Doppler ultrasound diagnosis of transient leg malperfusion caused by dynamic obstruction in a patient with chronic aortic dissection.

Leg malperfusion caused by dynamic obstruction is a serious complication of aortic dissection. A diagnosis of the malperfusion is difficult because it is made mainly on the basis of nonspecific symptoms such as intermittent claudication and numbness on walking. In the present study, we reported on a case of a 51-year-old man with leg malperfusion in chronic aortic dissection diagnosed by Doppler ultrasound. The combination of bisferious and dampened velocity waveform changes after walking may lead us to suspect a leg malperfusion caused by dynamic obstruction.

Impact of Elevated D-Dimer on Diagnosis of Acute Aortic Dissection With Isolated Neurological Symptoms in Ischemic Stroke.

BACKGROUND: Plasma D-dimer is known to be a useful clinical marker of thrombogenic status, and D-dimer is used as a diagnostic marker for acute aortic dissection (AAD). Little is known, however, regarding the clinical value of D-dimer for diagnosis of asymptomatic AAD in patients with ischemic stroke. We investigated whether D-dimer could be used for early diagnosis of AAD with isolated neurological symptoms in ischemic stroke patients. METHODS AND RESULTS: We evaluated a total of 1,236 consecutive patients with symptomatic ischemic stroke without chest or back pain who underwent either head computed tomography or magnetic resonance imaging. D-dimer was measured within 24 h after onset. There were 9 patients with Stanford type A AAD and they had significantly higher D-dimer than the patients without AAD (mean, 46.47±54.48 µg/ml; range, 6.9-167.1 µg/ml vs. 2.33±3.58 µg/ml, 0.3-57.9 µg/ml, P<0.001). When a cut-off of 6.9 µg/ml was adopted for d-dimer on the basis of receiver operating characteristics analysis, the sensitivity and specificity for AAD were 100% and 94.8%, respectively, while the positive and negative predictive values were 14.7% and 100%, respectively. CONCLUSIONS: D-dimer might be a useful marker for the early diagnosis of AAD with isolated neurological symptoms in ischemic stroke patients. Whole-body contrast-enhanced computed tomography should be performed in ischemic stroke patients who have high D-dimer.

Genetic analysis of young adult patients with aortic disease not fulfilling the diagnostic criteria for Marfan syndrome.

BACKGROUND: Although the existence of the young patients with aortic disease not fulfilling the diagnostic criteria for Marfan syndrome (MFS) has been known, the etiology of their disease has not yet been elucidated. The purpose of the present study was to elucidate the genetic and clinical features of the young patients with aortic disease not having MFS. METHODS AND RESULTS: Eighty young adult patients with aortic disease were examined. They were divided into a definite MFS (n=51) and a non-definite MFS group (n=29) according to the Ghent nosology. Clinical and genetic characteristics were compared between the 2 groups. Among 29 non-definite MFS probands, 1 (3%) FBN1, 2 (7%) TGFBR1, and 3 (10%) TGFBR2 mutations were found, and 4 ACTA2 mutations were found in the 23 probands examined without FBN1, TGFBR1, or TGFBR2 mutations. In total, more than 10 out of 29 (34%) probands in the non-definite MFS group were associated with genetic mutations. Skeletal involvement was less frequent in the non-definite than in the definite MFS group (7% vs 82%, P<0.01). CONCLUSIONS: In the probands with aortic diseases in young who cannot be diagnosed with MFS, mutations other than FBN1 mutations accounted for at least one-third of all causes of aortic disease.

Mutation of ACTA2 gene as an important cause of familial and nonfamilial nonsyndromatic thoracic aortic aneurysm and/or dissection (TAAD).

