[A Patient with Lung Cancer Experiencing Abdominal Aortic Aneurysm Rupture during Bevacizumab Treatment-Case Report].

CASE: Right pleural effusion was detected on chest X-ray performed prior to surgery for a right inguinal hernia in a 63-yearold man. Adenocarcinoma was diagnosed based on pleural effusion cytology results. A CT scan revealed mediastinal lymphadenopathy and pleural dissemination, but no obvious lung tumor; other examinations also did not reveal a primary tumor. We, therefore, diagnosed primary lung cancer(c-TxN2M1a, Stage ⅣA, according to the General Rules for Clinical and Pathological Record of Lung Cancer, 8th edition). An abdominal aortic aneurysm was also observed on CT. Since he was diagnosed with EGFR-negative lung cancer with malignant pleural effusion, we selected chemotherapy with cisplatin, pemetrexed, and bevacizumab(CDDP/PEM/Bev)and administered 2 courses without problems. He experienced no adverse events during the 3rd course and was discharged on day 8. However, he was transported to our emergency room at 20: 45 on treatment day 10 when he developed abdominal pain and nearly fainted. An abdominal aortic rupture was diagnosed by CT, and he was transported to another hospital because he could not be treated at our hospital. Information that this patient had been treated with Bev was not provided to the doctor on duty, and abdominal aortic graft replacement was immediately performed. The patient had a good postoperative course without anastomotic leakage and was discharged on day 7 after surgery. Bev is a monoclonal antibody for vascular endothelial growth factor. CONCLUSION: We report that this drug, bevacizumab, may be associated with abdominal aortic rupture.

[A Case of Advanced Squamous Cell Lung Cancer with Hemodialysis Treated with Carboplatin and Paclitaxel].

We herein describe a patient on hemodialysis with advanced squamous cell lung cancer who was treated with chemotherapy that consisted of carboplatin(CBDCA)and paclitaxel(PTX). A 54-year-old man who was undergoing a routine hemodialysis for chronic renal failure presented with cold symptoms and was prescribed antibiotics.As no symptomatic improvement was achieved, he was referred to the Department of Internal Medicine in our hospital, where computed tomographic scan findings raised the suspicion of lung cancer.He was then referred to the Department of Surgery.A bronchoscopy detected a tumor, which obstructed the right upper lobe bronchus, and the patient was diagnosed with squamous cell carcinoma.Based on the mediastinal lymph node enlargement that extended into the contralateral hilar region, the stage was determined to be III B(c-T3N3M0), and we initiated chemotherapy.The regimen was CBDCA plus PTX.The carboplatin dose area under the curve(AUC)was 4(100 mg at a glomerular filtration rate of 0)for the first course, AUC 5 for the second course, and AUC 6 for the third to sixth courses, and the PTX dose was 200mg/m2.Only mild adverse events were noted, and the patient achieved a partial response after 6 treatment courses.Only a few reports have described chemotherapies administered to patients with lung cancer on hemodialysis, and as such, evidence of useful drugs is not yet available.This makes it difficult to select the most appropriate treatment for such patients.We report our experience with this patient, with a relevant literature review.

Small subunit of a cold-resistant plant, Timothy, does not significantly alter the catalytic properties of Rubisco in transgenic rice.

Effects of overexpression of high activity-type Rubisco small subunit (RbcS) from a cold-resistant plant, timothy (Phleum pratense), on kinetic properties of Rubisco were studied in rice (Oryza sativa). The full-length mRNA sequence of timothy RbcS (PpRbcS1) was determined by 5'RACE and 3'RACE. The coding sequence of PpRbcS1 was fused to the chlorophyll a/b-binding protein promoter and introduced into rice. PpRbcS was highly expressed in leaf blade and accounted for approximately 30 % of total RbcS in homozygous transgenic lines. However, the catalytic turnover rate and K m for CO2 of Rubisco did not significantly change in these transgenic lines compared to non-transgenic rice, suggesting that PpRbcS1 is not effective for improvement of catalytic efficiency of rice Rubisco. The photosynthetic rate and growth were essentially unchanged, whereas the photosynthetic rate at low CO2 condition was marginally increased in transgenic lines. Rubisco content was significantly increased, whereas soluble protein, nitrogen, and chlorophyll contents were unchanged in transgenic lines compared to non-transgenic rice. Because the kinetic properties were similar, observed slight increase in photosynthetic rate at low CO2 is considered to be large due to increase in Rubisco content in transgenic lines. Introduction of foreign RbcS is an effective approach for the improvement of Rubisco kinetics and photosynthesis. However, in this study, it was suggested that RbcS of high activity-type Rubisco, even showing higher amino acid identity with rice RbcS, did not always enhance the catalytic turnover rate of Rubisco in rice. Thus, we should carefully select RbcS to be overexpressed before introduction.

