Acceleration of surgical angiogenesis in necrotic bone with a single injection of fibroblast growth factor-2 (FGF-2).

The aim of this study was to accelerate angiogenesis in necrotic bone by combining vascular bundle implantation and fibroblast growth factor-2 (FGF-2) administration. Twenty-four Japanese white rabbits were evaluated in this study. A portion of a rabbit iliac crest bone was removed as a free bone graft and frozen in liquid nitrogen to ensure complete cellular necrosis. A narrow hole was created in the bone and the graft was placed in the proximal thigh. In group 1, FGF-2 was injected into the hole at a single dose of 100 microg, and the saphenous artery and its venae comitantes were passed through the hole of the bone. In group 2, injection of saline into the hole and the vascular bundle implantation was used as a control. Neovascularization around the vessel was evaluated at weeks 1 and 2 after surgery. Neovascularization was observed along the implanted vascular bundle in both groups. At both 1 and 2 weeks after surgery, the vessel density of group 1 was significantly higher than that of group 2. The average length of newly formed vessels of group 1 was also significantly longer than that of group 2 at both 1 and 2 weeks after surgery. Both the vessel density and length were greater in week 2 animals than week 1. A local single injection of FGF-2 improved surgical angiogenesis in necrotic bone in this study. As FGF-2 is recognized as a potent mitogen for a variety of mesenchymal cells, the combination of vascular bundle implantation and FGF-2 administration may contribute to the treatment of ischemic osteonecrosis.     

In vitro and in vivo antibacterial activities of CS-834, a novel oral carbapenem.

CS-834 is a novel oral carbapenem antibiotic. This compound is an ester-type prodrug of the active metabolite R-95867. The antibacterial activity of R-95867 was tested against 1,323 clinical isolates of 35 species and was compared with those of oral cephems, i.e., cefteram, cefpodoxime, cefdinir, and cefditoren, and that of a parenteral carbapenem, imipenem. R-95867 exhibited a broad spectrum of activity covering both gram-positive and -negative aerobes and anaerobes. Its activity was superior to those of the other compounds tested against most of the bacterial species tested. R-95867 showed potent antibacterial activity against clinically significant pathogens: methicillin-susceptible Staphylococcus aureus including ofloxacin-resistant strains, Streptococcus pneumoniae including penicillin-resistant strains, Clostridium perfringens, Neisseria spp., Moraxella catarrhalis, most members of the family Enterobacteriaceae, and Haemophilus influenzae (MIC at which 90% of strains are inhibited, < or =0.006 to 0.78 microg/ml). R-95867 was quite stable to hydrolysis by most of the beta-lactamases tested except the metallo-beta-lactamases from Stenotrophomonas maltophilia and Bacteroides fragilis. R-95867 showed potent bactericidal activity against S. aureus and Escherichia coli. Penicillin-binding proteins 1 and 4 of S. aureus and 1Bs, 2, 3, and 4 of E. coli had high affinities for R-95867. The in vivo efficacy of CS-834 was evaluated in murine systemic infections caused by 16 strains of gram-positive and -negative pathogens. The efficacy of CS-834 was in many cases superior to those of cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil, especially against infections caused by S. aureus, penicillin-resistant S. pneumoniae, E. coli, Citrobacter freundii, and Proteus vulgaris. Among the drugs tested, CS-834 showed the highest efficacy against experimental pneumonia in mice caused by penicillin-resistant S. pneumoniae.     

Monoclonal immunotherapy with human monoclonal antibody(CLN-IgG) in glioma patients

It is well recognized that malignant gliomas escape an immune response by hiding behind the blood-brain barrier and by producing proteins that suppress systemic immunity. However, if gliomas can be made to be more immunogenic or if a tumor vaccine can be produced, then access to all tumor cells including those that infiltrate into the brain can be achieved through the patient's immune response. Several strategies have been investigated for immunotherapy. Laboratory studies and animal models have shown that these immune cells will attack the tumor cell, reduce the size of implanted tumors, and that the immune memory is sufficient to suppress tumor growth when the animal is rechallenges with a tumor implant. Since the development of hybridoma technology, monoclonal antibodies against human cancer cells have been produced and antigens have been identified. Hagiwara reported the production of a human monoclonal antibody, CLN-IgG, made by fusing UC 729-6, human lymphoblastoid B-cell line, with lymphocytes obtained from a patient with the cervical carcinoma. It has been reported that CLN-IgG recognized the antigen expressed in various histological types of human cancers including malignant gliomas. The effect of human monoclonal antibody(CLN-IgG) on malignant brain tumors was evaluated in patients with malignant glioma. Early phase II study was concluded that this specific immunotherapy with CLN-IgG is safe and effective therapy in patients with malignant glioma. We treated 10 cases of malignant gliomas with CLN-IgG. All patients had received radiotherapy and chemotherapy before this immunotherapy using the human monoclonal antibody. The human monoclonal antibody(CLN-IgG) was administered intravenously once or twice/week during 24 weeks. Six cases of glioblastoma, 1 medulloblastoma and 3 cases of potine glioma histologically unverified, were treated. Five cases of 6 glioblastomas died 4 to 12 months after this treatment, 3 cases of pontine glioma showed good responses, 2 cases showed marked decrease of tumor size and 1 case showed no regrowth of tumor on MRI imaging. For the above reasons, Human monoclonal antibody(CLN-IgG) might be useful as an immunotherapy of malignant gliomas.     

