Irish national real-world analysis of the clinical and economic impact of 21-gene oncotype DX® testing in early-stage, 1-3 lymph node-positive, oestrogen receptor-positive, HER2-negative, breast cancer.

PURPOSE: The treatment landscape of Oestrogen receptor-positive (ER-positive) breast cancer is evolving, with declining chemotherapy use as a result of Oncotype DX Breast Recurrence Score® testing. Results from the SWOG S1007 RxPONDER trial suggest that adjuvant chemotherapy may benefit some premenopausal women with ER-positive, HER2-negative disease with 1-3 positive lymph nodes (N1), and a Recurrence Score® (RS) of ≤ 25. Postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. We examine the clinical and economic impact of Oncotype DX® testing on treatment decisions in patients with N1 disease in Ireland using real world data. METHODS: From March 2011 to October 2022, a retrospective, cross-sectional observational study was performed of patients with ER-positive, HER2-negative N1 breast cancer, who had Oncotype DX testing across 5 of Ireland's largest cancer centres. Patients were classified into low risk (RS 0-13), intermediate risk (RS 14-25) and high risk (RS > 25). Data were collected via electronic patient records. Information regarding costing was provided primarily by pre-published sources. RESULTS: A total of 828 N1 patients were included in this study. Post Oncotype DX testing, 480 patients (58%) were spared chemotherapy. Of the patients who had a change in chemotherapy recommendation based on Oncotype DX testing, 271 (56%), 205 (43%), 4 (1%) had a RS result of 0-13, 14-25 and > 25 respectively. Use of Oncotype DX testing was associated with a 58% reduction in chemotherapy administration overall. This resulted in estimated savings of over €6 million in treatment costs. Deducting the assay cost, estimated net savings of over €3.3 million were achieved. Changes in the ordering demographics of Oncotype DX tests were identified after RxPONDER data were presented, with increased testing in women ≥ 50 years and a reduction in proportion of tests ordered for women < 50 years. CONCLUSION: Between 2011 and 2022, assay use resulted in a 58% reduction in chemotherapy administration and net savings of over €3.3 million.

Risks for Surgical Site Infection after Infra-inguinal Bypass

Aims To define the burden of wound complications in patients with infra-inguinal bypass surgery. Methods A retrospective review of 50 consecutive patients from January 2012 to July 2017. Data collected included patient demographics, operative details, length of stay (LOS) and postoperative complications. Results The average age was 64 years (range 25-88 years) and 10 had a body mass index (BMI) ≥25 kg/m2. Pre-operative methicillin-resistant Staphylococcus aureus (MRSA) screening was performed in 17 patients (n=4 positive). Surgical antimicrobial prophylaxis (SAP) continued longer than 24 hours in 25. Surgical site infection (SSI) was the most common complication (n=10) and associated with female gender (p= 0.039), high BMI (p=0.017), shorter preoperative (p=0.039) and longer postoperative LOS (p=0.022). Three of 46 patients and four of 38 had graft occlusion at 30 days and one year respectively. Conclusion Pre-operative co-morbidity (e.g., BMI reduction), and MRSA screening optimization and SAP are areas identified for improvement.

Improving therapeutic efficacy of IL-12 intratumoral gene electrotransfer through novel plasmid design and modified parameters.

