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1.
J Microsc ; 250(2): 122-129, 2013 May.
Article in English | MEDLINE | ID: mdl-23489021

ABSTRACT

Tantalum carbide samples have been subjected to high-temperature testing at ∼2300°C using an oxyacetylene torch to evaluate their potential for ultra-high temperature applications. While large samples cracked during the rapid heating, indicating their inability to withstand thermal shock, small samples survived the severe test conditions. The oxidation products formed were characterized and found to comprise different phases of Ta2 O5 . The ultra-high temperature experienced by the samples resulted in the formation of many interesting microstructures, including the formation of submicron sized grains, which has not been reported previously in the literature, as well as the expected evidence of melting.

2.
J Phys Chem A ; 115(41): 11144-55, 2011 Oct 20.
Article in English | MEDLINE | ID: mdl-21506545

ABSTRACT

We present a full molecular description of fragmentation reactions of protonated glycine (G) and its protonated dimer, H(+)G(2), by studying their collision-induced dissociation (CID) with Xe using a guided ion beam tandem mass spectrometer (GIBMS). In contrast to previous results, it is clear that H(+)G decomposes by loss of CO followed by H(2)O. Analysis of the energy-dependent CID cross sections provides the 0 K barriers for these processes as well as for the binding energy of the dimer after accounting for unimolecular decay rates, internal energy of reactant ions, and multiple ion-molecule collisions. Relaxed potential energy surface scans performed at the B3LYP/6-31G(d) level are used to map the reaction surfaces and identify the transition states (TSs) and intermediate reaction species for the reactions, structures that are further optimized at the B3LYP/6-311+G(d,p) level. Single-point energies of the key optimized structures are calculated at B3LYP and MP2(full) levels using a 6-311+G(2d,2p) basis set. These theoretical results are compared to extensive calculations in the literature and to the experimental energies. The combination of both experimental work and quantum chemical calculations allows for a complete characterization of the elementary steps of H(+)G and H(+)G(2) decomposition. These results make it clear that H(+)G is the simplest model for the ''mobile proton'', a key concept in understanding the fragmentation of protonated proteins.


Subject(s)
Glycine/chemistry , Protons , Thermodynamics , Dimerization , Quantum Theory
3.
J Phys Chem A ; 113(19): 5519-30, 2009 May 14.
Article in English | MEDLINE | ID: mdl-19368405

ABSTRACT

Gas-phase structures of cationized asparagine (Asn) including complexes with Li(+), Na(+), K(+), Rb(+), Cs(+), and Ba(2+), as well as protonated Asn, are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy utilizing light generated by a free electron laser. Experimental spectra for the alkali metal cation complexes exhibit systematic trends, whereas spectra for Ba(2+)(Asn) and H(+)(Asn) are more distinct. To identify the structures formed experimentally, measured IRMPD spectra are compared to spectra calculated at a B3LYP/6-311+G(d,p) level with several effective core potentials and basis sets evaluated for the heavy metal systems. The dominant conformation ascertained for complexes with the smaller metal cations, Li(+)(Asn) and Na(+)(Asn), is a charge-solvated, tridentate [N,CO,CO] structure that binds the metal cation with the amine group of the amino acid backbone and to the carbonyl oxygen atoms of the backbone and amino acid side chain. For the larger alkali metal cation complexes, K(+)(Asn), Rb(+)(Asn), and Cs(+)(Asn), an additional charge-solvated, tridentate [COOH,CO] structure that binds the metal cation with the two oxygen atoms of the backbone carboxylic acid group and the carbonyl oxygen atom of the Asn side chain may also be present. The Ba(2+)(Asn) spectrum is characteristic of a single charge-solvated [N,CO,CO] conformation, in contrast to Gly, Trp, Arg, Gln, Pro, Ser, Val, and Glu, which all take on a zwitterionic structure when complexed to Ba(2+). In no case do the cationized Asn complexes show definitive evidence of forming a zwitterionic structure in the complexes studied here. For H(+)(Asn), a mixture of two [N,CO] structures, which differ only in the orientation the side chain and are calculated to be nearly identical in energy, explains the experimental spectrum well.


