RESUMEN
BACKGROUND: Premature mortality is a well-documented adverse outcome for people living with severe mental illnesses (SMI). Emerging evidence suggests that area-level factors play a role that are experienced disproportionately by this population. This review assesses the potential association between area-level factors and mortality in people with SMI. METHOD: We searched Medline, EMBASE, PsychINFO, Social Policy and Practice, Web of Science and OpenGrey databases. Literature searches were conducted in May 2020 and updated in June 2023. Reference lists were hand-searched and authors of included studies contacted to identify additional studies and minimise publication biases. Narrative synthesis was used to appraise the included studies. The review protocol was registered on PROSPERO (CRD42019155447). RESULTS: Our searches identified 7 studies (8 papers), which were included in the review, and indicated evidence of an association between deprivation and mortality. One study suggested an association between mortality in SMI and urbanicity in low to middle income settings which was not observed in studies from high income settings. One study suggested a protective association of area-level ethnic density with mortality within urbanised settings. CONCLUSION: Consistent associations were reported between residence in areas of higher deprivation and increased risk of mortality in SMI. Two studies suggested an association between area-level ethnic density and urbanicity and mortality in SMI. Most studies were conducted across high income countries and therefore future research could benefit from similar investigations being conducted in low- and middle-income countries. These methods would inform health and social policies, including interventions to reduce premature mortality in SMI.
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Trastornos Mentales , Mortalidad Prematura , Humanos , Trastornos Mentales/epidemiología , Trastornos Mentales/mortalidad , Geografía MédicaRESUMEN
Hand and wrist infections can present with a spectrum of manifestations ranging from cellulitis to deep-space collections. The various infectious processes can be categorised as superficial or deep infections based on their respective locations relative to the tendons. Superficial hand infections are located superficial to the tendons and are comprised of cellulitis, lymphangitis, paronychia, pulp-space infections, herpetic whitlow, and include volar as well as dorsal subcutaneous abscesses. Deep hand infections are located deep to the tendon sheaths and include synovial space infections, such as infectious tenosynovitis, deep fascial space infections, septic arthritis, necrotising fasciitis, and osteomyelitis. Knowledge of hand and wrist compartmental anatomy is essential for the accurate diagnosis and management of hand infections. Although early and superficial infections of the hand may respond to non-surgical management, most hand infections are surgical emergencies. Multidetector computed tomography (MDCT), with its muliplanar reformation (MPR) and three-dimensional (3D) capabilities, is a powerful tool in the emergency setting for the evaluation of acute hand and wrist pathology. The clinical and imaging features of hand and wrist infections as evident on MDCT will be reviewed with emphasis on contiguous and closed synovial and deep fascial spaces. Knowledge of hand compartmental anatomy enables accurate characterisation of the infectious process and localise the extent of disease in the acute setting.
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Infecciones Bacterianas/diagnóstico por imagen , Mano/diagnóstico por imagen , Mano/microbiología , Tomografía Computarizada Multidetector/métodos , Muñeca/diagnóstico por imagen , Muñeca/microbiología , Humanos , Imagenología Tridimensional/métodosRESUMEN
The purpose of this study was to assess the use of a novel bone void filler consisting of Type I collagen and various growth factors (VEGF, TGFß-1, TGFß-2, IGF-1, BMP-2, BMP-3, and BMP-7) and surgical fixation to treat diaphyseal forearm pseudarthroses. Eleven patients underwent an osteosynthesis procedure for isolated pseudarthrosis fractures of the forearm (six radial and five ulnar diaphysis). The mean duration between the initial failed surgical fixation and re-operation was 38 weeks. Radiographic signs of fracture healing after the application of the bone void filler were noted at a mean of 5 weeks, and complete fracture consolidation was achieved at a mean of 6 weeks. All patients demonstrated improved range of motion and grip strength. Additionally, all patients were pain-free by 6 weeks. The combination of a novel bovine bone-derived bone void filler and stable internal fixation led to union and rapid healing of forearm pseudarthroses.
