Role of protein kinase D1 in vasoconstriction and haemodynamics in rats.

AIMS: Protein kinase D (PKD), once considered an effector of protein kinase C (PKC), now plays many pathophysiological roles in various tissues. However, little is known about role of PKD in vascular function. We investigated the role of PKD in contraction of rat aorta and human aortic smooth muscle cells (HASMCs) and in haemodynamics in rats. METHODS AND RESULTS: Isometric tension of rat aortic was measured to examine norepinephrine-induced contraction in the presence of PKD, PKC and Rho-kinase inhibitors. Phosphorylation of PKD1, myosin targeting subunit-1 (MYPT1), myosin light chain (MLC), CPI-17 and heat-shock protein 27 (HSP27), and actin polymerization were measured in the aorta. Phosphorylation of MYPT1 and MLC was also measured in HASMCs knocked down with specific siRNAs of PKD 1, 2 and 3. Intracellular calcium concentrations and cell shortening were measured in HASMCs. Norepinephrine-induced aortic contraction was accompanied by increased phosphorylation of PKD1, MYPT1 and MLC and actin polymerization, all of which were attenuated with PKD inhibitor CRT0066101. PKD1 phosphorylation was not inhibited by PKC inhibitor, chelerythrine or Rho kinase inhibitor, fasudil. In HASMCs, the phosphorylation of MYPT1 and MLC was attenuated by PKD1, but not PKD2, 3 knockdown. In HASMCs, CRT0066101 inhibited norepinephrine-induced cell shortening without affecting calcium concentration. Administration of CRT0066101 decreased systemic vascular resistance and blood pressure without affecting cardiac output in rats. CONCLUSIONS: PKD1 may play roles in aorta contraction and haemodynamics via phosphorylation of MYPT1 and actin polymerization in a calcium-independent manner.

Aortic arch plaque morphology in patients with coronary artery disease undergoing coronary computed tomography angiography with wide-volume scan.

BACKGROUND: Wide-volume scanning with 320-row multidetector computed tomography coronary angiography (CTCA-WVS) enables the assessment of the aortic arch plaque (AAP) morphology and coronary arteries without requiring additional contrast volume. This study aimed to investigate the prevalence of AAPs and their association with coronary artery disease (CAD) and major adverse cardiovascular events (MACEs) in patients who underwent CTCA-WVS. METHODS: This study included 204 patients without known CAD (mean age, 65 years; 53% men) who underwent CTCA-WVS. We evaluated the presence of aortic plaques in the ascending aorta, aortic arch, and thoracic descending aorta using CTCA-WVS. Large aortic plaques were defined as plaques of at least 4 mm in thickness. A complex aortic plaque was defined as a plaque with ulceration or protrusion. MACEs were defined as composite events of cardiovascular (CV) death, nonfatal myocardial infarction, and ischemic stroke. RESULTS: AAPs and large/complex AAPs were identified in 51% ( n = 105) and 18% ( n = 36) of the study patients, respectively. The prevalence of AAPs with large/complex morphology increased with CAD severity (2.1% in no CAD, 12% in nonobstructive CAD, and 39% in obstructive CAD). The univariate Cox hazard model demonstrated that the predictors associated with MACEs were diabetes, obstructive CAD, and large/complex AAPs. Independent factors associated with large/complex AAPs were male sex [odds ratio (OR), 2.90; P = 0.025], stroke history (OR, 3.48; P = 0.026), obstructive CAD (OR, 3.35; P = 0.011), and thoracic aortic calcification (OR, 1.77; P = 0.005). CONCLUSION: CTCA-WVS provides a comprehensive assessment of coronary atherosclerosis and thoracic aortic plaques in patients with CAD, which may improve the stratification of patients at risk for CV events.

Effects of vasopressin during a pulmonary hypertensive crisis induced by acute hypoxia in a rat model of pulmonary hypertension.

