Kunihide Nakamura

Adventitial Mast Cells Contribute to Pathogenesis in the Progression of Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is histologically characterized by medial degeneration and various degrees of chronic adventitial inflammation, although the mechanisms for progression of aneurysm are poorly understood. In the present study, we carried out histological study of AAA tissues of patients, and interventional animal and cell culture experiments to investigate a role of mast cells in the pathogenesis of AAA. The number of mast cells was found to increase in the outer media or adventitia of human AAA, showing a positive correlation between the cell number and the AAA diameter. Aneurysmal dilatation of the aorta was seen in the control (+/+) rats following periaortic application of calcium chloride (CaCl2) treatment but not in the mast cell–deficient mutant Ws/Ws rats. The AAA formation was accompanied by accumulation of mast cells, T lymphocytes and by activated matrix metalloproteinase 9, reduced elastin levels and augmented angiogenesis in the aortic tissue, but these changes were much less in the Ws/Ws rats than in the controls. Similarly, mast cells were accumulated and activated at the adventitia of aneurysmal aorta in the apolipoprotein E–deficient mice. The pharmacological intervention with the tranilast, an inhibitor of mast cell degranulation, attenuated AAA development in these rodent models. In the cell culture experiment, a mast cell directly augmented matrix metalloproteinase 9 activity produced by the monocyte/macrophage. Collectively, these data suggest that adventitial mast cells play a critical role in the progression of AAA.

Beneficial effect of prostaglandin E1 on blood flow to the gastric tube after esophagectomy

BACKGROUND A prospective study on the vasodilatory effect of prostaglandin E1 on blood flow to the gastric tube after esophagectomy is reported. METHODS Twelve patients with thoracic esophageal cancer who underwent esophagectomy were enrolled in this study. In all patients, the esophagogastrostomy was performed in the cervical region, and the stomach was used for reconstruction. Immediately after the creation of the gastric tube, baseline blood flow was measured at the oral end, in the center, and at the pyloric ring of the gastric tube using a laser Doppler flowmeter. The prostaglandin E1 group (n = 6) was then infused with prostaglandin E1 until postoperative day 2; the control group (n = 6) received saline. At +5 minutes and +40 minutes after administration, blood flow was again measured at the same three sites. RESULTS The control group did not show a significant increase of blood flow to any site over time. For the prostaglandin E1 group, blood flow at +40 minutes increased from the baseline measurements significantly at a rate of 63%, 39%, and 36%, respectively. CONCLUSIONS Prostaglandin E1 has a characteristic vasodilating effect on the area of impaired microcirculation of the gastric tube, thereby increasing blood flow to the affected area.

Detection of Total Assist and Sucking Points Based on Pulsatility of a Continuous Flow Artificial Heart: In Vitro Evaluation

We investigated the basic characteristics of the pulsatility of motor current with an in vitro mock circuit that consists of a sac-type pulsatile pump (simulating the natural left ventricle), three reservoirs, and our mixed flow pump (MFP). There are three alternatives at the inlet of the MFP: 1) the left atrium (LA), 2) the left ventricle (LV), and 3) both (LALV). The motor current waveform was monitored. The pump speed of the MFP was changed from 0 to 7,000 rpm. We calculated the index of motor current amplitude (ICA), which was obtained from the amplitude of the motor current waveform divided by the simultaneous mean value. The ICA plotted against the pump speed had a peak point (t-point) that highly corresponded with the turning point from partial to total left heart assistance. The ICA also had a second specific point (s-point) that corresponded with the beginning of severe sucking. In LV and LALV aortic bypass, t- and s-points could clearly be detected. In LA aortic bypass, however, early and severe sucking occurred, and t- and s-points were not manifest. These data suggest that the assist status of continuous flow artificial heart can be estimated by detecting the t- and s-points.

The effects of pulsatile and non-pulsatile cardiopulmonary bypass on renal blood flow and function.

