55 research outputs found

    Aberrant origin of left vertebral artery: a rare case

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    The Vertebral Artery (VA) is classically described as originating as the first branch of the ipsilateral subclavian artery. The VA origin is variable and has been identified at the aortic arch, Common Carotid Artery (CCA), and Internal Carotid Artery. The VA arising from the carotid artery is an extremely uncommon variant. Left VA origin from the left CCA has been reported only thrice. These rare anomalous origins of the VA usually are asymptomatic. We describe symptomatic aberrant origin of left vertebral artery from left common carotid artery, a rare case

    Pharmacokinetic investigation of dose proportionality with a 24-hour controlled-release formulation of hydromorphone

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    BACKGROUND: The purpose of this study was investigate the dose proportionality of a novel, once-daily, controlled-release formulation of hydromorphone that utilizes the OROS(® )Push-Pull™ osmotic pump technology. METHODS: In an open-label, four-way, crossover study, 32 healthy volunteers were randomized to receive a single dose of OROS(® )hydromorphone 8, 16, 32, and 64 mg, with a 7-day washout period between treatments. Opioid antagonism was provided by three or four doses of naltrexone 50 mg, given at 12-hour intervals pre- and post-OROS(® )hydromorphone dosing. Plasma samples for pharmacokinetic analysis were collected pre-dose and at regular intervals up to 48 hours post-dose (72 hours for the 64-mg dose), and were assayed for hydromorphone concentration to determine peak plasma concentration (C(max)), time at which peak plasma concentration was observed (T(max)), terminal half-life (t(1/2)), and area under the concentration-time curve for zero to time t (AUC(0-t)) and zero to infinity (AUC(0–∞)). An analysis of variance (ANOVA) model on untransformed and dose-normalized data for AUC(0-t), AUC(0–∞), and C(max )was used to establish dose linearity and proportionality. RESULTS: The study was completed by 31 of 32 subjects. Median T(max )(12.0–16.0 hours) and mean t(1/2 )(10.6–11.0 hours) were found to be independent of dose. Regression analyses of C(max), AUC(0–48), and AUC(0–∞ )by dose indicated that the relationship was linear (slope, P ≤ 0.05) and that the intercept did not differ significantly from zero (P > 0.05). Similar analyses with dose-normalized parameters also indicated that the slope did not differ significantly from zero (P > 0.05). CONCLUSION: The pharmacokinetics of OROS(® )hydromorphone are linear and dose proportional for the 8, 16, 32, and 64 mg doses. TRIAL REGISTRATION: Clinical Trials.gov NCT0039895

    Cyclic plastic deformation behaviour of PHT piping materials - an experimental investigation

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    The work presents the cyclic plastic deformation behaviour of two varieties of primary heat transport piping materials to understand the hardening/softening behaviour, load history memory, strain range effect, mean stress effect and ratcheting behaviour. Microstructural changes during cyclic deformation manifest in cyclic expansion of yield that could be used to explain the hardening/softening behaviour. Both the materials memories the prior history, however, the effect disappears after some time. Both the steels exhibit non-Masing behaviour due to inhomogeneous substructural changes. Non-Masing behaviour could be explained through cyclic expansion of yield. Engineering stress controlled ratcheting experiments were noted to be inadequate and under predict the ratcheting fatigue life. Importance of true stress controlled ratcheting experiments were discussed

    Multiaxial fatigue studies on carbon steel piping material of Indian PHWRs

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    The tests studies and analyses have been carried out in the area of “Multiaxial Fatigue” with an objective to improve the damage assessment methodologies and design rules. Nearly 50 numbers of fatigue tests were conducted on solid and tubular specimens of SA333Gr.6 material under pure axial, pure shear and combined axial-torsion in-phase/ out-of-phase loading combinations. A software has been developed for the evaluation of multiaxial fatigue damage for the analyses of tests data using different invariant fatigue models such as ASME Sec.III code procedures, von-Mises etc. The fatigue crack initiation life was predicted using the best fit axial fatigue life curve (without use of safety factors). These tests and their analyses have helped in understanding the fatigue failure behavior of piping material under complex cyclic loadings where the principal directions rotate during a loading cycle. The crack initiation angles have also been measured by analyzing the image of the tested specimens. The measured crack angles will help in validation of the critical plane based models

    Pharmacokinetic profile of a 24-hour controlled-release OROS(® )formulation of hydromorphone in the presence and absence of food