BACKGROUND: A pulmonary hypertensive crisis (PHC) can be a life-threatening condition. We established a PHC model by exposing rats with monocrotaline (MCT)-induced pulmonary hypertension to acute hypoxia, and investigated the effects of vasopressin, phenylephrine, and norepinephrine on the PHC. METHODS: Four weeks after MCT 60 mg kg-1 administration i.v., right ventricular systolic pressure (RVSP), systolic BP (SBP), mean BP (MBP), cardiac index (CI), and pulmonary vascular resistance index (PVRI) were measured. PHC defined as an RVSP exceeding or equal to SBP was induced by changing the fraction of inspiratory oxygen to 0.1. Rats were subsequently treated by vasopressin, phenylephrine, or norepinephrine, followed by assessment of systemic haemodynamics, isometric tension of femoral and pulmonary arteries, cardiac function, blood gas composition, and survival. RESULTS: PHC was associated with increased RV dilatation and paradoxical septal motion. Vasopressin increased MBP [mean (standard error)] from 52.6 (3.8) to 125.0 (8.9) mm Hg and CI from 25.4 (2.3) to 40.6 (1.8) ml min-1 100 g-1 while decreasing PVRI. Vasopressin also improved RV dilatation, oxygenation, and survival in PHC. In contrast, phenylephrine increased MBP from 54.8 (2.3) to 96.8 (3.2) mm Hg without improving cardiac pump function. Norepinephrine did not alter MBP. Vasopressin contracted femoral but not pulmonary arteries, whereas phenylephrine contracted both arterial beds. Hence, improvements with vasopressin in PHC might be associated with decreased PVRI and selective systemic vasoconstriction. CONCLUSIONS: In this rat model of a PHC, vasopressin, but not phenylephrine or norepinephrine, resulted in better haemodynamic and vascular recovery.

Long-term air-stable n-channel organic thin-film transistors using 2,5-difluoro-1,4-phenylene-bis{2-[4-(trifluoromethyl)phenyl]acrylonitrile}.

A long-term air-stable n-type organic semiconductor, 2,5-difluoro-1,4-phenylene-bis{2-[4-(trifluoromethyl)phenyl]acrylonitrile}, was synthesized by a high-yield simple procedure of Knoevenagel condensation with aldehyde and acetonitrile derivatives. A fabricated organic thin-film transistor (OTFT) using this compound exhibited good n-channel OTFT properties with a high electron mobility of 0.17 cm(2) V(-1) s(-1) and an on/off current ratio of 10(6) under both vacuum and ambient air operation. After storage in ambient air for 1 year, a stored n-channel OTFT still shows good n-channel OTFT performance with little degradation in ambient air operation.

Potential requirement of positron emission tomography apparatuses in Asia and latin america including Mexico.

The number of positron emission tomography (PET) machines has been increasing in regions of East-, Southeast-, and South-Asia as well as in Latin America including Mexico. This study was performed to assess the potential requirement of PET machines in 19 countries which already use PET in the aforementioned regions. Data on the number of PET machines and internationally available characteristics of the restrictive countries such as the land area, the total population, the gross national income (GNI), and the average life span of inhabitants were obtained from IAEA, UN, WB, and WHO. Correlation between the number of PET machines and the characteristics of each country was evaluated. The potentially required number of PET machines, which was obtained by adjusting the number of PET machines with statistically significant, correlative characteristics of each country, standardized on the state of Japan, were compared. The number of PET machines could be significantly correlated to the GNI of a country and the average life span of its inhabitants (P < 0.05). Based on Japan, most of the countries in the regions would require considerably more PET machines. With installation of the potentially required number of PET machines in each of the countries, the number of PET machine per 10(6) population would increase by 1.1- to 12-fold, in comparison with the current situation. With regards to the potentially required number of PET machines, most of the countries in these regions may require a considerable increase of PET machines. Nevertheless, some countries in the Asia seem to require outside assistance such as international support in order to introduce PET and enhance the efficacy of their health services.

[Usefulness of nuclear medicine extension code keeping the integrity with JJ1017].

OBJECTIVE: Working group on JJ1017 nuclear medicine domain extension code in the Japanese Society of Nuclear Medicine has created nuclear medicine extension codes keeping the integrity with JJ1017. The objective of this study was to investigate the usefulness of nuclear medicine extension codes in real clinical settings. METHOD: Nuclear medicine examinations of each institution were extracted from the examination master table and then the target subset of examinations to be coded with JJ1017 were identified. For this subset, working process was conducted, during which the followings compared conformity rate, application rate of representative frequently code set and compliance rate of nuclear medicine extension codes. RESULTS: Without using representative frequently code set, it was difficult to invent the same code for the same examination. By using the representative frequently code set, the same code expression could be invented for the same examination. Furthermore, using nuclear medicine extension codes additionally, these which could not be appropriately coded with representative frequently code set alone. CONCLUSION: Nuclear medicine extension codes keeping the integrity with JJ1017, was proved to be useful to improve the accuracy of coding.

