Airway eosinophil migration into lymph nodes in mice depends on leukotriene C4.

BACKGROUND: We previously demonstrated in mice that airway eosinophils traffic from the airway lumen into lung-draining paratracheal lymph nodes. However, mechanisms whereby eosinophils traverse from the lungs and home to paratracheal lymph nodes remain unclear. We investigated roles of cysteinyl leukotrienes in mediating eosinophil trafficking from lungs to paratracheal lymph nodes. METHODS: The expression of CCR7 was determined by flow cytometry. Transwell assays were used to test chemotactic responses of leukotriene C4 synthase-deficient and control airway eosinophils to the chemokine CCL19 ex vivo. Eosinophils from the spleens of IL-5 transgenic mice, fluorescently labeled ex vivo, were intratracheally injected into ovalbumin-sensitized and ovalbumin aerosol-challenged leukotriene C4 synthase-deficient and control mice. Eosinophils were identified by microscopy and flow cytometry in the lungs and paratracheal lymph nodes. RESULTS: Mouse eosinophils expressed CCR7, the receptor for CCL19, and responded chemotactically to CCL19. Leukotriene C4 synthase-deficient eosinophils exhibited impaired chemotaxis to CCL19 that was restored by exogenous leukotriene C4 . The migration of intratracheally injected eosinophils into paratracheal lymph nodes from distal alveolar lung was diminished in leukotriene C4 synthase-deficient mice compared with wild-type mice, with increased retention of eosinophils in the lungs of leukotriene C4 synthase-deficient mice. Exogenous administration of leukotriene C4 restored trafficking of eosinophils to paratracheal lymph nodes in leukotriene C4 synthase-deficient mice. CONCLUSIONS: Our findings that cysteinyl leukotrienes are involved in regulating airway and lung eosinophil migration into paratracheal lymph nodes identify previously unrecognized roles for the cysteinyl leukotrienes in regulating the pulmonary trafficking of eosinophils in experimental allergic asthma.

Editor's Choice - Subsequent Results for Arch Aneurysm Repair with Inner Branched Endografts.

OBJECTIVES: The aim was to evaluate the current results of aortic arch aneurysm repair using inner branched endografts performed in three high volume aortic endovascular centers and to compare them to the pioneering global experience with this technology. METHODS: Included patients underwent repair of aortic arch aneurysms >55 mm in diameter using inner branched endograft technology between April 2013 and November 2014. All patients were deemed unfit for open surgery. Inner branches were designed to perfuse the brachiocephalic trunk and the left common carotid artery in all cases. A left subclavian artery (LSA) revascularization was performed prior to the arch endovascular repair. Data were collected retrospectively in an electronic database. Parameters included length of procedure, fluoroscopy time, contrast volume, technical success, presence of endoleaks, early and late complications, and mortality. RESULTS: Twenty-seven patients were included in the study. Technical success was achieved in all cases. No patients died during the 30 day post-operative period. Early neurologic events included two major strokes (7.4%) and one minor stroke (3.7%). Transient spinal cord ischemia with full recovery was observed in two patients (7.4%). Four patients (14.8%) underwent early (<30 day) re-interventions; these were for an access complication, an ischemic limb and exploration of the left ventricle through a sternotomy in two patients. During follow up (median 12 months), one patient (3.7%) died from a remote thoraco-abdominal aneurysm rupture. There were three Type 2 endoleaks (11.1%). Two re-interventions (7.4%) were performed, one to treat a Type 2 endoleak and one to treat a septic false aneurysm. A significant decrease in overall mortality was observed when comparing patients from the early experience with patients from the current report. CONCLUSIONS: The early outcomes associated with this technology are favorable. Branched endografting of aortic arch aneurysms should be considered in patients unfit for open surgery.

Microwave endometrial ablation for hypermenorrhea treatment: a new era in Japan.

