RESUMEN
The metal assisted etching mechanism for Si nanowire fabrication, triggered by doping type and level and coupled with choice of metal catalyst, is still very poorly understood. We explain the different etching rates and porosities of wires we observe based on extensive experimental data, using a new empirical model we have developed. We establish as a key parameter, the tunneling through the space charge region (SCR) which is the result of the reduction of the SCR width by level of the Si wafer doping in the presence of the opposite biases of the p- and n-type wafers. This improved understanding should permit the fabrication of high quality wires with predesigned structural characteristics, which hitherto has not been possible.
RESUMEN
Binary homopolymer blends of two hydroxyl-terminated polystyrene (PS-OH) and polymethylmethacrylate (PMMA-OH) homopolymers (Mn â¼ 16000 g mol(-1)) were grafted on SiO2 substrates by high-temperature (T > 150 °C), short-time (t < 600 s) thermal treatments. The resulting brush layer was tested to screen preferential interactions of the SiO2 substrate with the different symmetric and asymmetric PS-b-PMMA block copolymers deposited on top of the grafted molecules. By properly adjusting the blend composition and the processing parameters, an efficient surface neutralization path was identified, enabling the formation, in the block copolymer film, of homogeneous textures of lamellae or cylinders perpendicularly oriented with respect to the substrate. A critical interplay between the phase segregation of the homopolymer blends and their grafting process on the SiO2 was observed. In fact, the polar SiO2 is preferential for the PMMA-rich phase that forms a homogeneous layer on the substrate, while the PS-rich phase is located at the polymer-air interface. During the thermal treatment, phase segregation and grafting proceed simultaneously. Complete wetting of the PS rich phase on the PMMA rich phase leads to the formation of a PS/PMMA bilayer. In this case, the progressive diffusion of PS chains toward the polymer-SiO2 interface during the thermal treatment allows tuning of the brush layer composition.
RESUMEN
Self-assembling block copolymers generate nanostructured patterns which are useful for a wide range of applications. In this paper we demonstrate the capability to control the morphology of the self-assembling process of PS-b-PMMA diblock copolymer thin films on unpatterned surfaces by means of fast thermal treatment performed in a rapid thermal processing machine. The methodology involves the use of radiation sources in order to rapidly drive the polymeric film above the glass transition temperature. Highly ordered patterns were obtained for perpendicular-oriented cylindrical and lamellar PS-b-PMMA block copolymers in less than 60 s. This approach offers the unprecedented opportunity to investigate in detail the kinetics of the block copolymer self-assembly during the early stages of the process, providing a much deeper understanding of the chemical and physical phenomena governing these processes.
RESUMEN
BACKGROUND: Dislocation of the elbow in children is considered to be a benign injury in most cases. The aim of this paper is to evaluate whether this condition has late sequelae in the adult age. The study consisted of a retrospective evaluation of patients under 15 years old at the time of injury. METHODS: 40 patients were selected for the follow-up evaluation. The mean age of the children at the time of injury was 10.9 years old (range 5-14 years). Four patients were lost to follow-up, so they were not considered for final clinical evaluation. For the other 36 patients, the follow-up examination was undertaken after an average of 15 years (range 7-22 years). The average age of the patients at the follow-up was 26 (range 18-34 years). RESULTS: At the end of follow-up period, there were few subjective complications. No redislocations occurred. None of the patients had been influenced by their elbow injury in their choice of occupation. X-rays were available for 27 patients. These were graded using Linscheid and Wheeler criteria and were excellent in 14 patients, good in 10 and fair in 3. CONCLUSIONS: Dislocation of the elbow in children is a benign injury in the majority of cases and has a good prognosis in the adult age too in spite of extensive damage to the periarticular structures. Ectopic ossifications are a common finding, but only large periarticular ectopic ossifications were associated with a decrease in range on motion. Extension loss is the most common sequelae. Level of evidence IV.
