RESUMEN
Omega-3 fatty acids have been implicated in the aetiology of depressive disorders, though trials supplementing omega-3 to prevent major depressive disorder (MDD) have so far been unsuccessful. Whether this association is causal remains unclear. We used two sample Mendelian randomization (MR) to investigate causality. Genetic variants associated with circulating omega-3 and omega-6 fatty acids in UK Biobank (UKBB, n = 115,078) were selected as exposures. The Psychiatric Genomics Consortium (PGC) genome-wide association studies (GWAS) of MDD (n = 430,775; cases = 116,209; controls = 314,566) and recurrent depression (rMDD, n = 80,933; cases = 17,451; controls = 62,482), were used as outcomes. Multivariable MR (MVMR) models were used to account for biologically correlated lipids, such as high- and low-density cholesterol and triglycerides, and to explore the relative importance of longer-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) using data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, n = 8866). Genetic colocalization analyses were used to explore the presence of a shared underlying causal variant between traits. Genetically predicted total omega-3 fatty acids reduced the odds of MDD (ORIVW 0.96 per standard deviation (SD, i.e. 0.22 mmol/l) (95% CIs 0.93-0.98, p = 0.003)). The largest point estimates were observed for eicosapentaenoic acid (EPA), a long-chain omega-3 fatty acid (OREPA 0.92; 95% CI 0.88-0.96; p = 0.0002). The effect of omega-3 fatty acids was robust to MVMR models accounting for biologically correlated lipids. 'Leave-one-out' analyses highlighted the FADS gene cluster as a key driver of the effect. Colocalization analyses suggested a shared causal variant using the primary outcome sample, but genomic confounding could not be fully excluded. This study supports a role for omega-3 fatty acids, particularly EPA, in the aetiology of depression, although pleiotropic mechanisms cannot be ruled out. The findings support guidelines highlighting the importance of EPA dose and ratio for MDD and question whether targeted interventions may be superior to universal prevention trials, as modest effect sizes will limit statistical power.
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Trastorno Depresivo Mayor , Ácidos Grasos Omega-3 , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/epidemiología , Ácidos Grasos Omega-3/sangre , Femenino , Masculino , Polimorfismo de Nucleótido Simple , Persona de Mediana Edad , Ácido Eicosapentaenoico/sangre , Ácidos Docosahexaenoicos/sangre , delta-5 Desaturasa de Ácido Graso , Ácido Graso Desaturasas/genética , Adulto , Ácidos Grasos Omega-6/sangre , Anciano , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Metabolic and inflammatory disorders commonly co-occur with depression and psychosis, with emerging evidence implicating immuno-metabolic dysfunction in their aetiology. Previous studies have reported metabolic dysfunction and inflammation in adults with depression and psychosis. However, longitudinal studies testing the direction of association, and the effects of different dimensions of early-life immuno-metabolic dysfunction on adult psychopathology are limited. METHODS: Using data from 3258 birth cohort participants we examined longitudinal associations of three metabolic hormones (leptin, adiponectin, insulin) at age 9 with risks for depression- and psychosis-spectrum outcomes at age 24. In addition, using nine immuno-metabolic biomarkers (leptin, adiponectin, insulin, interleukin-6, C-Reactive protein, low density lipoprotein, high density lipoprotein, triglycerides, and BMI), we constructed an exploratory bifactor model showing a general immuno-metabolic factor and three specific factors (adiposity, inflammation, and insulin resistance), which were also used as exposures. RESULTS: Childhood leptin was associated with adult depressive episode (adjusted odds ratio (aOR)= 1.31; 95% CI, 1.02-1.71) and negative symptoms (aOR=1.15; 95% CI, 1.07-1.24), but not positive psychotic symptoms. The general immuno-metabolic factor was associated with atypical depressive symptoms (aOR=1.07; 95% CI, 1.01-1.14) and psychotic experiences (aOR=1.21; 95% CI, 1.02-1.44). The adiposity factor was associated with negative symptoms (aOR=1.07; 95% CI 1.02-1.12). Point estimates tended to be larger in women, though 95% credible intervals overlapped with those for men. In women, the inflammatory factor was associated with depressive episodes (aOR=1.27; 95% CI, 1.03-1.57). CONCLUSIONS: While general immuno-metabolic dysfunction in childhood may contribute to risks for both psychotic and depressive symptoms in adulthood, childhood adiposity and inflammation appear to be particularly linked to affective (depressive and negative), but not positive psychotic symptoms.