Subject(s)
Asparagine/chemistry , Gases/chemistry , Metals/chemistry , Molecular Conformation , Organometallic Compounds/chemistry , Photons , Models, Molecular , Particle Size , Sensitivity and Specificity , Spectrophotometry, Infrared , Thermodynamics
4.
J Phys Chem A ; 112(41): 10156-67, 2008 Oct 16.
Article in English | MEDLINE | ID: mdl-18798601

ABSTRACT

The binding of Na (+) to arabinose (Ara), xylose (Xyl), glucose (Glc), and galactose (Gal) is examined in detail by studying the collision-induced dissociation (CID) of the four sodiated monosaccharide complexes with Xe using a guided ion beam tandem mass spectrometer (GIBMS). Analysis of the energy-dependent CID cross-sections provides 0 K sodium cation affinities for experimental complexes after accounting for unimolecular decay rates, internal energy of reactant ions, and multiple ion-neutral collisions. Quantum chemical calculations for a number of geometric conformations of each Na (+)(L) complex with a comprehensive analysis of the alpha and beta anomeric forms are determined at the B3LYP/6-311+G(d,p) level with single-point energies calculated at MP2(full), B3LYP, and B3P86 levels using a 6-311+G(2d,2p) basis set. This coordinated examination of both experimental work and quantum chemical calculations allows for determination of the bond energy for both the alpha and beta forms of each monosaccharide studied here. An understanding of the energetic contributions of individual structural characteristics as well as the energetic trends in binding among the monosaccharides is developed. Structural characteristics that affect the energetics of binding involve multidentate sodium cation coordination, ring sterics, and hydrogen bonding schemes. The overall trend in sodium binding affinities for the eight ligands follows beta-Ara < alpha-Ara < beta-Xyl < beta-Glc < alpha-Glc < alpha;-Xyl < alpha-Gal < beta-Gal.


Subject(s)
Computer Simulation , Models, Chemical , Monosaccharides/chemistry , Quantum Theory , Sodium/chemistry , Arabinose/chemistry , Cations/chemistry , Galactose/chemistry , Glucose/chemistry , Ligands , Xylose/chemistry
5.
J Phys Chem B ; 112(38): 12056-65, 2008 Sep 25.
Article in English | MEDLINE | ID: mdl-18729510

ABSTRACT

The binding of K(+) to aspartic acid (Asp), glutamic acid (Glu), asparagine (Asn), and glutamine (Gln) is examined in detail by studying the collision-induced dissociation (CID) of the four potassium cation-bound amino acid complexes with Xe using a guided ion beam tandem mass spectrometer (GIBMS). Formed by electrospray ionization, these complexes have energy-dependent CID cross sections that are analyzed to provide 0 K bond energies after accounting for unimolecular decay rates, internal energy of reactant ions, and multiple ion-molecule collisions. Quantum chemical calculations for a number of geometric conformations of each K(+)(L) complex are determined at the B3LYP/6-311+G(d,p) level with single-point energies calculated at B3LYP, B3P86, and MP2(full) levels using a 6-311+G(2d,2p) basis set. Theoretical bond dissociation energies are in good agreement with the experimental values. This coordinated examination of both experimental work and quantum chemical calculations allows for a comprehensive understanding of the molecular interactions of K(+) with the Asx and Glx amino acids. K(+) binding affinities for the amide complexes are systematically stronger than those for the acid complexes by 9+/-1 kJ/mol, which is attributed to an inductive effect of the OH group in the carboxylic acid side chain. Additionally, the K(+) binding affinity for the longer-chain amino acids (Glx) is enhanced by 5+/-1 kJ/mol compared to the shorter-chain Asx because steric effects are reduced. Further, a detailed comparison between experimental and theoretical results reveals interesting differences in the binding of K(+) and Na(+) to these amino acids.