Asunto(s)
Lesiones de Codo , Luxaciones Articulares/complicaciones , Adolescente , Niño , Preescolar , Codo , Estudios de Seguimiento , Humanos , Pronóstico , Estudios Retrospectivos , Factores de TiempoRESUMEN
A new HPLC method for the determination of glucosamine (2-amino-2-deoxy-D-glucose) in human synovial fluid was developed and validated. Synovial fluid samples were analyzed after a simple protein precipitation step with trichloroacetic acid using a polymer-based amino column with a mobile phase composed of 10 mM ammonium acetate (pH 7.5)-acetonitrile (20:80, v/v) at 0.3 mL/min flow rate. D-[1-13C]glucosamine was used as internal standard. Selective detection was performed by tandem mass spectrometry with electrospray source, operating in positive ionization mode and in multiple reaction monitoring acquisition (m/z 180-->72 and 181-->73 for glucosamine and internal standard, respectively). The limit of quantification (injected volume=3 microL) was 0.02 ng, corresponding to 10 ng/mL in synovial fluid. Calibration curves obtained using matrix-matched calibration standards and internal standard at 600 ng/mL were linear up to 2000 ng/mL. Precision values (%R.S.D.) were < or = 14% in the entire analytical range. Accuracy (%bias) ranged from -11% to 10%. The recoveries measured at three concentration levels (50, 800, and 1500 ng/mL) were higher than 89%. The method was successfully applied to measure endogenous glucosamine levels in synovial fluid samples collected from patients with knee osteoarthritis and glucosamine levels after oral administration of glucosamine sulfate (DONA) at the dose of 1500 mg/day for 14 consecutive days (steady-state).
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Glucosamina/metabolismo , Glucosamina/farmacología , Osteoartritis de la Rodilla/metabolismo , Espectrometría de Masa por Ionización de Electrospray/métodos , Líquido Sinovial/metabolismo , Acetonitrilos/química , Administración Oral , Calibración , Humanos , Concentración de Iones de Hidrógeno , Espectrometría de Masas/métodos , Osteoartritis de la Rodilla/tratamiento farmacológico , Polímeros/química , Reproducibilidad de los Resultados , Ácido Tricloroacético/químicaRESUMEN
OBJECTIVES: To propose an objective approach in order to determine the number of beds required for a hospital department by considering how recruitment fluctuates over time. To compare this approach with classical bed capacity planning techniques. METHODS: A simulated data-based evaluation of the impact that the variability in hospital department activity produces upon the performance of methods used for determining the number of beds required. The evaluation criteria included productive efficiency measured by the bed occupancy rate, accessibility measured by the transfer rate of patients due to lack of available beds and a proxy of clinical effectiveness, by the proportion of days during which there is no possibility for unscheduled admission. RESULTS: When the variability of the number of daily patients increases, the Target Occupancy Rate favors productive efficiency at the expense of accessibility and proxy clinical effectiveness. On the contrary, when the variability of the department activity is marginal, the Target Activity Rate penalizes the proxy of clinical effectiveness, and the Target Occupancy Rate underoptimizes productive efficiency. The method we propose led to a superior performance in terms of accessibility and proxy of clinical effectiveness at the expense of productive efficiency. Such a situation is suitable for intensive care units. In the case of other departments, a weighting procedure should be used to improve productive efficiency. CONCLUSIONS: This approach could be considered as the first step of a family of methods for quantitative healthcare planning.
Asunto(s)
Administración Hospitalaria , Capacidad de Camas en Hospitales/estadística & datos numéricos , Algoritmos , Eficiencia Organizacional , Humanos , Unidades de Cuidados Intensivos/organización & administración , Admisión del Paciente , Estados UnidosRESUMEN
OBJECTIVE: We investigated the synovial and plasma glucosamine concentrations in osteoarthritic patients following oral administration of crystalline glucosamine sulphate at the therapeutic dose of 1500mg once-a-day for 14 days. DESIGN: Twelve osteoarthritic patients (six males and six females) received 14 consecutive once-daily oral administrations of crystalline glucosamine sulphate soluble powder (1500mg), in an open fashion. Plasma and synovial fluid were collected simultaneously from the same patient, at baseline and, at steady state (3h after the last dose). Glucosamine was determined in plasma and synovial fluid by liquid chromatography-tandem mass spectrometry. RESULTS: Median endogenous glucosamine concentrations in plasma and synovial fluid were 52.0ng/ml (0.29microM) and 36.5ng/ml (0.21microM), respectively (P=0.001), and varied substantially among patients (41-121ng/ml and <10-67ng/ml, respectively). Three hours after the last dose, glucosamine concentrations resulted increased from baseline in all patients with median increases of 20.5 and 21.5 folds in plasma and synovial fluid, respectively, the difference being not statistically significant (P=0.11). In plasma, the median post-treatment value was 1282ng/ml (7.17microM) and ranged from 600 to 4061ng/ml (3.35-22.7microM). The median post-treatment synovial glucosamine concentration was 777ng/ml (4.34microM), i.e., significantly lower than in plasma (P=0.001), and ranged from 577 to 3248ng/ml (3.22-18.1microM). Plasma and synovial glucosamine concentrations were highly correlated and were in the 10microM range. CONCLUSIONS: Glucosamine is bioavailable both systemically and at the site of action (the joint) after oral administration of crystalline glucosamine sulphate in ostaeoarthritis patients. Steady state glucosamine concentrations in plasma and synovial fluid were correlated and in line with those effective in selected in vitro studies.