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Depresión , Trastornos Psicóticos , Adulto , Cohorte de Nacimiento , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Long chain polyunsaturated fatty acid (PUFA) levels have been implicated in the pathology of psychotic disorders. We investigated the relationship between childhood PUFA levels and later psychotic experiences (PE's) in a large birth cohort. METHODS: Plasma levels of Ω-3 and Ω-6 fatty acids (FA's) were assayed at ages 7 and 16 years. PE's were assessed at ages 12 and 18 years using a semi-structured interview. Primary outcome was any PE's at 18 years; sensitivity analyses examined incident PE's between ages 12 and 18 years, persistent PE's (at 12 and 18) and psychotic disorder at 18 years. Genetic instruments for Ω-3 and Ω-6 were derived and used in a multivariable Mendelian Randomization analysis. RESULTS: Higher levels of Ω-6 FA's AA, OA and AdA at age 7 years were weakly associated with a reduced risk for PE's at 18 years, however, effect sizes were small and attenuated after adjusting for confounders (strongest evidence for OA; adjusted OR, 0.842; 95% CI, 0.711, 0.998; p, 0.048). Total Ω-6 levels at age 16 years were associated with an increased odds of psychotic disorder at age 18 years. However, there was no association between Ω-6/Ω-3 ratio and psychosis outcomes, nor with genetic instruments of total Ω-3 or Ω-6 levels. CONCLUSIONS: There is no strong evidence that total plasma Ω-3 FA levels or Ω-6/Ω-3 ratios in childhood and mid-adolescence are associated with increased risk for PE's or psychotic disorder, but very marginal evidence that alterations in the Ω-6 pathway at developmental time points might influence risk2.
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Ácidos Grasos Omega-3 , Trastornos Psicóticos , Adolescente , Niño , Ácidos Grasos , Ácidos Grasos Omega-6 , Ácidos Grasos Insaturados , Humanos , Trastornos Psicóticos/epidemiologíaRESUMEN
BACKGROUND: Local excision is now accepted as a standard treatment option for certain patients with early rectal cancer. However, there is a higher risk of local recurrence than after radical surgery with total mesorectal excision. Adjuvant radiotherapy after local excision may reduce this excess risk, and yet retain the benefits of local excision, with rectal preservation. METHODS: A review of the literature pertaining to the use of adjuvant radiotherapy after local excision of rectal cancer and a discussion of current practice. RESULTS: We first considered local excision as a treatment option for early rectal cancer, looking at technical developments and the risks and benefits of organ preservation, in particular, the advantages for quality of life and the risk of leaving residual disease which may result in local recurrence. We then looked at reported outcomes for studies using adjuvant radiotherapy after local excision. Few of the studies routinely used modern endoscopic methods of local excision and only the recent used chemoradiation. Local recurrence rates after adjuvant radiotherapy have improved over time, with rates of around 3.5% in the recent studies. Adverse effects of adjuvant radiotherapy are not commonly described, but generally, they are relatively mild when described. We then discussed current practice regarding adjuvant radiotherapy, including pathological criteria, discussion of local recurrence risk with the patient and the importance of a surveillance regime to detect any recurrence at an early stage. CONCLUSION: We conclude that the current state of knowledge regarding adjuvant radiotherapy after local excision suggests a potential role in decreasing the risk of local recurrence but further studies are required to better define this effect, clarify which patients will gain the most benefit from this pathway, and identify those who should avoid exposure to the risks of radiotherapy.
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Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Calidad de Vida , Radioterapia Adyuvante , Neoplasias del Recto/radioterapia , Humanos , Pronóstico , Neoplasias del Recto/cirugíaRESUMEN
AIM: Early rectal cancer can be managed effectively with local excision, which is now the standard of care for many T1 lesions. However, the presence of unexpected adverse histopathological factors may indicate an increased risk of local recurrence, prompting consideration of completion radical surgery. Many patients are unfit or prefer to avoid radical surgery, relying instead on surveillance and early detection of recurrent disease. Recently, radiotherapy has shown promise as an adjuvant therapy in this group. This study assesses local recurrence rates after local excision with adjuvant radiotherapy at a single centre. METHOD: This was a retrospective review of a prospective database of all patients undergoing transanal endoscopic microsurgery (TEM) in a single institution. Data covering a 10-year period were analysed. RESULTS: Of 197 patients undergoing TEM for rectal cancer, 33 (17%) had adjuvant radiotherapy because of adverse histopathological features. At 3.2 years' median follow-up, there were three instances of local recurrence (9.1%). Estimated local recurrence at 1 and 3 years was 0% and 6.9%, compared to 16.8% and 21.2% in a propensity-score-matched group who were followed by surveillance alone. Local recurrence was diagnosed at a median of 23 months post-TEM in the radiotherapy group, compared to 8 months in the matched group. CONCLUSION: Radiotherapy after TEM is associated with a trend towards a reduced rate of local recurrence, even for high-risk disease. Radiotherapy would appear to offer a viable alternative to radical completion surgery in the presence of unforeseen adverse histopathological features, as long as a meticulous surveillance programme is in place.