The physiologic effects of pulsatile and non-pulsatile flow in cardiopulmonary bypass were compared in terms of the relationship between different flow rates and what effects these had on pulsatile and non-pulsatile flow. Forty adult mongrel dogs were used in this study and divided into 5 groups, each comprised of 8 animals, according to the flow rate during cardiopulmonary bypass, namely; 40, 60, 80, 100, or 120 ml/kg/min. The animals were perfused with either pulsatile or non-pulsatile flow for 1 hour, given randomly at the same mean flow rate. At flow rates of 80 and 100 ml/kg/min, the mean arterial blood pressure and total peripheral vascular resistance were significantly lower in pulsatile flow than in non-pulsatile flow, and the renal blood flow was significantly greater in pulsatile flow than in non-pulsatile flow. The renal arterial-venous lactate difference was significantly less in pulsatile flow than in non-pulsatile flow at a flow rate of 80 ml/kg/min, and the renal lactate extraction was significantly higher in pulsatile flow than in non-pulsatile flow at the same flow rate. The renal excess lactate was significantly lower in pulsatile flow than in non-pulsatile flow at a flow rate of 100 ml/kg/min. There were no significant differences in these parameters between the two types of perfusion at flow rates of 40, 60 or 120 ml/kg/min. Pulsatile flow was therefore apparently advantageous, when compared to non-pulsatile flow, in terms of hemodynamics, renal circulation, and metabolism of the kidney at flow rates of 80 and 100 ml/kg/min. However, when the flow rate was 120 ml/kg/min, pulsatile flow and non-pulsatile flow had the same effects.

Aneurysm of the Transverse Cervical Artery Occurring in Association with a Cavernous Hemangioma as a Complication of Klippel-Trenaunay Syndrome : Report of a Case

We report herein the case of a 14-year-old girl with Klippel-Trénaunay syndrome who developed an aneurysm of the transverse cervical artery. Because it was continuing to increase in size, with an associated risk of rupture, an aneurysmectomy was performed. Pathological examination of the resected specimen revealed a cavernous hemangioma located near the aneurysm. To our knowledge no other case of an aneurysm occurring in association with a cavernous hemangioma as a complication of Klippel-Trénaunay syndrome has ever been reported.

Outcome after valve surgery in octogenarians and efficacy of early mobilization with early cardiac rehabilitation

PurposeThis study aimed to compare postoperative complications and the surgical outcome in patients aged <80 years versus octogenarian patients. Another aim was to evaluate the safety and efficacy of early mobilization with early cardiac rehabilitation in octogenarians.MethodsA retrospective analysis was performed in 138 consecutive patients (group Y comprised 118 patients <80 years, and group O comprised 20 octogenarians) who had undergone valve surgery at the authors’ institution between July 2007 and December 2009. Furthermore, the efficacy of early mobilization with early cardiac rehabilitation and long-term results were analyzed in 40 consecutive octogenarian patients undergoing valve surgery from 2000. The late survival follow-up was 100% complete.ResultsRedo cardiac operations were more frequent (O group 15.0% vs. Y group 3.4%, P = 0.011), and the preoperative EuroSCORE was significantly higher in group O than in group Y (group O 16.4 ± 18.3 vs. group Y 7.5 ± 9.1, P = 0.001). The incidence of delirium/confusion and worsening of renal function after surgery was higher in group O. The hospital mortality was 1.7% in group Y and no hospital death in group O (P > 0.99). Early mobilization with early cardiac rehabilitation significantly reduced the incidence of postoperative delirium/confusion and increased the number of patients who could return directly home. The actuarial 5-year survival rate was 77.7% for octogenarians.ConclusionAlthough there were more high-risk patients among the octogenarians, valve surgery was a safe, lowrisk procedure with excellent long-term results. Early mobilization with early cardiac rehabilitation was significantly effective and safe for postoperative recovery in octogenarians after cardiac valve surgery.

Spleen plays an important role in maintaining tolerance after removal of the vascularized heart graft.