An estimated six million women in Japan suffer from excessive menstruation and the treatment of this disorder has been undergoing dramatic changes recently. In April 2012, microwave endometrial ablation (MEA) was approved for insurance coverage as a K863-3: a hysteroscopic endometrial ablation (17,810 points). Since the introduction of MEA to Shimane University Hospital in August 2007, authors (KN, KM) have performed the procedure in 96 patients with excessive menstruation. They have also evaluated its safety and its efficacy, not only by comparing it to the existing surgical treatment but by quantifying patients' satisfaction levels and symptom improvement. The authors conclude that MEA is a safe, effective, a low-cost treatment, and they recommend that it be considered as a standard treatment for conservative therapy-resistant excessive menstruation.

Two-dimensional crystallization conditions of human leukotriene C4 synthase requiring adjustment of a particularly large combination of specific parameters.

Human leukotriene C(4) synthase (LTC(4)S) forms highly ordered two-dimensional (2D) crystals under specific reconstitution conditions. It was found that control of a larger number of parameters than is usually observed for 2D crystallization of membrane proteins was necessary to induce crystal formation of LTC(4)S. Here, we describe the parameters that were optimized to yield large and well-ordered 2D crystals of LTC(4)S. Careful fractioning of eluates during the protein purification was essential for obtaining crystals. While the lipid-to-protein ratio was critical in obtaining order, four parameters were decisive in inducing growth of crystals that were up to several microns in size. To obtain a favorable diameter, salt, temperature, glycerol, and initial detergent concentration had to be controlled with great care. Interestingly, several crystal forms could be grown, namely the plane group symmetries of p2, p3, p312, and two different unit cell sizes of plane group symmetry p321.

[Vacuum-assisted closure therapy for the treatment of sternal wound infection after cardiac surgery].

Sternal wound infection is still one of the critical and challenging complications after cardiac surgery. Vacuum-assisted closure (VAC) therapy is a unique and simple system that helps promote wound healing. We report 3 cases with the sternal wound infection after cardiac surgery, in which VAC therapy was applied between January, 2005 and April, 2007. Two of them had good response to VAC therapy and had their wound healed after 3 and 5 weeks, respectively. However, the remaining case, in which bilateral internal thoracic artery had been taken down for coronary artery bypass grafting (CABG) and osteomyelitis of the sternum was not well controlled, did not respond to VAC therapy. Our results suggested that VAC might facilitate wound healing of the patients with sternal wound infection only after abscess was drained and opened, while it might not be useful for the patents with osteomyelitis.

Vacuum-assisted closure for bilateral severe ischemic foot after revascularization: a case report.

Vacuum-assisted closure (VAC) therapy is a unique system that helps promote wound healing. We report a case of severe ischemic foot in which VAC therapy markedly improved wound healing. A 73-year-old man underwent left axillopopliteal bypass and left 3rd, 4th , and 5th digital amputations for gangrene. Although his amputation stumps were complicated with methicillin-resistant Staphylococcus aureus (MRSA) infection, the stumps were successfully healed by VAC. He also had gangrene in his right 1st toe, which could not healed by VAC alone, and we performed right femoropopliteal bypass and right 1st digital amputation. The stump with MRSA infection was also successfully healed by VAC. Histopathologic examination revealed a lot of microvessels in the increased granulation tissue.

The six-year results of a combined surgical and endovascular repair for thoracoabdominal aortic aneurysm involving the visceral arteries.