The use of immunomodulatory cytokines has been shown effective in regressing a wide range of tumors. However, systemic delivery of recombinant cytokines results in serious, potentially life-threatening, adverse effects. By contrast, nucleic acid transfer via electroporation (EP) is a safe and effective method of delivering plasmid-encoded cytokines to tumors. Intratumoral delivery of IL-12 plasmid DNA by electroporation (IT-pIL12-EP) produced objective response rates in Phase 2 clinical trials in metastatic melanoma. However, only 17.9% of patients receiving IT-pIL12-EP show a complete therapeutic response. Here, we sought to improve the antitumor efficacy of our clinical IT-pIL12-EP plasmid electroporation platform. We evaluated multiple plasmid designs for IL-12 expression. IL-12 expression from a plasmid incorporating a picornavirus-derived co-translational P2A site was the most effective in expressing IL-12p70. In addition, modifying the electroporation parameters improved transfection efficiency and expression of plasmid-derived IL-12p70, as well as its downstream effector IFN-γ in vivo. Finally, using a murine melanoma model that is representative of the intended target patient population, we show that combining modified electroporation conditions with the pIL12-P2A plasmid expression enhances the systemic antitumor response. These improvements to the IT-pIL12-EP platform may improve patient clinical response rates and survival when translated to clinical trials.

Magnetic lateral flow immunoassay test strip development - Considerations for proof of concept evaluation.

Lateral flow immunoassays (LFIA) have grown to become the predominant test device format for the diagnostics and point-of-care industries. The demand for robust and reproducible LFIAs has been facilitated through scale-up production methods using specialized and automated instruments. However, the feasibility of a LFIA device can still be evaluated in a small-scale laboratory setting through controlled manual preparation methods. The advent of super-paramagnetic (SPMP) labels for use in lateral flow has heralded the possibility of highly sensitive and stable LFIAs. The methods used for the preparation of a magnetic LFIA prototype device using a reserved suite of laboratory equipment are described.

The effects of estuarine outflows on coastal marine ecosystems in New South Wales, Australia.

In the state of New South Wales (NSW), Australia, recent legislative action has focused on identifying key threats to the marine estate. We used a systematic literature review to evaluate the knowledge status of the effects of estuarine outflows on coastal marine ecosystems, within the environmental, hydrological, and physicochemical context of NSW waters. Results focussed on studies that measured outcomes for marine biota (n = 56). Trace elements and organochlorines were the most frequently studied contaminant types, with reported biological concentrations often below guideline values but detected at the highest concentrations adjacent to urban sources. Few studies measured the impacts of legacy and emerging contaminants to animal health, or the flow on effects to marine ecosystems in NSW. Our review highlights key biological and geographical data gaps in estuarine outflow research in NSW, particularly of the impact on ecosystems of exported carbon and nutrients to the oligotrophic waters of NSW.

Multidisciplinary neurosurgical rounds incorporating antimicrobial stewardship. Are they of benefit?

Background: In an era of increasing antimicrobial resistance, appropriate antimicrobials are essential to optimise patient outcomes. In 2017, antimicrobial use prevalence (AMU) on the two neurosurgical wards in our tertiary teaching hospital varied from 23% on ward A to 33% on ward B with 67% and 100% 'appropriate' prescriptions, respectively. In July 2018, a weekly antimicrobial stewardship multidisciplinary round led by a senior neurosurgery registrar commenced, attended by the antimicrobial stewardship team (AST). Research question: This report evaluates whether a multi-disciplinary approach on neurosurgical prescribing was beneficial, specifically in reducing AMU. Materials and methods: The following data was collected on AST rounds for 30 weeks in total from August 2018 to July 2019: number of patients on antimicrobials, appropriateness and stewardship actions. A questionnaire was distributed to neurosurgical doctors on two occasions to canvass opinions and attitudes on antimicrobial prescribing. Results: 1716 prescriptions were reviewed (mean 57.2 per week). Of these 321 (18.7%) included antimicrobial prescriptions; 200 on ward A (19.8%), and 121 on ward B (17%), representing a decrease in AMU from 2017. The majority of antimicrobial prescriptions, 271 (84.4%) were deemed appropriate. Stewardship actions were taken in 215 (67%) prescriptions.Fifteen questionnaires were completed by neurosurgical doctors. The majority, 87%, stated the AST round was helpful overall. 93% indicated that informal training on the AST round was a source of education in antibiotic prescribing. Discussion and conclusion: The weekly AST round provided a timely opportunity for multidisciplinary discussion, implementation of antimicrobial stewardship actions and opportunistic antimicrobial stewardship education.