Subject(s)
Amides/chemistry , Amino Acids, Acidic/chemistry , Potassium/chemistry , Cations/chemistry , Models, Molecular , Tandem Mass Spectrometry , Thermodynamics
6.
J Am Chem Soc ; 130(31): 10227-32, 2008 Aug 06.
Article in English | MEDLINE | ID: mdl-18613670

ABSTRACT

The deamidation of asparagine (Asn) residues is the most common type of spontaneous post-translational protein modification and plays a vital role in inflammation, protein transformation, apoptosis, aging, and a number of degenerative diseases. Here we present a full molecular description of asparagine deamidation in the Na(+)(Asn) complex by studying its collision-induced dissociation (CID) with Xe using a guided ion beam tandem mass spectrometer (GIBMS). Advanced methods for analysis of the energy-dependent CID cross section, considering both competing and sequential processes, provide the 0 K barrier for deamidation after accounting for unimolecular decay rates, internal energy of reactant ions, and multiple ion-neutral collisions. Relaxed potential energy surface scans performed at the B3LYP/6-31G(d) level identify the transition state (TS) and intermediate reaction species for Na(+)(Asn) deamidation, structures that are further optimized at the B3LYP/6-311+G(d,p) level. Single-point energies of the key optimized structures are calculated at MP2(full), B3LYP, and B3P86 levels using a 6-311+G(2d,2p) basis set. This coordinated application of both experimental work and quantum chemical calculations allows for a complete characterization of the elementary steps of this reaction and identification of the rate-limiting elementary step of Asn deamidation. The latter is measured to require 1.61 +/- 0.08 eV and involves formation of a cyclic succinic ring structure.


Subject(s)
Asparagine/metabolism , Sodium/metabolism , Thermodynamics , Amides/metabolism , Ammonia , Aspartic Acid , Peptides , Protein Processing, Post-Translational , Succinic Anhydrides , Tandem Mass Spectrometry
7.
J Phys Chem A ; 112(15): 3319-27, 2008 Apr 17.
Article in English | MEDLINE | ID: mdl-18355061

ABSTRACT

The binding of Na+ to aspartic acid (Asp), glutamic acid (Glu), asparagine (Asn), and glutamine (Gln) is examined in detail by studying the collision-induced dissociation (CID) of the four sodiated amino acid complexes with Xe using a guided ion beam tandem mass spectrometer (GIBMS). Analysis of the energy-dependent CID cross sections provides 0 K sodium cation affinities for the complexes after accounting for unimolecular decay rates, internal energy of the reactant ions, and multiple ion-molecule collisions. Quantum chemical calculations for a number of geometric conformations of each Na+(L) complex are determined at the B3LYP/6-311+G(d,p) level with single-point energies calculated at MP2(full), B3LYP, and B3P86 levels using a 6-311+G(2d,2p) basis set. This coordinated examination of both experimental work and quantum chemical calculations allows the energetic contributions of individual functionalities as well as steric influences of relative chain lengths to be thoroughly explored. Na+ binding affinities for the amide complexes are systematically stronger than those for the acid complexes by 14 +/- 1 kJ/mol, which is attributed to an inductive effect of the OH group in the carboxylic acid side chain. Additionally, the Na+ binding affinity for the longer-chain amino acids (Glx) is enhanced by 4 +/- 1 kJ/mol compared to the shorter-chain Asx because steric effects are reduced.


Subject(s)
Amides/chemistry , Amino Acids, Acidic/chemistry , Models, Chemical , Sodium/chemistry , Cations/chemistry , Kinetics , Rotation , Thermodynamics
8.
J Phys Chem A ; 112(15): 3328-38, 2008 Apr 17.
Article in English | MEDLINE | ID: mdl-18355065

