinoma.

BACKGROUND: Cancer stem cells (CSCs) may be postulated mediators of the chemoresistance. This study aimed to determine an effective signal inhibitor with effects on the proliferation of CSCs in combination with anticancer drugs. METHODS: We used three gastric cancer cell lines and three side population (SP)-enriched CSC cell lines. We examined the combined effects of inhibitors against stemness signals, including c-Met inhibitor SU11274, and five anticancer drugs on the CSC proliferation and mRNA expression of chemoresistance-associated genes. RESULTS: The IC50 of irinotecan in SP-enriched CSC was 10.5 times higher than parent OCUM-2M cells, whereas that of oxaliplatin, taxol, gemcitabine, and 5-fluorouracil was 2.0, 2.8, 2.0, and 1.2, respectively. The SP cell lines had higher expression levels of UGT1A1, ABCG2, and ABCB1 than their parent cell lines. There was a synergistic antiproliferative effect with a combination of SU11274 and SN38 in SP cells, but not other inhibitors. The SU11274 significantly decreased the expression of UGT1A1, but not ABCG2 and ABCB1. The SN38 plus SU11274 group more effectively suppressed in vivo tumour growth by OCUM-2M/SP cells than either group alone. CONCLUSION: Cancer stem cells have chemoresistance to irinotecan. The c-Met inhibitor may be a promising target molecule for irinotecan-based chemotherapy of gastric cancer.

Influence of medial meniscectomy on stress distribution of the femoral cartilage in porcine knees: a 3D reconstructed T2 mapping study.

OBJECTIVE: Previous studies have shown that meniscectomy results in an increase of local load transmission and may cause degeneration of the knee cartilage. Using 3D reconstructed T2 mapping, we examined the influence on the femoral cartilage under loading after medial meniscectomy. DESIGN: Ten porcine knees were imaged using a pressure device and a 3.0-T magnetic resonance imaging (MRI) system. Consecutive sagittal T2 maps were obtained in neutral alignment with and without compression, and under compression at 10° varus alignment. After medial meniscectomy, the aforementioned MRI was repeated. Cartilage T2 before and after meniscectomy under each condition were compared at the 12 regions of interest (ROIs) defined on the 3D weight-bearing area of the femoral cartilage. RESULTS: Before meniscectomy, large decreases in T2 under neutral compression were mainly seen at the anterior and central ROIs of the medial cartilage, which shifted to the posterior ROIs after meniscectomy. There were significant differences in decrease in T2 ratio with loading before and after meniscectomy (9.8%/4.3% at the anterior zone, 4.0%/11.4% at the posterior zone, P < 0.05). By applying varus compression, a more remarkable decrease in the cartilage T2 in posterior ROIs after meniscectomy was achieved. (Before/after meniscectomy: 8.7%/2.5% at the anterior zone, 7.2%/18.7% at the posterior zone, P < 0.05). CONCLUSIONS: Assuming a decrease in T2 with loading correlated with the applied pressure, a deficiency of the medial meniscus resulted in a shift of the primary area with a maximal decrease of cartilage T2 with loading posteriorly in the porcine knee joint, presumably reflecting the intraarticular environment of load transmission.

Three-dimensional patterns of early acetabular cartilage damage in hip dysplasia; a high-resolutional CT arthrography study.

OBJECTIVE: The purpose of this study was to examine the three-dimensional (3D) progression patterns of early acetabular cartilage damage in hip dysplasia using high-resolutional computed tomography (CT) arthrography. DESIGN: Thirty-two dysplastic hips of 26 Japanese symptomatic females including 21 hips in pre-stage of osteoarthritis (Kellgren-Lawrence (K-L) grade 0; mean patient age, 32.0 years) and 11 hips in early stage of osteoarthritis (K-L grade 1 or 2; mean patient age, 32.8 years) were examined. Isotropic high-resolutional CT arthrography with an image resolution of 0.5 mm in any orthogonal direction was performed. A 3D acetabular cartilage model was generated and we evaluated distribution of cartilage thickness in 12 zones after dividing the weight-bearing area of the hip joint in radial and lateral/medial directions. RESULTS: In pre-stage of osteoarthritis, significant differences in cartilage thickness were observed between the lateral and medial zones in all radial regions, most prominently in the antero-superior region. In early stage of osteoarthritis, no significant differences in cartilage thickness were observed, except in the most posterior region. The lateral-medial (LM) ratio was defined as cartilage thickness in the lateral zone divided by that in the medial zone, and hips with the LM ratio in the antero-superior region of <1.4 had significantly more extensive involvement of labral tears than hips with the LM ratio of ≥1.4. CONCLUSIONS: In hip dysplasia, acetabular cartilage damage was probably occurred in the antero-superior lateral area. The LM ratio may be a sensitive index to quantify early cartilage damage associated with extent of labral disorders.

