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1.
J Immunol ; 194(6): 2551-60, 2015 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-25667416

RESUMEN

The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired Ag-induced lymphocyte proliferation, reduced cytokine production by CD8(+) T lymphocytes, and decreased numbers of NK cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome. Inhibition or deletion of NFAT5 in normal human and murine cells recapitulated several of the immune deficits identified in the patient. These results provide evidence of a primary immunodeficiency disorder associated with organ-specific autoimmunity linked to NFAT5 deficiency.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Enfermedades Gastrointestinales/inmunología , Haploinsuficiencia/inmunología , Síndromes de Inmunodeficiencia/inmunología , Factores de Transcripción/inmunología , Animales , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/genética , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Células Cultivadas , Citocinas/inmunología , Citocinas/metabolismo , Análisis Mutacional de ADN , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/genética , Expresión Génica/inmunología , Haploinsuficiencia/genética , Humanos , Immunoblotting , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/genética , Células Jurkat , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Masculino , Ratones de la Cepa 129 , Ratones Noqueados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Adulto Joven
2.
Clin Gastroenterol Hepatol ; 13(3): 561-568.e1, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25218667

RESUMEN

BACKGROUND & AIMS: Little is known about how weight loss affects magnetic resonance imaging (MRI) of liver fat and volume or liver histology in patients with nonalcoholic steatohepatitis (NASH). We measured changes in liver fat and liver volume associated with weight loss by using an advanced MRI method. METHODS: We analyzed data collected from a previous randomized controlled trial in which 43 adult patients with biopsy-proven NASH underwent clinical evaluation, biochemical tests, and MRI and liver biopsy analyses at the start of the study and after 24 weeks. We compared data between patients who did and did not have at least 5% decrease in body mass index (BMI) during the study period. RESULTS: Ten of 43 patients had at least a 5% decrease in BMI during the study period. These patients had a significant decrease in liver fat, which was based on MRI proton density fat fraction estimates (18.3% ± 7.6% to 13.6% ± 13.6%, P = .03), a relative 25.5% reduction. They also had a significant decrease in liver volume (5.3%). However, no significant changes in levels of alanine aminotransferase or aspartate aminotransferase were observed with weight loss. Thirty-three patients without at least 5% decrease in BMI had insignificant increases in estimated liver fat fraction and liver volume. CONCLUSIONS: A reduction in BMI of at least 5% is associated with significant decrease in liver fat and volume in patients with biopsy-proven NASH. These data should be considered in assessing effect size in studies of patients with nonalcoholic fatty liver disease or obesity that use MRI-estimated liver fat and volume as end points.


Asunto(s)
Hígado/patología , Imagen por Resonancia Magnética , Enfermedad del Hígado Graso no Alcohólico/patología , Pérdida de Peso , Adulto , Anciano , Biopsia , Índice de Masa Corporal , Grasas , Femenino , Histocitoquímica , Humanos , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Radiografía , Ensayos Clínicos Controlados Aleatorios como Asunto
3.
Radiology ; 276(3): 775-86, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25875972

RESUMEN

PURPOSE: To determine per-lesion sensitivity and positive predictive value (PPV) of gadoxetic acid-enhanced 3-T magnetic resonance (MR) imaging for the diagnosis of malignant lesions by using matched (spatially correlated) hepatectomy pathologic findings as the reference standard. Materials and METHODS: In this prospective, institutional review board-approved, HIPAA-compliant study, 20 patients (nine men, 11 women; mean age, 59 years) with malignant liver lesions who gave written informed consent underwent preoperative gadoxetic acid-enhanced 3-T MR imaging for surgical planning. Two image sets were independently analyzed by three readers to detect liver lesions (set 1 without and set 2 with hepatobiliary phase [HBP] images). Hepatectomy specimen ex vivo MR imaging assisted in matching gadoxetic acid-enhanced 3-T MR imaging findings with pathologic findings. Interreader agreement was assessed by using the Cohen κ coefficient. Per-lesion sensitivity and PPV were calculated. RESULTS: Cohen κ values were 0.64-0.76 and 0.57-0.84, and overall per-lesion sensitivity was 45% (42 of 94 lesions) to 56% (53 of 94 lesions) and 58% (55 of 94 lesions) to 64% (60 of 94 lesions) for sets 1 and 2, respectively. The addition of HBP imaging did not affect interreader agreement but significantly improved overall sensitivity for one reader (P < .05) and almost for another (P = .05). Sensitivity for 0.2-0.5-cm lesions was 0% (0 of 26 lesions) to 8% (two of 26 lesions) for set 1 and 4% (one of 26 lesions) to 12% (three of 26 lesions) for set 2. Sensitivity for 0.6-1.0-cm lesions was 28% (nine of 32 lesions) to 59% (19 of 32 lesions) for set 1 and 66% (21 of 32 lesions) to 69% (22 of 32 lesions) for set 2. Sensitivity for lesions at least 1.0 cm in diameter was at least 81% (13 of 16 lesions) for set 1 and was not improved for set 2. PPV was 98% (56 of 57 lesions) to 100% (60 of 60 lesions) for all readers without differences between image sets or lesion size. CONCLUSION: Gadoxetic acid-enhanced 3-T MR imaging provides high per-lesion sensitivity and PPV for preoperative malignant liver lesion detection overall, although sensitivity for 0.2-0.5-cm malignant lesions is poor.