Radiation exposure and risk-benefit analysis in cancer screening using FDG-PET: results of a Japanese nationwide survey.

OBJECTIVE: The aim of this study was to estimate radiation exposure and evaluate the risks and benefits of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in cancer screening. METHODS: A nationwide survey of FDG-PET cancer screening was conducted in 2006, and the results were analyzed with a common index, "extension/shortening of the average life expectancy." RESULTS: The average estimated effective dose was 4.4 mSv (male 4.7 mSv; female 4.0 mSv) for dedicated PET and 13.5 mSv (male 14.2 mSv; female 12.8 mSv) for PET/computed tomography (CT). The risk-benefit break-even age from the viewpoint of radiation exposure was in the 40s for men and 30s for women for dedicated PET and in the 50s for men and 50s (variable injection dose) or 60s (constant injection dose) for women for PET/CT. CONCLUSIONS: FDG-PET cancer screening is beneficial for examinees above the break-even ages. The risks and benefits should be explained to examinees because of the larger radiation used in cancer FDG-PET screening compared with other X-ray tests.

Analysis of various malignant neoplasms detected by FDG-PET cancer screening program: based on a Japanese Nationwide Survey.

OBJECTIVE: The most distinctive feature of FDG-PET cancer screening program is the ability to find various kinds of malignant neoplasms in a single test. The aim of this survey is to clarify the range and frequency of various malignant neoplasms detected by FDG-PET cancer screening performed in Japan. METHODS: "FDG-PET cancer screening" was defined as FDG-PET or positron emission tomography and computed tomography (PET/CT) scan with or without other tests performed for cancer screening of healthy subjects. This survey was based on a questionnaire regarding FDG-PET cancer screening. We analyzed the situation of 9 less frequently found malignant neoplasms including malignant lymphoma, malignancy of head and neck, esophagus, hepatobiliary and gallbladder, pancreas, kidney, cervical and uterine, ovary, and bladder. RESULTS: The detailed information of subjects with the suspected 9 kinds of malignant neoplasms mentioned above in the FDG-PET cancer screening program was studied in a total of 1,219 cases from 212 facilities. A statistical significance between PET/CT and PET was found in relative sensitivity and PPV for renal cell cancer. Malignant lymphoma was frequently of indolent type, suspected head and neck cancers had many false-positive results, and pancreatic cancer detected in this program was often in the advanced stage even in asymptomatic subjects. The recommendation of combined screening modality to PET or PET/CT was as follows: gastric endoscopy for assessing early esophageal cancer; abdominal ultrasound for screening hepatobiliary and gallbladder cancer; pelvic magnetic resonance imaging for assessing gynecological and pelvic cancers; and the CA125 blood test for screening ovarian cancer. Delayed image was helpful depending on the type of suspected malignant neoplasm. CONCLUSION: We analyzed various types of malignant neoplasms detected by the FDG-PET cancer screening program and presented recommended combination of examinations to cover FDG-PET and PET/CT.

The Japanese national health screening and intervention program aimed at preventing worsening of the metabolic syndrome.

Similar to the healthcare systems in other industrialized countries, the Japanese healthcare system is facing the problem of increasing medical expenditure. In Japan, this situation may be primarily attributed to advanced technological developments, an aging population, and increasing patient demand. Japan also faces the problem of a declining youth population due to a low birth rate. Taken together, these problems present the healthcare system with a very difficult financial situation. Several reforms have been undertaken to contain medical expenditure, such as increasing employee copayment for health insurance from 10% to 20% in 1997 and from 20% to 30% in 2003 in order to curb unnecessary visits to medical institutions. Since the aging of the Japanese population is inevitable, a suitable method to contain medical expenditure may be to screen individuals who are likely to develop lifestyle-related diseases and conduct early intervention programs for them to prevent the development of diseases such as myocardial infarction or stroke that are costly to treat. If this goal is attained, it may contribute to the containment of medical expenditure as well as to improving the quality of life of the elderly. Therefore, the Japanese Ministry of Health, Labor and Welfare has decided to introduce a nationwide health screening and intervention program specifically targeting the metabolic syndrome commencing April 2008. Here, we discuss (1) the background of the Japanese healthcare system and the problems facing it, (2) the underlying objective and details of the new screening program, and (3) the expected impact of the program.