ABSTRACT

The deamidation and dehydration products of Na+(L), where L = asparagine (Asn), glutamine (Gln), aspartic acid (Asp), and glutamic acid (Glu), are examined in detail utilizing collision-induced dissociation (CID) with Xe in a guided ion beam tandem mass spectrometer (GIBMS). Results establish that the Na+(L) complexes decompose upon formation in our dc discharge/flow tube ion source to form a bis-ligand complex, Na+(L-HX)(HX), composed of a sodium cation, the (L-HX) decomposition product, and HX, where HX = NH3 for the amides and H2O for the acids. Analysis of the energy-dependent CID cross sections for the Na+(L-HX)(HX) complexes provides unambiguous identification of the (L-HX) fragmentation products as 3-amino succinic anhydride (a-SA) for Asx and oxo-proline (O-Pro) for Glx. Furthermore, these experiments establish the 0 K sodium cation affinities for these five-membered ring decomposition products and the H2O and NH3 binding affinities of the Na+(a-SA) and Na+(O-Pro) complexes after accounting for unimolecular decay rates, the internal energy of reactant ions, and multiple ion-molecule collisions. Quantum chemical calculations are determined for a number of geometric conformations of all reaction species as well as a number of candidate species for (L-HX) at the B3LYP/6-311+G(d,p) level with single-point energies calculated at MP2(full), B3LYP, and B3P86 levels using a 6-311+G(2d,2p) basis set. This coordinated examination of both the experimental work and quantum chemical calculations allows for a complete characterization of the products of deamidation and dehydration of Asx and Glx, as well as the details of Na+, H2O, and NH3 binding to the decomposition species.


Subject(s)
Amides/chemistry , Amino Acids/chemistry , Models, Chemical , Sodium/chemistry , Water/chemistry , Asparagine/chemistry , Aspartic Acid/chemistry , Glutamic Acid/chemistry , Glutamine/chemistry , Kinetics , Thermodynamics
9.
Am J Manag Care ; 7(18 Suppl): S567-70, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11727394

ABSTRACT

Despite the important reproductive and noncontraceptive benefits of hormonal therapy, both oral contraceptives (OCs) and hormone replacement therapy (HRT) are underutilized, with only a small portion of eligible women receiving therapy. Increased use of hormonal therapy will result in greater pharmacy costs, a concern in the present era of cost containment that is reflected in the wide variability in coverage of hormonal therapy provided by managed care organizations. However, pharmacoeconomic research demonstrates that relatively small expenditures in pharmacy costs for hormonal therapy result in significantly lower healthcare costs per patient, through the prevention of unintended pregnancy with OCs and the noncontraceptive health benefits of both OCs and HRT.


Subject(s)
Contraceptives, Oral, Hormonal/therapeutic use , Hormone Replacement Therapy/statistics & numerical data , Managed Care Programs/organization & administration , Pharmaceutical Services/organization & administration , Climacteric , Economics, Pharmaceutical , Female , Humans , Outcome Assessment, Health Care , United States
10.
Clin Ther ; 23(9): 1570-88, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11589269

ABSTRACT

BACKGROUND: Osteoporotic fractures are associated with significant morbidity, mortality, and health care costs. OBJECTIVE: The purpose of this paper is to present and validate a mathematical model that managed care organizations can apply to administrative claims data to help locate members at risk for osteoporotic fracture and estimate future fracture rates. METHODS: Using known risk factors from previous clinical studies, 92,000 members of a large Midwest health plan were placed in 1 of 4 risk categories based on historical claims markers: demographic/lifestyle (age, sex, smoking, alcoholism); steroid use; medical history (previous osteoporotic fracture, ordinary bone fracture, osteoporosis diagnosis, bone mineral density test); or steroid use with medical history. Logistic regression was used to assign a probability of fracture for the 4 groups over the next 2 years. These predictions were compared with actual fracture rates, and refined models were produced. The models were then validated by applying them to current data and comparing the predicted fracture rate for each group to known results. RESULTS: The model predicted that 1.26% of the study members would experience osteoporotic fracture over the next 2 years; the actual result was 1.27%. Within the 4 risk groups, the predicted fracture rates were lower than the actual rates for the demographic risk group (0.87% predicted vs 0.97% actual) and higher than the actual rates for the steroid use (1.78% predicted vs 1.58% actual), medical history (5.90% predicted vs 4.94% actual), and the steroid use with medical history groups (7.80% predicted vs 6.42% actual). CONCLUSION: The application of this risk model to an administrative claims database successfully identified plan members at risk for osteoporotic fracture.


