RESUMEN
Objective: We aimed to delineate a novel soluble Biglycan Neo-epitope-BGN262 in saliva from young reference and osteoarthritic horses in conjunction with the influence of short-term training exercise, riding surface hardness, circadian rhythm, and feeding on its soluble levels. Design: A custom-made inhibition ELISA was used for the quantification of BGN262 in saliva. Cohort 1: A cross-sectional study comprising reference (N â= â19) and OA horses (N â= â9) with radiographically classified subchondral bone sclerosis. Receiver operating characteristic curve analysis was performed to evaluate the robustness of BGN262. Cohorts 2 (N â= â5) & 3 (N â= â7): Longitudinal studies of sampling during a short-term training exercise (sand-fibre) and a cross-over design of short-training exercise on 2 different riding arenas (sand and sand-fibre), respectively. Capillary western immunoassay was used to determine the BGN262 molecular size in a selection of saliva samples collected from cohort 1. Results: Cohort 1: Salivary BGN262 levels were significantly higher in the OA group. The Receiver operating characteristic curve analysis showed an area under the curve of 0.8304 [0.6386 to 1.022], indicating a good separation from the reference group. Cohorts 2 & 3: Salivary BGN262 levels significantly changed during the exercise on sand and sand-fibre arena, with a trend towards higher levels for sand-fibre. The size of the BGN262 fragment determined by Capillary western assay was 18 âkDa. Conclusions: The data presented show saliva BGN262 levels as a novel biomarker in evaluating the influence of exercise, and interaction with riding arenas alongside assessing osteoarthritis severity.
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Nerve growth factor (NGF) is a neurotrophin with many functions. In humans, it is involved in inflammation, nerve growth, apoptosis and pain signalling. Increased concentrations of NGF in synovial fluid has been shown in humans and dogs with osteoarthritis. Despite osteoarthritis being a common problem in horses, no studies have previously been published on NGF in the equine joint. The aim of this study was to quantify NGF in equine synovial fluid from healthy joints, acutely inflamed septic joints and joints with structural changes associated with osteoarthritis. A secondary aim was to identify the localisation of NGF and its two receptors, TrkA and p75NTR, in healthy and osteoarthritic articular cartilage. NGF concentrations in synovial fluid from osteoarthritic joints (n = 27), septic joints (n = 9) and healthy joints (n = 16) were determined by ELISA. In addition, articular cartilage from osteoarthritic and healthy joints was examined for NGF, TrkA and p75NTR using immunohistochemistry staining. NGF was present in equine synovial fluid and articular cartilage. Compared to synovial fluid from healthy joints, NGF concentration was higher in synovial fluid from joints with structural osteoarthritic changes (P = 0.032) or acute septic inflammation (P = 0.006). In articular cartilage with severe osteoarthritic changes, there was more abundant positive immunohistochemistry staining for NGF and its receptors than in normal articular cartilage. Further studies should focus on identifying precursor forms of NGF, and on receptor expression and downstream signalling of TrkA and P75NTR in health and disease.
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Enfermedades de los Caballos/metabolismo , Articulaciones/química , Animales , Artritis Infecciosa/metabolismo , Artritis Infecciosa/veterinaria , Cartílago Articular/química , Ensayo de Inmunoadsorción Enzimática/veterinaria , Caballos , Inmunohistoquímica/veterinaria , Inflamación/metabolismo , Inflamación/veterinaria , Cojera Animal/metabolismo , Factor de Crecimiento Nervioso/análisis , Osteoartritis/metabolismo , Osteoartritis/veterinaria , Líquido Sinovial/químicaRESUMEN
BACKGROUND: Molecular serum markers that can identify early reversible osteoarthritis (OA) in horses are lacking. OBJECTIVES: We studied serum concentrations of a novel cartilage oligomeric matrix protein (COMP) neo-epitope in horses subjected to short-term exercise and with acute lameness. The effects of circadian rhythm and age were also evaluated. STUDY DESIGN: Longitudinal studies in healthy horses and cross-sectional comparison of lame and non-lame horses. METHODS: Sera were collected from five horses before and after short-term interval exercise and during full-day box rest. Sera from 32 acutely lame horses were used to evaluate age-related effects. Independent samples from control horses (n = 41) and horses with acute lameness (n = 71) were included. COMP neo-epitope concentrations were analysed using custom-developed inhibition ELISAs validated for equine serum. The presence of COMP neo-epitope was delineated in healthy and osteoarthritic articular cartilage with immunohistochemistry. RESULTS: COMP neo-epitope concentrations decreased after speed training but returned to baseline levels post-exercise. No correlations between age and serum COMP neo-epitope concentrations were found (r = 0.0013). The mean (±s.d.) serum concentration of COMP neo-epitope in independent samples from non-lame horses was 0.84 ± 0.38 µg/mL, and for lame horses was 5.24 ± 1.83 µg/mL (P<0.001). Antibodies against COMP neo-epitope did not stain normal articular cartilage, but intracytoplasmic staining was found in superficial chondrocytes of mild OA cartilage and in the extracellular matrix of moderately osteoarthritic cartilage. MAIN LIMITATIONS: ELISA was based on polyclonal antisera rather than a monoclonal antibody. There is a sex and breed bias within the groups of horses, also it could have been of value to include horses with septic arthritis and tendonitis and investigated joint differences. CONCLUSIONS: This COMP neo-epitope can be measured in sera, and results indicate that it could be a biomarker for pathologic fragmentation of cartilage in connection with acute joint lameness.
