Early angiographic results of multivessel off-pump coronary artery bypass grafting.

OBJECTIVES: Recently off-pump coronary artery bypass grafting (CABG) is being widely used for coronary revascularization. However, there is some evidence that off-pump surgery increases the risk of recurrent angina and the need for reintervention, suggesting poor graft quality or incomplete revascularization. We describe our experience to demonstrate the feasibility of multiple coronary revascularization in off-pump CABG (OPCAB). PATIENTS AND METHODS: From January 2002 to March 2003, 168 patients underwent OPCAB at our institute. In 16 of them, 6 to 9 vessels were revascularized in each patient. There were 14 males and 2 females with a mean age of 66 years (47 to 74 years). All patients had triple-vessel disease. Ten patients received in situ arterial grafts only which were harvested with the skeletonization technique using an ultrasonic scalpel. We used the Starfish heart positioner to expose lateral, posterior, and inferior walls of the heart with minimal hemodynamic compromise. RESULTS: All patients were discharged from the hospital without any serious complications. Postoperative angiography was performed in 87.5% within 1 month after operation. The patency rate was 96.6%. CONCLUSION: These results indicate that complete revascularization can be achieved in OPCAB in patients with diffuse coronary arterial disease. Complete revascularization with in situ arterial conduits only is technically feasible and yields a high early graft patency, even in the off-pump situation.     

Macular Microvasculature and Associated Retinal Layer Thickness in Pediatric Amblyopia: Magnification-Corrected Analyses

PurposeThe purpose of this study was to characterize macular microvasculature and structural retinal layers using magnification-corrected optical coherence tomography angiography (OCTA) images in children with amblyopia.MethodsThis prospective cross-sectional study included 22 children with unilateral amblyopia (4–11 years of age) receiving spectral-domain OCTA. Vessel densities in foveal and parafoveal regions of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were measured in amblyopic and fellow eyes using a customized image analysis program correcting the scale of retinal image with axial length. Iowa Reference Algorithms (Iowa Institute for Biomedical Imaging) were used to measure mean thickness values of 10 intra-retinal layers rescaled for image size correction.ResultsFoveal and parafoveal vessel densities in amblyopic eyes were lower than that of the fellow eyes in the SCP (fovea: P = 0.006 and parafovea: P = 0.003) and the DCP (P = 0.024 and P = 0.025, respectively). Amblyopic eyes had significantly smaller foveal avascular zone (FAZ) area than fellow eyes (P < 0.001). There were significant differences in retinal layer thickness between paired eyes, particularly in the inner retina in both foveal and parafoveal regions; retinal nerve fiber layer (RNFL) (P = 0.024 and P = 0.095, respectively), ganglion cell layer (P < 0.001 and P = 0.008), inner plexiform layer (IPL; P = 0.12 and P = 0.037), inner nuclear layer (P = 0.005 and P = 0.005), and outer plexiform layer (OPL; P = 0.02 and P = 0.057), except in the foveal IPL, the parafoveal RNFL, and OPL.ConclusionsUnilateral amblyopic eyes demonstrate reduced macular vessel density and thicker inner retinal layers compared with fellow eyes even after correcting for image magnification. Changes in macular microvasculature and structural layers may offer valuable insights in the development of amblyopia.     

Combined Assay of Serum Levels of CA125 and CA19-9 in Endometrial Carcinoma

Serum levels of CA125 and CA19-9 were examined in 225 cases with endometrial carcinoma before treatment and 32 cases with recurrent endometrial carcinoma. The positive rates in the 225 cases were 27.1% for CA125, 24.0% for CA19-9, and 38.7% for the combined assay. The serum levels of both CA125 and CA19-9 significantly increased with surgical staging. The presence of lymph node metastasis and extrauterine spread exhibited a marked influence on the serum levels of both CA125 and CA19-9. Myometrial invasion and vessel permeation also increased serum levels of CA125, whereas peritoneal cytology and adnexal metastasis exhibited no influence on CA125 levels or CA19-9 levels. Twenty-five of 33 cases who showed either more than 100 U/ml of CA125 level or more than 100 U/ml of CA19-9 level were classified as surgical stage III or IV. The combined assay demonstrated a 71.9% positive rate at the time of detection of the recurrence (65.6% for CA125, 43.7% for CA19-9). In 34.4% of the 32 recurrent cases, elevated levels of the tumor markers were the first sign of recurrence. These data indicate that the use of CA19-9 in combination with CA125 is noteworthy in the management of patients with endometrial carcinoma.     