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Sustitutos de Huesos/uso terapéutico , Colágeno Tipo I/uso terapéutico , Antebrazo/cirugía , Fijación Interna de Fracturas/métodos , Regeneración Tisular Dirigida/métodos , Péptidos y Proteínas de Señalización Intercelular/administración & dosificación , Seudoartrosis/terapia , Adulto , Terapia Combinada , Femenino , Fijación Interna de Fracturas/instrumentación , Liofilización , Humanos , Masculino , Persona de Mediana Edad , Osteogénesis , Seudoartrosis/diagnóstico , Resultado del Tratamiento , Adulto JovenRESUMEN
Oxygen isotope values of biogenic apatite have long demonstrated considerable promise for paleothermometry potential because of the abundance of material in the fossil record and greater resistance of apatite to diagenesis compared to carbonate. Unfortunately, this promise has not been fully realized because of relatively poor precision of isotopic measurements, and exceedingly small size of some substrates for analysis. Building on previous work, we demonstrate that it is possible to improve precision of delta18O(PO4) measurements using a 'reverse-plumbed' thermal conversion elemental analyzer (TC/EA) coupled to a continuous flow isotope ratio mass spectrometer (CF-IRMS) via a helium stream [Correction made here after initial online publication]. This modification to the flow of helium through the TC/EA, and careful location of the packing of glassy carbon fragments relative to the hot spot in the reactor, leads to narrower, more symmetrically distributed CO elution peaks with diminished tailing. In addition, we describe our apatite purification chemistry that uses nitric acid and cation exchange resin. Purification chemistry is optimized for processing small samples, minimizing isotopic fractionation of PO4(-3) and permitting Ca, Sr and Nd to be eluted and purified further for the measurement of delta44Ca and 87Sr/86Sr in modern biogenic apatite and 143Nd/144Nd in fossil apatite. Our methodology yields an external precision of +/- 0.15 per thousand (1sigma) for delta18O(PO4). The uncertainty is related to the preparation of the Ag3PO4 salt, conversion to CO gas in a reversed-plumbed TC/EA, analysis of oxygen isotopes using a CF-IRMS, and uncertainty in constructing calibration lines that convert raw delta18O data to the VSMOW scale. Matrix matching of samples and standards for the purpose of calibration to the VSMOW scale was determined to be unnecessary. Our method requires only slightly modified equipment that is widely available. This fact, and the demonstrated improvement in precision, should help to make apatite paleothermometry far more accessible to paleoclimate researchers.
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Espectrometría de Masas/métodos , Fosfatos/análisis , Apatitas/análisis , Apatitas/química , Calibración , Diseño de Equipo , Espectrometría de Masas/instrumentación , Isótopos de Oxígeno/análisis , Fosfatos/química , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Compuestos de Plata/análisis , Compuestos de Plata/químicaRESUMEN
Yeast glycogen metabolism responds to environmental stressors such as nutrient limitation and heat shock. This response is mediated, in part, by the regulation of the glycogen metabolic genes. Environmental stressors induce a number of glycogen metabolic genes, including GPH1, which encodes glycogen phosphorylase. Primer extension analysis detected two start sites for GPH1, one of which predominated. Sequences upstream of these sites included a possible TATA element. Mutation of this sequence reduced GPH1 expression by a factor of 10 but did not affect start site selection. This mutation also did not affect the relative induction of GPH1 upon entry into stationary phase. Three candidates for stress response elements (STREs) were found upstream of the TATA sequence. Mutation of the STREs showed that they were required for regulation of GPH1 expression in early stationary phase, and in response to osmotic shock and heat shock. These elements appeared to act synergistically, since the intact promoter exhibited 30-fold more expression in stationary phase than the sum of that observed for each element acting independently. HOG1, which encodes a MAP kinase, has been implicated in control mediated by STREs. For GPH1, induction by osmotic shock depended on a functional HOG1 allele. In contrast, induction upon entry into stationary phase was only partially dependent on HOG1. Furthermore, the heat shock response, which can also be mediated by STREs, was independent of HOG1. These observations suggest that the GPH1 STREs respond to more than one pathway, only one of which requires HOG1.