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Envejecimiento , Proteína de la Matriz Oligomérica del Cartílago/metabolismo , Ritmo Circadiano , Enfermedades de los Caballos/metabolismo , Cojera Animal , Condicionamiento Físico Animal , Animales , Biomarcadores , Proteína de la Matriz Oligomérica del Cartílago/sangre , Proteína de la Matriz Oligomérica del Cartílago/genética , Epítopos/genética , Epítopos/metabolismo , Femenino , Enfermedades de los Caballos/sangre , Enfermedades de los Caballos/diagnóstico , Caballos , Estudios Longitudinales , MasculinoRESUMEN
BACKGROUND: Clinical tools to diagnose the early changes of osteoarthritis (OA) that occur in the articular cartilage are lacking. OBJECTIVES: We sought to identify and quantify a novel cartilage oligomeric matrix protein (COMP) neoepitope in the synovial fluid from the joints of healthy horses and those with different stages of OA. STUDY DESIGN: In vitro quantitative proteomics and assay development with application in synovial fluids samples obtained from biobanks of well-characterised horses. METHODS: Articular cartilage explants were incubated with or without interleukin-1ß for 25 days. Media were analysed via quantitative proteomics. Synovial fluid was obtained from either normal joints (n = 15) or joints causing lameness (n = 17) or with structural OA lesions (n = 7) and analysed for concentrations of the COMP neoepitope using a custom-developed inhibition enzyme-linked immunosorbent assay (ELISA). Explants were immunostained with polyclonal antibodies against COMP and the COMP neoepitopes. RESULTS: Semitryptic COMP peptides were identified and quantified in cell culture media from cartilage explants. A rabbit polyclonal antibody was raised against the neoepitope of the N-terminal portion of one COMP fragment (sequence SGPTHEGVC). An inhibition ELISA was developed to quantify the COMP neoepitope in synovial fluid. The mean concentration of the COMP neoepitope significantly increased in the synovial fluid from the joints responsible for acute lameness compared with normal joints and the joints of chronically lame horses and in joints with chronic structural OA. Immunolabelling for the COMP neoepitope revealed a pericellular staining in the interleukin-1ß-stimulated explants. MAIN LIMITATIONS: The ELISA is based on polyclonal antisera rather than a monoclonal antibody. CONCLUSIONS: The increase in the COMP neoepitope in the synovial fluid from horses with acute lameness suggests that this neoepitope has the potential to be a unique candidate biomarker for the early molecular changes in articular cartilage associated with OA.