Assessment of the management of carcinomatous meningitis from breast cancer globally: a study by the Breast International Group Brain Metastasis Task Force.

BACKGROUND: Carcinomatous meningitis (CM) is a severe complication of breast cancer. The Breast International Group (BIG) carried out a survey to describe the approach to CM internationally. PATIENTS AND METHODS: A questionnaire on the management of CM was developed by the Brain Metastases Task Force of BIG and distributed to its groups, requesting one answer per group site. RESULTS: A total of 241 sites responded, 119 from Europe, 9 from North America, 39 from Central/South America, 58 from Asia, and 16 in Australia/New Zealand, with 24.5% being general hospitals with oncology units, 44.4% university hospitals, 22.4% oncology centers, and 8.7% private hospitals. About 56.0% of sites reported seeing <5 cases annually with 60.6% reporting no increase in the number of cases of CM recently. Nearly 63.1% of sites investigate for CM when a patient has symptoms or radiological evidence, while 33.2% investigate only for symptoms. For diagnosis, 71.8% of sites required a positive cerebrospinal fluid cytology, while magnetic resonance imaging findings were sufficient in 23.7% of sites. Roughly 97.1% of sites treat CM and 51.9% also refer patients to palliative care. Intrathecal therapy is used in 41.9% of sites, mainly with methotrexate (74.3%). As many as 20 centers have a national registry for patients with breast cancer with central nervous system metastases and of those 5 have one for CM. Most (90.9%) centers would be interested in participating in a registry as well as in studies for CM, the latter preferably (62.1%) breast cancer subtype specific. CONCLUSIONS: This is the first study to map out the approach to CM from breast cancer globally. Although guidelines with level 1 evidence are lacking, there is a high degree of homogeneity in the approach to CM globally and great interest for conducting studies in this area.

Fine-scale spatial and temporal variations in diets of the pipefish Stigmatopora nigra within seagrass patches.

Diets of the pipefish Stigmatopora nigra were analysed to determine if food availability was causing S. nigra to distribute according to habitat edge effects. Gut analysis found little difference in the diets of S. nigra at the edge and interior of seagrass patches, regardless of time of day or season. Fish diets did, however, vary with seagrass density: S. nigra in denser seagrass consumed more harpacticoid copepods and fewer planktonic copepods. The lack of difference in prey eaten by S. nigra at the edge and interior of patches suggests either that food was not determining S. nigra distribution patterns within patches or that differences in fish densities across patches meant that relative fish-prey densities were similar at edge and interior positions. Alternatively, any edge effects in diet might be masked by gradients in seagrass structure.

Tissue perfusion rate determined from the decay of oxygen-15 activity after photon activation in situ.

Rates of cerebral perfusion were obtained from measurements of the disappearance (wash-out) of oxygen-15 after in situ tissue activation with 45-million-volt x-rays. In an anesthetized cat, typical values were 90 milliliters per minute per 100 grams of tissue, with 55 percent wash-out. In a specific radiotherapy patient, the value was 65 milliliters per minute per 100 grams of tissue, with 63 percent wash-out of oxygen-15 through incorporation into tissue water.

Integrating edge effects into studies of habitat fragmentation: a test using meiofauna in seagrass.