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Recurrencia Local de Neoplasia/prevención & control , Proctectomía/estadística & datos numéricos , Radioterapia Adyuvante/estadística & datos numéricos , Neoplasias del Recto/terapia , Microcirugía Endoscópica Transanal/estadística & datos numéricos , Adulto , Anciano , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Proctectomía/métodos , Estudios Prospectivos , Radioterapia Adyuvante/métodos , Estudios Retrospectivos , Microcirugía Endoscópica Transanal/métodos , Resultado del TratamientoRESUMEN
AIM: Minimally invasive, organ-sparing surgery has been used increasingly for early rectal cancer in recent years. However, local recurrence remains a concern. This study presents a 10-year single-centre experience of recurrence after local excision for T1 rectal cancer. METHOD: Data were collected prospectively on all patients undergoing local excision by transanal endoscopic microsurgery (TEM) in a single institution. Data covering a 10-year period were analysed. RESULTS: In all, 192 patients underwent TEM for rectal cancer; 70 of these had T1 tumour in the TEM specimen and did not have preoperative radiotherapy. Four were managed with completion surgery following TEM and a further six had radiotherapy; 60 underwent surveillance alone. Local recurrence occurred in six patients; three underwent salvage surgery. Estimated local recurrence at 3 years was 7.2% for the surveillance alone group. CONCLUSIONS: Local recurrence rates were lower than previous studies. Better preoperative assessment, more effective local excision surgery and postoperative radiotherapy may be contributory factors to a better-than-predicted outcome. Local excision should be offered as part of standard of care for T1 rectal cancer in the presence of good preoperative selection and meticulous surveillance.
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Selección de Paciente , Neoplasias del Recto/cirugía , Vigilancia de Guardia , Microcirugía Endoscópica Transanal/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Periodo Posoperatorio , Estudios Prospectivos , Neoplasias del Recto/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Observational associations between cannabis and schizophrenia are well documented, but ascertaining causation is more challenging. We used Mendelian randomization (MR), utilizing publicly available data as a method for ascertaining causation from observational data. METHOD: We performed bi-directional two-sample MR using summary-level genome-wide data from the International Cannabis Consortium (ICC) and the Psychiatric Genomics Consortium (PGC2). Single nucleotide polymorphisms (SNPs) associated with cannabis initiation (p < 10-5) and schizophrenia (p < 5 × 10-8) were combined using an inverse-variance-weighted fixed-effects approach. We also used height and education genome-wide association study data, representing negative and positive control analyses. RESULTS: There was some evidence consistent with a causal effect of cannabis initiation on risk of schizophrenia [odds ratio (OR) 1.04 per doubling odds of cannabis initiation, 95% confidence interval (CI) 1.01-1.07, p = 0.019]. There was strong evidence consistent with a causal effect of schizophrenia risk on likelihood of cannabis initiation (OR 1.10 per doubling of the odds of schizophrenia, 95% CI 1.05-1.14, p = 2.64 × 10-5). Findings were as predicted for the negative control (height: OR 1.00, 95% CI 0.99-1.01, p = 0.90) but weaker than predicted for the positive control (years in education: OR 0.99, 95% CI 0.97-1.00, p = 0.066) analyses. CONCLUSIONS: Our results provide some that cannabis initiation increases the risk of schizophrenia, although the size of the causal estimate is small. We find stronger evidence that schizophrenia risk predicts cannabis initiation, possibly as genetic instruments for schizophrenia are stronger than for cannabis initiation.
