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OBJECTIVE: Two-dimensional (2D) transvaginal ultrasound (TVS) is an accessible and cost-effective diagnostic tool for the detection of adenomyosis. Different ultrasound features related to adenomyosis have been described, but the predictive value of each ultrasound sign and their combinations requires further investigation. We aimed to analyze the accuracy of 2D-TVS and describe possible combinations of ultrasound signs with a high predictive value in the diagnosis of adenomyosis. METHODS: This was a prospective multicenter study of patients scheduled for laparoscopic hysterectomy who had been examined using standardized 2D-TVS at nine expert centers specializing in the diagnosis and treatment of endometriosis. 2D-TVS examination included nine typical adenomyosis ultrasound features, comprising heterogeneous myometrium, myometrial linear striations, myometrial cysts, subendometrial microcysts, asymmetrical myometrial thickening, uterine enlargement, the 'question mark sign', thickening of the junctional zone and hyperechoic myometrial spots, in order to predict or exclude the presence of adenomyosis. Ultrasound examination results were compared with histology after hysterectomy. The diagnostic reliability of the nine ultrasound signs and their combinations, and the influence of concurrent fibroids on the accuracy of the results, were analyzed. RESULTS: A total of 202 patients were enrolled into the study. Histopathological examination revealed adenomyosis in 130 patients (64.4%). The accuracy of prediction of adenomyosis by 2D-TVS examination using all signs was 63.4% (positive predictive value, 71.5%; negative predictive value, 48.6%; sensitivity, 71.5%; specificity, 48.6%). Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy (55.7-62.1%) as individual ultrasound signs for the prediction of adenomyosis. The combination of the most accurate ultrasound signs (subendometrial microcysts, myometrial cysts and heterogeneous myometrium) improved the specificity of prediction (86.1%) when compared with that of these three single markers (35.2-81.7%). Uterine enlargement and asymmetry showed both low sensitivity (60.8% and 52.3%, respectively) and specificity (41.7% and 49.3%, respectively) as individual sonographic signs. CONCLUSIONS: Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy for the detection of adenomyosis in this study, while uterine enlargement and asymmetry led to high false-positive and false-negative results. A combination of ultrasound features including the most accurate signs increases specificity. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Adenomiosis , Quistes , Endometriosis , Femenino , Humanos , Adenomiosis/diagnóstico por imagen , Endometriosis/diagnóstico por imagen , Endometriosis/patología , Miometrio/diagnóstico por imagen , Miometrio/patología , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Ultrasonografía/métodosRESUMEN
We propose a solution to a long-standing problem: how to terminate multiple vortices in the heart, when the locations of their cores and their critical time windows are unknown. We scan the phases of all pinned vortices in parallel with electric field pulses (E-pulses). We specify a condition on pacing parameters that guarantees termination of one vortex. For more than one vortex with significantly different frequencies, the success of scanning depends on chance, and all vortices are terminated with a success rate of less than one. We found that a similar mechanism terminates also a free (not pinned) vortex. A series of about 500 experiments with termination of ventricular fibrillation by E-pulses in pig isolated hearts is evidence that pinned vortices, hidden from direct observation, are significant in fibrillation. These results form a physical basis needed for the creation of new effective low energy defibrillation methods based on the termination of vortices underlying fibrillation.
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Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: ⢠Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. ⢠Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. ⢠Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. ⢠Comprehensive chemosensory assessment should include gustatory screening. ⢠Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.
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Trastornos del Olfato/diagnóstico , Trastornos del Olfato/terapia , Humanos , Pruebas Neuropsicológicas , Olfatometría , Percepción Olfatoria , Calidad de VidaRESUMEN
BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.