Functional medial thickening and folding of the internal elastic lamina in coronary spasm.

Although there are a number of studies on vasospastic angina, the structural changes at the cellular level that occur in the coronary arterial wall during spasm are not well known. Coronary spasm was induced by brushing the coronary adventitia in nine anesthetized beagles, and structural changes in the spastic coronary segments were examined by light and electron microscopy, making comparisons with the adjacent nonspastic segments. The % diameter stenosis of the spastic segments as measured angiographically was 79.4±12% (mean±SD). Light microscopic changes in the spastic and nonspastic segments were as follows: medial thickness 1,512 vs. 392 µm (P<0.0001) and % diameter and % area stenoses of spastic segment 81.0% and 96.5%, respectively, indicating that spasm was induced by medial thickening. Circular smooth muscle cells (SMCs) in the media were arranged in parallel with the internal (IEL) and external (EEL) elastic lamina in nonspastic segments but radially rearranged in spastic segments. SMCs were classified by their patterns of connection to IEL into six types by electron microscopy. Of these, three contracted and pulled the IEL toward the EEL, causing folding of the IEL and waving of EEL resulting in thickening of the media and narrowing of the lumen. We conclude that coronary spasm was elicited by radial rearrangement of the medial SMCs due to their own contraction and resultant medial thickening and folding of IEL, creating a piston effect to narrow the lumen, i.e., spasm.

Possible role of damaged neoendothelial cells in the genesis of coronary stent thrombus in chronic phase. A dye staining angioscopic study.

The mechanism(s) underlying formation of coronary stent thrombus (ST) in chronic phase is yet unclear. Endothelial cells are highly antithrombotic, therefore, it is conceivable that neoendothelial cells (NECs) covering stent struts are damaged and cause ST. This study was performed to examine the role of damaged NECs covering coronary stent struts in the genesis of occlusive or nonocclusive ST in chronic phase.(1) Forty-four patients with acute coronary syndrome (17 females and 27 males) underwent dye-staining coronary angioscopy, using Evans blue which selectively stains damaged endothelial cells, 6 months after bare-metal stent (BMS) deployment. Neointimal coverage was classified into not covered (grade 0), covered by a thin layer (grade 1), and buried under neointima (grade 2) groups. (2) In 7 beagles, the relationships between neointimal thickness and ST were examined 6 months after BMS deployment. (3) The NECs on the struts were stained blue in 4 of 25 patients with grade 2 and in 11 of 20 patients with grade 0/1 (P < 0.05). ST was observed in none of the former and in 5 of the latter (P < 0.05). (4) In beagles, neointimal coverage was grade 0/1 when neointimal thickness was 80.2 ± 40.0 µm, whereas grade 2 when thickness was 184 ± 59.4 µm. ST was observed in 9 of 15 struts with neointimal thickness within 100 µm and in one of 17 struts with thickness over 100 µm (P < 0.05). ST arose from damaged NECs covering the stent struts. NECs may have been damaged due to friction between them and struts due to thin interposed neointima which might have acted as a cushion, resulting in ST.

Formation of web- and membrane-like structures on the edges of bare-metal coronary stents.

BACKGROUND: Web-like (W) and membrane-like (M) structures have been observed on coronary stent edges on angioscopy but their incidence and mechanisms remain obscure. METHODS AND RESULTS: First, 26 patients [acute coronary syndromes (ACS) in 10 and stable angina (SA) in 16] underwent angioscopy of the stented coronary artery immediately after, and 32 patients (ACS in 18 and SA in 14) 6 months after insertion of bare-metal stents. Second, angioscopy of the stented coronary artery was performed in 4 beagles 5 h after, and in 9 beagles 1 month after stenting. W and M were observed in patients with ACS and those with SA (80.0% vs 18.7%; P<0.05) immediately after and 6 months after stenting (55.5% vs 28.5%; NS). They were stained with Evans blue that selectively stains fibrin immediately after stent insertion, but not 6 months later. In beagles, W and M were observed in 75.0% at 5 h and in 66.6% 1 month later. Histologically, W and M were composed of fibrin at 5 h, whereas they were composed of collagen fibers at 1 month. CONCLUSIONS: W and M were frequently formed on the edges of coronary stents. They were formed with fibrin in the acute phase, whereas this fibrin was replaced by collagen fibers in the chronic phase.

Fluffy luminal surface of the non-stenotic culprit coronary artery in patients with acute coronary syndrome: an angioscopic study.