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Regulación Enzimológica de la Expresión Génica/genética , Regulación Fúngica de la Expresión Génica/genética , Glucógeno Fosforilasa/genética , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas Quinasas Activadas por Mitógenos/fisiología , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Secuencia de Bases , Clonación Molecular , Regulación Enzimológica de la Expresión Génica/fisiología , Regulación Fúngica de la Expresión Génica/fisiología , Glucógeno/metabolismo , Glucógeno Fosforilasa/biosíntesis , Glucógeno Fosforilasa/metabolismo , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Presión Osmótica , ARN Mensajero/química , Proteínas Recombinantes , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/fisiología , Análisis de Secuencia de ADN , TATA Box/genética , beta-Galactosidasa/análisisRESUMEN
Isocitrate dehydrogenase from Bacillus subtilis (BsIDH) is a member of a family of metal-dependent decarboxylating dehydrogenases. Its crystal structure was solved to 1.55 A and detailed comparisons with the homologue from Escherichia coli (EcIDH), the founding member of this family, were made. Although the two IDHs are structurally similar, there are three notable differences between them. First, a mostly nonpolar beta-strand and two connecting loops in the small domain of EcIDH are replaced by two polar alpha-helices in BsIDH. Because of a 13-residue insert in this region of BsIDH, these helices protrude over the active site cleft of the opposing monomer. Second, a coil leading into this cleft, the so-called "phosphorylation" loop, is bent inward in the B. subtilis enzyme, narrowing the entrance to the active site from about 12 to 4 A. Third, although BsIDH is a homodimer, the two unique crystallographic subunits of BsIDH are not structurally identical. The two monomers appear to differ by a domain shift of the large domain relative to the small domain/clasp region, reminiscent of what has been observed in the open/closed conformations of EcIDH. In Escherichia coli, IDH is regulated by reversible phosphorylation by the bifunctional enzyme IDH kinase/phosphatase (IDH-K/P). The site of phosphorylation is Ser(113), which lies deep within the active site crevice. Structural differences between EcIDH and BsIDH may explain disparities in their abilities to act as substrates for IDH-K/P.
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Bacillus subtilis/enzimología , Isocitrato Deshidrogenasa/química , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Escherichia coli , Isocitrato Deshidrogenasa/metabolismo , Datos de Secuencia Molecular , Conformación Proteica , Proteínas Serina-Treonina Quinasas/metabolismo , Alineación de Secuencia , Especificidad por SustratoRESUMEN
The isocitrate dehydrogenase kinase/phosphatase (IDHK/P) of E. coli is a bifunctional enzyme responsible for the reversible phosphorylation of isocitrate dehydrogenase (IDH) on a seryl residue. As such, it belongs to the serine/threonine protein kinase family. However, only a very limited homology with the well-characterized eukaryotic members of that family was identified so far in its primary structure. In this report, a new region of amino acids including three putative residues involved in the kinase activity of IDHK/P was identified by sequence comparison with eukaryotic protein kinases. In IDHK/P, these residues are Asp-371, Asn-377, and Asp-403. Their counterpart eukaryotic residues have been shown to be involved in either catalysis (former residue) or magnesium binding (the two latter residues). Site-directed mutagenesis was performed on these three IDHK/P residues, and also on the Glu-439 residue equivalent to that of the Ala-Pro-Glu motif found in the eukaryotic protein kinases. Mutations of Asp-371 into either Ala, Glu, or Gln residues drastically lowered the yield and the quality of the purification. Nevertheless, the recovered mutant enzymes were barely able to phosphorylate IDH either in vitro or after expression in an aceK (-) mutant strain. In contrast, mutation of either Asn-377, Asp-403, or Glu-439 into an Ala residue altered neither the yield of purification nor the maximal phosphorylating capacity of the enzyme. However, when IDH was phosphorylated in the presence of increasing concentrations of magnesium ions, the two former mutants displayed a much lower affinity for this cation, with a K(m) value of 0.6 or 0.8 mM, respectively, as compared to 0.1 mM for the wild-type enzyme. On the other hand, the Glu439Ala mutant has an affinity for magnesium essentially unaffected. Therefore, and in contrast to the current opinion, our results suggest that the catalytic mechanism of IDHK/P exhibits some similarities with that found in the eukaryotic members of the protein kinase family.
