RESUMEN
Coot is a molecular-graphics application for model building and validation of biological macromolecules. The program displays electron-density maps and atomic models and allows model manipulations such as idealization, real-space refinement, manual rotation/translation, rigid-body fitting, ligand search, solvation, mutations, rotamers and Ramachandran idealization. Furthermore, tools are provided for model validation as well as interfaces to external programs for refinement, validation and graphics. The software is designed to be easy to learn for novice users, which is achieved by ensuring that tools for common tasks are 'discoverable' through familiar user-interface elements (menus and toolbars) or by intuitive behaviour (mouse controls). Recent developments have focused on providing tools for expert users, with customisable key bindings, extensions and an extensive scripting interface. The software is under rapid development, but has already achieved very widespread use within the crystallographic community. The current state of the software is presented, with a description of the facilities available and of some of the underlying methods employed.
Asunto(s)
Cristalografía por Rayos X/métodos , Diseño de Software , ADN/análisis , ADN/química , Modelos Moleculares , Conformación de Ácido Nucleico , Estructura Terciaria de Proteína , Proteínas/análisis , Proteínas/química , ARN/análisis , ARN/químicaRESUMEN
Terbium(III) [Tb(III)] was shown to inhibit the hammerhead ribozyme by competing with a single magnesium(II) ion. X-ray crystallography revealed that the Tb(III) ion binds to a site adjacent to an essential guanosine in the catalytic core of the ribozyme, approximately 10 angstroms from the cleavage site. Synthetic modifications near this binding site yielded an RNA substrate that was resistant to Tb(III) binding and capable of being cleaved, even in the presence of up to 20 micromolar Tb(III). It is suggested that the magnesium(II) ion thought to bind at this site may act as a switch, affecting the conformational changes required to achieve the transition state.
Asunto(s)
ARN Catalítico/antagonistas & inhibidores , ARN Catalítico/metabolismo , Terbio/metabolismo , Sitios de Unión , Unión Competitiva , Catálisis , Cristalografía por Rayos X , Magnesio/metabolismo , Modelos Moleculares , Conformación de Ácido Nucleico , ARN Catalítico/química , Terbio/farmacologíaRESUMEN
The crystal structure of an unmodified hammerhead RNA in the absence of divalent metal ions has been solved, and it was shown that this ribozyme can cleave itself in the crystal when divalent metal ions are added. This biologically active RNA fold is the same as that found previously for two modified hammerhead ribozymes. Addition of divalent cations at low pH makes it possible to capture the uncleaved RNA in metal-bound form. A conformational intermediate, having an additional Mg(II) bound to the cleavage-site phosphate, was captured by freeze-trapping the RNA at an active pH prior to cleavage. The most significant conformational changes were limited to the active site of the ribozyme, and the changed conformation requires only small additional movements to reach a proposed transition-state.
Asunto(s)
Conformación de Ácido Nucleico , ARN Catalítico/química , Secuencia de Bases , Cristalización , Cristalografía por Rayos X , Congelación , Concentración de Iones de Hidrógeno , Magnesio/metabolismo , Manganeso/metabolismo , Modelos Moleculares , ARN Catalítico/metabolismoRESUMEN
Site-directed mutagenesis and Laue diffraction data to 2.5 A resolution were used to solve the structures of two sequential intermediates formed during the catalytic actions of isocitrate dehydrogenase. Both intermediates are distinct from the enzyme-substrate and enzyme-product complexes. Mutation of key catalytic residues changed the rate determining steps so that protein and substrate intermediates within the overall reaction pathway could be visualized.