Phylogenetic study of the species within the family Streptomycetaceae.

Species of the genus Streptomyces, which constitute the vast majority of taxa within the family Streptomycetaceae, are a predominant component of the microbial population in soils throughout the world and have been the subject of extensive isolation and screening efforts over the years because they are a major source of commercially and medically important secondary metabolites. Taxonomic characterization of Streptomyces strains has been a challenge due to the large number of described species, greater than any other microbial genus, resulting from academic and industrial activities. The methods used for characterization have evolved through several phases over the years from those based largely on morphological observations, to subsequent classifications based on numerical taxonomic analyses of standardized sets of phenotypic characters and, most recently, to the use of molecular phylogenetic analyses of gene sequences. The present phylogenetic study examines almost all described species (615 taxa) within the family Streptomycetaceae based on 16S rRNA gene sequences and illustrates the species diversity within this family, which is observed to contain 130 statistically supported clades, as well as many unsupported and single member clusters. Many of the observed clades are consistent with earlier morphological and numerical taxonomic studies, but it is apparent that insufficient variation is present in the 16S rRNA gene sequence within the species of this family to permit bootstrap-supported resolution of relationships between many of the individual clusters.

Establishment and characterization of a new hypoxia-resistant cancer cell line, OCUM-12/Hypo, derived from a scirrhous gastric carcinoma.

BACKGROUND: Many kinds of solid tumour have heterogeneously a hypoxic environment. Tumour hypoxia reported to be associated with more aggressive tumour phenotypes such as high metastatic ability and resistance to various anti-cancer therapies which may lead to a poorer prognosis. However, the mechanisms by which hypoxia affects the aggressive phenotypes remain unclear. METHODS: We established a scirrhous gastric carcinoma cell line (OCUM-12) from ascites associated with scirrhous gastric carcinoma, and a hypoxia-resistant cancer cell line (OCUM-12/Hypo) was cloned from OCUM-12 cells by continuous exposure to 1% oxygen. RESULTS: Histologic findings from orthotopic tumours derived from parent OCUM-12 cells and daughter OCUM-12/Hypo cells revealed poorly differentiated adenocarcinoma with extensive fibrosis that resembled human scirrhous gastric cancer. Necrotic lesions were frequently detected in the OCUM-12 tumours but were rarely found in the OCUM-12/Hypo tumours, although both types had multiple hypoxic loci. Apoptosis rate of OCUM-12 cells was increased to 24.7% at 1% O(2), whereas that of OCUM-12/Hypo was 5.6%. The OCUM-12/Hypo orthotopic models developed multiple metastases to the peritoneum and lymph nodes, but the OCUM-12 models did not. OCUM-12/Hypo cells showed epithelial-to-mesenchymal transition and high migratory and invasive activities in comparison with OCUM-12 cells. The mRNA expression levels of both E-cadherin and zonula occludens ZO-1 and ZO-2 decreased in OCUM-12/Hypo cells, and that of vimentin, Snail-1, Slug/Snail-2, Twist, ZEB-1, ZEB-2, matrix metalloproteinase-1 (MMP-1), and MMP-2 were increased in OCUM-12/Hypo cells. CONCLUSION: OCUM-12 and OCUM-12/Hypo may be useful for the elucidation of disease progression associated with scirrhous gastric cancer in the setting of chronic hypoxia.

Loading and knee alignment have significant influence on cartilage MRI T2 in porcine knee joints.