[Business administration of PET facilities: a cost analysis of three facilities utilizing delivery FDG].

BACKGROUND: PET (positron emission tomography) has been proved to be a powerful imaging tool in clinical oncology. The number of PET facilities in Japan has remarkably increased over the last decade. Furthermore, the approval of delivery FDG in 2005 resulted in a tremendous expansion of the PET institutions without a cyclotron facility. The aim of this study was to conduct a cost analysis of PET institutions that utilized delivery FDG. METHODS: Three PET facilities using delivery FDG were investigated about the costs for PET service. Fixed costs included depreciation costs for construction and medical equipments such as positron camera. Variable costs consisted of costs for medical materials including delivery FDG. The break-even point was analyzed in each of three institutions. RESULTS: In the three hospitals (A, B and C), the annual number of PET scan was 1,591, 1,637 and 914, while cost per scan was accounted as yen 110,262, yen 111,091, and yen 134,192, respectively. The break-even point was calculated to be 2,583, 2,679 and 2,081, respectively. CONCLUSIONS: PET facilities utilizing delivery FDG seemed to have difficulty in business administration. Such a situation suggests the possibility that the current supply of PET facilities might exceed actual demand for the service. The efficiency of resource allocation should be taken into consideration in the future health service researches on PET.

Relationship between (99m)Tc-GSA scintigraphic indices of liver function reserve and portal circulation in patients with chronic liver disease.

OBJECTIVES: In order to predict the prognosis or complications of portal hypertension in patients with chronic liver disease, it is important to evaluate both hepatic functional reserve and portal circulation. On (99m)Tc-galactosyl human serum albumin ((99m)Tc-GSA) scintigraphy, the index of blood clearance (HH15) and receptor index (LHL15) have been widely used to evaluate the hepatic functional reserve. However, the relationship between these indices and portal circulation is unknown. The purpose of this study was to examine the relationship between HH15 and LHL15 and portosystemic shunts evaluated with arteriographic portography or esophagogastroduodenoscopy. METHODS: A total of 82 patients with chronic liver disease (mean age, 66.7 years) who underwent (99m)Tc-GSA scintigraphy, arteriographic portography, and esophagogastroduodenoscopy were enrolled. HH15 and LHL15 were obtained from dynamic (99m)Tc-GSA scintigraphy. The patients were divided into three groups according to the arteriographic portography findings: group 1, no portal collateral circulation; group 2, mild collateral development; and group 3, moderate to severe collateral development. They were also divided into three groups based on the esophagogastroduodenoscopic findings: group A, no varices; group B, small-caliber varices; and group C, enlarged varices. The Kruskal-Wallis test was used to compare each index among these groups. Receiver operating characteristic (ROC) analysis was used to determine whether each index was an indicator for the presence of portosystemic shunts. RESULTS: Both HH15 and LHL15 differed significantly between groups 1 and 2 and between groups 1 and 3. However, only HH15 differed significantly between groups A and B and between groups A and C. On the basis of the ROC analysis, the HH15 threshold value of 0.62 yielded both excellent sensitivity (83.9%) and specificity (84.6%) for the presence of portosystemic shunts, as evaluated with arteriographic portography. The HH15 threshold value of 0.64 yielded both good sensitivity (66.1%) and specificity (69.2%) for the presence of portosystemic shunts, as evaluated with esophagogastroduodenoscopy, whereas no adequate threshold value of LHL15 was found for the presence of portosystemic shunts. CONCLUSIONS: HH15 is a potent indicator of the presence of portosystemic shunts in chronic liver disease.

Arteriovenous malformation of the gallbladder: CT and angiographic findings.

We encountered a case of arteriovenous malformation (AVM) of the gallbladder in a patient with hepatocellular carcinoma (HCC). Contrast-enhanced computed tomography (CT) showed serpentine vessels around and within the gallbladder wall. Angiography showed dilated and tortuous cystic arteries, a racemose vascular network, and early-filling cystic veins. Transcatheter arterial embolization of two cystic arteries feeding the AVM was performed with platinum microcoils prior to transcatheter arterial chemoembolization for HCC to prevent embolic particles from flowing into these arteries. Follow-up contrast-enhanced CT showed blood flow in the gallbladder AVM, which appeared to be fed by the arterial collaterals.

[Business administration of PET facilities: a nationwide survey for prices of PET screening and a cost analysis of three facilities].