Asunto(s)
Glucosamina/sangre , Glucosamina/uso terapéutico , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Líquido Sinovial/metabolismo , Administración Oral , Anciano , Anciano de 80 o más Años , Disponibilidad Biológica , Femenino , Glucosamina/metabolismo , Glucosamina/farmacocinética , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Ciliated cells in gastrectomies from patients dwelling in the Pacific and Atlantic basins have been reported previously. AIM: To compare all the results in an attempt to explain the findings. METHODS: Sections from 3406 gastrectomies were reviewed: 1966 and 1440 from the Atlantic and Pacific basins, respectively. Ciliated cells and intestinal metaplasia (IM) were recorded; IM was classified into focal or extensive IM. The total number of sections/gastrectomy was noted. RESULTS: In the Atlantic basin, 5% of specimens had ciliated metaplasia (CM); it was more frequent in intestinal carcinoma (IC; 9%) than diffuse carcinoma (DC; 3%) or miscellaneous gastric diseases (MGD; 3%). In the Pacific basin, the frequency of specimens with CM was 29%: it was more frequent in IC (43%) than in DC (16%) or MGD (10%). The difference between the frequency of CM in specimens with IC or with DC/MGD in the Atlantic and the Pacific basins was significant (p < or = 0.05). The presence of CM was influenced by age and the extent of IM in both basins, but not by sex or the number of sections investigated. CONCLUSIONS: CM-apparently an independent microscopic marker-was significantly higher in the Pacific than in the Atlantic basin. Environmental carcinogens involved in the evolution of IM and IC seem to be implicated in gastric ciliogenesis. Carcinogens that differ in nature and/or in strength in both basins might activate the latent natural genes encoding ciliated processes in gastric cells in patients subsequently developing gastric carcinoma, more notably of intestinal type.
Asunto(s)
Cilios/patología , Lesiones Precancerosas/etnología , Gastropatías/etnología , Estómago/patología , Adulto , Factores de Edad , Anciano , Américas/epidemiología , Europa (Continente)/epidemiología , Femenino , Gastrectomía , Mucosa Gástrica/patología , Humanos , Masculino , Metaplasia/etnología , Metaplasia/patología , Persona de Mediana Edad , Islas del Pacífico/epidemiología , Lesiones Precancerosas/patología , Antro Pilórico/patología , Factores Sexuales , Gastropatías/patología , Neoplasias Gástricas/etnología , Neoplasias Gástricas/patologíaRESUMEN
OBJECTIVE: The number of acute hospital beds is determined by health authorities using methods based on ratios and/or target bed occupancy rates. These methods fail to consider the variability in hospitalization demands over time. On the other hand, the implementation of sophisticated models requires the decision concerning the number of beds to be made by an expert. Our aim is to develop a new method that is as simple to use as the ratio method while minimizing the roundabout approaches of these methods. METHOD: A score was constructed with three parameters: number of transfers due to lack of space, number of days with no possibility for S unscheduled admissions and number of days with at least a threshold of U unoccupied beds. The optimal number of beds is the number for which both the mean and the standard deviation of the score reach their minimum. We applied this method to two internal medicine departments and one urological surgery department and we compared the solutions proposed by this method with those put forward by the ratio method. RESULTS: The solutions proposed by this method were intermediate to those calculated by the local and national length of Stays ratio methods. Simulating an unusual increase in admission requests had no consequence on the bed number selected, indicating that the method was robust. CONCLUSION: Our tool represents a real alternative to the ratio methods. A software has been developed and is now available for use.