Asunto(s)
Cristalografía por Rayos X , Isocitrato Deshidrogenasa/química , Mutagénesis Sitio-Dirigida , Sitios de Unión , Catálisis , Gráficos por Computador , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Isocitratos/metabolismo , Cinética , NADP/metabolismo , Conformación ProteicaRESUMEN
The three-dimensional structure of an active, disulfide cross-linked dimer of the ligand-binding domain of the Salmonella typhimurium aspartate receptor and that of an aspartate complex have been determined by x-ray crystallographic methods at 2.4 and 2.0 angstrom (A) resolution, respectively. A single subunit is a four-alpha-helix bundle with two long amino-terminal and carboxyl-terminal helices and two shorter helices that form a cylinder 20 A in diameter and more than 70 A long. The two subunits in the disulfide-bonded dimer are related by a crystallographic twofold axis in the apo structure, but by a noncrystallographic twofold axis in the aspartate complex structure. The latter structure reveals that the ligand binding site is located more than 60 A from the presumed membrane surface and is at the interface of the two subunits. Aspartate binds between two alpha helices from one subunit and one alpha helix from the other in a highly charged pocket formed by three arginines. The comparison of the apo and aspartate complex structures shows only small structural changes in the individual subunits, except for one loop region that is disordered, but the subunits appear to change orientation relative to each other. The structures of the two forms of this protein provide a step toward understanding the mechanisms of transmembrane signaling.
Asunto(s)
Receptores de Aminoácidos , Receptores de Superficie Celular/química , Secuencia de Aminoácidos , Ácido Aspártico/metabolismo , Sitios de Unión , Disulfuros/análisis , Enlace de Hidrógeno , Modelos Moleculares , Datos de Secuencia Molecular , Conformación Proteica , Receptores de Superficie Celular/metabolismo , Salmonella typhimurium/metabolismo , Difracción de Rayos XRESUMEN
The hammerhead RNA is a small catalytic RNA found in a number of RNA virus genomes and virus-like RNAs. The recently determined crystal structures of hammerhead ribozymes reveal how a small RNA motif can fold up into a conformation suitable for mediating RNA cleavage.
Asunto(s)
ARN Catalítico/química , ARN Catalítico/metabolismo , ARN/química , Secuencia de Bases , Cristalografía por Rayos X , Magnesio/química , Magnesio/metabolismo , Metales/farmacología , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , ARN/metabolismo , ARN Viral/química , ARN Viral/metabolismoRESUMEN
Our understanding of the relationship between the structure of RNA and its catalytic activity has advanced significantly in the past year. These advances include time-resolved crystallographic studies on the hammerhead ribozyme, as well as new structures of a group I intron, a lead(II)-cleavage ribozyme, a hepatitis delta virus ribozyme, and components of the spliceosome machinery and the peptidyl transferase center of the ribosome and, most significantly, the structure of the ribosome itself.
Asunto(s)
ARN Catalítico/metabolismo , Catálisis , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Conformación Proteica , Empalme del ARN , ARN Catalítico/químicaRESUMEN
BACKGROUND: The aspartate receptor is a transmembrane protein that mediates bacterial chemotaxis. The structures of the periplasmic ligand-binding domain reveal a dimer, each subunit with four alpha-helix bundles, with aspartate binding to one of two sites at the subunit interface. The transmembrane regions of the receptor were not included in these structures. RESULTS: To investigate the structure of the transmembrane region, we have made a mutant protein with two cross-links, restraining the subunit-subunit interface on both sides of the membrane, and have made an energy-minimized model of the transmembrane region. We demonstrate that the transmembrane helices form a coiled coil which extends from the periplasmic subunit through the membrane. We have constructed a model of the ligand-binding domains with the amino-terminal transmembrane helices. CONCLUSIONS: We draw three conclusions from our model. Firstly, the interface between receptor subunits in the intact receptor consists of an uninterrupted coiled coil. Secondly, this structure rules out several postulated mechanisms of signalling. Thirdly, side chain packing constraints within the helices dictate that local structural changes must be small, but are propagated over a long distance rather than being dissipated locally. Low energy changes in the conformation of side chains are a probable mechanism of signal transduction in the aspartate receptor.