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Estudio de Asociación del Genoma Completo/métodos , Uso de la Marihuana/epidemiología , Análisis de la Aleatorización Mendeliana/métodos , Esquizofrenia/epidemiología , Humanos , Polimorfismo de Nucleótido Simple , RiesgoRESUMEN
The aim of this study was to quantify connective tissue fibre orientation and alignment in young, old and glaucomatous human optic nerve heads (ONH) to understand ONH microstructure and predisposition to glaucomatous optic neuropathy. Transverse (seven healthy, three glaucomatous) and longitudinal (14 healthy) human ONH cryosections were imaged by both second harmonic generation microscopy and small angle light scattering (SALS) in order to quantify preferred fibre orientation (PFO) and degree of fibre alignment (DOFA). DOFA was highest within the peripapillary sclera (ppsclera), with relatively low values in the lamina cribrosa (LC). Elderly ppsclera DOFA was higher than that in young ppsclera (p < 0.00007), and generally higher than in glaucoma ppsclera. In all LCs, a majority of fibres had preferential orientation horizontally across the nasal-temporal axis. In all glaucomatous LCs, PFO was significantly different from controls in a minimum of seven out of 12 LC regions (p < 0.05). Additionally, higher fibre alignment was observed in the glaucomatous inferior-temporal LC (p < 0.017). The differences between young and elderly ONH fibre alignment within regions suggest that age-related microstructural changes occur within the structure. The additional differences in fibre alignment observed within the glaucomatous LC may reflect an inherent susceptibility to glaucomatous optic neuropathy, or may be a consequence of ONH remodelling and/or collapse.
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Envejecimiento/patología , Colágenos Fibrilares/ultraestructura , Glaucoma/patología , Imagenología Tridimensional/métodos , Microscopía/métodos , Disco Óptico/ultraestructura , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Conformación Molecular , Imagen Molecular/métodos , Disco Óptico/patología , Reproducibilidad de los Resultados , Dispersión del Ángulo Pequeño , Sensibilidad y Especificidad , Adulto JovenRESUMEN
AIM: Traditionally, pelvic floor retraining for faecal incontinence or obstructed defaecation has been delivered to patients through individual sessions with a specialist pelvic floor nurse, a resource-intensive practice. This study aimed to assess whether a similar outcome can be achieved by delivering retraining to patients in small groups, allowing considerable savings in the use of resources. METHOD: Data were collected prospectively in a pelvic floor database. Patients received pelvic floor retraining either individually or in a small group setting and completed baseline and follow-up questionnaires. Two hundred and fifteen patients were treated, 119 individually and 96 in a small group setting. Scores before and after treatment for the two settings were compared for the Gastrointestinal Quality of Life Index, the Fecal Incontinence Severity Index and the Patient Assessment of Constipation Symptoms. Additionally patients receiving group treatment completed a short questionnaire on their experience. RESULTS: The median change in Gastrointestinal Quality of Life Index score was 5 (range -62 to 73) for individual treatment and 4 (range -41 to 47) for group treatment, both showing statistically significant improvement. However, there was no significant difference between the settings. Similar results were obtained with the Fecal Incontinence Severity Index and Patient Assessment of Constipation Symptoms scores for the faecal incontinence and obstructed defaecation subgroups respectively. CONCLUSION: The majority of patients experienced symptomatic improvement following pelvic floor retraining and there was no significant difference in the resulting improvement according to treatment setting. As treatment costs are considerably less in a group setting, group pelvic floor retraining is more cost-effective than individual treatment.
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Terapia por Ejercicio/métodos , Incontinencia Fecal/terapia , Trastornos del Suelo Pélvico/terapia , Adulto , Anciano , Estreñimiento/psicología , Estreñimiento/terapia , Defecación , Terapia por Ejercicio/economía , Terapia por Ejercicio/psicología , Incontinencia Fecal/psicología , Femenino , Asignación de Recursos para la Atención de Salud/métodos , Humanos , Masculino , Persona de Mediana Edad , Diafragma Pélvico , Trastornos del Suelo Pélvico/psicología , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Selenium's (Se) protective effects against mercury (Hg) toxicity have been demonstrated; however, this is seldom considered in health assessments, where dietary exposure is still evaluated by Hg concentration alone. Se:Hg ratios and selenium health benefit values (Se HBVs) offer a more comprehensive seafood safety model. Here we describe total mercury (THg), methylmercury (MeHg) and Se concentrations in fish from a Hg-polluted estuary. Spatial variation in THg, MeHg and Se was evident, though all regions maintained Se:Hg ratio values >1. Se HBV varied between regions and in one region mean negative values (-5.17) were evident. This study provides the first evidence that quoting a single all-encompassing Se HBV is not appropriate when species demonstrate strong site fidelity. It highlights the need for research into Se-Hg relationships in environments with established Hg pollution and reinforces the assertion that Se concentration be considered in assessments of human health risk to Hg exposure.