Habitat fragmentation is thought to be an important process structuring landscapes in marine and estuarine environments, but effects on fauna are poorly understood, in part because of a focus on patchiness rather than fragmentation. Furthermore, despite concomitant increases in perimeter:area ratios with fragmentation, we have little understanding of how fauna change from patch edges to interiors during fragmentation. Densities of meiofauna were measured at different distances across the edges of four artificial seagrass treatments [continuous, fragmented, procedural control (to control for disturbance by fragmenting then restoring experimental plots), and patchy] 1 day, 1 week and 1 month after fragmentation. Experimental plots were established 1 week prior to fragmentation/disturbance. Samples were numerically dominated by harpacticoid copepods, densities of which were greater at the edge than 0.5 m into patches for continuous, procedural control and patchy treatments; densities were similar between the edge and 0.5 m in fragmented patches. For taxa that demonstrated edge effects, densities exhibited log-linear declines to 0.5 m into a patch with no differences observed between 0.5 m and 1 m into continuous treatments. In patchy treatments densities were similar at the internal and external edges for many taxa. The strong positive edge effect (higher densities at edge than interior) for taxa such as harpacticoid copepods implies some benefit of patchy landscapes. But the lack of edge effects during patch fragmentation itself demonstrates the importance of the mechanisms by which habitats become patchy.

Vulnerability of seagrass blue carbon to microbial attack following exposure to warming and oxygen.

Seagrass meadows store globally-significant quantities of organic 'blue' carbon. These blue carbon stocks are potentially vulnerable to anthropogenic stressors (e.g. coastal development, climate change). Here, we tested the impact of oxygen exposure and warming (major consequences of human disturbance) on rates of microbial carbon break-down in seagrass sediments. Active microbes occurred throughout seagrass sediment profiles, but deep, ancient sediments (~5000 yrs. old) contained only 3% of the abundance of active microbes as young, surface sediments (<2 yrs. old). Metagenomic analysis revealed that microbial community structure and function changed with depth, with a shift from proteobacteria and high levels of genes involved in sulfur cycling in the near surface samples, to a higher proportion of firmicutes and euraracheota and genes involved in methanogenesis at depth. Ancient carbon consisted almost entirely (97%) of carbon considered 'thermally recalcitrant', and therefore presumably inaccessible to microbial attack. Experimental warming had little impact on carbon; however, exposure of ancient sediments to oxygen increased microbial abundance, carbon uptake and sediment carbon turnover (34-38 fold). Overall, this study provides detailed characterization of seagrass blue carbon (chemical stability, age, associated microbes) and suggests that environmental disturbances that expose coastal sediments to oxygen (e.g. dredging) have the capacity to diminish seagrass sediment carbon stocks by facilitating microbial remineralisation.

Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition.

In addition to activating T and B lymphocytes, interleukin 1 (IL-1) induces several hematologic and metabolic changes typical of host responses to infection and injury. We now report a new biological property, namely, the induction of hypotension. Rabbits given a single intravenous injection of recombinant human IL-1-beta (5 micrograms/kg) rapidly developed decreased systemic arterial pressure, which reached the lowest levels after 50-60 min and slowly returned to pre-IL-1 values after 3 h. Associated with the hypotension, systemic vascular resistance and central venous pressure fell, while cardiac output and heart rate increased. These responses were prevented by ibuprofen given 15 min before the IL-1. A bolus injection of IL-1 followed by a 2-h infusion sustained the hypotension and was associated with leukopenia and thrombocytopenia. Ibuprofen given at the mid-point of the infusion reversed the changes in all hemodynamic parameters, but had no effect on the leukopenia or thrombocytopenia. Tumor necrosis factor (TNF) also induced a shock-like state in rabbits. When the dose of IL-1 or TNF was reduced to 1 microgram/kg, no hemodynamic changes were observed; however, the combination of these low doses of both cytokines resulted in a profound shock-like state including histological evidence of severe pulmonary edema and hemorrhage. Pretreatment with ibuprofen prevented the hemodynamic, leukocyte, and platelet changes induced by the low-dose cytokine combination, and ameliorated the pulmonary tissue damage. These results demonstrate that IL-1, like TNF, possesses the ability to induce hemodynamic and hematological changes typical of septic shock, and that the combination of IL-1 and TNF is more potent than either agent alone. These effects seem to require cyclooxygenase products, and suggest that intravenous cyclooxygenase inhibitors may be of therapeutic value in patients with IL-1/TNF-mediated shock.

Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coli.