Asunto(s)
Capacidad de Camas en Hospitales/estadística & datos numéricos , Planificación Hospitalaria/métodos , Algoritmos , Técnicas de Apoyo para la Decisión , Humanos , Tiempo de Internación/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Transferencia de Pacientes/estadística & datos numéricos , Programas InformáticosRESUMEN
Calcific tendinitis of the rotator cuff is a relatively frequent pathology and at times, in some phases, it is a disabling one: for this reason, numerous therapeutic options have been proposed. The authors propose an algorithm for the classification and treatment of calcific tendinitis and report their experience with arthroscopic treatment over a three-year period from 2001 to 2004. Based on the algorithm proposed, out of a total of 126 shoulders affected with calcific tendinitis of the rotator cuff for which debridement was indicated, 106 us-guided percutaneous surgeries (EPT), and only 20 arthroscopies were performed. Arthroscopy is indicated, on the basis of the algorithm that we followed, in patients affected by chronic and persistent calcific tendinitis who did not benefit from the execution of previous types of non-surgical treatment for a period of at least 6 to 12 months. Shoulder instability was found to be present in 8 patients out of 20 treated arthroscopically. After arthroscopy, short- and medium-term results were always positive with the exception of one case that evolved into adhesive capsulitis. Based on an analysis of this series, we were able to confirm the usefulness and clinical applicability of an algorithm to classify and treat calcific tendinitis of the rotator cuff; we also confirmed the role of arthroscopic treatment that in cases which did not respond to conservative procedures proved to be effective in resolving symptoms.
Asunto(s)
Artroscopía , Calcinosis/cirugía , Manguito de los Rotadores/cirugía , Articulación del Hombro/fisiopatología , Tendinopatía/cirugía , Adulto , Algoritmos , Calcinosis/diagnóstico , Calcinosis/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Manguito de los Rotadores/diagnóstico por imagen , Manguito de los Rotadores/patología , Manguito de los Rotadores/fisiopatología , Tendinopatía/diagnóstico , Tendinopatía/fisiopatologíaRESUMEN
Arthroscopic repair of wide rotator cuff ruptures is burdened by a percentage of recurrences that is greater than the repair carried out when an open technique is used. One of the main reasons for this difference can be searched for in the minor hold of stitching on the tendinous aspect obtained with arthroscopic repair. In fact, when an open technique is used, good hold can be guaranteed by using reinforced stitches such as the modified Mason-Allen. Thus, arthroscopic repair technique on the tendinous aspect, particularly in wide and massive injuries, must be improved. It was the purpose of this study to compare a new reinforced stitch that can easily be obtained in arthroscopy (simple stitch that orthogonally crosses a horizontal stitch previously knotted on the tendon: SS-HL), with traditional stitches (simple stitch, mattress-stitch and modified Mason-Allen stitch). Tests were carried out on sheep infraspinatus tendons in order to evaluate the resistance of pull-out. The SS-HL stitch showed resistance to loading that was similar to that when the modified Mason-Allen was used, but it was greater than that shown by the simple stitch (+48%) and the mattress stitch (+35%).
Asunto(s)
Artroplastia , Manguito de los Rotadores/cirugía , Técnicas de Sutura , Animales , Humanos , Lesiones del Manguito de los Rotadores , Ovinos , Técnicas de Sutura/instrumentación , Resultado del TratamientoRESUMEN
The occurrence of heterotopic ossifications constitutes a rare but possible complication in knee arthroplasty surgery. The authors retrospectively reviewed data for more than 250 patients submitted to knee arthroplasty with the purpose of ascertaining the incidence of the occurrence of heterotopic ossifications after surgery and of understanding any clinical repercussions and possible risk factors. A total of 14 cases of heterotopic ossifications were observed out of 276 knee arthroplasties (4.7%). Lesions were grade 1: 4, grade II: 3, grade III: 7. The authors stress the importance of local factors as compared to general ones and the need to adopt a respectful surgical method, avoiding notching or excessive trauma to the periosteum, as well as the need to define parameters in order to single out subjects at risk and in whom prophylaxis should be administered.