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OBJECTIVES: The aim of the current study was to evaluate the prevalence and the impact of sexual dysfunction, sexual distress and interpersonal relationships in patients with endometriosis. STUDY DESIGN: A questionnaire-based multicentre cohort study was conducted in eight tertiary referral centres in Austria and Germany. One hundred and twenty-five patients with histologically proven endometriosis and dyspareunia were included. The Female Sexual Function Index and the Female Sexual Distress Scale were used to screen women's sexuality. Additionally, we evaluated psychological parameters and pain intensity during/after sexual intercourse via a self-administered questionnaire. RESULTS: Female sexual distress and sexual dysfunction were observed in 97/125 and 40/125 patients. Statistically significant correlations were found between sexual dysfunction and pain intensity during/after sexual intercourse (p<0.01/p<0.01), a lower number of episodes of sexual intercourse per month (p<0.01), greater feelings of guilt towards the partner (p<0.01) and fewer feelings of femininity (p<0.01). Thirty-eight out of 125 women agreed that the primary motivation for sexual intercourse was to conceive and nearly half of women (46%) included stated that satisfying the partner acted as primary motivation for sexual contact. CONCLUSION: Overall, our findings demonstrate that dyspareunia as a common complaint in patients with endometriosis causes a severe impairment of sexual function, relationship and psychological wellbeing.
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Dispareunia/etiología , Endometriosis/complicaciones , Conducta Sexual , Adulto , Austria/epidemiología , Estudios de Cohortes , Dispareunia/epidemiología , Dispareunia/psicología , Endometriosis/epidemiología , Endometriosis/psicología , Femenino , Alemania/epidemiología , Humanos , Prevalencia , Calidad de Vida , Conducta Sexual/psicología , Conducta Sexual/estadística & datos numéricosRESUMEN
UNLABELLED: In gynecologic oncology lymphadenectomy is of prognostic and therapeutic importance because recurrence-free time and survival depend on the metastatic involvement of lymph nodes. Lymphadenectomies are not performed to such an extent as they are indicated. This might be due to a laborious or problematic preparation. The authors therefore report their experience in a seldom taught preparation of the left para-aortic compartment in the form of a learning curve. MATERIALS AND METHODS: To access the left para-aortic area, the descending colon is lifted to open the retroperitoneum along the line of Toldt. The mesentery of the descending colon was separated from the kidney along the fascia of Gerota by blunt preparation. Time was measured from the incision of the peritoneum until the renal vein was clearly visible. RESULTS: The authors collected the data from the first 25 preparations. Mean duration for the left para-aortic preparation was 7.8 minutes compared to 5.9 minutes for the right side. Duration of preparation of the left area dropped from 11.0 minutes within the first patients (#1 to #5) to 3.8 minutes in the last patients (#20 to #25). No complications were observed in the study group linked to the retromesenteric approach described. CONCLUSION: Retromesenteric para-aortic lymphadenectomy is quick to learn. The authors needed 20 preparations to observe a significant drop in the time needed for preparation. Retromesenteric para-aortic lymphadenectomy offers an excellent overview that lightens lymphadenectomy and therefore reduces the risks for patients.
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Neoplasias de los Genitales Femeninos/cirugía , Escisión del Ganglio Linfático/métodos , Adulto , Anciano , Aorta , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Espacio Retroperitoneal/cirugíaRESUMEN
BACKGROUND: The Y-box-binding protein (YB-1) is described as a potential oncogene highly expressed in tumors and associated with increased cell survival, proliferation, migration and anti-apoptotic signaling. The aim of our study was to examine the expression and role of YB-1 in human endometriosis (Eo) and its association with cell survival, proliferation and invasion. METHODS: We analyzed the gene and protein expression levels of YB-1 by quantitative real-time RT-PCR and immunoassays, respectively, in peritoneal macrophages, ovarian endometrioma and eutopic endometrial tissues/cells derived from women with (n= 120) and without (n= 91) Eo. We also evaluated the functional consequences of YB-1 knockdown in the Z12 Eo cell line by measuring cell proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid cell proliferation assay], invasion (Matrigel invasion assay) and spontaneous and tumour necrosis factor (TNFα)-induced RANTES (regulated upon activation, normal T-cell expressed and secreted chemokine) expression and apoptosis (ELISA-based assay). RESULTS: YB-1 gene and protein expression was statistically significantly higher in ovarian lesions, eutopic endometrium and peritoneal macrophages of patients with Eo in comparison with the control group. Interestingly, the strongest YB-1 expression was observed in the epithelial compartment of endometrial tissues. In the Z12 cell line, YB-1 knockdown resulted in significant cell growth inhibitory effects including reduced cell proliferation and increased rates of spontaneous and TNFα-induced apoptosis. Significantly, higher RANTES expression and decreased cell invasion in vitro were also associated with YB-1 inactivation. CONCLUSION: High YB-1 expression could have an impact on the development and progression of Eo. This study suggests the role of YB-1 as a potential therapeutic target for Eo patients.