Tumor necrosis factor (TNF) and IL-1 are thought to mediate many of the pathophysiologic changes of endotoxemia and Gram-negative bacteremia. In these studies, heat-killed Staphylococcus epidermidis were infused into rabbits to determine whether an endotoxin (LPS)-free microorganism also elicits cytokinemia and the physiologic abnormalities seen in Gram-negative bacteremia. S. epidermidis induced complement activation, circulating TNF and IL-1, and hypotension to the same degree as did one-twentieth the number of heat-killed Escherichia coli. Circulating IL-1 beta levels had a greater correlation coefficient (r = 0.81, P less than 0.001) with the degree of hypotension than TNF levels (r = 0.48, P less than 0.02). Leukopenia, thrombocytopenia, diffuse pulmonary capillary aggregation of neutrophils, and hepatic necrosis with neutrophil infiltration were observed to the same extent after either S. epidermidis or E. coli infusion. However, S. epidermidis infusion did not induce significant (less than 60 pg/ml) endotoxemia, whereas E. coli infusion resulted in high (11,000 pg/ml) serum endotoxin levels. S. epidermidis, E. coli, LPS, or S. epidermidis-derived lipoteichoic acid (LTA) induced TNF and IL-1 from blood mononuclear cells in vitro. E. coli organisms and LPS were at least 100-fold more potent than S. epidermidis or LTA. Thus, a shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli. These data provide further evidence that host factors such as IL-1 and TNF are common mediators of the septic shock syndrome regardless of the organism.

Carbon sequestration by Australian tidal marshes.

Australia's tidal marshes have suffered significant losses but their recently recognised importance in CO2 sequestration is creating opportunities for their protection and restoration. We compiled all available data on soil organic carbon (OC) storage in Australia's tidal marshes (323 cores). OC stocks in the surface 1 m averaged 165.41 (SE 6.96) Mg OC ha-1 (range 14-963 Mg OC ha-1). The mean OC accumulation rate was 0.55 ± 0.02 Mg OC ha-1 yr-1. Geomorphology was the most important predictor of OC stocks, with fluvial sites having twice the stock of OC as seaward sites. Australia's 1.4 million hectares of tidal marshes contain an estimated 212 million tonnes of OC in the surface 1 m, with a potential CO2-equivalent value of $USD7.19 billion. Annual sequestration is 0.75 Tg OC yr-1, with a CO2-equivalent value of $USD28.02 million per annum. This study provides the most comprehensive estimates of tidal marsh blue carbon in Australia, and illustrates their importance in climate change mitigation and adaptation, acting as CO2 sinks and buffering the impacts of rising sea level. We outline potential further development of carbon offset schemes to restore the sequestration capacity and other ecosystem services provided by Australia tidal marshes.

Collecting duct carcinoma of the kidney: a case report with variable immunohistochemistry.

BACKGROUND: Collecting duct carcinoma of the kidney is a rare tumour with distinctive clinical and histopathological features. Management of this malignancy remains a challenge because of advanced stage at presentation and aggressive clinical course. AIMS: We describe a case of Collecting Duct Carcinoma with variable immunohistochemistry and review the pathology and management. RESULTS: Our patient died shortly after commencing systemic chemotherapy. CONCLUSION: Advances in immunohistochemistry have aided in diagnosis of this tumour. Early detection and nephrectomy offer the best chance of cure. Newer chemotherapeutic regimens may improve survival in more advanced disease.

Measurement of the Postgraduate Educational Environment of Junior Doctors Training in Medicine at an Irish University Teaching Hospital.