OBJECTIVE: Physiological magnetic resonance imaging (MRI) under loading or knee malalignment conditions has not been thoroughly investigated. We assessed the influence of static loading and knee alignment on T2 (transverse relaxation time) mapping of the knee femoral cartilage of porcine knee joints using a non-metallic pressure device. METHODS: Ten porcine knee joints were harvested en bloc with intact capsules and surrounding muscles and imaged using a custom-made pressure device and 3.0-T MRI system. Sagittal T2 maps were obtained (1) at knee neutral alignment without external loading (no loading), (2) under mechanical compression of 140 N (neutral loading), and (3) under the same loading conditions as in (2) with the knee at 10 degrees varus alignment (varus loading). T2 values of deep, intermediate, and superficial zones of the medial and lateral femoral cartilages at the weight-bearing area were compared among these conditions using custom-made software. Cartilage contact pressure between the femoral and tibial cartilages, measured by a pressure-sensitive film, was correlated with cartilage T2 measurements. RESULTS: In the medial cartilage, mean T2 values of the deep, intermediate, and superficial zones decreased by 1.4%, 13.0%, and 6.0% under neutral loading. They further decreased by 4.3%, 19.3%, and 17.2% under varus loading compared to no loading. In the lateral cartilage, these mean T2 values decreased by 3.9%, 7.7%, and 4.2% under neutral loading, but increased by 1.6%, 9.6%, and 7.2% under varus loading. There was a significant decrease in T2 values in the intermediate zone of the medial cartilage under both neutral and varus loading, and in the superficial zone of the medial cartilage under varus loading (P<0.05). Total contact pressure values under neutral loading and varus loading conditions significantly correlated with T2 values in the superficial and intermediate zones of the medial cartilages. CONCLUSIONS: The response of T2 to change in static loading or alignment varied between the medial and lateral cartilages, and among the deep, intermediate, and superficial zones. These T2 changes were significantly related to the contact pressure measurements. Our results indicate that T2 mapping under loading allows non-invasive, biomechanical assessment of site-specific stress distribution in the cartilage.

Juzentaihoto (TJ-48), a traditional Japanese herbal medicine, influences hemoglobin recovery during preoperative autologous blood donation and after hip surgery.

OBJECTIVE: Preoperative autologous blood donation is a widely used alternative to allogenic transfusion in hip surgery. However, it has been reported that autologous blood donation may induce preoperative anemia. Juzentaihoto (TJ-48) (Tsumura Co., Tokyo, Japan) is a Japanese herbal medicine that has been used to alleviate anemia. We investigated the effect of TJ-48 on anemia in the perioperative period. PATIENTS AND METHODS: 18 hips of 18 female patients who underwent total hip arthroplasty or rotational acetabular osteotomy (RAO) were divided into two groups. Group A consisted of 9 hips of 9 patients who were treated with TJ-48 at a dose of 7.5 g per day from 21 days before surgery to the day before surgery. Group B consisted of 9 hips of 9 patients who did not take TJ-48. Preoperative autologous blood donation was performed 21, 14 and 7 days before surgery. All patients deposited 400 ml each time for a total of 1,200 ml. Hemoglobin level was recorded on preoperative Days 21, 14 and 7 and postoperative Days 1, 4, 7 and 14. RESULTS: During the preoperative period, repeated measures ANOVA showed a significant difference between the two groups in hemoglobin level (p = 0.04). Despite the lack of TJ-48 after surgery, the rate of hemoglobin decline in Group A was less than in Group B at all examination times. No patients with TJ-48 experienced side effects, including gastrointestinal symptoms and unusual laboratory data. CONCLUSION: TJ-48 is useful for treating anemia during preoperative autologous donation.

[Experience of chest wall reconstruction with newly developed material].

After the chest wall resection, its reconstruction is often needed. A 45-year-old male lung adenocarcinoma patient with chest wall invasion underwent upper lobectomy of the right lung with partial resection of 4-6th ribs. The size of the removed chest wall was 11 x 6.5 cm. We reconstructed the chest wall with Bard Composix E/X Mesh. This prosthesis is consisted of a polypropylene mesh and an expanded polytetrafluoroethylene sheet This material is seems to be useful in the reconstruction of chest wall in both preventing pulmonary adhesion and enabling good wound healing.

Mid-term results of cementless total hip replacement using a ceramic-on-ceramic bearing with and without computer navigation.