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Proteína de la Matriz Oligomérica del Cartílago/líquido cefalorraquídeo , Enfermedades de los Caballos/líquido cefalorraquídeo , Cojera Animal/líquido cefalorraquídeo , Osteoartritis/veterinaria , Animales , Biomarcadores , Glicoproteínas , Caballos , Proteínas Matrilinas , Osteoartritis/líquido cefalorraquídeo , Líquido Sinovial/metabolismoAsunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Tadalafilo/uso terapéutico , Adulto , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/tratamiento farmacológico , Método Doble Ciego , Células Endoteliales/efectos de los fármacos , Células Endoteliales/fisiología , Femenino , Antebrazo/irrigación sanguínea , Humanos , Resistencia a la Insulina , Masculino , Comidas , Persona de Mediana Edad , Periodo Posprandial/efectos de los fármacos , Flujo Sanguíneo Regional/efectos de los fármacos , Resultado del TratamientoRESUMEN
Sacral nerve stimulation (SNS) has become an established therapy worldwide for the treatment for fecal incontinence. A large number of papers have been published over the years, and SNS is generally considered very effective with improved continence and quality of life for most patients. However, the results are mostly expressed in the semi-quantitative terms, that is, patients' diaries translated into score points. The clinical value of SNS is questionable, especially as the patient groups are usually small and/or etiologically heterogenic and the follow-up period mostly short. The Health Technology Assessment organization in the west region of Sweden has recently evaluated the SNS with regard to evidence, efficacy and risks. Economic and ethical aspects raise serious questions on this expensive and not entirely risk-free treatment in routine medical care. Similar criticism has also been raised by other reviewers proposing a more thorough scientific assessment with well-designed randomized trials and comparison with other similar methods of treatment.
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Terapia por Acupuntura/métodos , Terapia por Estimulación Eléctrica/métodos , Incontinencia Fecal/terapia , Plexo Lumbosacro , Calidad de Vida , Nervio Tibial , Incontinencia Fecal/diagnóstico , Femenino , Humanos , Masculino , Pronóstico , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Macrophages are prominent in hypoxic areas of atherosclerotic lesions and their secreted cytokines, growth factors and activity of enzymes are involved in atherogenesis. Previously, we showed that 15-lipoxygenase (LOX)-2 is expressed in human monocyte-derived macrophages and that hypoxia increases 15-LOX-2 expression and secretion of pro-inflammatory molecules. Here we investigated whether human carotid plaque macrophages express 15-LOX-2 and whether its expression in macrophages is regulated by hypoxia through hypoxia-inducible factor 1alpha (HIF-1alpha). MATERIALS AND METHODS: Carotid plaques from 47 patients with high-grade symptomatic carotid artery stenosis were analysed using immunohistochemistry, and stained areas were quantified by digital image analysis. Carotid plaque macrophages were isolated with anti-CD14 immunobeads using an immunomagnetic bead technique. Primary macrophages were transfected with HIF-1alpha siRNA or control siRNA before extraction of RNA and medium analysis. RESULTS: In paired tissue sections, the extent of staining for CD68 correlated with staining for 15-LOX-2 but not for 15-LOX-1. In carotid plaque macrophages isolated with anti-CD14 immunobeads, 15-LOX-2 mRNA was expressed at high levels. In primary macrophages, 15-LOX-2 expression was significantly increased by incubation with the HIF-1alpha stabilizer dimethyloxalylglycine. Knockdown of HIF-1alpha significantly decreased production of the 15-LOX-2 enzyme products 12- and 15-hydroxyeicosatetraenoic acid. In carotid plaques, HIF-1alpha staining correlated with staining for 15-LOX-2. CONCLUSIONS: These results demonstrate that 15-LOX-2 is highly expressed in human plaques and is correlated with the presence of macrophages and HIF-1alpha. 15-LOX-2 enzyme activity can be modulated by HIF-1alpha. Thus, increased expression of 15-LOX-2 in macrophages in hypoxic atherosclerotic plaque may enhance inflammation and the recruitment of inflammatory cells.