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Exposición a Riesgos Ambientales/estadística & datos numéricos , Peces/metabolismo , Mercurio/análisis , Selenio/análisis , Contaminantes Químicos del Agua/análisis , Animales , Monitoreo del Ambiente , Humanos , Mercurio/metabolismo , Medición de Riesgo , Selenio/metabolismo , Contaminantes Químicos del Agua/metabolismoRESUMEN
Only two of 49 cats undergoing surgical ligation of congenital extra- and intrahepatic portosystemic shunts died perioperatively, a mortality rate comparable with the mortality rates of dogs undergoing surgical attenuation of congenital portosystemic shunts and cats in which the shunts are attenuated with an ameroid ring constrictor. Thirty (83 per cent) of the 36 cats for which long-term information was available were still alive at a median follow-up period of 47 months (range six to 105 months); the outcome was excellent (no clinical signs) in 20 of them (median follow-up 37 months, range six to 105 months) and good (minimal clinical signs) in seven (median follow-up 39 months, range 10 to 73 months) and none of these 27 cats was on any long-term medication or special diet. The only major cause of morbidity was the development of neurological signs in 18 (37 per cent) of the cats. These included seizures and a wide variety of other neurological signs, and their development and persistence was not affected by the presence of preoperative seizures, the type of shunt, the degree of shunt attenuation or the age of the cat. The serum concentrations of ammonia and preprandial bile acids were normal or significantly below normal in the cats with neurological signs. Liver histopathology was similar in the cats with and without neurological signs. Ten (56 per cent) of the 18 cats that developed neurological signs recovered normal neurological function long term.
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Enfermedades de los Gatos/epidemiología , Sistema Porta/anomalías , Sistema Porta/cirugía , Complicaciones Posoperatorias/veterinaria , Convulsiones/veterinaria , Animales , Enfermedades de los Gatos/mortalidad , Gatos , Femenino , Estudios de Seguimiento , Ligadura/métodos , Ligadura/veterinaria , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/mortalidad , Convulsiones/epidemiología , Convulsiones/mortalidad , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
m-Tetra(hydroxyphenyl)chlorin (m-THPC, Foscan, Temoporfin) has an unusually high photodynamic efficacy which cannot be explained by its photochemical properties alone. In vivo interactions are therefore of critical importance in determining this high potency. The pharmacokinetics of m-THPC in a rat tumour model was determined using (14)C m-THPC in an LSBD(1) fibrosarcoma implanted into BDIX rats. The photodynamic therapy (PDT) efficacy was determined at different drug administrations to light intervals and correlated with the tumour and plasma pharmacokinetic data. The plasma pharmacokinetics of m-THPC can be interpreted by compartmental analysis as having three half-lives of 0.46, 6.91 and 82.5 h, with a small initial volume of distribution, suggesting retention in the vascular compartment. Tissues of the reticuloendothelial system showed high accumulation of m-THPC, particularly the liver. PDT efficacy of m-THPC over the same time course seemed to exhibit two peaks of activity (2 and 24 h), in terms of tumour growth delay with the peak at 24 h postinjection correlating to the maximum tumour concentration. Investigation on tumour cells isolated from m-THPC-treated tumours suggested that the peak PDT activity at 2 h represents an effect on the vasculature while the peak at 24 h shows a more direct response. These results indicate that the in vivo PDT effect of m-THPC occurs via several mechanisms.
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Mesoporfirinas/farmacología , Mesoporfirinas/farmacocinética , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/farmacocinética , Animales , Modelos Animales de Enfermedad , Esquema de Medicación , Fibrosarcoma/tratamiento farmacológico , Semivida , Cinética , Masculino , Neoplasias Experimentales , Fotoquimioterapia , RatasRESUMEN
Patients with chronic renal impairment (CRI) are at greatly increased risk for premature vascular disease; however, little is known about its evolution. This paper describes a cohort of patients with CRI and reports study design, baseline demographic and biochemical data, and comparisons with two contemporaneous age- and sex-matched control groups, one with established coronary artery disease and the other without overt vascular disease. Among 369 individuals (median age, 63 years; range, 18 to 88 years; 67% men) with CRI, 34% had a history of vascular disease and 21% had electrocardiographic left ventricular hypertrophy (LVH). Even in those with mild renal impairment (serum creatinine < 2.1 mg/dL), approximately one third had vascular disease and 12% had LVH. A history of hypertension was present in 76% of the CRI group, but as compared with controls, systolic and diastolic blood pressures were not elevated. Low-density lipoprotein (LDL) cholesterol concentration also was not elevated, but CRI was associated with elevated serum triglyceride and plasma homocysteine levels and reduced high-density lipoprotein (HDL) cholesterol, hemoglobin, and serum albumin concentrations. Across the spectrum of CRI, more severe renal dysfunction was associated with lower levels of diastolic blood pressure, LDL and HDL cholesterol, albumin, and hemoglobin, but increased levels of plasma homocysteine. This cross-sectional analysis shows that vascular disease is common in individuals with mild CRI attending a nephrology program and also suggests trends in the levels of a number of potential vascular risk factors with respect to severity of renal dysfunction. These results will be further quantified in a prospective biennial follow-up.