Experience with three-port laparoscopic cholecystectomy

After considerable experience with laparoscopic cholecystectomy (LC) using four ports, we began using three-port LC in October 1993 and have performed 130 LCs with this procedure up to May 1996. The procedure was successful in 119 patients. In 6 patients fourth port was used, and in another 5, the procedure was converted to open laparo-tomy. Cooperative manipulation of the surgical instruments between the operator and assistant is very important for this procedure, for exposing Calot's triangle and dissecting the gallbladder from the gallbladder bed. The use of an ultrasonic aspiration system (Sumisonic ME 2400; Sumitomo Bakelite, Tokyo, Japan) made it easier to identify the cystic duct and artery, especially in patients with chronic inflammation or dense adhesions. We encountered no problems with cannulation into the cystic duct for intraoperative cholangiography, and there were no intra- and postoperative complications in this series. We achieved good results, similar to those achieved with the four-port technique. This technique is technically feasible and safe, and it has esthetic and cost advantages compared with the four-port technique. However, the operator who performs three-port LC should not hesitate to add another port, or to convert to open laparotomy, whenever any difficulties occur during this procedure, to prevent critical complications.     

Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway

Human gut microbiota is being increasingly recognized as a player in colorectal cancers (CRCs). Evidence suggests that Fusobacterium nucleatum (F. nucleatum) may contribute to disease progression and is associated with CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) in CRCs; however, to date, there are no reports about the relationship between F. nucleatum and molecular features in the early stage of colorectal tumorigenesis. Therefore, we investigated the presence of F. nucleatum in premalignant colorectal lesions. In total, 465 premalignant lesions (343 serrated lesions and 122 non‐serrated adenomas) and 511 CRCs were studied. We determined the presence of F. nucleatum and analyzed its association with molecular features including CIMP, MSI and microRNA‐31 status. F. nucleatum was detected in 24% of hyperplastic polyps, 35% of sessile serrated adenomas (SSAs), 30% of traditional serrated adenomas (TSAs) and 33% of non‐serrated adenomas. F. nucleatum was more frequently detected in CIMP‐high premalignant lesions than in CIMP‐low/zero lesions (p = 0.0023). In SSAs, F. nucleatum positivity increased gradually from sigmoid colon to cecum (p = 0.042). F. nucleatum positivity was significantly higher in CRCs (56%) than in premalignant lesions of any histological type (p < 0.0001). In conclusion, F. nucleatum was identified in premalignant colorectal lesions regardless of histopathology but was more frequently associated with CIMP‐high lesions. Moreover, F. nucleatum positivity increased according to histological grade, suggesting that it may contribute to the progression of colorectal neoplasia. Our data also indicate that F. nucleatum positivity in SSAs may support the “colorectal continuum” concept.     

The relationship between crystalline disorder and electronic structure of Pd nanoparticles and their hydrogen storage properties

We investigated the relationship between crystalline disorder and electronic structure deviations of Pd nanoparticles (NPs) and their hydrogen storage properties as a function of their particle diameter (2.0, 4.6 and 7.6 nm) using various synchrotron techniques. The lattice constant of the 2.0 nm-diameter Pd NPs was observed to be larger than that of the 4.6 or 7.6 nm-diameter Pd NPs. With increasing particle diameter the structural ordering was improved, the lattice constant and atomic displacement were reduced and the coordination numbers increased, as determined using high-energy X-ray diffraction, reverse Monte Carlo modelling and X-ray absorption fine structure spectroscopy. The structural order of the core part of the larger NPs was also better than that of the smaller NPs. In addition, the bond strength of the Pd–H formation increased with increasing particle diameter. Finally, the surface order of the Pd NPs was related to enhancement of the hydrogen storage capacity and Pd–H bond strength.

Smaller Pd nanoparticles have a high degree of disordering and a lower coordination number on the surface part, which causes a change in electronic structure to have different hydrogen storage properties.     

Technical options for the surgical management of extracranial carotid artery aneurysms. Three case reports

Three cases of extracranial carotid artery (ECA) aneurysm were treated with various surgical options. Two female patients (74 and 37-year-old women) presented with pulsatile masses in their necks, which were confirmed as ECA aneurysms. Another 65-year-old woman presented with a calcified mass in her neck caused by an ECA aneurysm. The first case was treated with aneurysmorrhaphy with primary closure, the second with replacement of the involved site with vascular prosthesis, and the third with a high flow bypass with proximal ligation of the internal carotid artery. All three different surgical techniques were successful. ECA aneurysms are rare and require careful selection of the surgical method according to etiology, shape, and location of the ECA aneurysm. Proficiency in various vascular reconstruction techniques is a desirable prerequisite for the surgeon in-charge.     

The use of an ileostomy connector to diminish the frequency of defecation prior to ileostomy closure in patients with a pelvic pouch

A new method for allowing stool passage into the pelvic pouch before ileostomy closure to verify the defecation state and diminish stool frequency is reported herein. This was accomplished by fitting an ileostomy connector connecting the proximal and distal openings of the diverting loop stoma. The ileostomy connector was initially in place for 6 h a day, the length of time being gradually increased until it was able to be left in for 24 h a day over a 3-month period. The calculated daily frequency of stools decreased from 24 to 6 or 7 times, and the mean daily frequency immediately after ileostomy closure was 6.5 times. Physiological study also showed an improvement, with squeeze pressure increasing from 35 cmH₂O to 116 cmH₂O and the maximum tolerated volume increasing from 35 ml before, to 90 ml 3 months following the use of an ileostomy connector. Thus, we conclude that an ileostomy connector may be useful to predict postoperative functional outcome and its complications, and to diminish the frequency of defecation before ileostomy closure in patients with a covering loop stoma.This study was submitted as a poster presentation at the meeting of the XIVth Biennial Congress of the University of Colon and Rectal Surgeons in Creta, Greece, October 25–29, 1992.