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    BACKGROUND: The objective of this study was to compare the pharmacokinetic profile of a novel, once-daily, controlled-release formulation of hydromorphone (OROS(® )hydromorphone) under fasting conditions with that immediately after a high-fat breakfast in healthy volunteers. The effect of the opioid antagonist naltrexone on fasting hydromorphone pharmacokinetics also was evaluated. METHODS: In an open-label, three-way, crossover study, 30 healthy volunteers were randomized to receive a single dose of 16 mg OROS(® )hydromorphone under fasting conditions, 16 mg OROS(® )hydromorphone under fed conditions, or 16 mg OROS(® )hydromorphone under fasting conditions with a naltrexone 50-mg block. Plasma samples taken pre-dose and at regular intervals up to 48 hours post-dose were assayed for hydromorphone concentrations. Analysis of variance was performed on log-transformed data; for mean ratios of 0.8 to 1.2 (20%), differences were considered minimal. Bioequivalence was reached if 90% confidence intervals (CI) of treatment mean ratios were between 80% and 125%. RESULTS: The mean geometric ratios of the fed and fasting treatment groups for maximum plasma concentration (C(max)) and area under the concentration-time curve (AUC(0-t); AUC(0-∞)) were within 20%. Confidence intervals were within 80% to 125% for AUC(0-t )and AUC(0-∞ )but were slightly higher for C(max )(105.9% and 133.3%, respectively). With naltrexone block, the hydromorphone C(max )increased by 39% and the terminal half-life decreased by 4.5 hours. There was no significant change in T(max), AUC(0-t )or AUC(0-∞). CONCLUSION: Standard bioavailability measures show minimal effect of food on the bioavailability of hydromorphone from OROS(® )hydromorphone. Naltrexone co-administration results in a slight increase in the rate of absorption but not the extent of absorption. TRIAL REGISTRATION: Clinical Trials.gov NCT0039929

    Novel Combination BMP7 and HGF Gene Therapy Instigates Selective Myofibroblast Apoptosis and Reduces Corneal Haze In Vivo.

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    PurposeWe tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models.MethodsEighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n = 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n = 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n = 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic studies. Gene therapy effects on corneal fibrosis and ocular safety were evaluated by slit-lamp microscope, stereo microscopes, quantitative real-time PCR, immunofluorescence, TUNEL, modified MacDonald-Shadduck scoring system, and Draize tests.ResultsPEI2-GNP-mediated BMP7+HGF gene therapy significantly decreased corneal fibrosis in live rabbits in vivo (Fantes scale was 0.6 in BMP7+HGF-treated eyes compared to 3.3 in -therapy group; P 104 gene copies per microgram DNA of BMP7 and HGF genes. The recombinant HGF rendered apoptosis in corneal myofibroblasts but not in fibroblasts. Localized topical BMP7+HGF therapy showed no ocular toxicity.ConclusionsLocalized topical BMP7+HGF gene therapy treats corneal fibrosis and restores transparency in vivo mitigating excessive healing and rendering selective apoptosis in myofibroblasts

    Marine Tar Residues: a Review

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    Abstract Marine tar residues originate from natural and anthropogenic oil releases into the ocean environment and are formed after liquid petroleum is transformed by weathering, sedimentation, and other processes. Tar balls, tar mats, and tar patties are common examples of marine tar residues and can range in size from millimeters in diameter (tar balls) to several meters in length and width (tar mats). These residues can remain in the ocean envi-ronment indefinitely, decomposing or becoming buried in the sea floor. However, in many cases, they are transported ashore via currents and waves where they pose a concern to coastal recreation activities, the seafood industry and may have negative effects on wildlife. This review summarizes the current state of knowledge on marine tar residue formation, transport, degradation, and distribution. Methods of detection and removal of marine tar residues and their possible ecological effects are discussed, in addition to topics of marine tar research that warrant further investigation. Emphasis is placed on ben-thic tar residues, with a focus on the remnants of the Deepwater Horizon oil spill in particular, which are still affecting the northern Gulf of Mexico shores years after the leaking submarine well was capped

    Proceedings of PVP2005 2005 ASME Pressure Vessels and Piping Division Conference Experimental Investigations on Effects of Simulated Seismic Loading on LBB Assessment of High Energy Piping

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    ABSTRACT The current Leak Before Break (LBB) assessment is based primarily on the monotonic fracture tearing instability. In it the maximum design accident load is compared with the fracturetearing resistance load. The effect of cyclic loading has generally not been considered in the fracture assessment of nuclear power plant piping. It is a well-known fact that the reversible cyclic loading decreases the fracture resistance of the material, which leads to increased crack growth. Indian nuclear power reactors consider Operational-Basis-Earthquake (OBE) and Safe-Shutdown-Earthquake (SSE) event in the design of various structures, systems and components. Keeping this in view a series of cyclic tearing test have been conducted on straight pipes, made of ASTM SA333 Gr.6 carbon steel. This is the material of primary heat transport (PHT) piping material of Indian Pressurised Heavy Water Reactor (PHWR). In this series 13 tests have been carried out on circumferentially through wall cracked seamless and circumferential seam welded straight pipes under reversible cyclic bending loading. All the tests have been conducted under quasi-static i.e. slow loading rates and the dynamic effect is not considered. The cyclic test results have been compared with the corresponding monotonic pipe fracture test results. These test results and its comparison with corresponding monotonic tearing clearly illustrates the need of addressing the reduction in apparent fracture toughness of material under reversible cyclic loading and safe number of load cycles in the LBB assessment
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