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Araquidonato 15-Lipooxigenasa/metabolismo , Estenosis Carotídea/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Macrófagos/enzimología , Anciano , Anciano de 80 o más Años , Antígenos CD/genética , Araquidonato 15-Lipooxigenasa/genética , Estenosis Carotídea/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Músculo Liso/metabolismo , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genéticaRESUMEN
OBJECTIVE: We investigated whether levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A(2) group IIA (sPLA(2)-IIA) and intercellular adhesion molecule-1 (ICAM-I) predict late outcomes in patients with acute coronary syndromes (ACS). DESIGN: Prospective longitudinal study. CRP (mg L(-1)), IL-6 (pg mL(-1)), sPLA(2)-IIA (ng mL(-1)) and ICAM-1 (ng mL(-1)) were measured at days 1 (n = 757) and 4 (n = 533) after hospital admission for ACS. Their relations to mortality and rehospitalization for myocardial infarction (MI) and congestive heart failure (CHF) were determined. SETTING: Coronary Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: Patients with ACS alive at day 30; median follow-up 75 months. RESULTS: Survival was related to day 1 levels of all markers. After adjustment for confounders, CRP, IL-6 and ICAM-1, but not sPLA(2)-IIA, independently predicted mortality and rehospitalization for CHF. For CRP, the hazard ratio (HR) was 1.3 for mortality (95% confidence interval (CI): 1.1-1.5, P = 0.003) and 1.4 for CHF (95% CI: 1.1-1.9, P = 0.006). For IL-6, HR was 1.3 for mortality (95% CI: 1.1-1.6, P < 0.001) and 1.4 for CHF (95% CI: 1.1-1.8, P = 0.02). For ICAM-1, HR was 1.2 for mortality (95% CI: 1.0-1.4, P = 0.04) and 1.3 for CHF (95% CI: 1.0-1.7, P = 0.03). No marker predicted MI. Marker levels on day 4 provided no additional predictive value. CONCLUSIONS: In patients with ACS, CRP, IL-6, sPLA(2)-IIA and ICAM-1 are associated with long-term mortality and CHF, but not reinfarction. CRP, IL-6 and ICAM-1 provide prognostic information beyond that obtained by clinical variables.
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Síndrome Coronario Agudo/sangre , Proteína C-Reactiva/análisis , Fosfolipasas A2 Grupo II/sangre , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-6/sangre , Anciano , Biomarcadores/sangre , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Readmisión del Paciente , Pronóstico , Estudios Prospectivos , Medición de Riesgo/métodos , Factores de TiempoRESUMEN
OBJECTIVES: Few studies have investigated the composition of unstable coronary plaques in vivo in humans. The aims of this study were to investigate if substances released from plaques during percutaneous coronary intervention (PCI) under distal protection could give information about plaque composition and also indicate possible biomarkers in plasma that may be used to identify patients at risk. METHODS AND RESULTS: Twenty patients with acute coronary syndromes undergoing PCI with distal protection were included. Plasma samples were taken before, during, and after the PCI in the aortic root, locally in the culprit vessel and intravenously. Plasma was analysed for possible markers of plaque instability. During PCI, local increases were observed for matrix metalloproteinase 9 (MMP-9), protein (P < 0.001) as well as activity (P < 0.001), interleukin 6 (IL-6; P < 0.01) and oxidized low-density lipoprotein (oxLDL; P = 0.01) in the culprit coronary artery. A systemic inflammatory response was also seen with increased levels of IL-10, MMP-3, serum amyloid A and C-reactive protein, but with no increase in MMP-9. CONCLUSIONS: Our study shows that local sampling of blood under distal protection may be used to analyse coronary plaques and to identify biomarkers for unstable plaques. Our results suggest that MMP-9 is a potential biomarker, and that IL-6, MMP9 and possibly oxLDL are released from plaques.
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Síndrome Coronario Agudo/terapia , Angioplastia Coronaria con Balón/métodos , Proteínas Sanguíneas/análisis , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/terapia , Metaloproteinasa 9 de la Matriz/sangre , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/inmunología , Adulto , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Enfermedad de la Arteria Coronaria/inmunología , Femenino , Humanos , Interleucina-10/sangre , Interleucina-6/sangre , Lipoproteínas LDL/sangre , Masculino , Metaloproteinasa 3 de la Matriz/sangre , Persona de Mediana Edad , Proteína Amiloide A Sérica/análisis , Manejo de Especímenes , Estadísticas no ParamétricasRESUMEN
Evidence based goals for the treatment and prevention of atherosclerosis in diabetes are given in international and national guidelines. The importance of optimal control of lipids and blood pressure has been shown in several studies. With available drugs and behavioural modifications the treatment goals can be reached in most cases. However, only a few patients with diabetes are treated optimally today. A major possibility to reduce cardiovascular disease in diabetes is to treat patients according to guidelines. New treatment targets may include specific treatment of the dyslipidaemia, manifested in high levels of small dense LDL and low HDL, active anti-inflammatory treatments, specific reduction of inflammatory activity in adipose tissue, reduced volume of adipose tissue, antioxidants and reduction of advanced glycosylation endproducts production. Possible strategies for these treatments are available, and should be evaluated in clinical trials.