Background. This study addresses the question of the mechanism for maintaining tolerance to donor alloantigen in the absence of antigen and the role of secondary lymphoid tissues. Methods. Depleting anti-CD4 antibody administration in conjunction with allogeneic heart transplantation generates donor-specific operational tolerance. Primary C57BL/6 heart grafts were transplanted into the neck cavity of the anti-CD4 antibody pretreated C3H/He mice. At day 50, functioning heart grafts were removed from tolerant mice. At day 100, a secondary C57BL/6 or a third-party heart was transplanted into the abdomen. Results. Anti-CD4 antibody therapy induced CD4+CD25+ regulatory T cells by 50 days after transplantation, as depleting anti-CD25 treatment in tolerant mice abrogated graft prolongation when spleen leukocytes were adoptively transferred to syngeneic mice. Tolerance was maintained by CD4+CD25+ regulatory T cells via a CTLA-4 signal at 100 days, even after removal of the primary graft at day 50. Administration of anti-CD25 antibody immediately after removal of the primary graft did not break tolerance, as five out of six second allografts transplanted at day 100 were accepted. Anti-CD25 antibody therapy in conjunction with splenectomy, but not thymectomy, immediately after removal of primary heart grafts at day 50 broke tolerance at day 100; all allografts were rejected. Conclusion. The spleen is important in maintaining CD4+CD25+ regulatory T cells after primary allograft removal.

Giant cell tumor of the rib

In a rare case of a giant cell tumor of rib origin, a 25-year-old woman to be evaluated for an abnormal mass shadow in chest radiography was strongly positive in a tuberculin skin test, but showed no evidence of active tuberculosis. Chest computed tomography showed a heterogeneous mass originating in the posterior end of the right fourth rib and containing multiple calcifications and cystic lesions. Magnetic resonance imaging showed a high signal intensity with low signal intensity areas. Bone scintigraphy showed an abnormal marked accumulation at the tumor site. A thoracoscopic examination was conducted prior to complete tumor resection, including the fourth rib and related muscles. The pathological diagnosis returned was a giant cell tumor of the bone. The patient did not undergo chemotherapy or radiotherapy, and remains well, and tumor-free at 6 months after surgery.

Combination of Adoptive Cell Transfer and Antibody Injection Can Eradicate Established Tumors in Mice–An in vivo study using anti-OX40mAb, anti-CD25mAb and anti-CTLA4mAb–

Boosting an effective immune response against established tumors remains a difficult challenge. This study shows the combination of 1) adoptive cell transfer using CD25 depleted splenocytes co-cultured with irradiated tumor cells, and 2) antibody injection therapy using CTLA4 blockade, the elimination of Treg and OX40, which together could eradicate an established MethA tumor in over 50% of the BALB/c mice. Each element of the protocol was shown to be necessary, as elimination of any factor except anti-CD25 antibody injection failed to eradicate the tumor.

Impact of smoking on outcome of resected lung adenocarcinoma

ObjectiveSmoking is a well-known causative factor of lung cancer and the association of smoking with adenocarcinoma is considered to be the weakest. We investigated the influence of smoking on postoperative prognosis in patients with lung adenocarcinoma.MethodsOne hundred and eighty-one consecutive patients of resected lung adenocarcinoma were studied retrospectively. The histologic subtype was subdivided into 2 groups: lepidic dominant histologic subtype, including adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic predominant invasive adenocarcinoma versus other subtypes.ResultsThe 5-year survival of ever smokers was significantly unfavorable than that of never smokers. Similarly, there was also a relationship between the patients’ survival and Brinkman index (BI), with unfavorable survival found in patients with greater smoking histories. Based on a multivariable analysis, pN status and BI were significant factors affecting the postoperative prognosis of patients undergoing surgery. However, gender, serum carcinoembryonic antigen (CEA) level, lepidic dominant histologic subtype and pure/mixed ground-glass opacity (GGO) were not prognostic factors although previous reports showed prognostic significance. These factors that we failed to find the prognostic significance were significantly associated with smoking.ConclusionThe smoking was significantly predictive of an unfavorable prognosis after surgery for lung adenocarcinoma. It is suggested that smoking is associated with serum CEA level, histologic subtype and GGO, resulting in unfavorable outcome.