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Endometriosis/metabolismo , Endometrio/metabolismo , Regulación de la Expresión Génica , Proteína 1 de Unión a la Caja Y/biosíntesis , Adulto , Apoptosis , Proliferación Celular , Supervivencia Celular , Quimiocina CCL5/metabolismo , Colágeno/química , Combinación de Medicamentos , Femenino , Humanos , Inflamación , Laminina/química , Macrófagos Peritoneales/citología , Macrófagos Peritoneales/metabolismo , Modelos Biológicos , Ovario/patología , Proteoglicanos/química , Linfocitos T/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Endometriosis is a common, benign and chronic gynecological disorder. It is also an estrogen-dependent disorder that can result in intractable dysmenorrhea, heavy and/or irregular periods, painful bowel movements and urination during menstruation and infertility and ultimatively in repeated surgeries. Although surgery to remove endometriotic lesions is effective in relieving endometriosis-associated pain, recurrence rates are high and many women require continuous medical therapy to control symptoms. Symptom relief with palliation of pain and optimization of the quality of life should be the main aim of the medical therapy. Different pharmacologic treatment options are currently available. The most widely exerted medical therapy for endometriosis involves gonadotropin-releasing hormone (GnRH) agonists and oral contraceptives. Also progestogens and androgen derivates are used. New treatment options that are currently under investigation are selective progestogen receptor modulators (SPRMs), aromatase inhibitors (AI), GnRH- antagonists, cyclooxygenase (COX)-2 inhibitors, angiogenesis disruptor's und immune modulators. Although these new agents are promising, further confirmation in randomized clinical trials is required.
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Endometriosis/tratamiento farmacológico , Endometriosis/cirugía , Femenino , Predicción , Hormonas/uso terapéutico , HumanosAsunto(s)
Edema Encefálico/etiología , Tronco Encefálico/patología , Eclampsia/patología , Leucoencefalopatías/patología , Adulto , Edema Encefálico/complicaciones , Edema Encefálico/patología , Femenino , Humanos , Leucoencefalopatías/complicaciones , Imagen por Resonancia Magnética , Examen Neurológico , Embarazo , SíndromeRESUMEN
BACKGROUND: Endometriosis is a benign and progressive disease with a high prevalence. Women with endometriosis, especially with atypical endometriosis, have a higher probability for developing ovarian cancer compared with women without endometriosis. The L1 cell adhesion molecule (L1CAM) is over expressed in ovarian and endometrial carcinomas and is associated with a bad prognosis. Here, we have analysed L1CAM expression in endometriosis. METHODS AND RESULTS: In our study with the samples from 79 patients with, and 37 patients without, endometriosis, we found that endometriosis cell lines and short-term cultures of endometrium from women with endometriosis expressed L1CAM at the mRNA and protein level. Quantitative RT-PCR analysis showed that L1CAM was expressed at significantly higher level in the epithelial compartment from patients with endometriosis compared with healthy controls (P = 0.0126). By immunohistochemical staining, 15 of 31 ovarian endometriotic lesions (48%) were shown to have L1CAM-positive staining. Of these 15 L1CAM-positive samples, 13 were atypical endometriotic lesions. Soluble L1 present in the conditioned medium of epithelial endometrium cultures from women with endometriosis was able to stimulate neurite outgrowth as measured in a chicken ganglion assay. CONCLUSIONS: We propose that L1CAM could promote endometriosis development by increasing enervation and aggravation. L1CAM expression is higher in atypical endometriosis compared with normal endometriosis.