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Dominio Catalítico , Escherichia coli/enzimología , Células Eucariotas/enzimología , Complejos Multienzimáticos/metabolismo , Fosfoproteínas Fosfatasas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Secuencia de Aminoácidos , Asparagina/genética , Asparagina/metabolismo , Ácido Aspártico/genética , Ácido Aspártico/metabolismo , Sitios de Unión/genética , Dominio Catalítico/genética , Escherichia coli/genética , Magnesio/metabolismo , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Fosfoproteínas Fosfatasas/genética , Fosforilación , Proteínas Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Alineación de SecuenciaRESUMEN
Between January 1, 1989 and July 31, 1995, voluntary preoperative screening tests for human immunodeficiency virus (HIV) infection, using an enzyme-linked immunosorbant assay, were completed on 2,727 patients who underwent elective orthopedic surgical procedures. There were 2,719 (99.7%) negative, 4 (0.15%) positive, and 3 (0.11%) false-positive results; 1 test was indeterminate (0.04%). All 4 positive patients were men with a mean age of 32 years (range: 26-43 years). Although the prevalence of positive tests is low in this setting, voluntary testing alerts the surgeon to higher risk patients, does not sacrifice patient care, and enables the incorporation of more extensive precautionary measures in the operating room to minimize occupational risks to the surgical team.
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Infecciones por VIH/epidemiología , Procedimientos Ortopédicos , Adulto , Procedimientos Quirúrgicos Electivos , Ensayo de Inmunoadsorción Enzimática , Infecciones por VIH/diagnóstico , Hospitales Comunitarios , Humanos , Masculino , Maryland/epidemiología , Prevalencia , Sensibilidad y EspecificidadRESUMEN
The patellofemoral articulation is a common and significant source of disability and discomfort in the aging population. This study examined the anatomy of the knee extensor mechanism in patients having primary total knee arthroplasties, characterized the anatomic variations of the extensor mechanism, and correlated these findings with the location and extent of osteoarthritic change of the patellar undersurface. Sixty-two knees (57 patients) were evaluated prospectively. Specific characteristics that were analyzed included the mean Outerbridge grade for rating patellar cartilage degeneration and anatomic patterns of the extensor mechanism. Knees with a quadriceps tendon width at 2 and 5 cm above the patella that differed by less than 1 cm had more statistically significant patellar degeneration in all patellar locations than knees with tendon width differences greater than 1 cm. Anatomic variations, such as tendons with minimal increments in width in the proximal-distal direction, may be associated with an increasing amount of patellar arthrosis at the lateral facet, central ridge, and, most significantly, medial facet.
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Articulación de la Rodilla/patología , Osteoartritis de la Rodilla/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/patologíaRESUMEN
OBJECTIVE: This study examined specific aspects of child sexual abuse in relation to symptom severity among hospitalized patients diagnosed with bulimia nervosa. METHOD: Participants were 45 hospitalized bulimic women who reported a history of child sexual abuse. Structured interviews were conducted in order to obtain detailed information regarding specific features of the abusive event(s). Participants also completed instruments that measured depression and eating pathology. RESULTS: There were no significant differences in severity of depression or eating disturbance among women reporting differing abusive experiences including intrafamilial versus extrafamilial abuse, abuse with or without the use of physical force, one versus multiple incidents, early abuse versus abuse occurring after age 14, contact versus noncontact abuse, disclosed versus undisclosed, and combined physical/sexual abuse versus sexual abuse alone. CONCLUSION: The specific characteristics of child sexual abuse are not related to the level of symptomatology for hospitalized bulimic patients. This study suggests that differences in the nature of the abuse may not be as important as the fact that the abuse occurred in the first place.