Asunto(s)
Estructura Secundaria de Proteína , Receptores de Aminoácidos/química , Transducción de Señal , Secuencia de Aminoácidos , Ácido Aspártico , Fenómenos Fisiológicos Bacterianos , Sitios de Unión , Membrana Celular/fisiología , Quimiotaxis , Gráficos por Computador , Reactivos de Enlaces Cruzados , Cisteína , Sustancias Macromoleculares , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Receptores de Aminoácidos/fisiología , S-Adenosilmetionina , Programas InformáticosRESUMEN
BACKGROUND: Bacterial signal recognition particle (SRP), consisting of 4.5S RNA and Ffh protein, plays an essential role in targeting signal-peptide-containing proteins to the secretory apparatus in the cell membrane. The 4.5S RNA increases the affinity of Ffh for signal peptides and is essential for the interaction between SRP and its receptor, protein FtsY. The 4.5S RNA also interacts with elongation factor G (EF-G) in the ribosome and this interaction is required for efficient translation. RESULTS: We have determined by multiple anomalous dispersion (MAD) with Lu(3+) the 2.7 A crystal structure of a 4.5S RNA fragment containing binding sites for both Ffh and EF-G. This fragment consists of three helices connected by a symmetric and an asymmetric internal loop. In contrast to NMR-derived structures reported previously, the symmetric loop is entirely constituted by non-canonical base pairs. These pairs continuously stack and project unusual sets of hydrogen-bond donors and acceptors into the shallow minor groove. The structure can therefore be regarded as two double helical rods hinged by the asymmetric loop that protrudes from one strand. CONCLUSIONS: Based on our crystal structure and results of chemical protection experiments reported previously, we predicted that Ffh binds to the minor groove of the symmetric loop. An identical decanucleotide sequence is found in the EF-G binding sites of both 4.5S RNA and 23S rRNA. The decanucleotide structure in the 4.5S RNA and the ribosomal protein L11-RNA complex crystals suggests how 4.5S RNA and 23S rRNA might interact with EF-G and function in translating ribosomes.
Asunto(s)
Proteínas Bacterianas/metabolismo , Secuencia Conservada , Proteínas de Escherichia coli , Escherichia coli/genética , Modelos Moleculares , Factor G de Elongación Peptídica/metabolismo , ARN Ribosómico/química , Partícula de Reconocimiento de Señal/metabolismo , Emparejamiento Base , Secuencia de Bases , Sitios de Unión/genética , Cristalografía por Rayos X , Dimerización , Nucleótidos de Guanina/química , Lutecio/química , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , ARN Bacteriano , ARN Ribosómico/metabolismoRESUMEN
Several new and unexpected insights into the metalloenzymology of ribozymes have been achieved in the past year. From a mechanistic point of view, the NMR and crystal structures of a small Pb(2+)-dependent ribozyme have been particularly revealing.
Asunto(s)
Metales/química , ARN Catalítico/química , Catálisis , Metales/metabolismo , ARN Catalítico/metabolismoRESUMEN
Orbital steering is invoked to explain how the three-dimensional structure of a small self-cleaving RNA, the hammerhead ribozyme, both prevents and enhances RNA autocatalysis. Within the conserved catalytic core of the ribozyme, the position of the 2' oxygen atom of the G8 ribose is observed to be aligned almost perfectly with the phosphorus atom and the 5' oxygen atom of the adjacent A9 phosphate group for self-cleavage via an in-line attack mechanism. Despite this apparent near-perfect atomic positioning, no cleavage takes place. The explanation proposed is that a network of hydrogen bonds in the ribozyme core orients or steers the orbitals containing the electron lone pairs of the attacking nucleophile (the 2' oxygen atom) away from the A9 phosphorus atom, eliminating overlap with the vacant phosphorus d-orbitals despite the near-perfect in-line positioning of the oxygen atom, thus preventing catalysis. Because of the near-perfect atomic positioning of the 2' oxygen atom relative to the phosphate group, orbital steering effects in this case are fortuitously uncoupled from conformational, distance and orientation effects, allowing an assessment of the catalytic power due purely to orbital steering. In contrast, a conformational change at the cleavage site is required to bring the 2' oxygen atom and the scissile phosphate group into atomic positions amenable to an in-line attack mechanism. In addition, the conformationally changed structure must then steer the lone-pair orbitals of the correctly positioned 2' oxygen atom toward the scissile phosphorus atom in order for cleavage to take place. We estimate that fulfillment of each of these two required changes may contribute separately an approximately 1000-fold rate enhancement, potentially accounting for a significant fraction of the catalytic power of this ribozyme. Orbital steering therefore appears to be a general phenomenon that may help to explain catalysis in both ribozymes and protein enzymes in a unified manner.