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Endometriosis/fisiopatología , Molécula L1 de Adhesión de Célula Nerviosa/metabolismo , Proteínas ADAM/biosíntesis , Proteína ADAM10 , Adulto , Secretasas de la Proteína Precursora del Amiloide/biosíntesis , Animales , Células Cultivadas , Embrión de Pollo , Medios de Cultivo/farmacología , Femenino , Humanos , Inmunohistoquímica , Proteínas de la Membrana/biosíntesis , Neuritas/efectos de los fármacos , Neuritas/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
PURPOSE: The objective of the study was to determine the feasibility of a new method of labeling sentinel lymph nodes in patients with endometrial cancer using blue dye. PATIENTS AND METHODS: 4 ml of blue dye was subserously administered in 25 patients with endometrial cancer at eight sites. After 8 min, sentinel lymph nodes were harvested. RESULTS: Detection rate was 92.0%, sensitivity was 62.5%, and negative predictive value was 92.5%. In two patients there was no detection of sentinel nodes and in addition in two patients only sentinel nodes were harvested due to minimal disease. No side effects occurred. CONCLUSIONS: This new and simple approach yielded a high pelvic detection rate. This new approach reveals a way to label sentinel nodes in endometrial cancer. Combining a different labeling agent with the proposed new method might overcome the lack of para-aortic sentinel detection.
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Neoplasias Endometriales/patología , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela/métodos , Anciano , Anciano de 80 o más Años , Neoplasias Endometriales/cirugía , Femenino , Humanos , Ganglios Linfáticos/cirugía , Metástasis Linfática , Persona de Mediana Edad , Colorantes de Rosanilina , Sensibilidad y EspecificidadRESUMEN
Monocyte chemotactic protein-1 (MCP-1) is an important determinant of macrophage infiltration in tumours. This study investigated the effect of tamoxifen and the gonadotrophin-releasing hormone agonist buserelin on MCP-1 in the human endometrial cancer cell line EFE-184. Reverse transcription polymerase chain reaction and Western blot analysis were used to determine MCP-1 mRNA and protein expression, respectively. Immunoreactive MCP-1 in the cell culture media was quantified by enzyme-linked immunosorbent assay. Tamoxifen inhibited MCP-1 mRNA and protein expression in endometrial cancer cells and inhibited MCP-1 secretion in a time- and dose-dependent manner at concentrations of 10(-7) to 10(-5) M. Buserelin had no significant effect on MCP-1 mRNA and protein expression. These results suggest that tamoxifen directly inhibits the expression of MCP-1 in this cell line by blocking the MCP-1 signalling pathways. These findings may contribute to the understanding of the mechanisms underlying the different effects of tamoxifen and gonadotrophin-releasing hormone agonists in the treatment of endometrial cancer.
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Antineoplásicos Hormonales/uso terapéutico , Buserelina/uso terapéutico , Quimiocina CCL2/metabolismo , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/metabolismo , Tamoxifeno/uso terapéutico , Línea Celular Tumoral , Quimiocina CCL2/genética , Femenino , Humanos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéuticoRESUMEN
Usually, the therapy of metastatic breast cancer consists of chemotherapy or endocrine therapy, because even in the case of isolated metastases in one organ, diffuse tumor cell dissemination exists, so that local surgical treatment does not seem sensible. Particurlarly in patients with hepatic or pulmonary metastases the indication for hepatic or pulmonary metastasectomy should be individualized, as hepatic or pulmonary metastases usually develop during a phase of disease, when extrahepatic or -pulmonary metastases also can be detected. Only in patients with long disease-free interval, with isolated hepatic or pulmonary metastases, and the possibility of R0-resection is hepatic or pulmonary metastasectomy a therapeutic option in selected cases.