We have developed a CT-based navigation system using infrared light-emitting diode markers and an optical camera. We used this system to perform cementless total hip replacement using a ceramic-on-ceramic bearing couple in 53 patients (60 hips) between 1998 and 2001. We reviewed 52 patients (59 hips) at a mean of six years (5 to 8) postoperatively. The mid-term results of total hip replacement using navigation were compared with those of 91 patients (111 hips) who underwent this procedure using the same implants, during the same period, without navigation. There were no significant differences in age, gender, diagnosis, height, weight, body mass index, or pre-operative clinical score between the two groups. The operation time was significantly longer where navigation was used, but there was no significant difference in blood loss or navigation-related complications. With navigation, the acetabular components were placed within the safe zone defined by Lewinnek, while without, 31 of the 111 components were placed outside this zone. There was no significant difference in the Merle d'Aubigne and Postel hip score at the final follow-up. However, hips treated without navigation had a higher rate of dislocation. Revision was performed in two cases undertaken without navigation, one for aseptic acetabular loosening and one for fracture of a ceramic liner, both of which showed evidence of neck impingement on the liner. A further five cases undertaken without navigation showed erosion of the posterior aspect of the neck of the femoral component on the lateral radiographs. These seven impingement-related mechanical problems correlated with malorientation of the acetabular component. There were no such mechanical problems in the navigated group. We conclude that CT-based navigation increased the precision of orientation of the acetabular component and control of limb length in total hip replacement, without navigation-related complications. It also reduced the rate of dislocation and mechanical problems related to impingement.

Contrast-enhanced multi-shot echo-planar FLAIR in the depiction of metastatic tumors of the brain: comparison with contrast-enhanced spin-echo T1-weighted imaging.

BACKGROUND: The usefulness of fast fluid-attenuated inversion-recovery (FLAIR) sequences after administration of contrast medium (f-FLAIR (+)) has been shown in depicting brain tumors including metastases and meningeal carcinomatosis. Contrast-enhanced multi-shot echo-planar FLAIR (Ms-EPI-FLAIR (+)), comprising combined sequences of f-FLAIR (+) and Ms-EPI, may provide the advantages of f-FLAIR (+) along with rapid acquisition. PURPOSE: To compare Ms-EPI-FLAIR (+) with post-contrast spin-echo T1-weighted imaging (SE-T1WI (+)) in the depiction of brain metastases. MATERIAL AND METHODS: In 14 patients with metastatic tumors of the brain, spin-echo precontrast T1-weighted imaging (SE-T1WI (-)), fast spin-echo T2-weighted imaging (FSE-T2WI), fast-FLAIR, SE-T1WI (+), and Ms-EPI-FLAIR (+) were acquired. For qualitative evaluation of SE-T1WI (+) and Ms-EPI-FLAIR (+), receiver operating characteristic (ROC) analysis was performed in two different readers. For quantitative analysis, the intensity ratios (intensity of tumor divided by intensity of peritumoral region) in SE-T1WI (+) and Ms-EPI-FLAIR (+) were compared. RESULTS: Although pre-contrast f-FLAIR detected 84 of 106 tumors, Ms-EPI-FLAIR (+) detected 98 of 106 tumors. In the ROC analysis for observers A and B, Az values in SE-T1WI (+) did not differ from values in Ms-EPI-FLAIR (+). Quantitatively, the intensity ratio in Ms-EPI-FLAIR (+) also did not differ from that in SE-T1WI (+). CONCLUSION: Detectability of brain metastases with Ms-EPI-FLAIR (+) is almost similar to that with SE-T1WI (+). Ms-EPI-FLAIR (+) could be an alternative to SE-T1WI (+) in the depiction of brain metastases.

Advantages of 70-kV CT Angiography for the Visualization of the Adamkiewicz Artery: Comparison with 120-kV Imaging.

BACKGROUND AND PURPOSE: Preprocedural identification of the Adamkiewicz artery is crucial in patients with aortic diseases. This study aimed to compare 70-kV CTA with conventional 120-kV CTA for the identification of the Adamkiewicz artery, examining differences in radiation dose and image quality. MATERIALS AND METHODS: We retrospectively analyzed 2 equal groups of 60 patients who had undergone 70-kV or 120-kV CTA to detect the Adamkiewicz artery before aortic repair. Size-specific dose estimate, the CT number of the aorta, and the contrast-to-noise ratio of the anterior spinal artery to the spinal cord were recorded. Furthermore, detectability of the Adamkiewicz artery was evaluated by using a 4-point continuity score (3, definite to 0, undetectable). RESULTS: There was significantly lower radiation exposure with 70-kV CTA than 120-kV CTA (median size-specific dose estimate, 23.1 versus 61.3 mGy, respectively; P < .001). CT number and contrast-to-noise ratio were both significantly higher in the 70-kV CTA group than the 120-kV group (999.1 HU compared with 508.7 HU, and 5.6 compared with 3.4, respectively; P < .001 for both). Detectability of the Adamkiewicz artery was not impaired in the 70-kV CTA group (90.0% versus 83.3% in the 120-kV group, P = .28). Moreover, the Adamkiewicz artery was detected with greater confidence with 70-kV CTA, reflected by a significantly superior continuity score (median, 3) compared with 120-kV CTA (median, 2; P = .001). CONCLUSIONS: Seventy-kilovolt CTA has substantial advantages for the identification of the Adamkiewicz artery before aortic repair, with a significantly lower radiation exposure and superior image quality than 120-kV CTA.