Asunto(s)
ARN Catalítico/química , ARN Catalítico/metabolismo , Secuencia de Bases , Sitios de Unión , Catálisis , Enlace de Hidrógeno , Modelos Moleculares , Conformación de Ácido Nucleico , Oxígeno/química , Oxígeno/metabolismo , Fosfatos/metabolismo , ARN Catalítico/genéticaRESUMEN
We have constructed a model structure that we believe represents the strongest possible physically and chemically reasonable representation of a hypothesized catalytically active hammerhead ribozyme structure in which a single divalent metal ion bridges the A9 and scissile phosphate groups. It has been proposed that such a structure arises from a conformational change in which the so-called ground-state structure (as observed by X-ray crystallography) rearranges in such a way that the pro-R oxygen atoms of both the A9 and scissile phosphate groups are directly coordinated by a single divalent metal ion in the transition-state of the hammerhead ribozyme cleavage reaction. We show that even the small subset of possible model structures that are consistent with these requirements, and that are stereochemically and sterically reasonable, are contradicted by experimental evidence. We also demonstrate that even a minimal subset of assumptions, i.e. that stems I and II are helical and that the two phosphate groups are coordinated by a divalent metal ion in the standard octahedral geometry, are sufficient to lead to this contradiction. We therefore conclude that such a mechanism of hammerhead ribozyme catalysis is untenable, at least in its present formulation.
Asunto(s)
Cationes Bivalentes/metabolismo , Metales/metabolismo , Conformación de Ácido Nucleico , Fosfatos/metabolismo , ARN Catalítico/química , ARN Catalítico/metabolismo , Secuencia de Bases , Sitios de Unión , Catálisis , Cristalización , Cristalografía por Rayos X , Activación Enzimática , Manganeso/metabolismo , Metales/química , Modelos Moleculares , Oxígeno/metabolismo , ARN Catalítico/genética , Reproducibilidad de los Resultados , TermodinámicaRESUMEN
The periplasmic domain of the aspartate chemotaxis receptor from Salmonella typhimurium has been crystallized in the presence and absence of bound aspartate. Both crystal forms were grown by precipitation with lithium sulfate and diffract to 1.8 A resolution. The aspartate receptor structure is believed to be prototypical of a large class of receptors including those for polypeptide growth factor hormones as well as those for small chemotaxis-affector molecules such as aspartate and serine.
Asunto(s)
Ácido Aspártico/metabolismo , Quimiotaxis , Receptores de Aminoácidos , Receptores de Superficie Celular/química , Salmonella typhimurium/metabolismo , Cristalización , Ligandos , Receptores de Superficie Celular/metabolismo , Difracción de Rayos XRESUMEN
To find conditions for obtaining diffraction-quality crystals of a hammerhead RNA rapidly and reproducibly, we employed a "double screening" procedure in which we screened six different RNA synthetic constructs against 48 crystallization conditions using a newly devised sparse matrix. We obtained crystals immediately and diffraction-quality crystals of the sixth RNA construct within six months of initiating the screening of additional RNA sequences. The best crystals diffract to 2.9 A resolution when flash-cooled at synchrotron X-ray sources. Solid-support chemical synthesis combined with sparse matrix screening should allow rapid production of diffraction-quality crystals of a variety of small RNAs, reducing the time commitment for initiating such crystallography projects from several years to several months. The synthetic approach also makes introduction of modified bases to prevent self-cleavage and to generate isomorphous heavy-atom derivative crystals a rapid and straightforward process.