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Neoplasias de la Mama/patología , Metástasis de la Neoplasia , Neoplasias de la Mama/cirugía , Femenino , Humanos , PronósticoRESUMEN
BACKGROUND: Suppression of endogenous LH production by mid-follicular phase GnRH-antagonist administration in controlled ovarian hyperstimulation protocol using recombinant (rec) FSH preparations void of LH activity may potentially affect ovarian response and the outcome of IVF treatment. The present study prospectively assessed the effect of using a combination of recFSH and recLH on ovarian stimulation parameters and treatment outcome in a fixed GnRH-antagonist multiple dose protocol. METHODS: 127 infertile patients with an indication for IVF or ICSI were recruited and randomized (using sealed envelopes) to receive a starting dose of either 150 IU recFSH (follitropin alpha) or 150 IU recFSH plus 75 IU recLH (lutropin alpha) for ovarian hyperstimulation. GnRH-antagonist (Cetrorelix) 0.25 mg was administered daily from stimulation day 6 onwards up to and including the day of the administration of recombinant HCG (chorion gonadotropin alpha). Gonadotropin dose adjustments were allowed from stimulation day 6 onwards, HCG was administered as soon as three follicles > or =18 mm were present. The primary outcome parameter was treatment duration until administration of HCG. RESULTS: Exogenous LH did not shorten the time necessary to reach ovulation induction criteria. Serum estradiol (E(2)) and LH levels were significantly higher on the day of HCG administration in the recLH-supplemented group (1924.7 +/- 1256.4 vs 1488.3 +/- 824.0 pg/ml, P < 0.03), and 2.1 +/- 1.4 vs 1.4 +/- 1.5 IU/l, P < 0.01, respectively). CONCLUSIONS: Except for higher E(2) and LH levels on the day of HCG administration, no positive trend in favour of additional LH was found as defined by treatment outcome parameters.
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Hormona Folículo Estimulante/uso terapéutico , Hormona Luteinizante/efectos adversos , Síndrome de Hiperestimulación Ovárica/inducido químicamente , Inducción de la Ovulación/métodos , Adulto , Gonadotropina Coriónica/uso terapéutico , Relación Dosis-Respuesta a Droga , Estradiol/sangre , Femenino , Fertilización In Vitro/métodos , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Hormona Liberadora de Gonadotropina/uso terapéutico , Antagonistas de Hormonas/uso terapéutico , Humanos , Infertilidad Femenina/terapia , Hormona Luteinizante/sangre , Hormona Luteinizante/uso terapéutico , Embarazo , Índice de Embarazo , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Some sensitive pollen-allergic patients may experience perennial symptoms, and for these patients it is vitally important to know the concentration of grass-pollen allergens in their homes. The main objective of this study was to detect predictors associated with high grass allergen concentration in settled house dust during and outside the grass pollination season. METHODS: We detected group 5 grass-pollen allergens in dust samples from randomly selected homes of three counties in the region of Sachsen-Anhalt: Hettstedt (n=183), Zerbst (n=152), and Bitterfeld (n=119). Dust samples were collected from the floors of living rooms (LR) and children's rooms (CR) from April 1996 to March 1998. RESULTS: Phl p 5 was detected in settled house dust in 91% of the homes. The range was between undetectable (<30 ng/m2) and 4300 ng Phl p 5/m2 sampling area during grass pollination, and 1300 ng Phl p 5/m2 outside the pollination season, respectively. We observed a partially higher concentration of indoor allergenic activity several weeks after the grass-pollen peak. A positive association was found between Phl p 5 levels and total dust amounts throughout the year. Thus, we assume that grass allergens accumulate in settled house dust. During pollination, the Phl p 5 levels are 1.8 times higher in homes where vacuuming of carpets takes place only once a week or less than in those vacuumed daily. Furthermore, higher concentrations of Phl p 5 in settled floor dust can be expected in homes located within suburban areas (mean ratio [MR] 1.74) and prefabricated slab buildings (MR=1.54). CONCLUSIONS: Quite high levels of Phl p 5 accumulate in settled house dust even during periods when no grass pollen is present in the atmosphere. The removal of dust by frequent cleaning reduces the indoor exposure to grass allergens. Such information is essential to train patients in allergen avoidance.