Asunto(s)
Artroplastia de Reemplazo de Rodilla/efectos adversos , Osificación Heterotópica/etiología , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Incidencia , Persona de Mediana Edad , Osificación Heterotópica/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: Most methods used to estimate ICU bed needs rely either on simple formulas that do not consider the actual needs of the population or on simulations that are too specific to be applicable to all hospitals. We sought to develop a universally applicable nonparametric method. DESIGN AND SETTING: For each day, the number of immediate patient transfers to other ICUs because of a full unit and the number of patients treated in the ICU were collected. The number of beds needed was selected according to the minimization of both the mean and the variance of three parameters (accessibility, safety, and efficiency). This method was applied to the ICU of a general hospital. Robustness of the model was assessed using outliers. MAIN RESULTS: During the 5-month study period, 215 ICU stays were collected. The method selected a ten-bed model whereas length-of-stay ratio and case-mix methods selected a twelve- and height-bed models respectively. An unusual increase in admission requests had no consequence on the bed number selected, indicating that the method was robust. None of the parameters were dependent on specific ICU characteristics, establishing that this method is applicable to any type of hospital ward. CONCLUSION: Our model is reliable for determining the number of beds needed in any type of ICU and can be used by all ICU managers. The software is available.
Asunto(s)
Capacidad de Camas en Hospitales/estadística & datos numéricos , Planificación Hospitalaria/métodos , Unidades de Cuidados Intensivos , Lechos , Hospitales Generales , Humanos , Tiempo de Internación , Transferencia de Pacientes , Estudios Retrospectivos , Estadísticas no ParamétricasRESUMEN
A wide variety of infectious, inflammatory, and other disorders affect the gastric mucosa in pediatric patients. The most common cause of gastritis in children is Helicobacter pylori infection, which is also responsible for the majority of duodenal ulcers. Acute erosive gastritis is most commonly the result of metabolic stress or drug or corrosive injury. Other major causes of gastritis include celiac disease, allergic disorders, and Crohn's disease. The distinctive clinical, endoscopic, and histologic features of these disorders are discussed.
Asunto(s)
Gastritis/microbiología , Gastritis/patología , Gastroscopía/métodos , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/aislamiento & purificación , Enfermedad Aguda , Adolescente , Biopsia con Aguja , Niño , Preescolar , Enfermedad Crónica , Femenino , Mucosa Gástrica/patología , Gastritis/diagnóstico , Humanos , Masculino , Pronóstico , Factores de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
A distinctive type of multilayered epithelium (ME) has been described at the neo-squamocolumnar junction and within columnar mucosa in patients with Barrett's esophagus (BE). This epithelium has morphologic and ultrastructural features of both squamous and columnar epithelium. Multilayered epithelium may represent an early or intermediate stage of columnar metaplasia; therefore, we performed this study to determine the morphologic and biologic characteristics of this epithelium and to gain insight into its derivation. Esophageal mucosal biopsies containing ME from 17 patients with BE were evaluated morphologically, stained with a variety of mucin histochemical stains; and also immunostained with antibodies against cytokeratins (CK) 13 (squamous epithelium marker); 14 (basal squamous epithelium marker) 7, 8/18, 19, and 20 (columnar epithelium markers), MIB-1 (proliferation marker); villin (intestinal brush border protein); and TGFalpha, EGFR, pS2, and hSP (enteric proliferation/differentiation regulatory peptides). The results were compared with normal esophageal squamous epithelium, normal gastric cardia epithelium, specialized-type intestinal epithelium (BE), and esophageal mucosal and submucosal gland duct epithelium. Multilayered epithelium expressed a pattern of mucin production (neutral mucin, sialomucin, and sulfomucin in 88%, 100%, and 71% of cases, respectively) and cytokeratin expression (CK 13 and 19 in the basal "squamoid" cells, CK 7, 8/18, 19, and 20 in the superficial "columnar" cells) similar to that of columnar epithelium in BE, and showed a high capacity for cellular proliferation (Ki-67-positive in 88% of cases) and differentiation (TGFalpha, EGFR, pS2 and villin-positive in 100%, 100%, 93%, and 66% of cases, respectively). The mucosal gland duct epithelium showed a similar phenotypic pattern and, in one case, was seen to give rise to ME at the surface of the mucosa. These data provide evidence in support of the hypothesis that ME represents an early or intermediate stage in the development of esophageal columnar metaplasia (BE). The mucosal gland duct epithelium may contain progenitor cells that can give rise to ME.