Asunto(s)
Conformación de Ácido Nucleico , ARN Catalítico/química , ARN Catalítico/síntesis química , Secuencia de Bases , Cristalización , Datos de Secuencia MolecularRESUMEN
The aspartate receptor is a transmembrane-signalling protein that mediates chemotaxis behaviour in bacteria. Aspartate receptors in Salmonella typhimurium and Escherichia coli exist as dimers of two subunits in the presence as well as in the absence of aspartate. We have previously reported the three-dimensional structures of the external ligand-binding domain of the S. typhimurium aspartate receptor with and without bound aspartate. The external or periplasmic region of the aspartate receptor is a dimer of four-alpha-helical bundle subunits; a single aspartate molecule binds to one of two sites residing at the subunit interface, increasing the affinity of the subunits for one another. Here we report the results of a detailed analysis of the aspartate receptor ligand-binding domain structure (residues 25 to 188). The dimer interface between the twofold related subunits consists primarily of contacts mediated by the side-chains of the N-terminal helix of each four-alpha-helical bundle subunit. The N-terminal helices pack approximately 20 degrees from parallel as an approximate coiled-coil super-secondary structure. We have refined aspartate receptor ligand-binding domain structures in the presence and in the absence of a bound aromatic compound, 1,10-phenanthroline, to 2.2 A and 2.3 A resolution, respectively, as well as crystal structures in the presence of specifically bound Au(I), Hg(II) and Pt(IV) complex ions at 2.4 A, 3.0 A and 3.3 A resolution, respectively. The possible biological relevance of the aromatic ligand-binding site and the metal ion-binding sites is discussed. The dimer of four-alpha-helical bundle subunits composing the periplasmic region of the S. typhimurium aspartate receptor provides a basis for understanding the results of mutational analyses performed on related chemotaxis transmembrane receptors. The crystal structure analysis provides an explanation for the way in which mutations in the E. coli aspartate receptor affect its binding to the periplasmic maltose-binding protein and how mutations in the more distantly related E. coli Trg chemotaxis receptor affect its binding to the periplasmic ribose and glucose-galactose binding proteins.
Asunto(s)
Ácido Aspártico/metabolismo , Proteínas Bacterianas/química , Proteínas de Escherichia coli , Fragmentos de Péptidos/química , Receptores de Aminoácidos/química , Salmonella typhimurium/química , Quimiotaxis , Escherichia coli/química , Oro/química , Oro/metabolismo , Proteínas de la Membrana/química , Mercurio/química , Mercurio/metabolismo , Modelos Moleculares , Fenantrolinas/química , Fenantrolinas/metabolismo , Platino (Metal)/química , Platino (Metal)/metabolismo , Conformación Proteica , Transducción de Señal , Difracción de Rayos XRESUMEN
BACKGROUND: The catalytic activity of RNA enzymes is thought to require divalent metal ions, which are believed to facilitate RNA folding and to play a direct chemical role in the reaction. RESULTS: We have found that the hammerhead, hairpin and VS ribozymes do not require divalent metal ions, their mimics such as [Co(NH3)6]3+, or even monovalent metal ions for efficient self-cleavage. The HDV ribozyme, however, does appear to require divalent metal ions for self-cleavage. For the hammerhead, hairpin and VS ribozymes, very high concentrations of monovalent cations support RNA-cleavage rates similar to or exceeding those observed in standard concentrations of Mg2+. Analysis of all reaction components by inductively coupled plasma-optical emission spectrophotometry (ICPOES) and the use of a variety of chelating agents effectively eliminate the possibility of contaminating divalent and trivalent metal ions in the reactions. For the hairpin ribozyme, fluorescence resonance energy transfer experiments demonstrate that high concentrations of monovalent cations support folding into the catalytically proficient tertiary structure. CONCLUSIONS: These results directly demonstrate that metal ions are not obligatory chemical participants in the reactions catalysed by the hammerhead, hairpin, and VS ribozymes. They permit us to suggest that the folded structure of the RNA itself contributes more to the catalytic function than was previously recognised, and that the presence of a relatively dense positive charge, rather than divalent metal ions, is the general fundamental requirement. Whether this charge is required for catalysis per se or simply for RNA folding remains to be determined.