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Bulimia/psicología , Abuso Sexual Infantil/psicología , Adolescente , Adulto , Bulimia/etiología , Niño , Preescolar , Trastorno Depresivo/etiología , Trastorno Depresivo/psicología , Femenino , Hospitalización , Humanos , Lactante , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
STUDY DESIGN: A retrospective case-control study evaluating risk factors for infection, causative organisms, and results of treatment in patients with cerebral palsy or myelomeningocele who underwent fusion for scoliosis was performed. OBJECTIVES: To identify risk factors for infection, and to characterize the infections in terms of infecting organisms and response to treatment. SUMMARY OF BACKGROUND DATA: No previous studies have analyzed risk factors or causative organisms, nor have they indicated results of treatment for infections in this group of patients. METHODS: After a 10-year retrospective review of 210 surgically treated patients, deep wound infections developed in 16 patients with myelomeningocele and 9 patients with cerebral palsy. These patients were studied extensively for possible risk factors, along with 50 uninfected patients matched for age, diagnosis, and year of surgery. Statistical testing was performed to identify risk factors. The courses of the infections were characterized in terms of organisms isolated and response to treatment. Treatment was performed in a stepwise fashion and classified in terms of the most successful step: debridement and closure, granulation over rods, or instrumentation removal. RESULTS: Of the 10 risk factors tested, 2 were found to be significant: degree of cognitive impairment and use of allograft. Findings showed that 52% of the infections were polymicrobial. Gram-negative organisms were isolated as commonly as gram-positive organisms. The most common organisms were coagulase-negative Staphylococcus, Enterobacter, Enterococcus, and Escherichia coli.- Debridement and closure were successful in 11 of 25 patients with deep wound infection. Of the 14 patients with infection not resolved by serial debridements and closure, 2 were managed successfully by allowing the wound to granulate over rods, and 7 required rod removal for persistent wound drainage. There were three symptomatic pseudarthroses. Infections resulting from gram-positive organisms were most often managed successfully with debridement and closure (P = 0.012). CONCLUSIONS: Patients with cerebral palsy or myelomeningocele who have severe cognitive impairment, and those who received allograft may be at increased risk for infection. Infections are more often polymicrobial and caused by gram-negative organisms than is typical for elective orthopedic procedures. This suggests an enteric source. Treatment with debridement and closure was not always successful. Patients in whom infection develops are then at increased risk for pseudarthrosis.
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Infecciones por Bacterias Grampositivas/etiología , Procedimientos Ortopédicos/efectos adversos , Escoliosis/cirugía , Infección de la Herida Quirúrgica/etiología , Adolescente , Adulto , Antibacterianos , Parálisis Cerebral/complicaciones , Niño , Drenaje , Quimioterapia Combinada/uso terapéutico , Femenino , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/terapia , Humanos , Masculino , Meningomielocele/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Escoliosis/complicaciones , Infección de la Herida Quirúrgica/diagnóstico , Resultado del TratamientoRESUMEN
OBJECTIVE: To define the epidemiology, clinical and radiographic presentation, treatment, and prognosis of atraumatic osteonecrosis of the humeral head. METHODS: Of the 1,056 patients managed for osteonecrosis of any joint between July 1, 1974, and December 1, 1996, 127 shoulders in 73 patients were treated for atraumatic osteonecrosis of the proximal humerus. Clinical and radiographic characterization of this patient cohort was performed. RESULTS: At presentation, there were 47 women and 26 men with a mean age of 41 years (range 20-60). Numerous associated factors were noted: alcohol use (38%), moderate smoking (30%), asthma (8%), and nephrosis (3%). A corticosteroid association was noted in 60 patients (82%) and 42 of the patients (58%) had an immunocompromising disease. The severity of humeral head osteonecrosis did not correlate with dose or duration of corticosteroid therapy. According to the modified Ficat and Arlet radiographic staging system, there were 20 shoulders with Stage I disease, 55 shoulders with stage II disease, and 52 shoulders with Stage ITI or IV disease. Seventy-four of the shoulders treated with core decompression (78%) had good to excellent clinical outcomes at a mean followup of 6 years (range 2-21). Fourteen of the 16 patients (88%) treated with hemiarthroplasty or total shoulder arthroplasty were clinically successful at a mean followup 4 years (range 2-11). CONCLUSION: We observed a low incidence of humeral head involvement in the osteonecrosis patient cohort (7% of all osteonecrosis patients), and a high incidence of corticosteroid use (82%). hip involvement (81%), and bilateral disease (74%). Osteonecrosis of the humeral head should be suspected in patients presenting with shoulder pain and a history of osteonecrosis in other joints. Hip screening for osteonecrosis is advocated in patients with shoulder involvement. Early detection of shoulder osteonecrosis may permit a more conservative, joint-sparing approach as an alternative to surgical management.