Comparison of drug-metabolizing activities in the livers of carcinogen-sensitive parent rats and carcinogen-resistant descendants.

Donryu strain albino rats were maintained on a diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) for nine successive generations. Some rats in the fourth to eighth generations showed marked resistance to the carcinogenic action of 3'-Me-DAB. In the liver where we found tumors, their size and number are smaller than in the corresponding original strain of rats fed on a diet containing 3'-Me-DAB. No significant differences were found in the total cytochrome P-450 contents or epoxide hydrolase activities of the livers of the resistant variant and the original strain, but the benzo(a)pyrene hydroxylase activity which is mainly attributed to cytochrome P-448 and glutathione S-transferase activity of the resistant variant were lower. The inductions of hepatic cytochrome P-488 and benzo(a)pyrene hydroxylase on administration of polychlorinated biphenyls or 3-methylcholanthrene were also lower in the resistant rats. In the mutagenicity test on Salmonella typhimurium TA 98 the liver 9000 X g supernatant fraction from 3'-Me-DAB-resistant F7 rats did not fully induce the mutagenicities of 3'-Me-DAB and several other carcinogens. Thus the resistance of F7 rats to the chemical carcinogen may be related to the lower activities of some drug-metabolizing enzymes and the poor inducibility of cytochrome P-448 in their liver, although selection of resistant rats should be continued for further generations before coming to a definite conclusion on biochemical basis of apparent resistance to 3'-Me-DAB.

[Completion pneumonectomy for pulmonary aspergillosis with hyper immunoglobulin-E syndrome].

A 22-year-old man was admitted to the department of pediatrics of our institute in February 2005, because of pulmonary aspergillosis. He had been diagnosed as hyper immunoglobulin-E syndrome in infancy, and repeated pulmonary infectious desease, such as pulmonary aspergillosis. He received art of right upper lobectomy by pulmonary aspergillosis at the age of 17. In February 2005, he had hemosputum and the chest X-ray showed a giant cavity with niveau in the right lung. In spite of medical treatment by antibiotics and antimycotics, the lesion rapidly increased in size. Therefore, right completion pneumonectomy and omentopexy around the bronchial stump was done. His postoperative course was uneventful.

Relations of preoperative hemodynamics and coronary blood flow to improved left ventricular function after valve replacement for aortic regurgitation.

In this study of the limits of reversibility of left ventricular function after aortic valve replacement for aortic regurgitation, measurements were made of pre- and postoperative coronary blood flow and left ventricular volumes. Eighteen patients who had undergone aortic valve replacement for pure aortic regurgitation using the Björk-Shiley valve or the Bicerval valve were restudied an average of 8 +/- 3 months after surgery. Postoperative left ventricular end-systolic and end-diastolic volumes returned to near normal values. The slight left ventricular wall thickening apparent before surgery remained unchanged after surgery and, consequently, left ventricular mass, though somewhat reduced, remained abnormally high. Ejection fraction, which was low preoperatively, returned to normal postoperatively. Total coronary sinus blood flow decreased after surgery, but coronary sinus blood flow per 100 g of left ventricular mass increased. This recovery of coronary flow per unit mass was believed to cause the improvement in left ventricular function. A significant correlation was found between postoperative systolic function and preoperative left ventricular end-systolic and end-diastolic volumes, wall thickness and, especially, left ventricular mass, the latter indicating that, if preoperative left ventricular mass is less than 350 g/m2, postoperative improvement of systolic function is attainable. Another significant correlation was indicated by measurements of coronary sinus blood flow per 100 g of left ventricular mass. If this is greater than 35 ml/min before surgery, a postoperative improvement in systolic function to within the normal range may be expected.