Subject(s)
Fractures, Bone/etiology , Osteoporosis/diagnosis , Osteoporosis/economics , Aged , Aged, 80 and over , Databases, Factual , Fractures, Bone/economics , Humans , Incidence , Insurance Benefits/economics , Insurance Claim Review/economics , Middle Aged , Models, Statistical , Risk Factors
11.
Proc Inst Mech Eng H ; 214(5): 479-87, 2000.
Article in English | MEDLINE | ID: mdl-11109855

ABSTRACT

A prototype flexible fixation system for the lumbar spine was subjected to tensile testing to failure and cyclic tensile testing in order to determine any regions of weakness. The system consisted of a spinous process hook and two laminar hooks made of stainless steel (316L). Each laminar hook was attached to the spinous process hook by a loop of polyester braid secured by a crimped metal sleeve. In five tensile tests, the system failed by irreversible deformation of the spinous process hook at 2.5 +/- 0.3 kN (mean +/- standard deviation). In three cyclic tests, in which the applied tension varied sinusoidally between 0.04 and 0.4 kN at a frequency of 5 Hz, failure occurred after less than 400,000 loading cycles. This occurred as a result of fatigue crack initiation and propagation in the spinous process hook. A finite element model showed a stress concentration in the region where the crack occurred, which raised the applied stress above the tensile fatigue strength of this stainless steel. The spinous process hook was redesigned for manufacture in a titanium alloy (Ti-6AI-4V ELI) to minimize artefacts in magnetic resonance imaging. Further finite element models showed no unacceptable stress concentrations.


Subject(s)
Computer-Aided Design , Internal Fixators/standards , Low Back Pain/surgery , Lumbar Vertebrae/surgery , Spinal Fusion/instrumentation , Alloys , Artifacts , Computer Simulation , Equipment Design , Equipment Failure , Finite Element Analysis , Humans , Magnetic Resonance Imaging , Materials Testing , Stress, Mechanical , Tensile Strength , Titanium
12.
Nephrol Dial Transplant ; 15(1): 23-7, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10607763

ABSTRACT

BACKGROUND: The incidence of renal vasculitis has previously been estimated using histological definitions or only a single clinical diagnosis, e.g. Wegener's Granulomatosis (WG). Our hospital is the single referral centre for the former Norwich Health Authority (NHA) which encompasses a stable, homogeneous, well-defined and studied population. We estimated the overall incidence of primary renal vasculitis and the incidence within individual clinical disease classifications. METHODS: All cases of primary renal vasculitis diagnosed within the NHA over 66 months (1992-1997) were identified by review of renal biopsies, the Norfolk Vasculitis Register, hospital discharge summaries and plasmapheresis records. Patients were classified using the 1990 American College of Rheumatology criteria for Polyarteritis Nodosa (PAN), Churg Strauss Syndrome (CSS) and Henoch-Schonlein Purpura; the Chapel Hill Consensus Conference Definitions for Microscopic Polyangiitis (mPA) and the Lanham criteria for CSS. Incidence figures were calculated using the NHA adult population of 413747 (1994). Ninety-five per cent confidence intervals (C.I.) were calculated using the poisson distribution. RESULTS: The overall annual incidence for primary renal vasculitis was 18/million (C.I. 12.9-24.4). The annual incidence of renal involvement of individual diseases was as follows: WG 7.9/million (95% C.I. 4.7-12.5); mPA 7.5/million (95% C. I. 4.4-12.0); PAN 7.0/million (95% C.I. 4.0-11.4); HSP 3.1/million (95% C.I. 1.2-6.3); CSS 1.3/million (95% C.I. 0.3-3.9). CONCLUSIONS: The annual incidence for primary renal vasculitis overall and the individual subtypes in Norfolk is much higher than previous European estimates. This may reflect an increasing incidence in primary renal vasculitis with time or underestimation in previous studies. However the incidence of renal vasculitis in our population is markedly lower than reported in Kuwait. There may therefore be true variation in incidence between populations which could have implications for the aetiology of primary vasculitis.