Asunto(s)
Medios de Contraste , Gadolinio DTPA , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Cuidados Preoperatorios , Estudios Prospectivos , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto Joven
4.
Hepatology ; 58(6): 1930-40, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23696515

RESUMEN

UNLABELLED: The magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) is a novel imaging-based biomarker that allows fat mapping of the entire liver, whereas the magnetic resonance spectroscopy-measured proton density fat fraction (MRS-PDFF) provides a biochemical measure of liver fat in small regions of interest. Cross-sectional studies have shown that MRI-PDFF correlates with MRS-PDFF. The aim of this study was to show the utility of MRI-PDFF in assessing quantitative changes in liver fat through a three-way comparison of MRI-PDFF and MRS-PDFF with the liver histology-determined steatosis grade at two time points in patients with nonalcoholic fatty liver disease (NAFLD). Fifty patients with biopsy-proven NAFLD who participated in a randomized trial underwent a paired evaluation with liver biopsy, MRI-PDFF, and MRS-PDFF at the baseline and 24 weeks. The mean age and body mass index were 47.8 ± 11.7 years and 30.7 ± 6.5 kg/m(2), respectively. MRI-PDFF showed a robust correlation with MRS-PDFF both at week 0 and at week 24 (r = 0.98, P < 0.0001 for both). Cross-sectionally, MRI-PDFF and MRS-PDFF increased with increases in the histology-determined steatosis grade both at week 0 and at week 24 (P < 0.05 for all). Longitudinally, patients who had a decrease (≥ 1%) or increase (≥ 1%) in MRI-PDFF (confirmed by MRS-PDFF) showed a parallel decrease or increase in their body weight and serum alanine aminotransferase and aspartate aminotransferase levels at week 24 (P < 0.05). This small increase or decrease in liver fat could not be quantified with histology. CONCLUSION: In this longitudinal study, MRI-PDFF correlated well with MRS-PDFF and was more sensitive than the histology-determined steatosis grade in quantifying increases or decreases in the liver fat content. Therefore, it could be used to quantify changes in liver fat in future clinical trials.


Asunto(s)
Biomarcadores/análisis , Hígado Graso/patología , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Adulto , Biopsia , Peso Corporal , Femenino , Humanos , Hígado/patología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico
5.
Phys Rev Lett ; 113(8): 086401, 2014 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-25192110

RESUMEN

We report results of exact diagonalization studies of the spin- and valley-polarized fractional quantum Hall effect in the N = 0 and N = 1 Landau levels in graphene. We use an effective model that incorporates Landau level mixing to lowest order in the parameter κ = ((e(2)/εℓ)/(hv(F)/ℓ)) = (e(2)/εv(F)h), which is magnetic field independent and can only be varied through the choice of substrate. We find Landau level mixing effects are negligible in the N = 0 Landau level for κ ≲ 2. In fact, the lowest Landau level projected Coulomb Hamiltonian is a better approximation to the real Hamiltonian for graphene than it is for semiconductor based quantum wells. Consequently, the principal fractional quantum Hall states are expected in the N = 0 Landau level over this range of κ. In the N = 1 Landau level, fractional quantum Hall states are expected for a smaller range of κ and Landau level mixing strongly breaks particle-hole symmetry, producing qualitatively different results compared to the N = 0 Landau level. At half filling of the N = 1 Landau level, we predict the anti-Pfaffian state will occur for κ ∼ 0.25-0.75.