Clinical results and in vivo valve function after implantation of a Bicer valve prosthesis in the aortic position.

Between December 1981 and June 1987, 71 patients underwent aortic valve replacement with a Bicer monostrut tilting disc prosthesis. Clinical results and in vivo function of the artificial valve were assessed. The average age of the 71 patients at the time of operation was 51.3 +/- 11.5 years. The hospital mortality rate was 2.8% (two patients) and there were no further deaths during a mean (+/- SD) follow-up period of 2.4 +/- 1.6 years (range 1 month to 5.5 years) after surgery. There was also no occurrence of thromboembolism or valve dysfunction. Function of the Bicer valve prosthesis was assessed in 17 patients: 5 with a 21 mm valve, 7 with a 23 mm valve and 5 with a 25 mm valve. Examination was performed on average 10.3 +/- 8.1 months after surgery. Valve function was examined at rest and during exercise performed with a bicycle ergometer. Pressure gradients at rest were low: 21 mm valve = 8 mm Hg, 23 mm valve = 3 mm Hg and 25 mm valve = 2 mm Hg; the gradients during exercise were 11, 8 and 8 mm Hg, respectively. The valves had the following effective orifice area at rest: 21 mm valve = 1.54 cm2, 23 mm valve = 4.20 cm2 and 25 mm valve = 3.76 cm2; during exercise, the respective areas were 1.57, 3.48 and 3.01 cm2. These valves are deemed to be sufficiently wide for effective valve function. Aortographic observation indicated mild regurgitation that was within reasonable limits and posed no problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Additive effects of nicorandil on coronary blood flow during continuous administration of nitroglycerin.

OBJECTIVES: We examined whether patients with ischemic heart disease (IHD) should be treated with nicorandil, an adenosine triphosphate-sensitive potassium channel opener, in addition to the regular use of nitrates. BACKGROUND: It has been reported that nicorandil possibly has additive effects on nitroglycerin (NTG) treatment for angina, but the mechanism is not clear. METHODS: We directly measured anterograde coronary blood flow (CBF) with a Doppler guide wire to examine the effects of intravenous administration of NTG (0.3 mg) and nicorandil (6 mg) during continuous administration of NTG at a sufficient dose (25 microg/min) in subjects with normal and stenotic coronary arteries. RESULTS: Additional systemic administration of NTG decreased anterograde CBF (normal -19.7%; stenotic -21.2%). In contrast, nicorandil increased anterograde CBF in both normal (54.6%) and stenotic (89.6%) coronary arteries, without the coronary steal phenomenon. There was a tendency toward nicorandil-dilated diameters in the patients with stenotic arteries (p = 0.06). There were no effects of additional administration on pulmonary artery wedge pressure. There was no difference in changes in heart rate and mean aortic blood pressure between NTG and nicorandil therapy. CONCLUSIONS: These results suggest that in patients treated with nitrates, additional administration of nicorandil is more useful, in terms of increasing CBF, than additional administration of nitrates. Adjunctive use of nicorandil with nitrates may provide the further benefit of myocardial protection and may improve the prognosis of patients with IHD.

Bone-Subtracted Spinal CT Angiography Using Nonrigid Registration for Better Visualization of Arterial Feeders in Spinal Arteriovenous Fistulas.

BACKGROUND AND PURPOSE: Pretreatment diagnosis for the location of shunts and arterial feeders of spinal arteriovenous fistulas is crucial. This study aimed to evaluate the utility of subtracted CT angiography imaging by using nonrigid registration (R-CTA) in patients with spinal arteriovenous fistulas compared with conventional CTA imaging. MATERIALS AND METHODS: The records of 15 consecutive subjects (mean age, 65 years; 2 women) who had undergone CTA and digital subtraction angiography for clinically suspected spinal arteriovenous fistula were reviewed. From CTA images obtained at the arterial and late arterial phases, warped images of the late arterial phase were obtained by using nonrigid registration that was adjusted to the arterial phase images. R-CTA images were then obtained by subtracting the warped images from the arterial phase images. The accuracies of using nonrigid registration and conventional spinal CTA and the time required for detecting arterial feeders in spinal arteriovenous fistulas were analyzed for each patient with DSA results as a standard reference. The difference between R-CTA and conventional spinal CTA was assessed by the Welch test and the McNemar χ(2) test. RESULTS: R-CTA had a higher accuracy compared with conventional spinal CTA (80% versus 47%, P = .025). The time for interpretation was reduced in R-CTA compared with conventional spinal CTA (45.1 versus 97.1 seconds, P = .002). CONCLUSIONS: Our subtracted CTA imaging by using nonrigid registration detects feeders of spinal arteriovenous fistulas more accurately and quickly than conventional CTA.