Asunto(s)
Esófago de Barrett/patología , Unión Esofagogástrica/patología , Mucosa Gástrica/patología , Adulto , Anciano , Anciano de 80 o más Años , Esófago de Barrett/etiología , Esófago de Barrett/metabolismo , Biomarcadores/análisis , Biopsia , Epitelio/anatomía & histología , Epitelio/metabolismo , Epitelio/patología , Unión Esofagogástrica/anatomía & histología , Unión Esofagogástrica/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Mucosa Gástrica/anatomía & histología , Mucosa Gástrica/metabolismo , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/metabolismo , Reflujo Gastroesofágico/patología , Humanos , Queratinas/metabolismo , Masculino , Metaplasia/etiología , Metaplasia/metabolismo , Metaplasia/patología , Persona de Mediana Edad , Mucinas/metabolismo , Estudios RetrospectivosRESUMEN
OBJECTIVE: The factors that influence the decision to do an adequate evaluation for a positive test for fecal occult blood in a middle-aged or elderly patient are largely unknown. Our study was undertaken to determine whether factors such as the number of positive Hemoccult II card windows, age, gender, family history of colon cancer, the patient's concern that he or she might have colon cancer, or history of rectal bleeding influence the evaluation performed. METHOD: A mass screening program for colon cancer was performed using unrehydrated Hemoccult II cards in the Boston area. RESULTS: Among the 23,593 Hemoccult II cards returned to Beth Israel Deaconess Medical Center, cards from 1,112 patients (4.7%) were found to be positive for one or more of the six possible card windows. Ninety percent, or 940 patients, over 40 yr of age had follow-up information available. As the number of positive windows increased from one to four, there was a significant trend (p < 0.001) for the adequacy of the evaluation to increase. Family history (p = 0.044) and a patient's worry that he or she might have colon cancer (p = 0.003) significantly improved a patient's chance for an adequate evaluation. CONCLUSIONS: Hemoccult testing is not followed by an adequate evaluation in a significant proportion of patients. Our study points out for the first time that the number of positive Hemoccult windows significantly influences the decision-making.
Asunto(s)
Adenocarcinoma/diagnóstico , Neoplasias del Colon/diagnóstico , Tamizaje Masivo/métodos , Sangre Oculta , Adenocarcinoma/epidemiología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/epidemiología , Heces/química , Femenino , Humanos , Masculino , Massachusetts/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Sensibilidad y Especificidad , Distribución por SexoRESUMEN
BACKGROUND & AIMS: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. We aimed to assess whether clinical, biological, and histologic parameters in quiescent UC predict time to clinical relapse. METHODS: Seventy-four patients with clinically and endoscopically determined inactive UC were followed up for 1 year or for a shorter period if they had a relapse. Serum erythrocyte sedimentation rate; C-reactive protein, interleukin (IL)-1beta, IL-6, and IL-15 values; anti-neutrophil cytoplasmic antibody titers; and rectal biopsy specimens were obtained at baseline, at 6 and 12 months, and/or at relapse. Multivariate survival analysis was performed to determine independent predictors of clinical relapse. RESULTS: Twenty-seven patients relapsed (19/42 women; 8/32 men). Multivariate Cox regression analysis retained younger age (P = 0.003; hazard ratio, 0.4 per decade), greater number of prior relapses in women (P < 0.001; hazard ratio, 1.6 per prior relapse), and basal plasmacytosis (P = 0.003; hazard ratio, 4.5) on rectal biopsy specimens as predictors of shorter time to clinical relapse. Kaplan-Meier survival curves showed the 20-30-year-old age group and women with more than 5 prior relapses to be groups with shorter times to relapse. CONCLUSIONS: Younger age, multiple previous relapses (for women), and basal plasmacytosis on rectal biopsy specimens were independent predictors of earlier relapse. These findings may help identify patients with inactive UC who will require optimal maintenance medical therapy.