The authors report a case of a combined endovascular and open repair (hybrid procedure) for a mycotic thoracoabdominal aneurysm (TAAA) including its 6-year result. A 72-year-old man with diabetes mellitus, old brain infarction and moderate aortic stenosis was transferred to the hospital because of obstinate fever and back pain, The initial computed tomography (CT) scan revealed giant (TAAA), and from the laboratory findings, the white blood cell and C-reactive protein (CRP) were significantly elevated 12,400/mm3 and 23.9 mg/dL respectively. Based on the CT and laboratory findings, a mycotic TAAA was highly suspected. After the remission of inflammation, graft replacement with reconstruction of celiac trunk (CA) and superior mesenteric artery (SMA) was performed via spiral incision under extracorporeal circulation. two months after the first operation, the patient complained about his back pain again. CT showed a pseudoaneurysm which formed at the distal anastomotic site. A hybrid procedure was deemed to be the most appropriate for such patient who needs a second operation. First bilateral renal artery bypass (ilio-renal artery bypass) were done using the saphenous vein grafts (SVGs). Following bypass grafting to renal arteries, endovascular aneurysm repair was performed with handmade stent-graft which was fabricated using a self-expanding "Z" stent and woven Dacron graft. The postoperative course was uneventful, and follow-up CT showed the aneurysm to have shrunk with no endoleaks. At six months after hybrid procedure, the shrinkage of the aneurysm sac and the patency of the graft to renal arteries were confirmed by a CT scan. A hybrid procedure is considered to be useful and feasible for the poor surgical candidate with severe comorbidities, hostile abdomen and a complex anatomy. The long-term results of this hybrid procedure is considered to be promising.

Cysteinyl leukotrienes mediate the enhancing effects of indomethacin and aspirin on eosinophil production in murine bone marrow cultures.

BACKGROUND: Prostaglandin E(2) (PGE(2)) suppresses, while indomethacin and aspirin enhance, eosinophil production in murine liquid bone-marrow cultures. Because cysteinyl leukotrienes (cys-LTs) enhance human eosinophil colony formation, we investigated whether the effects of indomethacin and aspirin on murine bone-marrow were due to blockade of PGE(2) production alone, or involved further promotion of cys-LTs production/signalling. EXPERIMENTAL APPROACH: BALB/c liquid bone-marrow cultures were established with IL-5, alone or associated with indomethacin, aspirin, or cys-LTs. The effects of preventing cys-LT production or signalling were assessed. KEY RESULTS: Indomethacin and aspirin counteracted the suppression of eosinophil production by exogenous PGE(2). LTD(4), LTC(4) and LTE(4) enhanced IL-5-dependent eosinophil production and further counteracted the effect of exogenous PGE(2). The 5-lipoxygenase activating protein (FLAP) inhibitor, MK886, a leukotriene synthesis inhibitor, zileuton, the CysLT(1) receptor antagonists, MK571 and montelukast, or inactivation of the LTC(4) synthase gene, abolished effects of indomethacin and aspirin. MK886 and zileuton were ineffective but MK571 and montelukast were effective, against LTD(4). Indomethacin, aspirin and LTD(4) failed to enhance eosinophil production in bone-marrow from CysLT1 receptor-deficient mice. Indomethacin, aspirin and LTD(4) no longer counteracted the effects of exogenous PGE(2) in the presence of MK571 and montelukast. MK886, MK571 and montelukast had no effect by themselves, or in association with PGE(2). CONCLUSIONS AND IMPLICATIONS: Dependence on the FLAP/5-lipoxygenase/LTC(4) synthase pathway and receptor signalling shows that cyclo-oxygenase inhibitors act here through endogenous cys-LTs. While PGE(2) does not act by suppressing cys-LT production, cys-LTs override PGE(2) signalling. Eosinophil production is therefore coordinately regulated by both pathways.

Common hepatic artery aneurysm branching from the superior mesenteric artery. Report of a case.

A 58-year-old man was notified as having a mass in the head of the pancreas at medical checkup on September 26, 2000. He was admitted to our department after being diagnosed as having an aneurysm in the common hepatic artery, branching from the superior mesenteric artery (SMA), based on selective SMA angiography. From an abdominal midline incision, we were able to reach his common hepatic artery aneurysm (CHAA) by mobilizing the pancreas through the route lateral to the greater curvature of the stomach. This aneurysm arose in the common hepatic artery immediately after branching from the SMA. After proximal and distal control of the SMA and common hepatic artery, the aneurysm was incised and the distal hepatic artery was anastomosed end to side to the SMA. The patient had an uneventful postoperative course.

Quantitative air-plethysmographic venous function and ambulatory venous pressure in patients with primary varicose vein.