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Enfermedades Cardiovasculares/etiología , Fallo Renal Crónico/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Presión Sanguínea , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Trastornos Cerebrovasculares/sangre , Trastornos Cerebrovasculares/epidemiología , Trastornos Cerebrovasculares/etiología , HDL-Colesterol/sangre , Estudios de Cohortes , Enfermedad Coronaria/sangre , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/etiología , Creatinina/sangre , Estudios Transversales , Diabetes Mellitus/epidemiología , Femenino , Hemoglobina A/análisis , Homocisteína/sangre , Humanos , Hipertrofia Ventricular Izquierda/sangre , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/etiología , Fallo Renal Crónico/sangre , Masculino , Persona de Mediana Edad , Estado Nutricional , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/epidemiología , Enfermedades Vasculares Periféricas/etiología , Prevalencia , Estudios ProspectivosRESUMEN
OBJECTIVES: This study was designed to determine the effects of folic acid therapy on endothelial function in patients with coronary artery disease (CAD). BACKGROUND: Hyperhomocysteinemia, a risk factor for CAD, may cause atherosderosis by oxidative endothelial injury. Folic acid reduces plasma homocysteine, but the effect on adverse vascular events is unknown. METHODS: In a double-blind placebo-controlled trial, 90 patients (mean age [range] 63 [46 to 79] years, 79 men) with CAD were randomized to either folic acid 5 mg or placebo daily for 12 weeks. Endothelial function was assessed by measuring: 1) flow-mediated endothelium-dependent dilation (EDD) of the brachial artery; 2) combined serum nitrite/nitrate (NOx) concentrations and; 3) plasma von Willebrand factor (vWF) concentration. RESULTS: At the end of the study, plasma homocysteine was lower in the folic acid group compared with the placebo group (mean [95% confidence interval] 9.3 (8.5 to 10.1) vs. 12.3 [11.3 to 13.4] micromol/l, p < 0.001). Although there were no significant differences in EDD, serum NOx or plasma vWF between the two groups, there was a greater increase in EDD from baseline in the folic acid group compared to placebo (1.2 [0.7 to 1.8] vs. 0.4 [-0.3 to 1.1]%, p = 0.07). CONCLUSIONS: Folic acid reduced plasma homocysteine and was associated with a trend toward improved endothelial function in patients with CAD. The absence of an unequivocally positive result may have been due to inadequate sample size or chance. This reinforces the need for the results of large randomized controlled trials before the implementation of routine folic acid supplementation.
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Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/fisiopatología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Ácido Fólico/uso terapéutico , Homocisteína/sangre , Anciano , Enfermedad Coronaria/sangre , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nitratos/sangre , Nitritos/sangre , Flujo Sanguíneo Regional , Factor de von Willebrand/análisisRESUMEN
BACKGROUND: Considerable evidence suggests that hyperhomocysteinemia is an independent vascular risk factor that promotes atherosclerosis by inducing endothelial dysfunction. Although folic acid reduces hyperhomocysteinemia, the effect on adverse vascular events is unknown. We hypothesized that in patients with chronic renal failure, a condition associated with both hyperhomocysteinemia and atherosclerosis, treatment with folic acid would improve endothelial function. METHODS AND RESULTS: In a prospective, double-blind protocol, 100 patients (mean age 62 years, 67 men) with predialysis chronic renal failure were randomized to 5 mg folic acid or placebo daily for 12 weeks. Endothelial function was assessed by measuring (1) endothelium-dependent dilation of the brachial artery, (2) combined serum nitrite/nitrate concentrations, and (3) plasma von Willebrand factor concentration. Baseline characteristics of the 2 groups were similar. At the end of the study, both serum and red cell folate concentrations were greater in the folic acid group than the placebo group [mean (95% CI) 39.0 (29.8 to 51.0) versus 7.7 (6.6 to 8.9) microg/L and 739 (613 to 891) versus 220 (184 to 262) microg/L, respectively; both P<0.001]. Despite a reduction in hyperhomocysteinemia in the folic acid group compared with the placebo group [15.1 (14.1 to 16.2) versus 20.1 (18.2 to 22.2) micromol/L; P<0.001], there were no significant differences in endothelium-dependent dilation, combined serum nitrite/nitrate concentrations, or plasma von Willebrand factor concentration between the 2 groups. CONCLUSIONS: High-dose folic acid lowers but fails to normalize hyperhomocysteinemia in patients with predialysis chronic renal failure. This was not accompanied by an improvement of endothelial function and suggests that treatment with folic acid may not reduce the burden of vascular disease in uremia.