BACKGROUND: A positive learning environment in which postgraduate doctors are supported, supervised and nurtured, is likely to lead to enhanced professional satisfaction and improved patient care. AIMS: The aims of the current study were to use the PHEEM inventory to determine the aspects of their current learning environment which junior doctors rate most and least positively. METHODS: The PHEEM questionnaire was administered to all junior doctors working in medical subspecialties at Galway University Hospitals in Ireland. A response rate of 60 % (n = 61) was obtained. RESULTS: The mean total PHEEM score was 82.88 ± 18.99, corresponding to an educational environment with more positive than negative aspects but with room for improvement. The mean total PHEEM score (±standard deviation) of registrars (89.65 ± 20.92) exceeded that of Interns (84.00 ± 15.26) and SHOs (75.12 ± 18.09). Over half (55 %) of the individual items were rated by the junior doctors as more positive than negative. Nineteen items (48 %) pointed to areas in need of enhancement, whilst 3 items were rated as satisfactory or better. Analysis of qualitative data confirmed that deficiencies exist in various aspects of the educational climate, including protected educational time, access to suitable learning opportunities, the nature of tasks performed by junior doctors, the hospital bleep protocol, implementation of the European Working Time Directive, feedback and career guidance. CONCLUSIONS: Recommendations stemming from this study should lead to improvements in the quality of the educational environment of junior doctors and may stimulate similar evaluations in other teaching hospitals.

Thermal compression and molding of atherosclerotic vascular tissue with use of radiofrequency energy: implications for radiofrequency balloon angioplasty.

The combined delivery of pressure and thermal energy may effectively remodel intraluminal atherosclerotic plaque and fuse intimal tears. To test these hypotheses with use of a non-laser thermal energy source, radiofrequency energy was delivered to postmortem human atherosclerotic vessels from a metal "hot-tip" catheter, block-mounted bipolar electrodes and from a prototype radiofrequency balloon catheter. Sixty-two radiofrequency doses delivered from a metal electrode tip produced dose-dependent ablation of atherosclerotic plaque, ranging from clean and shallow craters with histologic evidence of thermal compression at doses less than 40 J to tissue charring and vaporization at higher (greater than 80 J) doses. Lesion dimensions ranged between 3.14 and 3.79 mm in diameter and 0.20 and 0.47 mm in depth. Tissue perforation was not observed. To test the potential for radiofrequency fusion of intimal tears, 5 atm of pressure and 200 J radiofrequency energy were delivered from block-mounted bipolar electrodes to 48 segments of human atherosclerotic aorta, which had been manually separated into intima-media and media-adventitial layers. Significantly stronger tissue fusion resulted (28.5 +/- 3.3 g) with radiofrequency compared with that with pressure alone (4.8 +/- 0.26 g; p less than 0.0001). A prototype radiofrequency balloon catheter was used to deliver 3 atm of balloon pressure with or without 200 J radiofrequency energy to 20 postmortem human atherosclerotic arterial segments. In 10 of 10 radiofrequency-treated vessels, thermal "molding" of both normal and atherosclerotic vessel wall segments resulted with increased luminal diameter and histologic evidence of medial myocyte damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of Eurocollins and University of Wisconsin solution in single flush preservation of the ischemic reperfused lung: an in vivo rabbit model.

The standard preservation technique in lung transplantation is cold single pulmonary artery flush (PAF) with Eurocollins solution (ECS). We compared ECS with University of Wisconsin (UW) solution, with and without added indomethacin, in single PAF preservation in an in vivo rabbit model of warm ischemia-reperfusion lung injury. Six groups of four New Zealand white rabbits each underwent isolation and hilar stripping of the left lung. In the four experimental groups, the left lung was flushed with (15 ml/kg) of cold ECS or UW solution, with or without added indomethacin, before warm ischemia for 120 minutes and before reperfusion for 60 minutes. The remaining two groups were the nonischemic and the ischemic "no flush" controls. Transcapillary flux of 99mTechnitium-labeled albumin and electron microscopy were used to demonstrate lung injury. Pulmonary vascular resistance (PVR) and thromboxane B2 (TXB2) concentrations were measured. There was a significant rise in PVR after ischemia/reperfusion in the ischemic control group (54.7 +/- 13.9 to 117.8 +/- 20.7 mm Hg/L.min-1, P < 0.05). The net rise in PVR after ischemia-reperfusion was significantly smaller in the two groups in which indomethacin was added (16.8 +/- 17.5 and 4.5 +/- 10.6 mm Hg/L.min-1 for UW and ECS, respectively) compared with the ischemic control (63.1 +/- 24.6 mm Hg/L.min-1, P < 0.05). Post-reperfusion TXB2 levels tended to be lower in the nonischemic control group and in the indomethacin-flush groups. We conclude that the increase in PVR produced by unilateral ischemia-reperfusion lung injury in this model was improved by single PAF perfusion. There was no significant difference between UW solution and ECS in this regard. The addition of indomethacin to the flush solution was associated with lower PVRs as well as morphologic improvement by electron microscopy. These findings may indicate a prominent role for the provision of PG synthesis inhibition during preservation for lung transplantation.