6.
Endoscopy ; 46(2): 149-52, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24415526

RESUMEN

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of lymph nodes is used for staging of gastrointestinal malignancies. False-positive rates of 5 % - 7 % are not well understood. Elements of EUS examinations that contribute to false-positive cytological findings were investigated. PATIENTS AND METHODS: 13 patients undergoing EUS staging of gastrointestinal luminal malignancy were consecutively enrolled together with 3 patients with extraluminal tumors (pancreas, lung) defined as controls. After EUS, cellular debris and fluid were collected from the FNA needle catheter, instrument channel, and endoscope tip for cytologic and histologic investigation. RESULTS: 6 of 13 patients (46 %) had malignant cells contaminating the FNA needle catheter, instrument channel, or endoscope tip. Malignant cells were present in the instrument channel in 5 cases (38 %), exterior tip of echoendoscope in 4 (31 %) and needle catheter in 2 (15 %). CONCLUSIONS: Echoendoscopes used for FNA in patients with luminal tumors are at risk for malignant cell contamination of the instrument channel, FNA needle catheter, and echoendoscope tip. FNA needle contamination can contribute to false-positive findings.


Asunto(s)
Adenocarcinoma/patología , Carcinoma de Células Escamosas/patología , Neoplasias del Sistema Digestivo/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Neoplasias Pulmonares/patología , Adenocarcinoma/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico por imagen , Neoplasias del Sistema Digestivo/diagnóstico por imagen , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/instrumentación , Reacciones Falso Positivas , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Estadificación de Neoplasias , Estudios Prospectivos , Método Simple Ciego
7.
Hepatology ; 56(3): 922-32, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22431131

RESUMEN

UNLABELLED: Bile acid sequestrants (BAS) lower plasma low density lipoprotein levels and improve glycemic control. Colestimide, a BAS, has been claimed by computed tomography to reduce liver fat. Therefore, we examined the efficacy of colesevelam, a potent BAS, to decrease liver fat in patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Liver fat was measured by a novel magnetic resonance imaging (MRI) technique, the proton-density-fat-fraction (PDFF), as well as by conventional MR spectroscopy (MRS). Fifty patients with biopsy-proven NASH were randomly assigned to either colesevelam 3.75 g/day orally or placebo for 24 weeks. The primary outcome was change in liver fat as measured by MRI-PDFF in colocalized regions of interest within each of the nine liver segments. Compared with placebo, colesevelam increased liver fat by MRI-PDFF in all nine segments of the liver with a mean difference of 5.6% (P = 0.002). We cross-validated the MRI-PDFF-determined fat content with that assessed by colocalized MRS; the latter showed a mean difference of 4.9% (P = 0.014) in liver fat between the colesevelam and the placebo arms. MRI-PDFF correlated strongly with MRS-determined hepatic fat content (r(2) = 0.96, P < 0.0001). Liver biopsy assessment of steatosis, cellular injury, and lobular inflammation did not detect any effect of treatment. CONCLUSION: Colesevelam increases liver fat in patients with NASH as assessed by MRI as well as MRS without significant changes seen on histology. Thus, MRI and MRS may be better than histology to detect longitudinal changes in hepatic fat in NASH. Underlying mechanisms and whether the small MR-detected increase in liver fat has clinical consequences is not known.


Asunto(s)
Alilamina/análogos & derivados , Anticolesterolemiantes/uso terapéutico , Hígado Graso/tratamiento farmacológico , Hígado Graso/patología , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Alilamina/uso terapéutico , Clorhidrato de Colesevelam , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Estudios Prospectivos
8.
Surg Endosc ; 27(9): 3478-84, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23494511

