Exercise after heparin administration: new therapeutic program for patients with-option arteriosclerosis oblitrans.

BACKGROUND: A prospective study examined whether a combination of an exercise program and heparin administration improves the clinical symptoms of patients with arteriosclerosis obliterans (ASO) without an indication for surgical revascularization because of the lack of distal target vessels or other reasons such as high surgical risk or lack of a vein conduit from previous coronary artery bypass surgery. METHODS AND RESULTS: A total of 19 consecutive patients with symptomatic non-option ASO diagnosed by angiography were randomly assigned to 3 groups: heparin + exercise (walking for 60 min after heparin injection [3,000 units/day IV for 14 days], n = 6), heparin administration only (n = 6), and exercise only (n = 7). Plasma levels of hepatocyte growth factor (HGF) were serially measured before and after intravenous administration of heparin. Ankle brachial pressure index was measured and treadmill exercise test (2.5 km/h, 12% slope) was performed before the 2-week treatment, just after finishing treatment, and 12 weeks after beginning the treatment. Ophthalmic examinations, including visual acuity test, ocular fundoscopy and fluorescein angiographic fundus photography, were performed before and 12 weeks after the treatment program. In all patients, HGF levels increased more than 4-fold of the basal level at 30 min after heparin injection. Maximum walking time was significantly higher in the heparin + exercise group than in the other 2 groups (p < 0.05). There were no patients who showed pathological retinal angiogenesis. CONCLUSION: The combination of an exercise program and heparin administration improves the clinical symptoms of patients with non-option ASO.     

Endothelial Progenitor Cells Dysfunction and Senescence: Contribution to Oxidative Stress

The identification of endothelial progenitor cells (EPCs) has led to a significant paradigm in the field of vascular biology and opened a door to the development of new therapeutic approaches. Based on the current evidence, it appears that EPCs may make both direct contribution to neovascularization and indirectly promote the angiogenic function of local endothelial cells via secretion of angiogenic factors. This concept of arterial wall repair mediated by bone marrow (BM)-derived EPCs provided an alternative to the local “response to injury hypothesis” for development of atherosclerotic inflammation. Increased oxidant stress has been proposed as a molecular mechanism for endothelial dysfunction, in part by reducing nitric oxide (NO) bioavailability. EPCs function may also be highly dependent on a well-controlled oxidant stress because EPCs NO bioavailability (which is highly sensitive to oxidant stress) is critical for their in vivo function. The critical question is whether oxidant damage directly leads to an impairment in EPCs function. It was revealed that activation of angiotensin II (Ang II) type 1 receptor stimulates nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase in the vascular endothelium and leads to production of reactive oxygen species. We observed that Ang II accelerates both BM- and peripheral blood (PB)-derived EPCs senescence by a gp91phox-mediated increase of oxidative stress, resulting in EPCs dysfunction. Consistently, both Ang II receptor 1 blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors have been reported to increase the number of EPCs in patients with cardiovascular disease. In this review, we describe current understanding of the contributions of oxidative stress in cardiovascular disease, focusing on the potential mechanisms of EPCs senescence.Key Words: Endothelial progenitor cell, oxidative stress, senescence, angiotensin II, telomerase, nitric oxide.     

Endoscopic approach to pulmonary diseases: Usefulness of the mediastinoscopy

The purposes of this study are to show the diagnostic values and the role of the mediastinoscopy for the respiratory diseases. From 1971 to 1998, mediastinoscopy were performed on 1664 patients admitted to our hospital with respiratory diseases. For the superior mediastinal diseases, mediastinal tumor and lymphadenopathies without cancer, two or three samples were obtained by mediastinoscopy. For lung cancer, biopsy was routinely performed at the 6 nodal stations, right and left paratracheal (#2), right and left tracheobronchial (#4), pretracheal (#3), and subcarinal (#7) lymphnodes. From 1994, we have used video-mediastinoscopy, which was combined with scope and TV-camera. Using video-mediastinoscopy, many staffs could observe the mediastinal findings on TV-monitor during mediastinal manipulation. The positive findings were observed in 17% (221/1299) for lung cancer, 100% (32/32) for sarcoidosis, 100% (2/2) for malignant lymphoma, 65% (11/17) for mediastinal tumor, 9.8% (13/132) for pulmonary tuberculosis. The positive rate according to the histological types of lung cancer were 20.5% (148/721) for adenocarcinoma, 9.4% (39/415) for squamous cell carcinoma, 31.6% (24/76) for small cell carcinoma, 21.3% (10/47) for large cell carcinoma. Complications developed in a total of 3.6%, and these were bronchial arterial damage(1.8%), recurrent nerve paralysis(0.7%), azygos vein damage (0.4%), pleural rupture(0.4%), superior vena cava damage(0.2%) and tracheal laceration(0.1%). However, there were no severe complications and operative deaths in this series. Mediastinoscopy is a minimal invasive and safety surgical procedure that is widely used as a diagnostic method for investigating the superior mediastinum, mediastinal tumor and lymphadenopathies. It is useful for obtaining histological diagnosis, as well as for staging lung cancer. Video-mediastinoscopy is more safety and educational, because many staffs could observe the findings.     