Subject(s)
Kidney Diseases/epidemiology , Vasculitis/epidemiology , Adult , Churg-Strauss Syndrome/epidemiology , England/epidemiology , Epidemiologic Factors , Female , Granulomatosis with Polyangiitis/epidemiology , Humans , IgA Vasculitis/epidemiology , Kidney Diseases/classification , Male , Polyarteritis Nodosa/epidemiology , Vasculitis/classification
16.
Med Eng Phys ; 20(8): 620-4, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9888241

ABSTRACT

The stress levels in the femoral component of a total hip prosthesis (Corin Taper Fit, Corin Medical Ltd, Cirencester, Gloucestershire, UK) were calculated by finite element (FE) analysis. This prosthesis has two holes drilled in the shoulder to engage a stem introducer. There were no unacceptable stress levels around these holes. Instead the maximum stresses were around the periphery of the shaft of the stem, as has been observed for FE analyses of conventional designs. Three prostheses were also subjected to cyclic mechanical testing (peak load 2.3 kN) according to the appropriate British Standard. The holes were examined for cracks, before and after testing, by stereomicroscopy. All three specimens were able to withstand 5 million loading cycles with no evidence of damage. Thus it is possible to design a femoral component with holes in the shoulder, to accommodate a stem introducer, without creating unacceptable stress concentrations.


Subject(s)
Hip Prosthesis , Computer Simulation , Hip Joint/physiology , Humans , Prosthesis Design , Stress, Mechanical
17.
Transfusion ; 37(1): 5-11, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9024483

ABSTRACT

BACKGROUND: Platelet concentrates (PCs) may be subjected to temperatures outside 20 to 22 degrees C during shipping or storage, which may have an adverse effect on platelet quality. STUDY DESIGN AND METHODS: These studies systematically evaluated the effect of short-term exposure (< or = 24 hours) of platelets to temperatures above 22 degrees or below 20 degrees C as part of standard 5-day PC storage at 22 degrees C, as well as the effect of long-term storage (5 days) at 24 and 26 degrees C. For the short-term exposure studies, up to 6 units of Day 1 standard PCs were mixed, split, and returned to the containers. Test units were then stored without agitation in an incubator at a specific temperature (4, 12, 16, or 18 degrees C) for various times up to 24 hours, after which they were stored with agitation at 22 degrees C. One unit acted as control and was stored at 20 to 22 degrees C throughout the 5-day storage period. Loss of platelet discoid shape was determined photometrically by the extent of shape change assay, by an increase in apparent platelet size by morphologic evaluation, and by swirling. RESULTS: A gradual loss of platelet discoid shape occurred at temperatures below 20 degrees C. For similar periods, a greater difference between test and control PCs was observed in units held at 4 degrees C than in those held at 16 degrees C. The data were fitted to an equation to relate platelet discoid shape (% of control) to exposure temperature and time. Assuming that a 20-percent decrease or more in the extent of shape change assay represents a significant loss in platelet viability, the equation predicts that such a loss occurs when the platelets are exposed to 16 degrees C for > or = 16 hours, to 12 degrees C for > or = 10 hours, or to 4 degrees C for > or = 6 hours, whereas exposure to 18 degrees C for < or = 24 hours has no significant effect. Storage for 5 days at temperatures < or = 26 degrees C was not associated with any significant reduction in platelet discoid shape or other measures of platelet quality. CONCLUSION: There was a gradual loss of platelet discoid shape at exposure temperatures < 20 degrees C, which worsened as temperatures decreased and exposure times increased to 24 hours. This relationship can be described in an equation that could be used as a guideline for allowable exposure conditions.


Subject(s)
Blood Platelets , Blood Preservation , Cryopreservation , Blood Platelets/cytology , Blood Platelets/metabolism , Blood Platelets/physiology , Cell Size , Cell Survival , Humans , Microscopy, Phase-Contrast , Platelet Aggregation , Time Factors
18.
Am J Med ; 101(4A): 4A71S-74S; discussion 4A74S-75S, 1996 Oct 08.
Article in English | MEDLINE | ID: mdl-8900340

ABSTRACT

Coronary artery disease (CAD) is responsible for nearly $140 billion in healthcare expenditures each year. A major opportunity for cost savings lies in reducing the overutilization of hospitalization for CAD patients. This goal may be accomplished through several strategies: more precise diagnosis of CAD, primary and secondary prevention, and early intervention. Underutilization of health services and treatment also contributes to higher overall medical costs. Even though drug therapy incurs costs, effective medications can produce substantial savings by reducing the need for additional medical care. For example, lipid-lowering agents are particularly cost effective when used as secondary prevention in patients with CAD; however, only 25% of patients receive such therapy. Likewise, not all patients who suffer acute myocardial infarction are treated with any of the agents proven to reduce the risk of subsequent adverse cardiovascular events. The elimination of variability in prescribing practices should help optimize the cost effectiveness of therapies aimed at reducing CAD risk.