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Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Apolipoproteínas/análisis , Aterosclerosis/etiología , Aterosclerosis/prevención & control , Enfermedades Cardiovasculares/etiología , Angiopatías Diabéticas/prevención & control , Dislipidemias/etiología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Resistencia a la Insulina/fisiología , Lipoproteínas LDL/sangre , Guías de Práctica Clínica como AsuntoRESUMEN
OBJECTIVE: Failure after ileal pouch-anal anastomosis (IPAA) is reported with a frequency of 10-20%. The failed IPAA can be excised or defunctioned. Indications for excision and further management of an indefinitely diverted pouch are poorly described. The aim of the present investigation was to investigate pouch-related problems and the histopathological pattern of the pouch mucosa in this group of patients. METHOD: In a cohort of 620 patients having IPAA with a median follow-up of 14 years, 56 patients with failure were identified. The patients with defunctioned pouches were assessed with regard to pouch-related problems and endoscopy with biopsies was performed. Biopsies were stained with haematoxylin-eosin, PAS for neutral mucins and Alcian blue/high iron diamine for sialomucins/sulphomucins. Morphological changes were grouped into three types modified according to Veress and assessed for dysplasia. RESULTS: Twenty-two patients with an indefinitely diverted pouch were found. The follow-up time after surgery for failure was 10 years. Thirteen patients completed the follow-up. Except for two patients with pelvic/perineal pain, there were no clinical problems. The majority of patients displayed mild to moderate macroscopic signs of inflammation. Morphologically, findings ranged from a preserved mucosal pattern to intense inflammatory reaction. No case of dysplasia or carcinoma was found. CONCLUSION: Most patients with an indefinitely diverted pouch had no complaints regarding the pouch. There was no case of dysplasia. Indefinite diversion may be preferable to pouch excision, especially given the associated morbidity.
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Reservorios Cólicos , Adolescente , Adulto , Anastomosis Quirúrgica , Reservorios Cólicos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ganglios Linfáticos Agregados/patología , Insuficiencia del TratamientoRESUMEN
BACKGROUND: Conflicting views regarding the use of ileorectal anastomosis (IRA) in ulcerative colitis (UC) exist and this controversy prompted us to review our experience, especially against the background of the current tendency to choose the ileal pouch-anal procedure (IPAA). METHODS: Thirty-two consecutive patients with IRA were studied. Complications, failure rate, reasons for failure and functional results were assessed. The median follow-up time was 3.5 years. RESULTS: The overall complication rate was 28%. The rectum was excised in 4 patients, indicating a failure rate of 12%. The mean daily evacuation frequency was 5.6. Despite urgency occurring in one-third of the patients, continence function was well preserved. CONCLUSIONS: Employed on a selective basis, IRA is a safe procedure with low mortality and morbidity and good prospects for success in many patients with UC. The patients must be prepared to submit to life-long rectoscopy surveillance.
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Colectomía , Colitis Ulcerosa/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo , Íleon/cirugía , Recto/cirugía , Adulto , Anciano , Anastomosis Quirúrgica , Reservorios Cólicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Resultado del TratamientoRESUMEN
BACKGROUND: Most surgeons consider Crohn's colitis to be an absolute contraindication for a continent ileostomy, due to high complication and failure rates. This opinion may, however, be erroneous. The results may appear poor when compared with those after pouch surgery in patients with ulcerative colitis (UC), but the matter may well appear in a different light if the pouch patients are compared with Crohn's colitis patients who have had a proctocolectomy and a conventional ileostomy. METHODS: We assessed the long-term outcomes in a series of patients with Crohn's colitis who had a proctocolectomy and a continent ileostomy (59 patients) or a conventional ileostomy (57 patients). The median follow-up time was 24 years for the first group and 27 years for the second group. RESULTS: The outcomes in the two groups of patients were largely similar regarding both mortality and morbidity; the rates of recurrent disease and reoperation with loss of small bowel were also similar between groups. CONCLUSIONS: The possibility of having a continent ileostomy, thereby avoiding a conventional ileostomy-even if only for a limited number of years--may be an attractive option for young, highly motivated patients.