RESUMEN

BACKGROUND: To demonstrate the feasibility of an innovative technique for the surgical management of rectal cancer, we performed transanal minimally invasive surgery assisted low anterior resection with total mesorectal excision (TAMIS-assisted LAR with TME) in a cadaver model. Transanal LAR via natural orifice transluminal endoscopic surgery has been reported in cadaveric series using rigid transanal platforms. This procedure has not been described using a combination of a single incision laparoscopy and TAMIS transanal endoscopic platform. We describe the first cadaveric series of TAMIS-assisted LAR with TME. METHODS: TAMIS-assisted LAR with TME was successfully performed in five fresh human cadavers. The procedure was performed using the mini-Gelpoint single incision platform and the Gelpoint Path TAMIS platform (Applied Medical, Rancho Santa Margarita, CA). The variables recorded were age, body mass index (BMI), operative time, complications, and specimen length. The grade of the TME was determined by evaluation of the specimen by photo documentation by a gastrointestinal pathologist. RESULTS: All cadavers were male with a mean age of 71 ± 8 years and mean BMI of 28 ± 3 kg/m(2). The mean operative time was 200 ± 55 min (range 128-249 min). The quality of the TME was grade I (complete) with intact mesorectum in all five cases. The mean specimen length was 36.8 ± 3.4 cm. CONCLUSIONS: TAMIS-assisted LAR with TME was feasible. A high-quality TME can be achieved using this innovative technique. Transanal endoscopic total mesorectal dissection may revolutionize the surgical management of rectal cancer. However, multicenter clinical trials are needed to further evaluate the oncologic safety and surgical outcomes of transanal endoscopic TME using various platforms before widespread application of this new technique.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Cirugía Endoscópica por Orificios Naturales/métodos , Recto/cirugía , Abdomen/cirugía , Anciano , Canal Anal , Cadáver , Estudios de Factibilidad , Humanos , Masculino , Neumoperitoneo Artificial
9.
Ann Diagn Pathol ; 17(4): 322-6, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23660273

RESUMEN

Molecular studies are part of standard care for cancer patients. Bone, a common and sometimes sole site of metastasis, requires decalcification for morphological examination. Many commonly used decalcification agents contain strong acids that degrade nucleic acids. The paradigm shift in oncology, with biomarker targeted therapy and gene expression profiling analysis, requires sufficient nucleic acid recovery from bone biopsy specimens. We systematically studied the effects of a spectrum of decalcification agents on the quantity and quality of RNA and DNA recovered from bone biopsies. Multiple bone biopsies of similar size and cellularity were fixed in 10% neutral-buffered formalin, randomized to various decalcification agents for 2 hours then processed, and embedded. Tissue lysates were obtained from unstained sections and nucleic acid isolated. DNA and RNA were quantified. Assessment of DNA and RNA integrity was accomplished by comparison of the average cycle threshold by polymerase chain reaction of selected housekeeping genes for each agent. Results were then analyzed by 2-sample t test. There was a significant decrease in both DNA and RNA yield and integrity with strong acids (hydrochloric, nitric) vs 14% EDTA and formic acid. DNA yield was (mean nanograms) 6.15 vs 68.68 (P<.001) and RNA was (mean nanograms) 121.53 vs 288.89 (P=.003), respectively. DNA integrity (mean cycle threshold) was 35.79 vs 30.16 (P<.001), and RNA was 33.03 vs 26.5 (P<.001), respectively. Decalcification of bone biopsies with EDTA or formic acid agents was associated with a significant improvement in recovered nucleic acid quantity and quality.


Asunto(s)
Huesos/efectos de los fármacos , ADN/efectos de los fármacos , Ácido Edético/farmacología , Formiatos/farmacología , ARN/efectos de los fármacos , Adulto , Biopsia , ADN/análisis , ADN/aislamiento & purificación , Técnica de Descalcificación , Formaldehído , Humanos , Masculino , Persona de Mediana Edad , Adhesión en Parafina , ARN/análisis , ARN/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa , Fijación del Tejido
10.
Ann Diagn Pathol ; 16(5): 385-7, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21546296

RESUMEN

A definitive link between Schistosoma hematobium infection and squamous cell carcinoma of the bladder has been identified. A weaker association between S japonicum infection and colorectal neoplasia has been proposed, although reports are limited to case reports, a case series, and epidemiologic studies. Virtually all cases presented in the literature describe intestinal-type adenocarcinoma occurring in association with S japonicum. We here describe a 40-year-old male Filipino patient with signet ring cell carcinoma of the rectum and evidence of infection by S japonicum.


Asunto(s)
Carcinoma de Células en Anillo de Sello/parasitología , Neoplasias del Recto/parasitología , Schistosoma japonicum/aislamiento & purificación , Esquistosomiasis Japónica/parasitología , Adulto , Animales , Antihelmínticos/uso terapéutico , Carcinoma de Células en Anillo de Sello/tratamiento farmacológico , Carcinoma de Células en Anillo de Sello/patología , Colostomía , Humanos , Masculino , Terapia Neoadyuvante , Praziquantel/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Esquistosomiasis Japónica/tratamiento farmacológico , Esquistosomiasis Japónica/patología
11.
Dig Dis Sci ; 56(6): 1884-8, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21445581