Approximately 20% of aortic aneurysm and/or dissection (AAD) cases result from inherited disorders, including several systemic and syndromatic connective-tissue disorders, such as Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome, which are caused by mutations in the FBN1, COL3A1, and TGFBR1 and TGFBR2 genes, respectively. Nonsyndromatic AAD also has a familial background, and mutations of the ACTA2 gene were recently shown to cause familial AAD. In the present study, we conducted sequence analyses of the ACTA2 gene in 14 unrelated Japanese patients with familial thoracic AAD (TAAD), and in 26 with sporadic and young-onset TAAD. Our results identified three mutations of ACTA2, two novel [p.G152_T205del (c.616+1G>T), p.R212Q] and one reported (p.R149C), in the 14 patients with familial TAAD, and a novel mutation (p.Y145C) of ACTA2 in the 26 sporadic and young-onset TAAD patients, each of which are considered to be causative for TAAD. Some of the clinical features of these patients were the same as previously reported, whereas others were different. These findings confirm that ACTA2 mutations are important in familial TAAD, while the first sporadic and young-onset TAAD case with an ACTA2 mutation was also identified.

[Abnormal bone marrow uptake of 99mTc-tetrofosmin in myelodysplastic syndrome with ineffective hematopoiesis: a case report].

Eighty-four-year-old male patient with liver cirrhosis, suffered from dyspnea on August 2006. Four months later, his symptom has remained and he was admitted to our hospital. A white blood cell decrease and anemia were observed by the blood test. He underwent echocardiography and 99mTc-tetrofosmin myocardial scintigraphy (99mTc-Tf) at rest, which showed no abnormal cardiac imaging. But 99mTc-Tf whole-body planar imaging showed extremely increased bone marrow uptake. 99mTc-HMDP bone scintigraphy also showed abnormal hot spots in the same skeletal regions. Bone marrow biopsy revealed myelodysplastic syndrome like findings. 201Tl and 99mTc as tracers for myocardial perfusion imagings were used to evaluate coronary heart disease, but increased uptake of these tracers were reported in malignant tumors and bone metastasis. He did not have malignant tumor or bone metastasis, so increased uptake of 99mTc-Tf and 99mTc-HMDP was thought to be caused by hyperactive flow with ineffective hematopoiesis. We report a case that abnormal skeletal uptake of 99mTc-Tf which was caused by ineffective hematopoiesis of myelodysplastic syndrome.

Coexistent true aortic aneurysm as a cause of acute aortic dissection.

BACKGROUND: Aortic aneurysms are found in 5-20% of patients with acute aortic dissection (AAD). Coexisting aortic aneurysms might potentially influence the incidence of AAD. The purpose of this study was to elucidate the role of coexistent aortic aneurysms in AAD. METHODS AND RESULTS: A total of 140 patients with AAD were enrolled in the present study. Clinical characteristics of the patients were evaluated in relation to the locations of aortic segments affected by the dissection as well as of the coexistent aortic aneurysm. Among the 140 study patients, 34 (24%) had true aortic aneurysms. Patients with coexistent aortic aneurysm were significantly older than those without (72 +/- 11 years vs 65 +/- 14 years, P=0.012) and had higher incidence of thrombosed false lumen (62% vs 38%, P=0.017), and coronary artery disease (26% vs 8%, P=0.006). Twenty-two of these 34 (65%) patients had a thoracic aortic aneurysm (TAA), and this frequency of TAA was much higher than that observed in the general population. Furthermore, among all patients with AAD, 12 patients (9%) might be associated with development of AAD. CONCLUSIONS: The current study showed that nearly one-quarter of AAD patients had coexisting true aortic aneurysms, and suggests that TAA are likely to be associated with development of AAD.

Characteristics in phenotypic manifestations of genetically proved Marfan syndrome in a Japanese population.

Diagnosis of Marfan syndrome (MS) is made according to the Ghent nosology, which is based on data from European and American populations. The validity of applying the Ghent nosology to other than Western populations is an ongoing discussion because there may be racial differences in basic physical features. The validity of applying the Ghent nosology to patients other than Westerners suspected of having MS was examined. One hundred thirteen Japanese patients who were suspected of having MS and underwent genetic analysis were examined to see whether they fulfilled the Ghent nosology. Of 113 patients, MS was diagnosed in 58 patients/51 probands. Of these 51 probands, 46 (90%) showed mutations in the Fibrillin-1 gene(FBN1) and were enrolled in this study. The frequency of each manifestation of Ghent nosology in the Japanese population was compared with those reported in the FBN1 Universal Mutation Database that was mainly obtained from the Western population (n = 1,013 probands). Frequencies were lower in the Japanese population than the Western population of the manifestations of arm span to height ratio >1.05 (20% vs 55%; p <0.01), scoliosis (40% vs 53%; p <0.05), reduced extension at elbows (2% vs 16%; p <0.05), and joint hypermobility (46% vs 63%; p <0.05). In conclusion, we found a lower frequency of skeletal manifestations of MS in Japanese patients than reported in the database for Western patients with MS. It was possible that the diagnosis of MS according to the Ghent nosology for Japanese patients was underestimated, especially for skeletal involvements.