Asunto(s)
Colitis Ulcerosa/patología , Interleucinas/sangre , Adulto , Biomarcadores , Sedimentación Sanguínea , Proteína C-Reactiva/metabolismo , Colitis Ulcerosa/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Interleucina-1/sangre , Interleucina-15/sangre , Interleucina-6/sangre , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recurrencia , Factores Sexuales , Análisis de SupervivenciaRESUMEN
The pathogenesis of short segment Barrett's esophagus (SSBE) and intestinal metaplasia (IM) of the gastroesophageal junction (IMGEJ) are poorly understood. Also, these conditions are difficult to distinguish from one another based solely on endoscopic and pathologic criteria. Therefore, the aim of this study was to evaluate the immunophenotypic features of SSBE and IMGEJ and to compare the results with lesions of known etiologies: long segment BE (LSBE) caused by reflux disease and Helicobacter pylori-induced IM of the gastric antrum (IMGA). Routinely processed mucosal biopsy specimens from 11 patients with LSBE, 17 with SSBE, 10 with IMGEJ, 16 with IMGA, 17 with a normal nonmetaplastic GEJ, and 7 patients with a normal gastric antrum were immunohistochemically stained with monoclonal antibodies to: Das1, an antibody shown to react specifically with colonic goblet cells; 45M1, an antibody that recognizes the M1 gastric mucin antigen; and cytokeratin (CK) 7 and 20, antibodies that have previously been reported to show specific staining patterns in BE versus IMGA. Also evaluated was nonintestinalized mucinous epithelium from LSBE, SSBE, and also the normal GEJ and gastric antrum. LSBE, SSBE, and IMGEJ showed similar prevalences of Das1 (91% versus 88% versus 100%) and 45M1 reactivity (100% versus 100% versus 100%), and a similar pattern of CK7/20 reactivity (diffuse strong CK7 staining of the surface and crypt epithelium, and strong surface and superficial crypt CK20 staining) (91% versus 94% versus 90%). In contrast, although 45M1 reactivity in IMGA (93%) was similar to that of the other three groups, IMGA showed a significantly lower prevalence of Das positivity (13%, p < 0.001), and only a 14% prevalence of the CK7/20 staining pattern that was predominant in the other three groups (p < 0.001). Das1, 45M1, and CK7/20 staining were similar in nonintestinalized "cardia-type" mucinous epithelium from LSBE, SSBE, and the GEJ, but all were distinct from the normal gastric antrum. In summary, the immunophenotypic features of SSBE and IMGEJ are similar and closely resemble those seen in classic LSBE, but are distinct from IMGA. This may indicate that IM in LSBE, SSBE and at the GEJ have similar biologic properties. Based on our data, SSBE and IMGEJ cannot be distinguished on the basis of their immunophenotype.
Asunto(s)
Esófago de Barrett/patología , Unión Esofagogástrica/patología , Anticuerpos , Esófago de Barrett/inmunología , Biomarcadores/análisis , Unión Esofagogástrica/inmunología , Unión Esofagogástrica/virología , Reflujo Gastroesofágico/inmunología , Reflujo Gastroesofágico/patología , Humanos , Inmunofenotipificación/métodos , Proteínas de Filamentos Intermediarios/análisis , Queratina-20 , Queratina-7 , Queratinas/análisis , Metaplasia/inmunología , Metaplasia/patología , Estudios RetrospectivosRESUMEN
The cyclin-dependent kinase inhibitor p27 is a negative regulator of the transition from G1 to S phase of the cell cycle, protects against inflammatory injury and promotes epithelial differentiation. Because p27 protein has been shown to be abnormally expressed both in dysplasia associated with Barrett's esophagus and in sporadic colorectal adenomas, we used immunohistochemistry to evaluate p27 expression in inflammatory bowel disease (IBD)-associated dysplasia and carcinomas. Normal, inflamed, and transitional mucosa, sporadic adenomas, and sporadic colonic carcinomas were studied as controls. In normal colonic epithelium p27 expression was restricted to the superficial, terminally differentiated cells. In colitic and inflamed diverticular mucosa p27 was expressed in the base of the crypts in 86 and 70% of cases, respectively. Similarly, in transitional mucosa adjacent to sporadic carcinomas p27 was expressed in the base of the crypts in all cases. Strong p27 expression extended more frequently from the base of the crypts to superficial cells in IBD-associated dysplasia than in sporadic adenomas (P < 0.007). Twenty of 20 (100%) IBD-associated carcinomas showed low p27 expression (<50% nuclei positive) compared to 6 of 20 (30%) stage-matched sporadic colorectal carcinomas (P < 0.001). We conclude (i) aberrant p27 protein expression in inflamed and IBD-associated nondysplastic mucosa is indistinguishable from that found in transitional mucosa adjacent to sporadic carcinomas; (ii) p27 is overexpressed in dysplastic lesions, perhaps as an attempt to counterbalance proliferative stimuli; and (iii) IBD-associated colorectal carcinomas have significantly lower p27 expression, commonly associated with poor prognosis, than stage-matched sporadic colorectal carcinomas. These findings further substantiate the existence of divergent molecular pathogenetic pathways between these types of carcinomas and suggest an intrinsically more aggressive behavior of IBD-associated colon carcinomas compared to sporadic ones.