BACKGROUND: Approximately 15% of acute coronary syndrome (ACS) cases have no significant coronary stenosis. Mechanisms underlying the attacks are, however, unknown. METHODS AND RESULTS: The clinical study had 254 patients with ACS; 38 patients (31 females and 7 males; aged 51.0 ± 8.0 years) had no significant coronary stenosis on angiography. They underwent a dye-staining angioscopy of the suspected culprit coronary artery using Evans blue, which selectively stains fibrin and damaged endothelial cells. A fluffy coronary luminal surface was observed in the suspected culprit artery in all 38 patients. The fluffy luminal surface was stained blue with Evans blue. In animal experiments involving 5 beagles, 10% hydrogen peroxide solution was injected into the iliac arteries to damage endothelial cells, which was then followed by blood reperfusion, and then the artery was examined by intravascular microscopy and histology. In the beagles, the arterial segment, where the thrombus had been formed, exhibited a fluffy luminal surface after a washout of the thrombus, and the surface was stained blue. Histologically, the fluffy surfaces were composed of damaged endothelial cells attached by multiple fibrin threads and platelets. CONCLUSIONS: It was considered that the coronary segment exhibiting a fluffy luminal surface was the culprit lesion and that the fluffy surface was caused by residual thrombi after dispersion of an occlusive thrombus, which had formed on the damaged endothelial cells.

Weak ferromagnetism derived from spin canting in an amido-bridged homochiral Mn(iii) 1-D coordination polymer.

A homochiral one-dimensional (1D) Mn(iii) coordination polymer [MnL]n (1) was synthesised employing the N3O-donor tetradentate ligand (L = 2-hydroxy-N-[2-[[(2-aminophenyl)methylene]amino]-2-methylpropyl]-benzamide). The X-ray structure of 1 and its magnetic properties were investigated in detail. The crystal structure of 1 shows a homochiral helical arrangement in which spontaneous resolution has occurred, despite the ligand being achiral. Magnetic characterization revealed an antiferromagnetic interaction between manganese(iii) ions (J = -2.48 cm-1, g = 1.96) that leads to an antiferromagnetic spin-ordering phase transition at TN≈ 7 K. Noteworthily, 1 exhibits weak ferromagnetism with a relatively large coercive field of 3.0 kOe based on the spin canting, indicating the formation of a homochiral weak ferromagnet.

Crystal structure of [2-({2-[(2-azanidyl-benzyl-idene)amino]-benzyl-idene}amino)-4-chloro-phenol-ato]nickel(II).

The title complex, [Ni(C20H14ClN3O)], with an asymmetrically chloride-appended Schiff base ligand has been synthesized and structurally characterized at 100 K. In the compound, the central nickel(II) ion has a square-planar coordination geometry with N3O donors of the π-conjugated tetra-dentate Schiff base ligand. In the crystal, the complexes are connected into an inversion dimer via an Ni⋯Ni inter-action [3.1753 (5) Å] and a pair of π-π inter-actions [centroid-centroid distance = 3.8416 (16) Å]. The dimers are linked via a C-H⋯Cl hydrogen bond, forming a chain along the c-axis direction. The dimer chains inter-act with each other through π-π inter-actions [centroid-centroid distance = 3.8736 (16) Å], forming a layer expanding parallel to the ac plane.

Initial and long-term outcomes of sirolimus-eluting stents for calcified lesions compared with bare-metal stents.

The aim of this study was to compare the initial and long-term outcomes of sirolimus-eluting stents (SES) and bare-metal stents (BMS) in patients with calcified lesions without performing rotational atherectomy. The subjects were 79 consecutive lesions (38 in the SES group and 41 in the BMS group) which were confirmed to have superficially calcified lesions by intravascular ultrasound. In all lesions, the stent was implanted after predilatation with a balloon. The patient characteristics were not different between the 2 groups. All procedures were successfully performed in both groups. Vessel area was significantly smaller in the SES group than in the BMS group (11.01 +/- 3.88 mm(2) versus 13.08 +/- 3.49 mm(2), P < 0.005), as was the lumen area (5.41 +/- 2.31mm(2) versus 6.48 +/- 2.04 mm(2), P < 0.005). Minimum stent area was significantly smaller in the SES group than in the BMS group (5.61 +/- 1.54 mm(2) versus 6.69 +/- 1.74 mm(2), P < 0.01). In cases in whom angiographic follow-ups were performed, the late loss was significantly smaller in the SES group than in the BMS group (0.19 +/- 0.49 mm versus 0.76 +/- 0.48 mm, P < 0.001). The restenosis rate was significantly lower in the SES group than in the BMS group (8.8% versus 33.3%, P < 0.05) and the TLR rate tended to be lower in the SES group (7.9% versus 19.5%). Stent thrombosis was not observed in either group. The results suggest that SES are more effective than BMS and can be used safely when treating calcified lesions if predilatation with a balloon is possible.