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Reservorios Cólicos , Enfermedad de Crohn/complicaciones , Ileostomía/métodos , Proctocolectomía Restauradora/métodos , Proctocolitis/cirugía , Adulto , Enfermedad de Crohn/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Ileostomía/efectos adversos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Probabilidad , Proctocolectomía Restauradora/efectos adversos , Proctocolitis/complicaciones , Proctocolitis/etiología , Proctocolitis/mortalidad , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
An ileo-pouch anal anastomosis (IPAA) has become the gold standard procedure for ulcerative colitis and familial adenomatous polyposis. Clinical results on the pelvic pouch procedure have often been encouraging; when confronted with the different surgical options, the majority of patients select IPAA as the best operation. However, even if IPAA is a great innovation, it is by no means the first choice for all patients. For patients old enough to join in a responsible discussion, the pros and cons of the various operations must be carefully described; the choice of surgical procedure must meet the patient's wishes and appear soundly based to the surgeon. The young age of most patients has to be considered and a long follow-up time is required to establish whether and, if so, to what extent the operation may adversely impact the patient's continence, sex life, fertility, and quality of life. The risk of cancer transformation in the residual rectal mucosa in the muscular or columnar cuff is another important factor that may influence the eventual decision. This article critically reviews our experience and the literature.
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Canal Anal/cirugía , Reservorios Cólicos/normas , Recurrencia Local de Neoplasia/diagnóstico , Reservoritis/diagnóstico , Calidad de Vida , Anastomosis Quirúrgica , Reservorios Cólicos/efectos adversos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Incontinencia Fecal , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia/cirugía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Reservoritis/epidemiología , Proctocolectomía Restauradora/efectos adversos , Proctocolectomía Restauradora/métodos , Pronóstico , Reoperación , Medición de Riesgo , Infección de la Herida Quirúrgica/diagnóstico , Infección de la Herida Quirúrgica/epidemiología , Análisis de SupervivenciaRESUMEN
AIM: Some of the rare complications reported in patients with an ileopouch anal anastomosis (IPAA) after coloectomy for chronic ulcerative colitis are dysplasia and carcinoma. The supposed pathway is for the ileal pouch mucosa to go through adaptational changes then is to progress through the phases of chronic pouchitis, dysplasia and subsequently to adenocarcinoma. In many of these studies however, the dysplasia-cancer sequence is inconclusive since the carcinoma might have developed from the ileal mucosa itself or from residual viable rectal mucosa left behind. The purpose of this study was therefore to study the long-term ileal mucosal adaptation patterns and the incidence and grading of dysplasia in the ileal pouch mucosa in patients previously operated on for ulcerative proctocolitis. PATIENTS AND METHODS: Forty-five patients who had been operated on with an IPAA (25 males/20 females), with a median age of 54 years (range 34-76), were invited for clinical examination and pouch endoscopy including mucosal biopsies. The duration of their colitis until surgery was median 6 years (range 1-28) and the time median interval from start of disease until time of follow up 24.8 years (range 17-46). Three independent pathologists from two different centres reviewed sequential mucosal biopsies taken from separate sites of the pouch for dysplasia and mucosal adaptation patterns. RESULTS: The type C pattern with a severe inflammation in lamina propria together with severe atrophy of villi, sometimes with ulceration and granulation tissue, was observed by the two pathologists from one centre in 15 of 45 (33.3%) patients and in 11 (24.4%) of 45 by the third pathologist, respectively. As regards dysplasia one pathologist group evaluated 2/45 (4.4%) cases as low-grade dysplasia while the third pathologist considered one of these cases as indefinite for dysplasia and one as reactive. There was in this respect full agreement between the two centres in 43 (95.6%) of 45 cases. Neither high-grade dysplasia nor invasive carcinoma was diagnosed. CONCLUSION: Dysplastic transformation within the ileal pouch mucosa in patients operated for ulcerative proctocolitis is rare even after a long follow-up. These results are reassuring for both patients and surgeons. There seem to be no solid grounds to support routine surveillance for dysplasia in the ileal pouch mucosa in these patients. The surveillance for neoplastic changes in the remaining muscular/epithelial cuff is a separate issue however.