Subconjunctival doxifluridine administration suppresses rat choroidal neovascularization through activated thymidine phosphorylase

PURPOSE: Doxifluridine (5'-deoxy 5-fluorouridine) is an oral anticancer drug with antiangiogenic effects, with vasoclastic action that is enhanced by a major member of the pyrimidine phosphorylases, thymidine phosphorylase (TP). Previous studies have demonstrated that TP is upregulated in the lesions where pathologic angiogenesis occurs and TP itself promotes angiogenesis. To investigate the possible role of TP and doxifluridine in choroidal neovascularization (CNV), the expression level of TP was measured and the effect of doxifluridine was investigated in rat eyes with experimental CNV. METHODS: CNV was induced in rat eyes by diode laser photocoagulation. The expression level of TP in the laser-treated and control eyes was examined with high-performance liquid chromatography (HPLC). For the evaluation of CNV activity, the intensity of fluorescein leakage from the photocoagulated lesions was scored, and the areas of CNV lesions were measured histologically in the control eyes and eyes treated with a subconjunctival injection of doxifluridine 14 days after photocoagulation. RESULTS: The expression level of TP was higher in the laser-treated eyes than in the control eyes. Fluorescein leakage from the CNV lesions significantly decreased in the eyes given a subconjunctival injection of doxifluridine compared with the control. Histologic analysis demonstrated that both the areas of CNV lesions and the degree of vascular formation in the subretinal membrane were reduced in the doxifluridine-treated eyes compared with the control eyes. CONCLUSIONS: TP may be involved in the formation of CNV. Subconjunctival injection of doxifluridine significantly reduced experimental CNV activity without apparent adverse effects. These results suggest the possibility that doxifluridine can be beneficial in treating CNV.     

Alterations in retinal nerve fiber layer thickness following indirect traumatic optic neuropathy detected by nerve fiber analyzer,GDx-N

PURPOSE: To evaluate changes in the retinal nerve fiber layer following traumatic optic neuropathy. DESIGN: Observational case report. METHODS: A patient presented with visual loss after an accident. Scanning laser polarimetry was performed. RESULTS: Thickness of the retinal nerve fiber layer increased immediately after the trauma but then progressively decreased. Severe loss was observed at day 90 and then ceased. Enlargement of the optic disk cup was also observed. CONCLUSIONS: This is the first report documenting early transient increase followed by progressive loss of the retinal nerve fiber layer in traumatic optic neuropathy.     

Laparoscopic trans-peritoneal hernioplasty (TAPP) is useful for obturator hernias: report of a Case

A 71-year-old female presented to our hospital due to pain from the right hip joint to the lower abdomen. The pain had suddenly appeared and spontaneously disappeared more than 10 times during the past 2 years. She had visited many hospitals, but remained undiagnosed. The patient underwent a computed tomography (CT) scan of the pelvis, and a soft tissue shadow was seen between the external obturator and pectineal muscles. She was diagnosed with a right obturator hernia and underwent elective repair by laparoscopic trans-peritoneal hernioplasty (TAPP). 1 year has passed since the surgery, without any recurrence of the abdominal pain. Obturator hernias are rare, and most cases are found as incarcerated hernias. It is rare to find an obturator hernia without intestinal obstruction, or with the recurrent pain as in our case. We herein report a case in which an obturator hernia was undiagnosed and intermittent pain was experienced for 2 years prior to TAPP, which appears to have successfully treated the hernia.     

Development of a therapeutic adenoviral vector for cholangiocarcinoma combining tumor-restricted gene expression and infectivity enhancement

Cholangiocarcinoma is an invasive malignancy that is most often unresectable upon diagnosis and unresponsive to chemotherapy and radiation. While adenoviral gene therapy has shown promise in treating many tumors, systemic toxicity and low tumor transduction efficiency have hampered its application in many gastrointestinal cancers. To overcome these difficulties, we have constructed an adenoviral vector utilizing a tumor-specific promoter (TSP) for selective transgene expression and a vector with an RGD-motif in the fiber-knob region for infectivity enhancement. In seeking a TSP for cholangiocarcinoma, Secretory Leukoprotease Inhibitor, Midkine, Gastrin Releasing Peptide, VEGF, Cox-2M, and Cox-2L promoters were configures in adenoviral vectors, and evaluated in cholangiocarcinoma cells lines (Oz and SkChA-1). Luciferase assays demonstrated that Cox-2 promoters (M and L) showed the highest promoter activity, with Cox-2M appearing slightly stronger than Cox-2L. Infectivity enhanced vectors with RGD-motif in the fiber-knob region were also constructed with the luciferase transgene driven by a CMV control and the Cox-2M and Cox-2L promoters. Subsequent luciferase assays comparing the unmodified vectors to the RGD-modified versions demonstrated higher levels of luciferase activity than the RGD-infected cells. This paradigm was then applied to a therapeutic HSV-TK/GCV model by constructing RGD-enhanced HSV-TK vectors driven by Cox-2M and Cox-2L promoters. In vitro cytocidal effect analysis confirmed that the RGD-modified, cox-2 (M and L) driven vectors showed a stronger cytocidal effect upon gancyclovir administration than the vectors with wild-type fiber. The Cox-2 promoter demonstrates a favorable selectivity profile for cholangiocarcinoma, and RGD-modification further enhances transduction efficiency. This combination has potential to overcome the obstacles to clinical application of adenoviral gene therapy in cholangiocarcinoma. Presented at the Forty-Third Annual Meeting of The Society for Surgery of The Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation).     