Prevention of renal damage by angiotensin II blockade, accompanied by increased renal hepatocyte growth factor in experimental hypertensive rats.

Hepatocyte growth factor (HGF) is a unique growth factor that has many protective functions against renal damage. Our previous study demonstrated that HGF stimulated the growth of endothelial and epithelial cells without the replication of mesangial cells. Moreover, angiotensin (Ang) II significantly decreased local HGF production in mesangial cells. Therefore, we examined the effects of Ang II blockade on renal HGF expression and renal damage in experimental hypertensive rats. An angiotensin-converting enzyme inhibitor (cilazapril; 10 mg. kg(-1). d(-1)), an Ang II type 1 receptor antagonist (E-4177; 30 mg. kg(-1). d(-1)), hydralazine (8 mg. kg(-1). d(-1)), and vehicle were administered to 16-week-old stroke-prone spontaneously hypertensive rats (SHR-SP) for 3 weeks. Renal damage was evaluated with a computer analysis system, and renal HGF mRNA was measured by Northern blot analysis. Blood pressure of SHR-SP was significantly decreased by all drug treatments compared with vehicle. Moreover, cilazapril, E-4177, and hydralazine significantly decreased the thickening and necrosis of blood vessels compared with vehicle. Similarly, degeneration and necrosis of glomeruli were also markedly improved by cilazapril and E-4177 (P<0.01). We next examined the effects of Ang II blockade on renal HGF expression in SHR-SP. Renal HGF mRNA was markedly decreased in SHR-SP compared with Wistar-Kyoto rats, although Ang II blockade by cilazapril and E-4177 but not hydralazine significantly increased renal HGF mRNA in SHR-SP. Ang II blockade significantly increased renal HGF (a protective growth factor for tubular epithelial cells); thus, we examined tubular histological appearance. Degeneration and necrosis of tubules were significantly improved by cilazapril and E-4177 treatment (P<0.01). In addition, cell infiltration into the glomeruli and hemorrhage were also significantly reduced in SHR-SP treated with cilazapril or E-4177. The present data demonstrated the prevention of renal damage by Ang II blockade in SHR-SP, which was accompanied by a significant increase in renal HGF mRNA. Given the strong mitogenic activity and antiapoptotic actions of HGF on endothelial and epithelial cells, we believe that increased local HGF production by the blockade of Ang II may improve renal function in hypertension.

Activation of the brain angiotensin system by in vivo human angiotensin-converting enzyme gene transfer in rats.

The possibility of the brain-specific expression of a component of the renin-angiotensin system was evaluated in the present study. We used the hemagglutinating virus of Japan-liposome complex to transfect human angiotensin-converting enzyme (ACE) cDNA, driven by the cytomegalovirus enhancer and beta-actin promoter, into the lateral cerebroventricle of male Sprague-Dawley rats. We evaluated the time course of hemodynamics, the tissue levels of angiotensin (Ang) II and vasopressin, and ACE activity. Intracerebroventricular transfection of the human ACE gene increased both blood pressure and heart rate. Transfected rats exhibited higher concentrations of brain Ang II and increased brain ACE activity. This activation of the brain angiotensin system was accompanied by increased vasopressin production. The increases in blood pressure and heart rate were abolished by intracerebroventricular administration of an ACE inhibitor or Ang II type 1 receptor antagonist. The expression of the transgene was widely distributed in the periventricular cell layer, the cortex, the hypothalamic nuclei, and the brain stem. Expression in the neuronal cells persisted for up to 14 days. Thus, this hemagglutinating virus of Japan-liposome method is a highly efficient system for gene delivery and is extremely useful for functional gene transfection. This novel hypertensive model may enable characterization of the functions of the renin-angiotensin system in the brain and determination of its role in the pathogenesis of hypertension.