RESUMO
Although not as common as solitary lesions, multiple schwannomas do occur, even in single nerve lesions. We report a rare case of a 47-year-old female patient who presented with multiple schwannomas with inter-fascicular invasion in the ulnar nerve above the cubital tunnel. Preoperative MRI revealed a 10-cm multilobulated tubular mass along the ulnar nerve above the elbow joint. During excision under 4.5° loupe magnification, we separated three ovoid yellow-colored neurogenic tumors of different sizes, but there were still remaining lesions as it was difficult to completely separate lesions from the ulnar nerve due to the risk of iatrogenic nerve ulnar nerve injury. The operative wound was closed. Postoperative biopsy confirmed the diagnosis of the three schwannomas. During the follow-up, the patient recovered without neurological symptom or limitations in range of motion, and there were no neurological abnormalities. At 1year after surgery, small lesions remained in the most proximal part. However, the patient had no clinical symptoms and was satisfied with the surgical results. Although a long-term follow-up is necessary for this patient, we were able to obtain good clinical and radiological results.
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Articulação do Cotovelo , Neurilemoma , Feminino , Humanos , Pessoa de Meia-Idade , Nervo Ulnar/patologia , Nervo Ulnar/cirurgia , Seguimentos , Cotovelo , Neurilemoma/diagnóstico , Neurilemoma/patologia , Neurilemoma/cirurgiaRESUMO
Objective: To investigate the expression of lipoic acid synthase gene (LIAS) and nuclear factor-erythroid 2-related factor 2 gene (NRF2) in peripheral blood mononuclear cells (PBMCs) from patients with silicosis and their correlation with silicosis. Methods: A total of 45 healthy controls and 107 patients with silicosis were randomly selected in this study in May 2019. PBMCs were isolated from peripheral blood and NRF2 protein expression was detected by immunofluorescence. The mRNA levels of LIAS and NRF2 in PBMCs were determined by real-time PCR. The dose-response relationship beween LIAS and NRF2 mRNA expression levels and their association with silicosis were analyzed by restricted cubic spline (RCS) and logistic regression. Results: Compared with the control group, the number of monocytes in the case group was significantly increased, and the forced expiratory volume in the first second (FEV(1.0)) decreased, the difference was statistically significant (P<0.05) . The positive expression rate of NRF2 in PBMCs of silicosis patients in stage â group was significantly higher than that in the control group, and the positive expression rate of NRF2 in silicosis patients in stageâ ¡ and â ¢ groups was lower than that in silicosis patients in control group and stage â group (P<0.01) . Results of RCS showed that there was a linear dose-response relationship between LIAS and NRF2 mRNA expression (overall correlation test, χ(2)=213.710, P<0.01; non-linear test, χ(2)=1.340, P=0.511) . There was a positive correlation between mRNA expression of LIAS and that of NRF2 (r=0.651, P<0.01) . The results of multivariate analysis showed that LIAS and NRF2 were increased the risk of incidence in silicosis patients with stageâ (OR=11.184, 4.332, P<0.05) and NRF2 was the protective factor in silicosis patients with stage â ¡ and â ¢ (OR=0.225, 0.208, P<0.05) after adjusting for potential confounding factors including age, education level, BMI and smoking. Conclusion: There is a linear dose-response relationship between the expression of LIAS and NRF2 mRNA in PBMCs of silicosis patients, LIAS and NRF2 are involved in the pathogenesis of silicosis.
Assuntos
Fator 2 Relacionado a NF-E2 , Silicose , Humanos , Leucócitos Mononucleares , Fator 2 Relacionado a NF-E2/genética , Silicose/genética , SulfurtransferasesRESUMO
Anterior segment ischemia (ASI) is a potentially serious but rare complication of strabismus surgery. Among several risk factors, ASI occurs after strabismus surgery because of the nature of the anterior segment circulation. Disinsertion of rectus muscles leads to a decrease in the blood supply to the various anterior segment structures. We report a series of retrospective and prospective studies performed by our group focused on determining the risk of anterior segment ischemia following strabismus surgery, diagnosis, and modifications to surgical techniques to minimize the impact on anterior segment circulation. We found a significant decrease in postoperative anterior segment blood flow when operating vertical rectus muscles. Plication procedures preserve anterior segment circulation, and modifications to the technique allow the performance of adjustable sutures. Small adjustable selective procedures that spare the ciliary vessels have been demonstrated to be effective in patients with vertical and torsional diplopia. Ciliary sparing augmented adjustable transposition surgery decreases the risk of anterior segment ischemia while allowing management of potential post-operative alignment complications. Finally, ocular coherence tomography angiography is a valuable quantitative and qualitative technique to evaluate anterior segment ischemia. Strabismus surgeons should be aware of the risks of anterior segment ischemia when operating vertical rectus muscles. Modifications to standard surgical techniques allow surgeons to perform complex strabismus surgery in patients at risk for anterior segment ischemia.