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Húmero/diagnóstico por imagen , Húmero/patología , Osteonecrosis/diagnóstico por imagen , Osteonecrosis/epidemiología , Adulto , Estudios de Cohortes , Femenino , Humanos , Húmero/fisiopatología , Masculino , Persona de Mediana Edad , Osteonecrosis/etiología , Osteonecrosis/terapia , Radiografía , Factores de RiesgoRESUMEN
The results of a study conducted in 1996 by the "Groupe de recherche en ergothérapie communautaire" (GREC), indicate that the quality of occupational therapy services in community settings is infrequently evaluated. A conceptual framework supporting such a process is presented in the context of client-centered services with a focus on continuous health care improvement. Both the research process leading to the design of an assessment tool, and its congruence with the beliefs and values of the profession, are explored. Finally, some issues relating to the implementation of a formal evaluation process are discussed.
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Servicios de Salud Comunitaria/normas , Terapia Ocupacional/normas , Satisfacción del Paciente , Garantía de la Calidad de Atención de Salud/métodos , Encuestas y Cuestionarios , Servicios de Salud Comunitaria/organización & administración , Análisis Factorial , Humanos , Terapia Ocupacional/organización & administración , Proyectos Piloto , Quebec , Reproducibilidad de los ResultadosRESUMEN
Osteonecrosis is a disease that leads to joint destruction and often involves large joints, such as the hips, knees, and shoulders. Nontraumatic osteonecrosis of the adult elbow, to the best of the authors' knowledge, has not been reported. Nine adult patients with atraumatic osteonecrosis of 11 elbows were identified. The mean age at presentation was 36 years (range, 26-63 years); five patients were women and four were men. Six elbows involved the capitellum, three involved the lateral epicondyles, one involved the trochlea and radial head, and one involved medial and lateral epicondylar disease. All patients were receiving corticosteroid therapy, and no relationship between the duration or the amount of corticosteroid use and the severity of the osteonecrosis was found. Seven patients with radiographic Stage I and Stage II disease responded well to nonoperative treatments consisting of activity modification, analgesics, and a brief period of immobilization. Nonoperative treatment failed in two patients with Stage III disease, and they had core decompressions for pain relief. One patient with late Stage III disease in both elbows underwent bilateral total elbow arthroplasties. In contrast to the pediatric population, osteonecrosis of the adult elbow potentially can lead to end stage arthritis. If the osteonecrosis is diagnosed early, nonoperative treatment may be effective in relieving pain, although the long-term results of these treatments remain unknown.
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Articulación del Codo , Osteonecrosis/cirugía , Corticoesteroides/efectos adversos , Adulto , Artroplastia , Descompresión Quirúrgica , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteonecrosis/diagnóstico , Osteonecrosis/etiología , Factores de Riesgo , Resultado del TratamientoRESUMEN
The csrA gene encodes a small RNA-binding protein, which acts as a global regulator in Escherichia coli and other bacteria (T. Romeo, Mol. Microbiol. 29:1321-1330, 1998). Its key regulatory role in central carbon metabolism, both as an activator of glycolysis and as a potent repressor of glycogen biosynthesis and gluconeogenesis, prompted us to examine the involvement of csrA in acetate metabolism and the tricarboxylic acid (TCA) cycle. We found that growth of csrA rpoS mutant strains was very poor on acetate as a sole carbon source. Surprisingly, growth also was inhibited specifically by the addition of modest amounts of acetate to rich media (e.g., tryptone broth). Cultures grown in the presence of >/=25 mM acetate consisted substantially of glycogen biosynthesis (glg) mutants, which were no longer inhibited by acetate. Several classes of glg mutations were mapped to known and novel loci. Several hypotheses were examined to provide further insight into the effects of acetate on growth and metabolism in these strains. We determined that csrA positively regulates acs (acetyl-coenzyme A synthetase; Acs) expression and isocitrate lyase activity without affecting key TCA cycle enzymes or phosphotransacetylase. TCA cycle intermediates or pyruvate, but not glucose, galactose, or glycerol, restored growth and prevented the glg mutations in the presence of acetate. Furthermore, amino acid uptake was inhibited by acetate specifically in the csrA rpoS strain. We conclude that central carbon flux imbalance, inhibition of amino acid uptake, and a deficiency in acetate metabolism apparently are combined to cause metabolic stress by depleting the TCA cycle.