The purpose of this study is to analyze the business administration of PET facilities based on the survey of the price of PET cancer screening and cost analysis of PET examination. The questionnaire survey of the price of PET cancer screening was implemented for all PET facilities in Japan. Cost data of PET examination, including fixed costs and variable costs, were obtained from three different medical institutions. The marked price of the PET cancer screening was 111,499 yen in average, and the most popular range of prices was between 80,000 yen and 90,000 yen. Costs of PET per examination were accounted for 110,675 yen, 79,158 yen and Y11,644 yen in facility A, B and C, respectively. The results suggested that facilities with two or more PET/CT per a cyclotron could only secure profits. In Japan, the boom in PET facility construction could not continue in accordance with increasing number of PET facilities. It would become more essential to analyze the appropriate distribution of PET facilities and the adequate amount of PET procedures from the perspective of efficient utilization of the PET equipments and supply of PET-related healthcare.

Cortical activation shortly after cochlear implantation.

We evaluated the cortical activations in postlingually deaf cochlear implant (CI) users in the early period (0-2 months) of CI usage. The subjects were 8 early CI users and 8 normal subjects. With tone burst stimuli (1 kHz) delivered to the right side, strong and broad activation of the ipsilateral (right) primary auditory cortex with 2 peaks and weaker activation of the contralateral (left) temporal lobe were observed in early CI users, in a clear contrast with the normal subjects in whom activation was observed in a small area of the contralateral (left) primary cortex. With word stimuli, activation of the superior frontomedian cortex presumably including the supplementary motor area and the neighboring cingulate gyri was observed in early CI users, which was absent in normal subjects. The activation in the immediate association cortices near the primary area was lower in early CI users, while the periphery of the association cortex seemed to be more mobilized.

Extraosseous accumulation of 99mTc-MDP in lymph node metastases of small cell carcinoma of the esophagus.

We report a case of esophageal carcinoma that showed extraosseous accumulation of 99mTc-MDP in lymph node metastases to the cervical and paracardial lymph nodes. There are few cases showing abnormal extraosseous accumulation of 99mTc-MDP in esophageal cancer lesion. The patient was a 53-year-old man with advanced esophageal cancer. Bone scintigraphy demonstrated extraosseous accumulations in left supraclavicular and paracardial lymph node metastases. The histopathological diagnosis was small cell carcinoma of the esophagus, which is a rare disease with aggressive behavior and poor prognosis. Our patient underwent 2 courses of systemic chemotherapy (CDDP + VP16), but died of rapidly growing systemic metastases 5 months after the initial treatment.

FDG-PET after radiotherapy is a good prognostic indicator of rectal cancer.

UNLABELLED: In the management of rectal cancer after the combined therapy of the radiation and surgical operation, the evaluation of the prognosis is important. Although fluoro- 18-deoxyglucose positron emission tomography (FDG-PET) is considered as a useful tool for evaluation of therapeutic effect of this cancer as well as the other cancers, however, there are few articles that clearly describe the appropriate procedure of the FDG-PET in order to obtain the best prognostic value. The purpose of the present study is to compare several variations of a semi-quantification method, the Standardized Uptake Values (SUV) and to determine the most appropriate parameter, for the prognostic prediction and to propose the quantitative guideline of the FDG-PET. Especially, the authors focused on the SUV after radiotherapy, which had not been considered as a key quantitative value, as it was rather taken as a mere indicator of the therapeutic (radiotherapeutic) effect, not a direct indicator of the prognosis for the cancer itself. METHODS: Forty patients with rectal cancer in the lower rectal region underwent two series of FDG-PET study before and after pre-operative radiotherapy. Their SUVs were calculated from FDG-PET data and compared with the results of the long-term follow-up of the patients as well as with histopathological outcomes. RESULTS: All 40 patients had high FDG uptake before radiotherapy. The mean value of SUV before radiotherapy (SUV1) was 7.6. After radiotherapy, the mean value of SUV (SUV2) decreased to 4.2. There was a significant difference in SUV2 between the groups with and without recurrence (p < 0.05), however, SUVI or SUV ratio (SUV2/SUV1) displayed no significant difference with the incidence of recurrence. CONCLUSION: SUV2 was considered to be a good prognostic indicator for long-term prognosis of rectal cancer patients. SUV1 nor SUV ratio SUV2/SUV1 did not have the equivalent prognostic usefulness. Subsets of patients with SUV2 greater than 3.2 should be observed closely.