Subject(s)
Hypercholesterolemia/drug therapy , Myocardial Infarction/drug therapy , Cost-Benefit Analysis , Humans , Hypercholesterolemia/economics , Managed Care Programs , Myocardial Infarction/economics , Risk Assessment
19.
Med Interface ; 9(1): 101-7, 1996 Jan.
Article in English | MEDLINE | ID: mdl-10153789

ABSTRACT

As MCOs explore opportunities for delivering more cost-effective medical care, prioritization based on drug utilization reviews alone may not adequately highlight those disease states that consume a disproportionate share of overall resource cost; the daily cost of pharmacotherapy may not reflect the overall economic effect. As the elderly proportion of the population grows, the treatment of congestive heart failure may represent for MCOs an increasingly important opportunity to achieve acceptable or even improved outcomes while controlling the costs of hospitalization and other resources. The introduction of new pharmaceuticals presents an ongoing challenge for managed care to determine whether they offer a pharmacoeconomic advantage over current treatment regimens. This paper reports on an economic assessment made between a new and an existing loop diuretic in the treatment of congestive heart failure.


Subject(s)
Diuretics/economics , Diuretics/therapeutic use , Drug Costs/statistics & numerical data , Heart Failure/drug therapy , Heart Failure/economics , Managed Care Programs/economics , Aged , Cost Control , Drug Utilization Review , Female , Furosemide/economics , Furosemide/therapeutic use , Health Care Costs/statistics & numerical data , Hospitalization/economics , Humans , Male , Middle Aged , Patient Compliance , Sulfonamides/economics , Sulfonamides/therapeutic use , Torsemide
20.
Br J Haematol ; 91(1): 212-8, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7577636

ABSTRACT

In these studies, platelet ageing during in vitro at 22 degrees C was compared with in vivo ageing using isotope labelling. Paired fresh and 5-d-stored platelets had a mean residual life-span (MRL) of 4.8 +/- 0.7 d and 3.2 +/- 0.9 d, respectively. After 2.1 +/- 0.4 d in vivo circulation, the MRL of the fresh platelets was equivalent to that of the 5-d-stored in vitro platelets. This suggests that platelet ageing for 5 d in vitro at 22 degrees C corresponds to 2.1 d in vivo ageing at 37 degrees C. Thus, the relative ageing at 22 degrees C in vitro was (2.1 d/5 d) = 0.42 of that at 37 degrees C in vivo. A similar ageing ratio (0.44) was obtained by measurement of the decrease in MRL during storage at 22 degrees C of platelets stored for 1, 5, 7, 10 and 14 d relative to the decrease in MRL of fresh platelets in vivo. ATP turnover rate at 22 degrees C was compared to the rate of 37 degrees C by measurement of the rates of platelet oxygen consumption and lactate production in vitro. In vitro ATP turnover at 22 degrees C versus 37 degrees C, was found to be 10.5 +/- 1.0 versus 21.6 +/- 1.4 mumol/10(12) plts/min, respectively. Thus, the ATP turnover ratio (0.48) at these two temperatures suggests that the relative decrease in ageing at 22 degrees C compared to 37 degrees C is similar to the relative decrease in metabolic rate at this temperature.


Subject(s)
Blood Platelets/cytology , Blood Preservation/methods , Adenosine Triphosphate/blood , Blood Platelets/metabolism , Cell Survival , Cellular Senescence , Humans , Lactates/blood , Lactic Acid , Oxygen Consumption , Platelet Transfusion , Temperature
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