AIM: The purpose of this study was to investigate the relationship between air-plethysmographic volume parameters under standard exercise loading and foot venous pressure parameters under ideal exercise loading in patients with primary varicose veins. METHODS: Seventy-one lower limbs in 39 patients with primary varicose veins and 8 lower limbs in 4 healthy controls were examined. The patients included 12 males and 27 females, ranging in age from 36 to 79 years. Eighteen limbs were asymptomatic (class 0) limbs, 28 limbs had symptoms of swelling or heaviness (class 1), and 25 had skin lesions (class 2+3). The patients and controls were examined with duplex scanning, air-plethysmography, and ambulatory foot venous pressure measurement. RESULTS: The mean ambulatory venous pressure (AVP) was significantly higher in the class 2+3 limbs than in the other classes, but it was not significantly higher in class 1 than in class 0. There were no significant differences between the class 2+3 limbs and class 1 limbs in any of the air-plethysmographic parameters. However, the VFI in the class 0 limbs was significantly different from that in the other 2 groups. Among all parameters examined, the venous filling index (VFI) was the most closely correlated with the AVP. All air-plethysmographic parameters were negatively correlated with the VRT. CONCLUSIONS: Among non-invasive air-plethysmographic volume parameters, VFI is the most reliable indicator for quantitative evaluation of calf pump function.

Relationships between matrix metalloproteinases and tissue inhibitor of metalloproteinases in the wall of abdominal aortic aneurysms.

AIM: The pathologic feature of aortic aneurysm is considered to be the remodeling of the aortic wall, involving fragmentation and decrease of elastic fibers in the tunica media. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, have been implicated in collagen and elastin degeneration within the aortic wall. The precise relationship among MMPs and tissue inhibitor of metalloproteinases (TIMPs) is still unclear. We have studied the expression of MMP-2, MMP-9 tissue inhibitor of metalloprotein-1 (TIMP-1), TIMP-2 and membrane type 1-MMP (MT-1-MMP) in the wall of small AAAs (30-45 mm), large AAAs (>45 mm) and controls (<25 mm). We investigated the relationship among expressions of MMP-2, TIMP-2 and MT1-MMP in the walls. METHODS: The aortic walls in the patients with AAA were harvested from the maximum diameter, while the aortic walls in autopsy cases were harvested as controls. We analyzed tissue distribution of cell types by immunochemistry, protein expression by Western blotting and mRNA expression by competitive polymerase chain reaction. RESULTS: They consisted of 11 in controls, 8 in small AAAs and 26 in large AAAs. Among the MMPs-positive-cells, mainly macrophage, MMP-2-positive cells were in the intima, but MMP-9-positive cells in the intima and adventitia. In the small size, MMP-2 and MMP-9 mRNA were higher than those of control. In the large size, MT1-MMP and MMP-9 mRNA were higher than those of the controls. In the mRNA level of the whole AAA, significant correlations were present between MMP-2 and MMP-9, between MMP-2 and TIMP-1, and between MMP-9 and TIMP-1. These expressions were confirmed by Western blotting. CONCLUSION: We concluded as follows: 1) MMP-2 and MMP-9 may play an important role in the developmental process of AAA. 2) TIMP-1 plays an important role of interacting MMP-2 and/or MMP-9. 3) MMP-2 and MT1-MMP may play an important role in the early stages of AAAs.

Long-term effects of hormone replacement therapy on bone mineral density in girls oophorectomized in adolescence.

The object of this study was to examine the effects of hormone replacement therapy (HRT) on bone mineral density (BMD) and physical development in oophorectomized adolescent girls. Two adolescent girls had bilateral ovaries removed as the treatment of advanced ovarian neoplasms at 12 years of age, and have been receiving HRT for more than 10 years. The changes in BMD and physical development were recorded. Both patients entered puberty and developed mature female physiques, despite the 3 years' absence of estrogen exposure immediately after oophorectomy. BMD recovered soon after the start of HRT and was kept within the normal range. Normal physical development, including bone mineral density, can be achieved with HRT in adolescent girls castrated before puberty.