RESUMEN

BACKGROUND: Although pancreatic rests have characteristic endoscopic features, confirming a histological diagnosis may be desirable to exclude other significant pathology. AIMS: The aim of this study was to assess the efficacy and safety of endoscopic band ligation snare polypectomy (EBLSP) for removal of suspected pancreatic rests and to compare the diagnostic yield to other endoscopic tissue sampling methods. METHODS: An electronic endoscopic report database was searched for patients referred for evaluation of incidentally found gastric antral subepithelial lesions. Tissue sampling technique, pathology, and complications were recorded. RESULTS: Removal of suspected pancreatic rests with EBLSP was successful in all 21 cases without complications. Nineteen of 21 (90%) who underwent EBLSP had a histological diagnosis of heterotopic pancreas compared with 5 of 14 (36%) who underwent tissue sampling with biopsy and/or snare (P = 0.001). The endoscopic characteristics of the histology proven pancreatic rests were an antral subepithelial mass with central umbilication measuring 6-10 mm in diameter and located 2-6 cm from the pylorus in the 3-7 o'clock position. CONCLUSIONS: Endoscopic band ligation snare polypectomy resection of gastric antral lesions suspected to be pancreatic rests had a diagnostic yield superior to standard biopsy forceps and snare polypectomy techniques. However, because all pathologically confirmed pancreatic rests had typical endoscopic appearances of pancreatic rests, it may not be necessary to obtain histologic diagnosis for every suspected gastric antral heterotopic pancreas.


Asunto(s)
Enfermedades Pancreáticas/congénito , Enfermedades Pancreáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Ligadura , Masculino , Persona de Mediana Edad , Páncreas/patología
12.
Ann Diagn Pathol ; 15(5): 355-7, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20952282

RESUMEN

Amphicrine tumors are defined by evidence of both glandular and neuroendocrine differentiation in the same cell. These are extremely rare tumors, with only scattered case reports in the pancreas and stomach. We here report a case of amphicrine carcinoma occurring in apparent isolation in the liver. The tumor was characterized by signet ring cell morphology, mucicarmine, and periodic acid Schiff with diastase (PASD) positivity, and expression of chromogranin, synaptophysin, villin, and CDX2. No other tumor was identified by radiological or endoscopic examination of the gastrointestinal tract. The patient is disease-free 22 months after the resection. We speculate that this represents the first reported occurrence of primary amphicrine carcinoma of the liver.


Asunto(s)
Carcinoma , Neoplasias Hepáticas , Amilasas , Factor de Transcripción CDX2 , Carcinoma/diagnóstico , Carcinoma/metabolismo , Carcinoma/patología , Carcinoma/cirugía , Carmín , Cromograninas/metabolismo , Proteínas de Homeodominio/metabolismo , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Proteínas de Microfilamentos/metabolismo , Persona de Mediana Edad , Coloración y Etiquetado , Sinaptofisina/metabolismo
13.
Radiographics ; 28(3): 747-69, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18480482

RESUMEN

Cirrhotic livers are characterized by advanced fibrosis and the formation of hepatocellular nodules, which are classified histologically as either (a) regenerative lesions (eg, regenerative nodules, lobar or segmental hyperplasia, focal nodular hyperplasia) or (b) dysplastic or neoplastic lesions (eg, dysplastic foci and nodules, hepatocellular carcinomas). The differentiation of these lesions is important because regenerative nodules are benign, whereas dysplastic and neoplastic nodules are premalignant and malignant, respectively. However, their accurate characterization may be difficult even at histopathologic analysis. Differential diagnosis may be facilitated by comparing the clinical and pathologic findings with radiologic imaging features; in particular, nodule size, vascularity, hepatocellular function, and Kupffer cell density assessed at magnetic resonance (MR) imaging are suggestive of the correct diagnosis. MR imaging is more useful than computed tomography for such assessments because it provides better soft-tissue contrast and a more nuanced depiction of different tissue properties. Moreover, a wider variety of contrast agents is available for use in MR imaging. Familiarity with the MR imaging characteristics of cirrhosis-associated hepatocellular nodules is therefore important for optimal diagnosis and management of cirrhotic disease.