The effect of complete tenotomy on blood flow to the anterior segment of the canine eye.

The relative importance of the anterior ciliary arteries to blood flow to the anterior segment and the quadrant distribution of blood to the iris, ciliary body, and ciliary processes were determined in canines with the use of 15 +/- 3 mum 103Ru microspheres with the reference blood flow method. Recti muscles were isolated in both eyes. Then with one eye serving as a sham-operated control, anterior ciliary artery blood flow was disrupted by recti tenotomy immediately prior to microsphere injection. Tenotomy resulted in a significant decrease in blood flow to the anterior segment (0.14 +/- 0.03 ml/min/gm vs. 0.26 +/- 0.05 in the untenotomized control) and to the unit iris, ciliary body and ciliary processes (I, CB, CP) (0.92 +/- 0.16 ml/min/gm vs. 1.44 +/- 0.22 in the untenotomized control). Blood flow values for the anterior segment and the unit I, CB, CP in the tenotomized eye were 50% to 60% of those of the control eyes, indicating that the majority of blood flow to the canine anterior segment is not disrupted by complete tenotomy. In the control eye, blood flow values for the medial quadrant of the unit I, CB, CP were significantly higher (p < 0.05) than those of the inferior or superior quadrants. Blood flow values for all quadrants in tenotomized eyes were 55% to 70% of those for control eyes. Therefore the anterior ciliary arteries do not contribute the majority of blood flow to the canine anterior segment.

Inhibition of thrombosis by a selective fibrinogen receptor antagonist without effect on bleeding time.

Membrane glycoprotein alpha IIb beta 3 on platelets plays a pivotal role in hemostasis by mediating RGD-(arginine-glycine-aspartic acid)-dependent platelet adhesion and aggregation. Antagonists of alpha IIb beta 3 ligand binding function, such as antibodies, snake venom peptides, or synthetic RGD-containing peptides can completely inhibit platelet aggregation in vitro and cause significant prolongation of bleeding times when injected into experimental animals. The in vitro and in vivo properties of an alpha IIb beta 3 specific RGD-containing peptide 2G (G(Pen)GHRGDLRCA) were compared to two non-specific RGD-containing peptides 1N (G(Pen)GRGDTPCA) and 2H (GRGDSPDG). All three peptides have similar IC50 values in human platelet aggregation (14-22 microM) and ELISA-based alpha IIb beta 3 receptor assays (0.2-0.3 microM) but show different inhibitory activity (IC50 values) in the alpha v beta 5 (2G = 10 microM; 1N = 0.06 microM; 2H = 0.05 microM) and alpha 5 beta 1 receptor assays (2G = 8.3 microM; 1N = 0.06 microM; 2H = 0.04). The alpha IIb beta 3 specific peptide 2G had no effect on monolayers of human saphenous vein endothelial cells while 1N and 2H caused many cells to detach and contract. Peptides 2G and 1N inhibited ADP-stimulated ex vivo platelet aggregation in dogs in a dose dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)