The analysis of the usefulness of laparoscopic microwave coagulation therapy for hepatocellular carcinoma in patients with poor hepatic reserve by serial measurements of IL-6, cytokine antagonists, and C-reactive protein.

BACKGROUND: Little is known about the effectiveness of laparoscopic microwave coagulation therapy (L-MCT) for hepatocellular carcinoma (HCC) in patients with liver cirrhosis and poor hepatic reserve. Here, we analyzed the usefulness of laparoscopic MCT by comparing the serum levels of IL-6, cytokine antagonists, and C-reactive protein (CRP) following L-MCT with those following MCT with the open method (O-MCT). METHODS: Sixteen patients with hepatocellular carcinoma (HCC) were separated into L-MCT and O-MCT groups according to ICGR15 (ICGR15 30%<:L-MCT, 30%> :O-MCT). Nine patients with poorer hepatic reserve received L-MCT, while seven patients with relatively good hepatic reserve received O-MCT. Serum levels of cytokine antagonists (interleukin-6, IL-6; interleukin-1 receptor antagonist, IL-1ra; soluble tumor necrosis factor receptor type I, sTNF-R55) and C-reactive protein (CRP) were simultaneously measured on serial postoperative days (POD) by immunoassay. RESULTS: Postoperative serum levels of IL-6, IL-1ra, and CRP were significantly elevated on POD-1 and returned to the preoperative levels on POD-7 in both L-MCT and O-MCT groups. In contrast, no significant elevation of sTNF-R55 was found during the period in both groups. In addition, no statistical differences were found in the levels of IL-6, IL-1ra, sTNF-R, and CRP between the groups, except that the level of IL-6 on POD-1 in L-MCT group was significantly lower than that in the O-MCT group. CONCLUSION: These results suggested that the surgical stress by L-MCT in patients with poorer hepatic reserve were almost equal to that by O-MCT in patients with relatively good hepatic reserve, indicating the usefulness of L-MCT for HCC patients with poorer hepatic reserve. We recommend the laparoscopic approach for future patients with the criterion that ICGR15 is over 30%.

Analysis of host response to hepatectomy by simultaneous measurement of cytokines in the portal vein, caval vein and radial artery.

We analysed the host response to hepatectomy by simultaneous measurement of various cytokines and their antagonists in the portal vein, caval vein and radial artery in 10 patients with hepatocellular carcinoma. Concentrations of tumour necrosis factor-alpha (TNF), interleukin (IL) 1 beta, IL-2, IL-6, IL-10, soluble TNF receptor type I (sTNF-R), soluble IL-2 receptor (sIL-2R), IL-1 receptor antagonist (IL-1ra), soluble CD14 (sCD14) and endotoxin were determined just before and 1 h after hepatectomy. The values of IL-6, sTNF-R and IL-1ra were significantly increased after hepatectomy at each sampling site. In contrast, the levels of sIL-2R and sCD14 after hepatectomy were significantly decreased, and the levels of IL-1 beta, IL-2 and IL-10 were below the detection limits. Differences in cytokine concentrations between sampling sites revealed that the surgical stress of hepatectomy induced significant IL-1ra production in the liver and sTNF-R and IL-6 production in the lungs. These results suggest that hepatic resection is followed by the production of cytokine antagonists, such as IL-1ra, sTNF-R and IL-6, which could represent an important regulatory mechanism against surgical stress.

[Cardiac surgery for chronic dialysis patients].

Chronic dialysis patients who received open heart surgery were examined, and main concern was perioperative management. There were 12 chronic dialysis patients and open heart surgeries were performed between October 1990 and June 2000. The patients were comprised of 7 men and 5 women with the average age being 64 with plus or minus 7.9. The operative procedure of 6 coronary artery bypass grafting (CABG) [on-pump], 1 CABG + mitral valve replacement (MVR), 3 aortic valve replacement (AVR), 1 mitral valvuloplasty (MVP) and 1 ascending aorta replacement were performed. All patients were discharged from the hospital with good conditions 27.1 days after operation. There were no hospital deaths. One postoperative complication of mediastinitis of the sternum has been found. A conventional dialysis was performed the day before the operation and an intra-operative hemodialysis (HD) was performed, placing a dialyzer into a cardiopulmonary system during the operation. For the perioperative management, HD was started the day or 2 days after the operation with no immediate postoperative hemocatharsis and returned to the normal HD 7 days after the operation. The result of the perioperative management has been good.