Asunto(s)
Carcinoma Hepatocelular/patología , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/métodos , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadística como Asunto
14.
Appl Immunohistochem Mol Morphol ; 15(3): 242-7, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17721266

RESUMEN

Approximately 10% to 20% of nonsmall cell lung cancer patients respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as gefitinib. Responders are mostly nonsmokers and women with tumors displaying bronchioloalveolar features. Mutations of the tyrosine kinase domain of the EGFR gene have been associated with a clinical response to gefitinib. A recent study reported that the terminal respiratory unit (TRU)-type adenocarcinoma shares the clinical profile and EGFR mutations of gefitinib responders. EGFR immunoreactivity in this context has not been reported in the literature. We performed a detailed immunohistochemical analysis of EGFR expression on 124 consecutive lung resection specimens for malignancy, to survey the EGFR immunoreactivity in lung cancers in general and to correlate EGFR immunoreactivity with EGFR mutations and TRU-type histology. EGFR positivity was seen most frequently in squamous cell carcinomas (77%), followed by TRU-type adenocarcinomas (63%), large cell carcinomas (23%), and non-TRU-type adenocarcinomas (12%). A distinctive basally oriented cytoplasmic positivity was observed exclusively in TRU-type adenocarcinomas. EGFR mutation was identified in 6 of 54 cases studied and all 6 cases were TRU-type adenocarcinomas. Five of six cases with EGFR mutation were positive for EGFR immunostain with the basal cytoplasmic localization. In conclusion, EGFR immunoreactivity with basal cytoplasmic pattern was exclusively seen in TRU-type adenocarcinoma and a subset of these cases was seen with EGFR mutations in the responders to EGFR inhibitor therapy.


Asunto(s)
Adenocarcinoma/diagnóstico , Receptores ErbB/análisis , Receptores ErbB/genética , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patología , Anciano , Análisis Mutacional de ADN , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Mutación
15.
J Manag Care Pharm ; 13(2): 155-62, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17330976

RESUMEN

BACKGROUND: The simultaneous use of multiple prescription medications has been associated with an increased risk of adverse drug events and other drug-related complications, especially in the elderly. OBJECTIVE: To quantify the prevalence of use of multiple medications among a sample of Department of Defense (DoD) health care beneficiaries, aged 65 years and older, who used their TRICARE (military health care services) benefit to obtain prescription medication. METHODS: Outpatient pharmacy fill records were analyzed for a 10% random sample of 1.27 million TRICARE beneficiaries aged 65 years and older who obtained 1 or more prescription medications in the 90-day period from December 1, 2004, through February 28, 2005. The First DataBank generic code number was used to identify drugs and to calculate the mean number of medications obtained and the mean, frequency, and type of American Hospital Formulary System drug therapy categories. Statistical significance for gender and age subgroups was tested via independent t tests. RESULTS: There were 1,268,162 users of the TRICARE pharmacy benefit in the 90-day study period from December 1, 2004, through February 28, 2005, approximately 72.7% of 1,744,072 eligible beneficiaries. The 10% sample of these users (n=126,682) accounted for 1,091,699 pharmacy fill records for 761,043 unique medications, or an average of 6.01 [SD 4.01] unique medications per user, distributed across an average of 3.80 [2.08] therapeutic categories; 8.8% of users received 1 medication, 50.0% received 5 or more medications from an average of 3 therapeutic categories, and 2.8% obtained 16 or more medications from an average of 8 therapeutic categories. Multiple drug use was more prevalent among women relative to men, with an average of 6.28 [4.12] medications from 4.03 [2.11] therapeutic categories for women versus an average of 5.69 [3.85] medications from an average of 3.80 [2.08] therapeutic categories for men (P <0.001). The prevalence of multiple drug use peaked among beneficiaries aged 80 to 84 years. Cardiovascular drugs, central nervous system agents, and hormones and synthetic substitutes were the 3 most common therapeutic categories used by 77%, 48%, and 42% of beneficiaries, respectively. CONCLUSION: This baseline analysis documented the common use of multiple medications among TRICARE beneficiaries. The DoD faces a challenge similar to that of Medicare Part D drug plans to cost-effectively monitor and optimize pharmacotherapy for its older beneficiaries.


Asunto(s)
Seguro de Servicios Farmacéuticos , Personal Militar , Polifarmacia , Anciano , Anciano de 80 o más Años , Prescripciones de Medicamentos , Femenino , Humanos , Masculino , Estados Unidos
16.
Appl Immunohistochem Mol Morphol ; 14(4): 390-6, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17122634