Enteroscopy

Wireless capsule endoscopy and double-balloon endoscopy are new methods of enteroscopy that have been introduced in recent years. Wireless capsule endoscopy is an epoch-making examination method that makes possible an endoscopic imaging examination of the entire small intestine without discomfort and without confining patients to a medical facility. Although it is expected to be useful as an initial examination for finding diseases of the small intestine, it cannot be used for biopsy or treatment. One risk associated with the capsule endoscopy technique is entrapment by strictures. Double-balloon endoscopy is based on a new insertion technique in which two balloons, one at the distal end of the endoscope and the other at the distal end of an overtube, are operated in combination, and the endoscope is inserted while simultaneously shortening the intestine. It can be inserted through either the mouth or the anus, allowing the observation of the entire gastrointestinal tract. It features excellent maneuverability even in the distal small intestine, and enables back-and-forth observation, biopsy, and endoscopic treatment at any given site. These two new enteroscopy techniques are expected to lead to innovations in how diseases of the small intestine are approached.     

Transcatheter Versus Surgical Aortic Valve Replacement in Young,Low-Risk Patients With Severe Aortic Stenosis

Transcatheter aortic valve replacement (TAVR) is approved for all patient risk profiles and is an option for all patients irrespective of age. However, patients enrolled in the low- and intermediate-risk trials were in their 70s, and those in the high-risk trials were in their 80s. TAVR has never been systematically tested in young (<65 years), low-risk patients. Unanswered questions remain, including the safety and effectiveness of TAVR in patients with bicuspid aortic valves; future coronary access; durability of transcatheter heart valves; technical considerations for surgical transcatheter heart valve explantation; management of concomitant conditions such as aortopathy, mitral valve disease, and coronary artery disease; and the safety and feasibility of future TAVR-in-TAVR. The authors predict that balancing these questions with patients’ clear preference for less invasive treatment will become common. In this paper, the authors consider each of these questions and discuss risks and benefits of theoretical treatment strategies in the lifetime management of young patients with severe aortic stenosis.     

Case Report: Determination of Primary Foci of Metastatic Tumors by p53 Mutational Analysis in Intraesophageal Multiple Carcinomas

It is well known that squamous carcinomasfrequently develop multifocally, either synchronously ormetachronously, in the upper aerodigestive tract (1).Such phenomena were first reported by Slaughter et al in 1953, and they were named fieldcancerization (2). Using recent molecular biologytechniques, these multiple carcinomas have been revealedto arise from independent origins (3). Esophagealcarcinomas have been reported to frequently metastasize tothe lymph nodes even at the early stage of tumorextension (4). Furthermore, simultaneous multifocalcancer development is not rare in the esophagus (5). In cases of intraesophageal multiple carcinomaswith lymph node metastases, the primary focus of themetastatic tumors cannot be identified by conventionalhistologic examination. Here we report a case of intraesophageal multiple carcinomas in whichthe attributed foci of lymph nodal metastases could beclearly identified by analyzing the p53 gene mutationalstatus used as a clonal marker.     

The role of apheresis therapy in living donor liver transplantation

Liver transplantation is a radical therapy for end-stage liver disease. The severe shortage of transplantable organs is, however, a big problem, not only in liver transplantation but also other organ transplants. Although in Japan, transplantation of organs obtained from brain-dead donors (BDD) has been allowed since October 1997, to date only 27 BDD have been obtained. It has become difficult to procure liver grafts from BDD, therefore we must use liver grafts from living donors. The living-donor liver transplantation (LDLT) program started in 1990 in Japan, and is still the major form of liver transplantation because of the scarcity of cadaveric donors. In the Department of Transplant Surgery, Kyoto Hospital (Kyoto, Japan), the accumulated number of LDLT cases exceeded 955 up to October 2003. In order to perform LDLT under safer conditions, apheresis plays a major role in Japan due to the prevalence of LDLT where later retransplantation is difficult. Clinical indications of apheresis for LDLT are mainly use as a bridge before transplantation, and liver support after transplantation. We describe the effect of apheresis therapy for LDLT patients with nephritic and hepatic problems.