Asunto(s)
Endotelio Vascular/efectos de los fármacos , Ácido Fólico/uso terapéutico , Hematínicos/uso terapéutico , Homocisteína/sangre , Fallo Renal Crónico/tratamiento farmacológico , Anciano , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/efectos de los fármacos , Arteria Braquial/fisiopatología , Método Doble Ciego , Endotelio Vascular/fisiopatología , Eritrocitos/metabolismo , Femenino , Ácido Fólico/sangre , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Nitratos/sangre , Nitritos/sangre , Placebos , Estudios Prospectivos , Diálisis Renal , Ultrasonografía , Vasodilatación/efectos de los fármacos , Factor de von Willebrand/metabolismoRESUMEN
BACKGROUND: Endothelial dysfunction plays an important role in the development of atherosclerotic vascular disease, which is the leading cause of mortality in patients with chronic renal failure. OBJECTIVE: To examine the relation between predialysis renal failure and endothelial function. DESIGN: Two groups were studied: 80 patients with non-diabetic chronic renal failure and 26 healthy controls, with similar age and sex distributions. Two indices of endothelial function were assessed: high resolution ultrasonography to measure flow mediated endothelium dependent dilatation of the brachial artery following reactive hyperaemia, and plasma concentration of von Willebrand factor. Endothelium independent dilatation was also assessed following sublingual glyceryl trinitrate. The patients were divided into those with and without overt atherosclerotic vascular disease. RESULTS: Although patients with chronic renal failure had significantly impaired endothelium dependent dilatation compared with controls (median (interquartile range), 2.6% (0.7% to 4.8%) v 6.5% (4.8% to 8.3%); p < 0.001) and increased von Willebrand factor (254 (207 to 294) v 106 (87 to 138) iu/dl; p < 0.001), there was no difference between renal failure patients with and without atherosclerotic vascular disease. Within the chronic renal failure group, endothelium dependent dilatation and von Willebrand factor were similar in patients in the upper and lower quartiles of glomerular filtration rate (2.7% (0.7% to 6.7%) v 2.8% (1.1% to 5.0%); and 255 (205 to 291) v 254 (209 to 292) iu/dl, respectively). Endothelium independent dilatation did not differ between the renal failure or control groups and was also similar in patients with renal failure irrespective of the degree of renal failure or the presence of atherosclerotic vascular disease. CONCLUSIONS: Endothelial function is abnormal in chronic renal failure, even in patients with mild renal insufficiency and those without atherosclerotic vascular disease, suggesting that uraemia may directly promote the development of atherosclerosis early in the progression of chronic renal failure.
Asunto(s)
Arteriosclerosis/fisiopatología , Endotelio Vascular/fisiopatología , Fallo Renal Crónico/fisiopatología , Arteriosclerosis/sangre , Arteriosclerosis/diagnóstico por imagen , Estudios de Casos y Controles , Endotelio Vascular/diagnóstico por imagen , Femenino , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/diagnóstico por imagen , Masculino , Ultrasonografía , Factor de von Willebrand/análisisRESUMEN
BACKGROUND: A minority of hospitals in the UK have a high-dependency unit (HDU). One reason for this is a lack of evidence supporting its benefit. This study sought to compare the outcomes of patients undergoing major abdominal surgery with regard to HDU utilization. METHODS: Data were collected prospectively from two groups of patients over 10 months. Patients in the no-HDU group underwent major abdominal surgery in a hospital without an HDU and returned to a general surgical ward. The other group was managed initially in an HDU. Data collected included Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) scores, complications, deaths and length of stay. RESULTS: Physiological and operative scores as calculated on the RAJIS POSSUM software were similar in both groups. The HDU group comprised 121 patients. Sixty-four developed a complication whereas 58.81 were expected to, giving an observed : expected (O : E) ratio of 1.09. Sixteen deaths occurred and 14.54 were expected (O : E ratio 1.10). Some 50 per cent stayed in hospital longer than was predicted. The no-HDU group comprised 71 patients. Fifty-nine developed a complication compared with 33.82 expected (O : E ratio 1.74). Ten deaths occurred, whereas 8.88 were expected, giving an O : E ratio of 1.13. Some 63 per cent stayed longer than predicted. The O : E ratios for morbidity were significantly different (P < 0.0005). The complications that occurred more frequently in the absence of an HDU were chest infection, arrhythmias and hypotension. CONCLUSION: Postoperative management on an HDU was associated with fewer cardiorespiratory complications. There was no difference in mortality rate but there was a trend towards shorter hospital stay.