The reactivity of compounds having cyclopropane ring as the reactive site of drugs with DNA bases.

Theoretical calculations were performed to study the transition state structures (TSs) and activation energies (deltaE not equal) for S(N)1 and S(N)2 type nucleophilic binding reactions of cyclopropane (3) and its derivatives. The results were compared with those of ethylene oxide (1), aziridine (2), and these derivatives. These parent three-membered ring compounds were chosen as reactive sites of drugs (such as mutagens or carcinogens).

Theoretical study on chlorine and hydrogen shift in cycloheptatriene and cyclopentadiene derivatives.

The transition structures (TSs) for chlorine 1,7-shift and 1,5-shift in 1,7,7-trichlorocycloheptatriene (1) and those of chlorine 1,5-shifts in 1,5,5-trichlorocyclopentadiene (3) and 1,2,5-trichloro-1,3-pentadiene (5) derivatives have been located with density functional theory (DFT) at the Becke3LYP/6-311G [and Becke3LYP/6-311+G] level. The calculational results were compared with those for corresponding hydrogen shifts in nonsubstituted molecules (cycloheptatriene (2), cyclopentadiene (4), and 1,3-pentadiene (6)). The following points were clarified: (1) The activation energy (Delta E(++)) for chlorine 1,7-shift in 1 was evaluated to be only +50.1 [+49.2] kJ/mol, which is smaller than that (+69.9 [+68.3]) for a 1,5-shift, supporting the theory that the conversion between two equivalent A and A' proceeds through a TS for direct chlorine 1,7-shift (Figure 1), rather than through a TS for a 1,5-shift (Figure 2). (2) The considerable amount of charge separation between a migrating chlorine atom (Cl(m)) and a seven-membered ring (-0.53 and +0.47 for Merz-Singh-Kollman scheme) occurs in a chlorine 1,7-shift, which is in good contrast to the result that the migrating hydrogen atom (H(m)) for a 1,7-shift in cycloheptatriene (2) carries almost no charge (Figure 3). This large charge separation can stabilize the TS for the chlorine 1,7-shift pathway. (3) The Delta E(++) values for suprafacial hydrogen 1,7-shift in 2 are quite large (+288.0 [+284.8] kJ/mol), much larger than that (+166.8 [+167.0]) for a 1,5-shift in 4 which is orbital symmetrically allowed (Figure 3). The calculation suggests that the chlorine 1,7-shift in 1 occurs easily at room temperature (actually observed experimentally) by proceeding via concerted suprafacial 1,7-shift through the zwitterionic TS with the significant assistance of Coulomb interaction between charged fragments (negatively charged chlorine atom and positively charged tropylium ring), rather than via a suprafacial 1,5-sigmatropic pathway. Other cases studied in this paper showed usual results predicted by orbital symmetrical consideration.

[Relationship between lung-to-heart uptake ratio of technetium-99m-tetrofosmin during exercise myocardial single photon emission computed tomographic imaging and the number of diseased coronary arteries in patients with effort angina pectoris without myocardial infarction].