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Transformación Celular Neoplásica/patología , Colitis Ulcerosa/cirugía , Reservorios Cólicos/patología , Mucosa Intestinal/patología , Neoplasias/patología , Proctocolectomía Restauradora/efectos adversos , Adulto , Anciano , Biopsia con Aguja , Estudios de Cohortes , Colitis Ulcerosa/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Reservoritis/patología , Proctocolectomía Restauradora/métodos , Medición de RiesgoRESUMEN
AIMS/HYPOTHESIS: Type 2 diabetes is a major risk factor for cardiovascular disease. Monocyte recruitment and inflammatory activation are crucial steps in the development of atherosclerosis and several receptors are involved in these processes. The aim of this study was to investigate levels of CD14 and the beta(2)-integrin subunits CD11b and CD18 on monocytes from women with diabetes or impaired glucose tolerance. METHODS: A population-based sample of 112 Swedish women, who were aged 64 years and had diabetes mellitus or impaired or normal glucose tolerance, was investigated. Cell surface receptors were analysed with flow cytometry and serum inflammation markers and soluble adhesion molecules with enzyme-linked methods. RESULTS: The monocytic CD14 expression and serum levels of C-reactive protein, IL-6 and soluble adhesion molecules were higher in the diabetes group than in the group with normal glucose tolerance. Monocytic CD18 was elevated both in the diabetes and in the impaired glucose tolerance groups. The levels of monocytic surface markers correlated with BMI and to a lesser extent with glycaemic control. CONCLUSIONS/INTERPRETATION: The increased monocytic expression of important surface receptors together with elevated serum inflammation markers supports the concept of increased inflammation in type 2 diabetes and may be an important factor for the risk of atherosclerosis.
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Antígenos CD18/sangre , Diabetes Mellitus/sangre , Intolerancia a la Glucosa/sangre , Inflamación/sangre , Receptores de Lipopolisacáridos/sangre , Antígenos CD/sangre , Arteriosclerosis/epidemiología , Biomarcadores/sangre , Índice de Masa Corporal , Antígeno CD11b/sangre , Diabetes Mellitus/fisiopatología , Femenino , Intolerancia a la Glucosa/fisiopatología , Prueba de Tolerancia a la Glucosa , Humanos , Persona de Mediana Edad , Monocitos/inmunología , Monocitos/fisiologíaRESUMEN
BACKGROUND: Excision of the ileal pouch-anal anastomosis (IPAA) with construction of a conventional ileostomy is in general the ultimate procedure after unsuccessful salvage surgery. Conversion of the IPAA to a continent ileostomy (CI) is an alternative. METHODS: The clinical outcome of 13 patients operated with conversion of IPAA into CI was evaluated. Median follow-up was 6 years. One patient was lost to follow-up. RESULTS: There were two failures with pouch excision. At follow-up, ten patients with intact CI were fully continent and none needed to use a stoma appliance. Revisional surgery had been required in 8 patients. CONCLUSIONS: Conversion of a failed IPAA into CI is a feasible procedure that may be considered an alternative to Brooke's ileostomy in motivated patients. The operation should ideally be done in specialized units.
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Reservorios Cólicos/efectos adversos , Ileostomía/métodos , Proctocolectomía Restauradora/efectos adversos , Adulto , Colitis/cirugía , Colitis Ulcerosa/cirugía , Incontinencia Fecal/etiología , Incontinencia Fecal/cirugía , Femenino , Humanos , Masculino , Fístula Rectal/etiología , Fístula Rectal/cirugía , Reoperación , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
OBJECTIVE: Human body fat mass is to a large extent genetically determined, but little is known about the susceptibility genes for common obesity. Interleukin-6 (IL-6) suppresses body fat mass in rodents, and IL-6 treatment increases energy expenditure in both rodents and humans. The -174 G/C single-nucleotide polymorphism (SNP) in the IL-6 gene promoter is common in many populations, and -174 C-containing promoters have been found to be weaker enhancers of transcription. Moreover, a SNP at position -572 in the IL-6 promoter has recently been reported to affect transcription. The objective was to investigate the association between the IL-6 gene promoter SNPs and obesity. DESIGN: Trans-sectional association study of IL-6 gene promoter SNPs and indices of obesity. SUBJECTS: Two study populations, the larger one consisting of hypertensive individuals (mean age 57 y, 73% males, n=485) and the other consisting of 20 y younger nonobese healthy females (n=74). MEASUREMENTS: Genotyping for the -174 IL-6 G/C and the -572 G/C SNPs, body mass index (BMI), serum leptin levels, serum IL-6 levels, C-reactive protein, fasting blood glucose and various blood lipids. RESULTS: The common -174 C allele (f(C)=0.46), but not any -572 allele, was associated with higher BMI and higher serum leptin levels in both study populations. In the larger population, there were significant odds ratios for the association of CC (2.13) and GC (1.76) genotypes with overweight (BMI>25 kg/m(2)). Moreover, as the C allele was common, it accounted for a significant population-attributable risk of overweight (12%; CI 2-21%), although its average effect was modest in this sample. CONCLUSION: Genetically determined individual differences in production of IL-6 may be relevant for the regulation of body fat mass.