Asunto(s)
Cuidados Críticos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Cuidados Posoperatorios/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Especialidades Quirúrgicas , Reino UnidoRESUMEN
BACKGROUND: A large number of scoring systems for assessing a patient's risk of complications or death has been developed over recent years. This is a review of those that are of relevance to general surgeons. METHODS: A Medline literature search was performed to identify all articles concerning 'severity of illness', 'morbidity', 'mortality' and 'postoperative complications' in the field of surgery from 1966 to 1997. Further searches were performed to find papers about specific identified scoring systems, and relevant articles from the reference lists of these were also sought. RESULTS AND CONCLUSION: The advantages of an accurate assessment of a patient's risk include, on an individual level, the opportunity to give a more accurate prognosis and choose the most appropriate treatment. If the risk of an adverse outcome is known for a group of patients, the actual outcome can be compared with the predicted outcome, and comparison can be made between groups in different surgical units for the purposes of audit or research. The Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) is the most appropriate of the currently available scores for general surgical practice.
Asunto(s)
Medición de Riesgo/métodos , Índice de Severidad de la Enfermedad , Procedimientos Quirúrgicos Operativos , APACHE , Cuidados Críticos , Estado de Salud , Humanos , Insuficiencia Multiorgánica/mortalidad , Pronóstico , Sepsis/mortalidad , Heridas y Lesiones/mortalidadRESUMEN
Fibromuscular dysplasia (FMD) is one of the most important mimics of vasculitis. FMD is more prevalent in women and may cause infarcts of organ systems including the brain, intestines, and extremities. These acute clinical presentations often raise the suspicion of vasculitis and therefore rheumatologists will be asked to evaluate these patients. One of the frequent manifestations of FMD is renal artery involvement. Angiographic evaluation often shows a "string of beads" appearance of the renal arteries but sometimes only tapering of the vascular lumen or cutoffs may be seen. In contrast, hepatic artery involvement with FMD occurs much less frequently and may initially present with life threatening intraabdominal bleeding. Celiac angiograms of these patients often show aneurysms, a presentation similar to vasculitis. Only a high level of suspicion for FMD and careful evaluation of clinical facts will lead to correct diagnosis. This will prevent the wrong diagnosis of vasculitis and subsequent treatment with potentially toxic medications. We present 2 cases of FMD involving the renal and hepatic arteries that illustrate this diagnostic challenge.
Asunto(s)
Aneurisma Roto/complicaciones , Displasia Fibromuscular/complicaciones , Displasia Fibromuscular/diagnóstico , Infarto/complicaciones , Vasculitis/diagnóstico , Adulto , Angiografía , Diagnóstico Diferencial , Femenino , Arteria Hepática/diagnóstico por imagen , Humanos , Riñón/irrigación sanguínea , Masculino , Persona de Mediana Edad , Arteria Renal/diagnóstico por imagenRESUMEN
Fifty-nine evacuating proctograms were performed over a 4 month period. We sought to identify how useful this technique is in diagnosing the cause of various anorectal symptoms and indicating which treatment option may be beneficial to the patient. The main reasons for referral were faecal soiling (60%) and obstructed defaecation (47%). Of the proctograms, 90% revealed some pathology. The most common abnormalities detected were rectocele (56%), rectal intussusception (39%), enterocele (19%) and rectal prolapse (12%). Of the patients, 45% were treated with an operation specific to the pathology detected on the proctogram; 29% did not require any active treatment and the remainder were managed with biofeedback conditioning or injection sclerotherapy. Evacuating proctography is of value in providing a diagnosis in patients with anorectal symptoms and thereby allowing specific treatment, operative or nonoperative, to be directed to the underlying pathology.