RESUMEN

Mutation of the platelet-derived growth factor receptor-alpha (PDGFRA) gene has been well documented as an alternative oncogenic mechanism in a subset of gastrointestinal stromal tumors (GISTs) lacking c-kit mutations. However, the role of PDGFRA immunohistochemistry in the diagnosis of GISTs has not been well studied. We investigated PDGFRA immunoreactivity in GISTs and in other intra-abdominal mesenchymal tumors, and correlated PDGFRA expression with CD117 positivity and with the mutational status of PDGFRA and c-kit genes. In addition, expression of phosphorylated AKT, an activated downstream molecule in the PDGFRA and c-kit signaling pathways, was correlated with PDGFRA and CD117 status. A total of 39 GISTs and 20 other mesenchymal tumors in the abdomen were included in this study. Thirty-five of 39 GIST cases (89.7%) were positive for PDGFRA and 19 of these 35 positive cases were strongly positive. Five of 20 non-GIST lesions (25%) were positive for PDGFRA, but none of these cases were strongly positive. With one exception, PDGFRA-positive cases were also positive for CD117. Phosphorylated AKT positivity was not associated with the immunoreactivity or mutation of PDGFRA and c-kit, suggesting that the activation of AKT is probably independent of the activation of PDGFRA and c-kit in GISTs. Of 14 GISTs assayed, 4 had mutations in c-kit at exons 11 or 17, and 4 had mutations in PDGFRA at exons 12 or 18. Three of 4 GIST cases with PDGFRA mutations show epithelioid morphology and strong PDGFRA immunoreactivity with prominent perinuclear dotlike accentuation (so-called Golgi pattern). In conclusion, strong PDGFRA positivity with Golgi pattern is a useful adjunct in the diagnosis of GISTs with PDGFRA mutation.


Asunto(s)
Neoplasias Abdominales/metabolismo , Tumores del Estroma Gastrointestinal/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Neoplasias Abdominales/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fibroma/metabolismo , Fibroma/patología , Tumores del Estroma Gastrointestinal/patología , Humanos , Inmunohistoquímica , Leiomioma/metabolismo , Leiomioma/patología , Masculino , Persona de Mediana Edad , Mutación , Neurilemoma/metabolismo , Neurilemoma/patología , Proteína Oncogénica v-akt/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Proteínas S100/metabolismo , Sarcoma/metabolismo , Sarcoma/patología , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patología
17.
J Psychosom Res ; 60(3): 263-71, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16516658

RESUMEN

PURPOSE: The association between obesity and depression remains equivocal. The purpose of this study was to describe the prevalence and association of obesity and depressive symptoms among military personnel. METHODS: A cross-sectional analysis was performed using data (N=10,040) from the U.S. Department of Defense (DoD) Survey of Health-Related Behaviors. Prevalence odds ratios were calculated to describe the association between obesity and depressive symptoms. RESULTS: Approximately 10% of active duty men and 4% of active duty women were obese. The prevalence of depressive symptoms ranged from approximately 16% of overweight men to 49% of obese women. Obese men and women and underweight men had increased odds of depressive symptoms as compared with normal-weight individuals. CONCLUSIONS: The DoD should emphasize prevention and regular screening for obesity and depressive symptoms to improve readiness and reduce health care costs and disease burden in this cohort.


Asunto(s)
Depresión/epidemiología , Depresión/etiología , Personal Militar/psicología , Personal Militar/estadística & datos numéricos , Obesidad/epidemiología , Obesidad/psicología , Adulto , Índice de Masa Corporal , Estudios Transversales , Depresión/diagnóstico , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Obesidad/diagnóstico , Prevalencia , Índice de Severidad de la Enfermedad , Estados Unidos/epidemiología
18.
Am J Health Promot ; 20(5): 334-41, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16706004

RESUMEN

PURPOSE: To assess the status of U.S. military retirees and their spouses 38 to 64 years of age relative to select Healthy People 2010 objectives and to identify sociodemographic characteristics associated with select health behaviors. DESIGN: Cross-sectional analyses with self-reported standardized measures from the U.S. Department of Defense Population Health Survey, 2003. SETTING: The continental United States. SUBJECTS: U.S. military retirees and their spouses 38 to 64 years of age. MEASURES: Data for this study were self-reported responses to the Population Health Survey. Dichotomous variables were created to indicate whether each Healthy People 2010 objective had been met. Each objective was measurable with the survey by using the definitions set forth in Healthy People 2010. These objectives included healthy weight and obesity based on body mass index (height and weight); daily fruit, vegetable, and grain-product consumption; physical inactivity, moderate physical activity, and vigorous physical activity; binge drinking; cigarette use; and smoking-cessation attempts. RESULTS: The study population did not meet any of the Healthy People 2010 objectives included in this study. Sociodemographic characteristics that were associated with this result included being male, not having a college degree, and a less-than-excellent self-reported general health status. CONCLUSION: Health-promotion interventions are needed to improve the health status of this population and to achieve the goals set forth in Healthy People 2010.