OBJECTIVES: Increased lung uptake of thallium-201 in exercise myocardial perfusion imaging is a reliable marker of multivessel disease in patients with ischemic heart disease. This study investigated whether the lung-to-heart uptake ratio with techenetium-99m(99mTc)-tetrofosmin also provides valuable information to detect patients with multivessel disease. METHODS: Fifty-three consecutive patients (35 men, 18 women, mean age 66 +/- 11 years; single-vessel disease: 29, double-vessel disease: 16, triple-vessel disease: 8) with stable effort angina pectoris without prior myocardial infarction and 17 control subjects (12 men, 5 women, mean age 62 +/- 9 years) underwent exercise myocardial perfusion imaging with 99mTc-tetrofosmin and coronary angiography in January 2000 to December 2002. The lung-to-heart uptake ratio was calculated on an anterior projection before reconstruction of the exercise single photon emission computed tomographic images. RESULTS: The mean lung-to-heart uptake ratio was 0.34 +/- 0.04, 0.38 +/- 0.07, 0.41 +/- 0.05, and 0.46 +/- 0.09, in patients with normal coronary, single-vessel disease, double-vessel disease, and triple-vessel disease, respectively. Significantly higher lung-to-heart uptake ratio was associated with more diseased vessels (p < 0.05). Multivessel disease could be detected with a sensitivity of 67% and a specificity of 74% if the cut-off point of the lung-to-heart uptake ratio was set as 0.4. Combining lung-to-heart uptake ratio with conventional myocardial perfusion imaging improved the sensitivity to detect multivessel disease to 83% and the specificity to 74%. CONCLUSIONS: Lung-to-heart uptake ratio measured by exercise myocardial scintigraphy with 99mTc-tetrofosmin can provide clinically useful information to detect multivessel disease in patients with ischemic heart disease.

Preparation, structure, and unique thermal [2+2], [4+2], and [3+2] cycloaddition reactions of 4-vinylideneoxazolidin-2-one.

The terminal allene C(alpha)=C(beta) bonds of 4vinylidene-2-oxazolidinone (2) readily undergo [2+2] cycloaddition with a wide variety of terminal alkynes, alkenes, and 1,3-dienes irrespective of their electronic nature under strictly thermal activation conditions (70-100 degrees C) and provide 3substituted (Z)-methylenecyclobutenes 6, 3substituted methylenecyclobutanes 7 and 8, and 3vinylmethylenecyclobutanes 9, respectively, in good to excellent yields. Alkenes react with 2 with complete retention of configuration. The [2+2] cycloaddition is concluded to proceed via a concerted [(pi(2s)+pi(2s))(allene) + pi(2s)] Hückel transition state on the basis of experimental evidences and quantum mechanical methods. Some highly polarized enones and nitrile oxide, on the other hand, react with 2 selectively at the internal C(4)=C(alpha) double bonds and give spiro compounds 10 and 11, respectively. The bent allene bonds (173-176 degrees) and the unique reactivity associated with 2 are attributed to a low-lying LUMO (C(alpha)=C(beta)) that is substantiated by a through-space sigma*(N-SO(2))-pi*(C(alpha)=C(beta)) orbital interaction.

Paradoxical regional myocardial uptake between 201Thallium and 123I-BMIPP SPECT in patients with cardiomyopathy.

The clinical significance of the paradoxical mismatched phenomenon between (201)Tl and (123)I-BMIPP is still unknown. We report two cases that revealed paradoxical regional myocardial uptake between two tracers in patients with cardiomyopathy. There may be abnormal myocardium in these patients where active transportation of (201)Tl is disturbed and passive transportation of (123)I-BMIPP is not disordered.

The incidence of discrepant regional myocardial uptake between 201 thallium and 123 I-BMIPP SPECT in patients with coronary heart disease.

Myocardial perfusion and fatty acid uptake at rest were assessed by SPECT with 201Tl (Tl) and 123I-BMIPP (BMIPP) in 50 consecutive patients with coronary heart disease. Discrepant regional myocardial uptake was observed in 19 patients and classified into the following two groups: mismatch (MM; Tl uptake > BMIPP uptake, n = 14, mean age, 66 years) and paradoxical mismatch (PM; Tl uptake < BMIPP uptake, n = 5, mean age, 68 years). In the MM group, 77% was single- or zero-vessel disease and the artery-perfused region in the mismatched area was almost always ischemia related. Sixty percent of the regions observed with the PM were related to the inferior wall. In the PM group, 80% of cases were associated with multivessel stenoses and 60% of cases was suffered from ischemic attack within a week before scintigraphy. In conclusion, mismatch was related to abnormal fatty acid uptake caused by coronary heart disease. Although the paradoxical mismatch might mainly be related to diaphragmatic attenuation of Tl scans and augmented artifacts of BMIPP scans in the inferior wall, we should not overlook severe coronary heart disease in patients with paradoxical mismatched phenomenon.