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Contaminantes Atmosféricos/análisis , Alérgenos/efectos adversos , Polvo/efectos adversos , Poaceae/efectos adversos , Polen/efectos adversos , Contaminantes Atmosféricos/inmunología , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/análisis , Alérgenos/análisis , Estudios Transversales , Polvo/análisis , Composición Familiar , Pisos y Cubiertas de Piso , Alemania/epidemiología , Vivienda , Humanos , Modelos Lineales , Proteínas de Plantas/efectos adversos , Proteínas de Plantas/análisis , Valor Predictivo de las Pruebas , Distribución Aleatoria , Rinitis Alérgica Estacional/etiología , Estaciones del AñoRESUMEN
The human endometrium is a complex tissue comprised of different cell types, including epithelial, stromal, inflammatory, perivascular, and blood vessel cells. The hormonal receptivity and distribution of these cell populations change during the menstrual cycle. Cyclical endometrial growth is dependent on its ability to regenerate a vascular capillary network, which grows in parallel with the proliferation and differentiation of the endometrial lining. Natural hormonal effects on the endometrium and endocrine manipulation of this tissue, in response to the use of exogenous steroid therapies, can affect endometrial capillary proliferation and function, leading to clinical abnormalities of uterine bleeding. We propose that the regulation of endometrial angiogenesis is mediated indirectly via complex interactions among cell types. Our laboratory has focused on a prototypical member of the angiogenic proteins, vascular endothelial growth factor (VEGF)-A. In this paper we present data demonstrating that VEGF-A expression in normal endometrial epithelial and stromal cells and in Ishikawa adenocarcinoma cells is increased by an ovarian steroid, estradiol. Infiltrating immune cells, particularly polymorphonuclear granulocytes, also are sources of VEGF-A. In inflammatory conditions involving the endometrium (e.g., endometriosis), a proinflammatory cytokine, IL-1beta, can mediate neoangiogenesis by inducing VEGF-A gene transcription. Thus, endometrial vascularization is effected by both endocrine and paracrine pathways.
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Sistema Endocrino/fisiología , Endometrio/irrigación sanguínea , Neovascularización Fisiológica/fisiología , Comunicación Paracrina/fisiología , Células Cultivadas , Citocinas/farmacología , Endometrio/citología , Factores de Crecimiento Endotelial/metabolismo , Femenino , Regulación del Desarrollo de la Expresión Génica/fisiología , Humanos , Inmunohistoquímica , Linfocinas/metabolismo , Embarazo , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Esteroides/farmacología , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
This paper describes the effects that nasal dilators have on olfactory ability. Experimental results demonstrate that nasal dilators increase odorant identification, lower odorant threshold, and increase perceptual odorant intensity. In other experiments, magnetic resonance imaging (MRI) data demonstrates that the size of the nasal cavity especially around the region of the nasal valve is increased when nasal dilators are worn. Additionally, pneumotachograph data demonstrates that during a sniff, the peak flow, maximum flow rate, volume, and duration are all increased when nasal dilators are worn. Taken together, the increase in olfactory ability can most easily be explained by an increase in both the amount and the proportion of inspired odorant molecules that are directed to the olfactory mucosa and are, therefore, available for odorant perception.
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Dilatación/métodos , Nariz/anatomía & histología , Percepción/fisiología , Olfato/fisiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nariz/fisiología , Odorantes , Umbral Sensorial/fisiologíaRESUMEN
The peroxisome proliferator-activated receptors (PPARs) alpha and gamma are nuclear receptors that play important roles in inflammatory diseases like ulcerative colitis and arthritis. In this study, we examined the possible role of PPARs in macrophage attraction into the peritoneal cavity of patients with endometriosis. We identified PPAR-alpha and -gamma messenger RNA by RT-PCR and protein by immunoblotting of lysates of peritoneal macrophages and monocytic U937 cells. Using immunocytochemistry, we localized PPAR-alpha and -gamma within the nuclei of both cell types. Monocyte chemotactic activity of peritoneal fluid from patients with endometriosis was quantified in Boyden chambers. Migration of U937 cells was increased by WY 14643 and reduced by rosiglitazone. Peritoneal fluid from patients with endometriosis activated U937 cells transiently transfected with a PPAR-alpha/GAL4 luciferase reporter. By contrast, peritoneal fluid did not cause significant activation of PPAR-gamma/GAL4 constructs. The U937 cells transiently transfected with a PPAR response element luciferase reporter showed disease stage-dependent up-regulation when treated with peritoneal fluid from patients with endometriosis. Treatment with peritoneal fluid from healthy controls down-regulated PPAR response element transactivation. We conclude that peritoneal fluid of endometriosis patients contains activators of PPAR-alpha that stimulate macrophage chemotaxis. Inhibitors of PPAR-alpha or activators of PPAR-gamma could be developed for the treatment of inflammation associated with endometriosis.