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Acetatos/metabolismo , Proteínas Bacterianas/genética , Proteínas de Escherichia coli , Escherichia coli/fisiología , Regulación Bacteriana de la Expresión Génica , Genes Reguladores , Proteínas de Unión al ARN/genética , Proteínas Represoras , Factor sigma/genética , Aminoácidos/metabolismo , Proteínas Bacterianas/metabolismo , Carbono/metabolismo , Ciclo del Ácido Cítrico , Medios de Cultivo/química , Escherichia coli/genética , Genes Bacterianos , Glucógeno/genética , Glucógeno/metabolismo , Glioxilatos/metabolismo , Mutación , Proteínas de Unión al ARN/metabolismo , Factor sigma/metabolismoRESUMEN
Isocitrate dehydrogenase (IDH)(1) of Escherichia coli is regulated by a bifunctional protein, IDH kinase/phosphatase. In this paper, we demonstrate that the effectors controlling these activities belong to two distinct classes that differ in mechanism and in the locations of their binding sites. NADPH and isocitrate are representative members of one of these effector classes. NADPH inhibits both IDH kinase and IDH phosphatase, whereas isocitrate inhibits only IDH kinase. Isocitrate can "activate" IDH phosphatase by reversing product inhibition by dephospho-IDH. Mutations in icd, which encodes IDH, had parallel effects on the binding of these ligands to the IDH active site and on their effects on IDH kinase and phosphatase, indicating that these ligands regulate IDH kinase/phosphatase through the IDH active site. Kinetic analyses suggested that isocitrate and NADPH prevent formation of the complex between IDH kinase/phosphatase and its protein substrate. AMP, 3-phosphoglycerate, and pyruvate represent a class of regulatory ligands that is distinct from that which includes isocitrate and NADPH. These ligands bind directly to IDH kinase/phosphatase, a conclusion which is supported by the observation that they inhibit the IDH-independent ATPase activity of this enzyme. These effector classes can also be distinguished by the observation that mutant derivatives of IDH kinase/phosphatase expressed from aceK3 and aceK4 exhibited dramatic changes in their responses to AMP, 3-phosphoglycerate, and pyruvate but not to NADPH and isocitrate.
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Escherichia coli/enzimología , Fosfoproteínas Fosfatasas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Adenosina Monofosfato/metabolismo , Sustitución de Aminoácidos , Ácidos Glicéricos/farmacología , Cinética , Modelos Químicos , NADP/metabolismo , NADP/farmacología , Fosfoproteínas Fosfatasas/química , Proteínas Serina-Treonina Quinasas/química , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Especificidad por SustratoRESUMEN
The purposes of this study were to evaluate the efficacy of intraoperative surgeon-elected reinfusion drain placement and to determine whether drainage at 90 minutes is useful in predicting the need for a reinfusion drain. In the standard drain hip arthroplasty group, 6 of 30 patients (20%) received a reinfusion, similar to the 11 of 41 patients (27%) in the reinfusion drain group. In the total knee arthroplasty group, 38 of 45 patients (84%) in the standard group had reinfusion, similar to the 23 of 27 patients (85%) in the reinfusion drain group. The surgeon could not predict intraoperatively which patients would need a subsequent reinfusion drain. However, in more than 94% of the cases, one could know by 90 minutes postoperatively whether a reinfusion would be necessary. We believe that a drain that can be converted to a reinfusion drain in the recovery room would be the most cost-effective drain system.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Transfusión de Sangre Autóloga/métodos , Drenaje , Cuidados Intraoperatorios , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Multiple pathophysiologies for osteonecrosis have been postulated and various associated risk factors defined for this disease. However, the pathologic findings of the end stage disease are thought to be similar in all patients. To the author's knowledge, there are no data in the literature comparing the pathologic characteristics of osteonecrosis in a quantitative manner between groups of patients with different associated risk factors. The current study examined the pathologic features of core decompression specimens from the femoral head in a group of patients with osteonecrosis associated with corticosteroid therapy and compared them with specimens from patients with osteonecrosis with no history of corticosteroid therapy. The study group comprised 65 patients (96 hips); 45 patients (68 hips) in the corticosteroid group and 20 patients (28 hips) in the noncorticosteroid group. In the corticosteroid group, 65% of dead bone was identified histologically (44 of 68) as compared with 46% (13 of 28) in the noncorticosteroid group. Specimens staged according to the histologic grading system of Arlet and Durroux revealed the corticosteroid group had a higher incidence of late stage lesions than did the noncorticosteroid group. This was found even though the two groups had similar radiographic staging distribution. The hips in patients who used alcohol were comparable pathologically to the hips in patients who used corticosteroids. This study emphasizes that the histologic features of necrosis and repair are similar in corticosteroid and noncorticosteroid osteonecrosis. However, there were differences in the distribution of viable bone and pathologic stage of the lesions in the two groups, suggesting a more rapid evolution of changes in the corticosteroid group.