Asunto(s)
Predisposición Genética a la Enfermedad , Interleucina-6/genética , Obesidad/genética , Polimorfismo Genético , Regiones Promotoras Genéticas , Adulto , Índice de Masa Corporal , Femenino , Genotipo , Humanos , Interleucina-6/sangre , Leptina/sangre , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: The objective of this study was to assess the relationship between inflammation, endothelial activation and incipient atherosclerosis in type 2 diabetes. DESIGN: Cross-sectional study. Setting and subjects. We studied 239 type 2 diabetic patients [71 with clinical cardiovascular disease (CVD)] and 78 healthy control subjects, aged 50-75 in a single research centre. METHODS: Carotid intima-media thickness (IMT) was determined by ultrasound. Circulating intracellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, ultra-sensitive C-reactive protein, human serum amyloid A, interleukin-6, monocyte colony-stimulating factor, secretory nonpancreatic phospholipase A(2) type IIA, glucose, HbA1c, and lipid/lipoprotein variables were measured. RESULTS: Carotid IMT was significantly thicker in diabetic patients than healthy controls across the whole age range. IMT was also thicker in diabetic patients with, than without, CVD, but this difference disappeared after controlling for confounding factors. Concentrations of the inflammatory and endothelial markers except IL-6 were significantly higher in the diabetic patients than in healthy controls, but comparable in diabetic patients with and without CVD. The main determinants of IMT in the diabetic patients were blood pressure, age and diabetes duration. CONCLUSIONS: Low-grade inflammation and endothelial activation are increased in diabetic patients but do not associate with IMT or clinical CVD. The inflammatory reaction seems to be rather a feature of the metabolic syndrome than a direct determinant of atherosclerosis.
Asunto(s)
Arterias Carótidas/patología , Diabetes Mellitus Tipo 2/patología , Angiopatías Diabéticas/patología , Endotelio Vascular/patología , Factores de Edad , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Arterias Carótidas/diagnóstico por imagen , Estudios de Casos y Controles , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/sangre , Selectina E/sangre , Endotelio Vascular/metabolismo , Femenino , Humanos , Hipertensión/sangre , Hipertensión/patología , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-6/sangre , Modelos Lineales , Masculino , Persona de Mediana Edad , Proteína Amiloide A Sérica/análisis , Túnica Íntima/diagnóstico por imagen , Túnica Íntima/patología , Ultrasonografía , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
BACKGROUND: The purpose of this study was to assess sexuality in patients with ulcerative colitis (UC), before and one year after an ileal-pouch anal anastomosis (IPAA). METHODS: Group I comprised 14 medically treated patients (7 M) and Group II comprised 29 patients (18 M), operated with colectomy and ileostomy, with preservation of the rectum. Patients were interviewed about desire, excitement and general sexual satisfaction before and one year after the IPAA operation. RESULTS: Most of the patients had restarted sexual activity < or = 3 months after surgery. Sexual desire and desire for intercourse had not changed from before the IPAA operation. In Group I, one woman suffered from dyspareunia both before and after the IPAA. In Group II, three women had dyspareunia before the IPAA and four after surgery. Erection and ejaculation were normal in all men before the IPAA operation. After IPAA, one man in Group I and two men in Group II had loss of ejaculation. In Group 1, 10 out of 14 patients were satisfied with their sexual life both before and after the IPAA. In Group II the corresponding figures were 15 out of 28 before and 22 after IPAA surgery. CONCLUSIONS: A third of the patients stated that they were dissatisfied with their sexual life before IPAA. Although a few patients experienced sexual imperfections such as loss of ejaculation and dyspareunia, the majority of patients in both groups considered that the overall general satisfaction with their sexual life had normalized considerably after surgery.