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  • 1
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: NNC 55-0396 is a structural analog of mibefradil (Ro 40-5967) that inhibits both T-type and high-voltage-activated (HVA) Ca2+ channels with a higher selectivity for T-type Ca2+ channels. The inhibitory effect of mibefradil on HVA Ca2+ channels can be attributed to a hydrolyzed metabolite of the drug: the methoxy acetate side chain of mibefradil is removed by intracellular enzymes, thus it forms (1 S,2S)-2-(2-(N-[(3-benzoimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphtyl hydroxy dihydrochloride (dm-mibefradil), which causes potent inhibition of HVA Ca2+ currents. By replacing the methoxy acetate chain of mibefradil with cyclopropanecarboxylate, a more stable analog was developed (NNC 55-0396). The acute IC50 of NNC 55-0396 to block recombinant Cav3.1 T-type channels expressed in HEK293 cells is ∼7 μM, whereas 100 μM NNC 55-0396 has no detectable effect on high voltage-activated currents in INS-1 cells. Block of T-type Ca2+ current was partially reduced by membrane hyperpolarization and was enhanced at high stimulus frequency. Washing NNC 55-0396 out of the recording chamber did not reverse the T-type Ca2+ current activity, suggesting that the compound dissolves in or passes through the plasma membrane to exert its effect; however, intracellular perfusion of the compound did not block T-type Ca2+ currents, arguing against a cytoplasmic route of action. We conclude that NNC 55-0396, by virtue of its modified structure, does not produce the metabolite that causes inhibition of L-type Ca2+ channel channels, thus rendering it more selective to T-type Ca2+ channels.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1540-8191
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract Background: Between 1989 and 1992 100 consecutive patients aged 80 or older underwent isolated coronary artery bypass grafting (CABG) in our institution. Eighty-six percent had angina grade III or IV symptoms. Methods: Emergency surgery was required in 31, urgent surgery in 30, and elective surgery in 39 patients. The average left ventricular ejection fractions (LVEF) in these groups were 36%, 43%, and 45% respectively. The operative mortality was 8% for these octogenarians compared to 2% in the younger cohort (p = 0.002). It was zero in elective cases and 13% (8/61) in urgent and emergency cases. It was increased by preoperative admission to coronary care unit (CCU) (p = 0.02), urgency of operation (p = 0.02), the use of intra-aortic balloon pump (IABP) (p = 0.0002), preoperative renal dysfunction (p 〈 0.03), and ± 3 grafts (p 〈 0.04). The late mortality was increased by LVEF ± 20% (p = 0.03) and operation from CCU (p 〈 0.05). On multivariate stepwise logistic regression analysis, the use of IABP (p 〈 0.0003) and preoperative renal dysfunction (p 〈 0.02) were independent predictors of operative mortality. LVEF ± 20% was the only independent predictor (p 〈 0.02) of late mortality. Results: Actuarial survival was noted to be 87%, 80%, 77%, and 73%, respectively, at 1, 2, 3, and 4 years, with two cardiac-related late deaths. Long-term follow-up revealed that 97% of patients had no or minimal anginal symptoms. Conclusions: Due to increasing use of nonsurgical options, the profile of elderly referred for CABG currently involves gravely ill patients with comorbidities. CABG under elective conditions, before deterioration of left ventricular function, can achieve normal life expectancy and good symptomatic relief in octogenarians.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Ground water 36 (1998), S. 0 
    ISSN: 1745-6584
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Geosciences
    Notes: The objective of this study is to assess the effects of variable density ground water flow on capture zones for pumping wells on islands and the ability of numerical and analytical methods to account for these effects. Mathematical modeling is used to simulate variable density ground water flow for an island aquifer system. Coupled fresh water-salt water transport equations derived using sharp interface theory are solved using the finite-element method. Reverse particle tracking is used to compute the capture zone for a well. Sensitivity studies are completed using a quasi-three-dimensional model to identify the influence of variable density flow on the computed zone of contribution to a pumping well. Quantitative results indicate that the size and shape of the capture zone are sensitive to the natural geometry of the fresh water lens and the effects of fresh water-salt water upconing. This is especially true for pumping wells located close to the coastline. For the conditions considered in this study, accounting for variable density ground water flow resulted in capture zones approximately 21% larger than those predicted assuming a uniform fresh water aquifer thickness and constant hydraulic gradient. This effect of variable density flow on the predicted capture zones diminished away from the coastline. The study results serve to caution model users of the limitations inherent in using analytical methods to compute capture zone delineations for island aquifers.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 6 (1980), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Contact dermatitis 53 (2005), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Contact dermatitis 48 (2003), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 585 (1990), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of dermatology 29 (1990), S. 0 
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Ground water 36 (1998), S. 0 
    ISSN: 1745-6584
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Geosciences
    Notes: Inferred increases in 1981 to 1997 pumping records suggest that by the year 2020, the majority of Nantucket Island municipal wellfields will be pumping near or at capacity. A sharp-interface model is used in this study to assess the impact of projected increases in pumping from the Wyers Valley and proposed State Forest municipal wellfields on Nantucket Island, Massachusetts. The model was first calibrated as part of a sensitivity study using a nine-year record of monthly water level data from a monitoring well network and salinity data from a deep borehole completed near the island's center. Best-fit values of hydraulic conductivity and specific storage obtained in the sensitivity analysis are in good agreement with those measured by single and multiple well aquifer tests across the island.The calibrated model was used to assess hydrologic conditions across the island between 1997 and 2020 due to projected increases in municipal wellfield pumping. Transient simulation results suggest that salt water will invade the well screen of the deep (32 m) Wyers Valley production well by the year 2014. Further, the width of the fresh water/salt water mixing zone under the municipal wellfields will triple by 2020 due to increasing seasonal fluctuations in pumping required to accommodate summer tourism. Using published estimates of 2020 municipal wellfield pumping, wellhead delineation zones were also calculated using a variety of assumptions regarding the island's fresh water lens geometry (uniform, variable thickness with no upconing; variable thickness with upconing). Results indicate that the calculated delineation zones are most sensitive to island geometry and, to a lesser extent, to the fresh water lens thickness.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Sedimentology 2 (1963), S. 0 
    ISSN: 1365-3091
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences
    Type of Medium: Electronic Resource
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