Chronobiological analysis by ambulatory blood pressure monitoring of the hyperbaric and hypobaric indexes for evaluation of the antihypertensive effect of long-acting nifedipine.

BACKGROUND: It has been suggested that chronobiology can provide new insights into the evaluation and treatment of cardiovascular disease. In the present study the hyperbaric index (hyperBI) and hypobaric index (hypoBI) were compared with the mean blood pressure (BP) over 24 h to evaluate the antihypertensive effect of long-acting nifedipine on essential hypertension. METHODS AND RESULTS: Fourteen patients were treated with nifedipine CR (20-40 mg/day) for 6 months. Ambulatory BP monitoring was performed before and after treatment. The hyperBI (mmHg . h/day) was calculated as the integrated BP area above the conventional upper limit (140/90 mmHg for the daytime and 120/80 mmHg at night), and the hypoBI was calculated as the integrated BP area below the conventional lower limit (110/60 mmHg for the daytime and 100/50 mmHg at night). At baseline, both the systolic and diastolic 24-h hyperBI values closely correlated with the 24-h mean BP (r=0.994 and 0.935, p<0.0001). Treatment with nifedipine significantly lowered both the 24-h mean systolic and diastolic BP (143+/-14/89 +/-12 to 124+/-16/80+/-8 mmHg, p<0.001/p=0.001), as well as the casual BP (167+/-11/101 +/-8 to 140+/-13/86+/-10 mmHg, p<0.001/p<0.01). Reduction of both the systolic and diastolic hyperBI values was statistically significant over the 24-h period (274+/-266 to 90+/-155, p=0.009; 145+/-187 to 41+/-63, p=0.024), as well as during the daytime (200+/-181 to 66+/-116, p=0.014; 105+/-120 to 24+/-38, p=0.017) and at night (systolic, 74+/-106 to 24+/-52, p=0.021). The 24-h mean BP was normalized, but a small excess BP load persisted despite treatment. There was no significant increase of systolic hypoBI during the 24-h period (1+/-2 to 25+/-30, p=0.065), the daytime (0+/-0 to 14+/-38, p=0.20), or at night (1+/-3 to 11+/-19, p=0,052). Similar findings were obtained for diastolic hypoBI. CONCLUSIONS: Nifedipine CR improved the 24-h hyperBI and mean BP without causing excessive hypotension. These 2 parameters have a close relationship when assessment is done by 24-h BP monitoring. The hyperBI and hypoBI may assist in providing adequate antihypertensive therapy for individual patients by detecting an excessive BP load or hypotension, respectively.

Atrial septal pacing to resynchronize atrial contraction and improve atrial transport function.

OBJECTIVES: Atrial septal pacing via a trans-septal breakthrough site within the right atrial septum can shorten global atrial activation time, resulting in significant reduction of recurrence of atrial fibrillation events. This study examined whether this pacing method will lead to resynchronization of atrial contraction and its benefit on hemodynamic function can be maintained for 24 months. METHODS: Thirty patients with atrial fibrillation and delayed atrial conduction were enrolled (17 males, 13 females, mean age 73 +/- 7 years). Trans-septal breakthrough site within the right atrial septum was identified through pacing from the dorsal left atrium. Continuous atrial septal pacing at the trans-septal breakthrough site was performed for 24 months. Time difference (TD) between right and left atrial contractions was measured during atrial septal pacing and sinus rhythm by pulse Doppler echocardiography of the trans-tricuspid (P-At) and mitral (P-Am) blood flows (TD = P-Am - P-At). RESULTS: The atrial lead was screwed near the fossa ovalis in 29 of 30 patients. Atrial septal pacing yielded significantly shorter P wave duration (101.9 +/- 10.4 vs 139.6 +/- 14.7 msec, p < 0.001), leading to significant reduction of TD in atrial contraction (-8.8 +/- 10.0 vs 29.8 +/- 13.6 msec, p < 0.001)as compared to sinus rhythm. Both shorter P wave duration and reduced TD during atrial septal pacing remained statistically significant during the follow-up period as compared to sinus rhythm. Both left atrial diameter and A to E ratio of filling waves at mitral valve were significantly decreased at 12 months and remained decreased at 24 months. CONCLUSIONS: Atrial septal pacing at the trans-septal breakthrough site can resynchronize atrial contraction and results in improved hemodynamic effects during 24 months of follow-up.