Effect of Inflammation on Costimulation Blockade-Resistant Allograft Rejection

Previously, we reported that allogeneic skin grafts were rapidly rejected by CD28 and CD40 ligand double deficient mice mediated by CD8⁺ T cells. These results indicated that some elements in addition to CD28- and CD40-mediated costimulation provide stimulatory signals for the activation of donor-specific CD8⁺ T cells. In this report, we investigated the role of inflammation associated with transplantation on costimulation-independent priming of CD8⁺ T cell during graft rejection. B6 RAG1 KO mice were transplanted with BALB/c-skin and adoptively transferred with syngeneic CD8⁺ T cells the same day or 50 days after transplantation. When blockade of CD28- and CD40-mediated costimulation failed to prevent acute rejection of freshly transplanted skin grafts, it efficiently delayed rejection of well-healed skin grafts. These results showed that factors associated with transplantation have essential roles in inducing costimulation blockade-resistant allograft rejection. Costimulation blockade failed to prevent acute graft-infiltration of NK cells and increasing expression of intragraft IL-12 and IL-15. These factors may trigger the graft-infiltration and priming of CD8⁺ T cells to induce costimulation blockade-resistant allograft rejection.     

Deficiency of insulin receptor substrate-1 impairs skeletal growth through early closure of epiphyseal cartilage.

Morphological analyses in and around the epiphyseal cartilage of mice deficient in insulin receptor substrate-1 (IRS-1) showed IRS-1 signaling to be important for skeletal growth by preventing early closure of the epiphyseal cartilage and maintaining the subsequent bone turnover at the primary spongiosa. Introduction: IRS-1 is an essential molecule for intracellular signaling by IGF-I and insulin, both of which are potent anabolic regulators of cartilage and bone metabolism. To clarify the role of IRS-1 signaling in the skeletal growth, morphological analyses were performed in and around the epiphyseal cartilage of mice deficient in IRS-1 (IRS-1(-/-)), whose limbs and trunk were 20-30% shorter than wildtype (WT) mice. MATERIALS AND METHODS: The epiphyseal cartilage and the primary spongiosa at proximal tibias of homozygous IRS-1(-/-) and WT male littermates were compared using histological, immunohistochemical, enzyme cytohistochemical, ultrastructural, and bone histomorphometrical analyses. RESULTS: In and around the WT epiphyseal cartilage, IRS-1 and insulin-like growth factor (IGF)-1 receptors were widely expressed, whereas IRS-2 was weakly localized in bone cells. Chronological observation revealed that height of the proliferative zone and the size of hypertrophic chondrocytes were decreased in WT mice as a function of age, and these decreases were accelerated in the IRS-1 (-/-) cartilage, whose findings at 12 weeks were similar to those of WT at 24 weeks. In the IRS-1(-/-) cartilage, proliferating chondrocytes with positive proliferating cell nuclear antigen (PCNA) or parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor immunostaining had almost disappeared by 12 weeks. Contrarily, TUNEL+ apoptotic cells were increased in the hypertrophic zone, at the bottom of which most of the chondrocytes were surrounded by the calcified matrix, suggesting the closure of the cartilage. In the primary spongiosa, bone volume, alkaline phosphatase (ALP)+ osteoblasts, TRACP+ osteoclasts, and the osteopontin-positive cement line were markedly decreased. Bone histomorphometrical parameters for both bone formation and resorption were significantly lower in IRS-1(-/-) mice, indicating the suppression of bone turnover. CONCLUSION: The IRS-1(-/-) epiphyseal cartilage exhibited insufficient proliferation of chondrocytes, calcification of hypertrophic chondrocytes, acceleration of apoptosis, and early closure of the growth plate. Thus, the data strongly suggest that IRS-1 signaling is important for the skeletal growth by preventing early closure of the epiphyseal cartilage and by maintaining the subsequent bone turnover at the primary spongiosa.