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Quimiotaxis , Endometriosis/patología , Monocitos/fisiología , Receptores Citoplasmáticos y Nucleares/fisiología , Proteínas de Saccharomyces cerevisiae , Factores de Transcripción/fisiología , Apoptosis , Líquido Ascítico/química , Línea Celular , Núcleo Celular/química , Proteínas de Unión al ADN , Femenino , Proteínas Fúngicas/genética , Humanos , Immunoblotting , Inmunohistoquímica , Macrófagos Peritoneales/química , Macrófagos Peritoneales/fisiología , Monocitos/química , Cavidad Peritoneal/patología , ARN Mensajero/análisis , Receptores Citoplasmáticos y Nucleares/análisis , Receptores Citoplasmáticos y Nucleares/genética , Proteínas Recombinantes de Fusión , Factores de Transcripción/análisis , Factores de Transcripción/genética , TransfecciónRESUMEN
Chemoattraction of macrophages and T cells into the normal endometrium and inflammatory sites within endometriotic foci is mediated by chemokine gene expression. mRNA transcripts encoding regulated on activation, normal T-cell-expressed and -secreted (RANTES), a monocyte and T-cell chemokine, were demonstrated in the stroma of normal endometrium and endometriotic implants using in situ mRNA hybridization. Epithelial glands failed to express RANTES mRNA. In histological serial sections, we observed CD68-positive macrophages in the stroma of endometriotic implants adjacent to regions with prominent RANTES mRNA hybridization. In adjacent sections, monoclonal antibodies against tumor necrosis factor (TNF)-alpha showed this cytokine to be localized to stromal and epithelial compartments of the endometriotic implant with weak staining in unaffected ovarian tissue. Subconfluent monolayers of endometriotic stromal cells were tested for RANTES gene expression in situ, but we could only detect RANTES mRNA in isolated stromal cells after treatment with TNF-alpha. No RANTES mRNA was observed in unstimulated stromal cells or TNF-alpha stimulated or unstimulated epithelial cells. The data are consistent with a model in which proinflammatory cytokines (eg, TNF-alpha) induce RANTES gene expression limited to specific cells within endometrial and endometriotic stroma. Production of this chemokine, in turn, stimulates recruitment of CD68-positive macrophages into these tissues.
Asunto(s)
Quimiocina CCL5/genética , Endometriosis/metabolismo , Endometrio/metabolismo , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Comunicación Autocrina , Células Cultivadas , Quimiocina CCL5/biosíntesis , Quimiocina CCL5/inmunología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Macrófagos/química , Comunicación Paracrina , ARN Mensajero/biosíntesis , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
The odorant confusion matrix (OCM) is an odorant identification test in which the number of correct odorant identifications quantifies the level of olfactory function. As with other confusion matrices, the OCM reflects distortions of sensory perception as errors in identification. Previous work with the OCM suggests that, within an individual, hyposmia is associated with a stable shift in odorant perception. The current study examined whether consistent shifts in odorant perception are also characteristic of the various pathologies that lead to an olfactory loss. In a retrospective study, OCM response patterns for 135 hyposmic patients were fit into a five-dimensional space in which the distances between subjects reflected the dissimilarities between their OCM response patterns. Multivariate regression was performed relating position in the five-dimensional space to each of 11 factors representing 33 demographic and medical history variables. One factor, named congestion (gathering the variables of past polyposis, current polyposis, and current nasal obstruction due to swelling), was significantly indicative of patterns of responses on the OCM, independent of the level of hyposmia. These data suggest that conductive olfactory loss may be associated with alterations in odorant perception, which are reflected in consistent odorant confusions. Such alterations in perception may eventually serve as a basis for a clinical test to provide differential diagnoses as to the sources of olfactory losses.