Asunto(s)
Necrosis de la Cabeza Femoral/patología , Adulto , Anciano , Consumo de Bebidas Alcohólicas , Médula Ósea/patología , Descompresión Quirúrgica , Femenino , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Necrosis de la Cabeza Femoral/etiología , Necrosis de la Cabeza Femoral/cirugía , Glucocorticoides/uso terapéutico , Tejido de Granulación/patología , Articulación de la Cadera/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , RadiografíaRESUMEN
Callaghan has suggested that the most important factor in obtaining optimal results after total hip arthroplasty may be the ability to determine when to use cemented or cementless fixation. This article has presented the indications and relative contraindications for use of proximally porous-coated prostheses. Midterm results suggest that with appropriate patient selection, excellent clinical results can be achieved with currently available proximally porous-coated prostheses. Use of proximally coated prostheses is indicated for primary total hip arthroplasty in patients aged >70 years with good bone stock. Relative contraindications are based on interference with bone ingrowth or with the ability to achieve a congruent fit, both of which preclude establishment of rigid initial stability. These conditions include metabolic bone disease such as osteoporosis, osteomalacia, Gaucher's disease, sickle cell disorders, and Paget's disease; significant anatomical distortion, as seen in developmental dysplasia of the hip with anteversion, prior osteotomy, or intertrochanteric fracture; Dorr type C bone; and current treatment with radiation, chemotherapy, indomethacin, or diphosphonates. The same relative contraindications to use are applicable in revision situations. Further, proximally porous-coated prostheses should not be used for revision arthroplasty in the setting of massive bone loss, limited life expectancy, or inability to participate in protected weight bearing. These devices may be used successfully in revision arthroplasty when the hip has minimal or moderate bone loss, and occasionally in the setting of severe bone loss. As further information is revealed through the long-term (10-20 years) results of proximally coated prostheses, further refinements and knowledge of the indications and contraindications for the use of these prostheses will be revealed.
Asunto(s)
Prótesis de Cadera , Artroplastia de Reemplazo de Cadera/métodos , Contraindicaciones , Fémur , Estudios de Seguimiento , Humanos , Diseño de Prótesis , Factores de RiesgoRESUMEN
Glucokinase (GK) is expressed in the pancreatic beta-cells and liver, and plays a key role in the regulation of glucose homeostasis. The enzymatic activity and thermal stability of wild-type (WT) GK and several mutant forms associated with maturity-onset diabetes of the young type 2 (MODY-2) were determined by a steady-state kinetic analysis of the purified expressed proteins. The eight MODY-2 mutations studied were Ala53Ser, Val367Met, Gly80Ala, Thr168Pro, Arg36Trp, Thr209Met, Cys213Arg, and Val226Met. These missense mutations were shown to have variable effects on GK kinetic activity. The Gly80Ala and Thr168Pro mutations resulted in a large decrease in Vmax and a complete loss of the cooperative behavior associated with glucose binding. In addition, the Gly80Ala mutation resulted in a sixfold increase in the half-saturating substrate concentration (S0.5) for ATP, and Thr168Pro resulted in eight- and sixfold increases in the S0.5 values for ATP and glucose, respectively. The Thr209Met and Val226Met mutations exhibited three- and fivefold increases, respectively, in the S0.5 for ATP, whereas the Cys213Arg mutation resulted in a fivefold increase in the S0.5 for glucose. These mutations also led to a small yet significant reduction in Vmax. Of all the mutations studied, only the Cys213Arg mutation had reduced enzymatic activity and decreased thermal stability. Two mutants, Ala53Ser and Val367Met, showed kinetic and thermal stability properties similar to those of WT. These mutants had increased sensitivities to the known negative effectors of GK activity, palmitoyl-CoA, and GK regulatory protein. Taken together, these results illustrate that the MODY-2 phenotype may be linked not only to kinetic alterations but also to the regulation of GK activity.