Left renal artery aneurysm with left accessory renal arteries. A case report.

A 57-year-old man was suspected of having a left renal artery aneurysm on enhanced computed tomography (CT) findings. Aortic angiography showed 3 left renal arteries with an aneurysm of the distal main renal artery. A 3 mm upper pole renal artery which crossed near the aneurysm was preserved. Dissection of the aneurysm was followed by arterial reconstruction with end-to-end anastomosis.

Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics.

Cysteinyl-leukotrienes and prostaglandin D2 generated by the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways, respectively, cause bronchoconstriction, leukocyte recruitment, and bronchial hyperresponsiveness in asthma. We characterized the cellular expression of 5-LO and COX enzymes using immunohistochemistry on bronchial biopsies from 12 allergic asthmatic patients before and during seasonal exposure to birch pollen. Bronchial responsiveness (p = 0.004) and symptoms (p < 0.005) increased and peak expiratory flow (PEF; p < or = 0.02) decreased in the pollen season. In-season biopsies had 2-fold more cells immunostaining for 5-LO (p = 0.02), 5-LO-activating protein (FLAP; p = 0.04), and leukotriene (LT)A4 hydrolase (p = 0.05), and 4-fold more for the terminal enzyme for cysteinyl-leukotriene synthesis, LTC4 synthase (p = 0.02). Immunostaining for COX-1, COX-2, and PGD2 synthase was unchanged. Increased staining for LTC4 synthase was due to increased eosinophils (p = 0.035) and an increased proportion of eosinophils expressing the enzyme (p = 0.047). Macrophages also increased (p = 0.019), but mast cells and T-lymphocyte subsets were unchanged. Inverse correlations between PEF and 5-LO(+) cell counts link increased expression of 5-LO pathway enzymes in eosinophils and macrophages within the bronchial mucosa to deterioration of lung function during seasonal allergen exposure.

Cirsoid aneurysm after hysterectomy.

Cirsoid aneurysm, an uncommon abnormal either congenital or acquired arteriovenous communication, is described. As massive life-threatening bleeding can be a consequence, diagnosis is very important. Earlier, angiography was the only imaging method available for visualizing vascular lesions and recent developments in imaging techniques have made diagnostic imaging of cirsoid aneurysms possible using ultrasonography, color flow mapping, magnetic resonance imaging and magnetic resonance angiography. In this report, a patient with intrapelvic cirsoid aneurysm posthysterectomy who died 8 h after she had been kicked in the abdomen is described and the results obtained by various imaging techniques are discussed.

Standardized multicolored magnetic resonance images of gynecologic lesions.

PURPOSE: The purpose of this study was to develop a convenient and simple method for visualizing in color the features of gynecologic lesions by combining T1- and T2-weighted magnetic resonance images using RGB (red-green-blue) color channels. MATERIALS AND METHODS: T1- and T2-weighted film images of gynecologic lesions were digitized using a film-scanner. The signal intensities of fat on T1-weighted images were converted to 133% of those on T2-weighted images. Additive multicolored images in the RGB color system were produced from T1- and T2-weighted images using color axes of a complementary color pair for a total of 84 typical gynecological lesions. RESULTS: Tissues were displayed in color as follows: fat: light tan; urine: light blue: muscle: dark brown; endometrium: light blue; leiomyomas with cystic degeneration: cyanblue; cellular leiomyoma: yellowish brown; endometrial cyst: orange. The images of female intrapelvic structures and gynecologic lesions were semi-natural in appearance. CONCLUSION: Standardization of fat intensities provides a simple method for multicolored visualization of the features of gynecologic lesions.