Asunto(s)
Conductas Relacionadas con la Salud , Encuestas Epidemiológicas , Programas Gente Sana/organización & administración , Medicina Militar/organización & administración , Personal Militar/psicología , Jubilación/estadística & datos numéricos , Adulto , Estudios Transversales , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Personal Militar/estadística & datos numéricos , Objetivos Organizacionales , Asunción de Riesgos , Esposos/psicología , Estados Unidos
19.
Am J Prev Med ; 50(1): 77-86, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26232906

RESUMEN

INTRODUCTION: Military sexual trauma (MST) includes sexual harassment or sexual assault that occurs during military service and is of increasing public health concern. The population prevalence of MST among female and male veterans who served during Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) has not been estimated to our knowledge. The purpose of this study is to assess the population prevalence and identify military correlates of MST, sexual harassment, and sexual assault among OEF/OIF veterans. METHODS: MST was assessed in the 2009-2011 National Health Study for a New Generation of U.S. Veterans, a survey of 60,000 veterans who served during the OEF/OIF eras (response rate, 34%, n=20,563). Weighted prevalence estimates and AORs of MST, sexual harassment, and sexual assault among women and men were calculated. Gender-stratified logistic regression models controlled for military and demographic characteristics. Data analyses were conducted in 2013-2014. RESULTS: Approximately 41% of women and 4% of men reported experiencing MST. Deployed men had lower risk for MST compared with non-deployed men, though no difference was found among women. However, veterans reporting combat exposure during deployment had increased risk for MST compared with those without, while controlling for OEF/OIF deployment. Among women, Marines and Navy veterans had increased risk for MST compared with Air Force veterans. MST was significantly higher among veterans who reported using Veterans Affairs healthcare services. CONCLUSIONS: These prevalence estimates underscore the importance of public awareness and continued investigation of the public health impact of MST.


Asunto(s)
Delitos Sexuales/psicología , Acoso Sexual/psicología , Veteranos/psicología , Adulto , Campaña Afgana 2001- , Femenino , Humanos , Guerra de Irak 2003-2011 , Masculino , Persona de Mediana Edad , Personal Militar/estadística & datos numéricos , Prevalencia , Delitos Sexuales/estadística & datos numéricos , Acoso Sexual/estadística & datos numéricos , Encuestas y Cuestionarios , Estados Unidos , United States Department of Veterans Affairs
20.
Obstet Gynecol ; 105(3): 598-606, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15738031

RESUMEN

OBJECTIVE: To assess whether significant variations in observed cesarean rates in U.S. military hospitals may be attributed to differences in clinical case mix. METHODS: Hospital discharge records for births in U.S. military hospitals in 2002 were grouped into mutually exclusive clinical strata to calculate predicted cesarean rates for subgroups defined by maternal race, health plan, hospital location, delivery volume, teaching status, and neonatal intensive care unit (NICU) status. The 95% confidence interval (CI) around each standardized ratio (SR) of the observed-to-predicted cesarean rate was used to assess statistical significance. RESULTS: Observed cesarean rates were significantly higher than predicted rates for small hospitals (23.1% and 20.4%, respectively, SR 1.13, 95% CI 1.08-1.19), teaching hospitals (23.7% and 22.5%, respectively, SR 1.05, 95% CI 1.02-1.08), black women (25.1% and 22.8%, respectively, SR 1.10, 95% CI 1.05-1.14), and other minorities (22.7%, and 21.6%, respectively, SR 1.05, 95% CI 1.01-1.09). No significant differences between observed and predicted cesarean rates were found across hospital locations or NICU status. Significant differences found for non-managed care beneficiaries were attributed to teaching status of the hospitals in which they delivered. CONCLUSION: Clinical case mix does not adequately account for the relatively high rates of cesarean delivery observed for small hospitals and teaching hospitals and among black women in the study population. Further study is recommended to identify additional clinical and nonclinical factors that should be considered when comparing performance across institutions, health plans, or individual providers.


Asunto(s)
Cesárea/estadística & datos numéricos , Hospitales Militares/estadística & datos numéricos , Adulto , Parto Obstétrico/estadística & datos numéricos , Femenino , Tamaño de las Instituciones de Salud , Hospitales de Enseñanza/estadística & datos numéricos , Humanos , Unidades de Cuidado Intensivo Neonatal , Embarazo , Embarazo de Alto Riesgo , Ajuste de Riesgo , Estados Unidos
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