Asunto(s)
ARN Catalítico/metabolismo , Catálisis , Cationes Monovalentes , Quelantes , Virus de la Hepatitis Delta/genética , Hidrólisis , Concentración OsmolarRESUMEN
The objective of this study was to evaluate the costs and benefits of influenza vaccination for the population aged 65 years and over, from the perspectives of individuals and health insurers, government and society. The annual incremental direct medical costs and benefits of influenza vaccination (compared with the nonvaccination, or 'do nothing', option) were evaluated using New Zealand healthcare resource usage and unit cost data [in 1992 New Zealand dollars ($NZ); $NZ1 = $US0.5458, June 1992] applied to cohort studies reported in the literature. The costs and benefits to society as a result of vaccination of people aged 65 years and older (20% of people in this age group are currently vaccinated) were estimated to be: (i) additional direct medical costs of vaccination of $NZ1.42 million [$NZ17.78 per vaccination]; (ii) direct medical costs avoided of $NZ5.35 million ($NZ67.18 per vaccination); and (iii) net benefits of $NZ3.93 million ($NZ49.40 per vaccination). The direct medical costs avoided per dollar cost of vaccination were $NZ1.04 for individuals, $NZ4.69 for government and $NZ3.78 for society as a whole. If the vaccination uptake for this group is increased in 20% increments, the net benefit to society increases by a further $NZ3.93 million per year at each step. If the economic evaluation is extended to include vaccination of at-risk individuals under 65 years of age, net benefits to society increase by 15%. Influenza vaccination for people aged 65 years and over is cost effective from the perspective of society, government and the individual. If the vaccination rate for at-risk individuals in New Zealand could be increased to 60%, the net benefits reported in this study would increase by 200%. However, the costs of promotion and education to achieve this vaccination rate would need to be deducted from the net benefits. Strategies to increase the vaccination rate include altering the cost of vaccinations to the individual, intensifying education and promotion programmes, and changing the mode of delivery.
Asunto(s)
Vacunas contra la Influenza/economía , Gripe Humana/economía , Análisis Costo-Beneficio , Humanos , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/prevención & control , Nueva ZelandaRESUMEN
This study sought to evaluate the changes in direct medical costs and life-years gained or lost by adding enalapril to conventional treatment (digoxin and diuretics) for heart failure (HF). The published results of the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial, and a decision analytical model developed by the University of Pennsylvania, were used in combination with New Zealand data to undertake the evaluation. All costs were measured in 1993 New Zealand dollars ($NZ) [$NZ1 = $US0.5509, September 1993]. Potential net cost savings per patient treated over a 4-year period were $NZ652 together with an additional 2 months of life gained. If these individual potential cost savings are extended to the New Zealand population who have HF (but are at present not receiving an ACE inhibitor) then $NZ6 517 000 in discounted health sector costs could be avoided. The model was sensitive to changes in the price of enalapril, to estimates of the population with HF, the percentage of the population with HF treated with enalapril, and to hospital unit costs for nonfatal cases of HF. The study demonstrated that the addition of enalapril to the conventional treatment of HF was cost effective when compared with conventional medical therapy alone.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/economía , Antihipertensivos/economía , Técnicas de Apoyo para la Decisión , Enalapril/economía , Insuficiencia Cardíaca/economía , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Costos y Análisis de Costo , Digoxina/uso terapéutico , Diuréticos/uso terapéutico , Enalapril/uso terapéutico , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Masculino , Nueva Zelanda , Disfunción Ventricular Izquierda/tratamiento farmacológico , Disfunción Ventricular Izquierda/economíaRESUMEN
The purpose of this study was to establish the incidence of surgical amputation for critical leg ischaemia in New Zealand, and estimate the hospital, prostheses and indirect costs of this intervention. The cost of amputations was then compared with the cost of treating such patients with iloprost. The study was retrospective. Individual patient records relating to 1991 for both public and private hospitals were analysed. Unit costs relevant to 1991 were applied to the volume data of patients and procedures to derive total costs. Costs were estimated on an incremental basis taking a societal perspective. Conservative estimates were obtained for hospital costs, prostheses and for production loss (loss of output or productivity). Total cost was $NZ15.9 million (hospital and prosthesis cost $NZ13.1 million, production loss $NZ2.8 million). The total quantified cost per amputation was $NZ23 038 (hospital and prosthesis cost $NZ19 020, production loss $NZ4017). 32% of patients requiring amputations were in the working age group. The theoretical avoidance of amputation by treatment with iloprost resulted in net savings of hospital and prosthetic costs of between $NZ6660 and $NZ8720 per patient. Amputation for critical leg ischaemia is costly and has a high mortality, but for iloprost treatment to be cost effective in a New Zealand hospital setting, patients must be targeted and a success rate of at least 55% achieved in avoidance of amputation and reduction of pain while at rest.
Asunto(s)
Amputación Quirúrgica , Iloprost , Isquemia , Enfermedades Vasculares Periféricas , Amputación Quirúrgica/economía , Miembros Artificiales/economía , Costo de Enfermedad , Análisis Costo-Beneficio , Grupos Diagnósticos Relacionados , Costos de Hospital , Humanos , Iloprost/economía , Iloprost/uso terapéutico , Incidencia , Isquemia/tratamiento farmacológico , Isquemia/epidemiología , Isquemia/cirugía , Pierna , Nueva Zelanda , Enfermedades Vasculares Periféricas/tratamiento farmacológico , Enfermedades Vasculares Periféricas/epidemiología , Enfermedades Vasculares Periféricas/cirugía , Estudios RetrospectivosRESUMEN
Benign prostatic hyperplasia (BPH) has been regarded as part of the normal aging process in men and little attention has been focused on the cost of the disease in New Zealand. The purpose of this study was to estimate the direct and indirect costs of treating BPH in both the public and the private sectors in New Zealand. The costs of treatment were estimated from public and private hospital data on admissions for BPH, obtained from the New Zealand Department of Health, medical insurance reimbursement schedules, hospital ward costs at one centre, and urology and general practitioner consultation fees. The length of time spent off work, as a measure of indirect costs, during urological investigations or treatment was estimated from interviews with urologists. The annual 1991 total direct medical costs of treated BPH as primary diagnosis in New Zealand were estimated at $NZ16 million (the average of the end-month mid-point exchange rate for the first quarter of 1992 was $US0.5457 per $NZ1), and the costs of lost production plus loss of leisure time by patients was estimated at $NZ4 million (1992 dollars). Patients with a principal diagnosis of BPH stayed on average 8.9 days in a public hospital and 4.6 days in a private hospital. Based on the above costs, if the average length of stay of public hospital patients could be reduced to that of private hospital patients, then hospital ward costs for BPH could fall by 37% and the total direct medical costs by 21%. The most commonly performed surgical operation for BPH was transurethral prostatectomy (TURP). For operations performed in a public hospital, patients stayed on average 8.5 days, while patients whose operations were performed in private hospitals stayed 4.3 days. The mean age of these public hospital patients was 71 years compared with 67 years for those in private hospitals. A complication rate of 2.02% was recorded for TURP in public hospitals but audits (conducted by the researchers) in both public and private settings indicated that the complication rate was substantially under-recorded.