Assuntos
Segmento Anterior do Olho/irrigação sanguínea , Oftalmopatias , Isquemia , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Estrabismo/cirurgia , Oftalmopatias/diagnóstico , Oftalmopatias/etiologia , Oftalmopatias/terapia , Humanos , Isquemia/diagnóstico , Isquemia/etiologia , Isquemia/prevenção & controle , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Procedimentos Cirúrgicos Oftalmológicos/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: This prospective, randomised, controlled study was performed to evaluate the usefulness of the McGrath VL compared with Macintosh laryngoscopy in children with expected normal airway during endotracheal intubation, by comparing the time to intubation and difficulty of intubation. METHODS: Eighty-four patients aged 1-10 years who underwent endotracheal intubation for elective surgery were randomly assigned to the McGrath group (n = 42) or the Macintosh group (n = 42). Anaesthesia was induced with 2.5-3.0 mg/kg of propofol and sevoflurane 5-8 vol%. Orotracheal intubation was performed 2 min after injection of rocuronium 0.6 mg/kg with McGrath VL or Macintosh laryngoscope; the primary outcome was the time to intubation. The Cormack and Lehane glottic grade, intubation difficulty score (IDS), and success rate on intubation were assessed. Haemodynamic changes were also recorded. RESULTS: As the primary outcome, median time to intubation [interquartile range] did not differ between the McGrath group and the Macintosh group (25.0 [22.8-28.3] s vs. 26.0 [24.0-29.0] s, P = 0.301). The incidence of grade I glottic view was significantly higher in the McGrath group than in the Macintosh group (95% vs. 74%, P = 0.013). Median IDS was lower in the McGrath group than in the Macintosh group (0 [0-0] vs. 0 [0-1], P = 0.018). There were no significant differences in success rate on intubation or haemodynamics between the two groups. CONCLUSIONS: McGrath VL provides better laryngeal views and lower IDS but similar intubation times and success rates compared with the Macintosh laryngoscope in children with normal airway.
Assuntos
Intubação Intratraqueal/métodos , Laringoscopia , Gravação em Vídeo , Criança , Pré-Escolar , Humanos , Lactente , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND: Pain is considered as being one cause of post-operative emergence agitation (EA) from sevoflurane anaesthesia. The purpose of this study was to investigate the pure effect of post-operative pain on EA after sevoflurane anaesthesia in preschool children undergoing excision of scalp nevi. METHODS: Forty-four children, 1-7 years old, undergoing scalp nevus excision were enrolled. Patients were randomly assigned to two groups: the remifentanil group received single intravenous injection of short-acting synthetic opioid, remifentanil 1 µg/kg just before the scalp incision, and the block group received scalp nerve block with 0.25% ropivacaine after intubation. The end-tidal sevoflurane concentration was maintained around 1.5 vol% unless the mean arterial pressure is out of ±20% range of preoperative values during surgery in both groups. Watcha behaviour scale for EA and face, legs, activity, cry, consolability (FLACC) scale scores for pain were recorded post-operatively. RESULTS: There was no difference in end-tidal sevoflurane concentration between the two groups during surgery and the emergence period. Agitation incidence and scores were not different between the two groups during the recovery period. FLACC scale was significantly lower in the block group than in the remifentanil group at post-anaesthesia care unit (PACU) arrival, at 10 and 20 min after PACU arrival, respectively. CONCLUSION: The scalp nerve block decreased the early post-operative pain after paediatric nevus excision, but it did not decrease the incidence of EA with sevoflurane anaesthesia.
Assuntos
Bloqueio Nervoso , Nevo/cirurgia , Dor Pós-Operatória/prevenção & controle , Agitação Psicomotora/prevenção & controle , Couro Cabeludo/inervação , Couro Cabeludo/cirurgia , Amidas , Anestésicos Inalatórios , Anestésicos Intravenosos , Anestésicos Locais , Criança , Comportamento Infantil , Pré-Escolar , Delírio do Despertar , Feminino , Humanos , Lactente , Masculino , Éteres Metílicos , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/psicologia , Piperidinas , Estudos Prospectivos , Agitação Psicomotora/epidemiologia , Agitação Psicomotora/psicologia , Remifentanil , Ropivacaina , Sevoflurano , Método Simples-CegoRESUMO
OBJECTIVE: This study assesses the association between abdominal aortic calcification (AAC) and renal function of living kidney donors and evaluate AAC as a surrogate marker for nephrosclerosis. METHODS: Between January 2010 and March 2013, 287 donors who underwent living donor nephrectomy were enrolled. We analyzed computed tomography angiographies and quantified AAC scores by calculating the Agatston score for the abdominal aorta. The donors were stratified into the non-AAC group (AAC score = 0; n = 238) and the AAC group (AAC score >0; n = 49). The relationship between AAC and perioperative estimated glomerular filtration rate was analyzed. For the 180 donors consenting to implantation biopsy, the nephrosclerosis score was defined as the sum of abnormalities, including glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis. RESULTS: The mean AAC score was 185.5 ± 263.3 in the AAC group. The AAC group was older than the non-AAC group (51.1 ± 6.1 vs 37.9 ± 11 years; P < .001). Perioperative renal function was not different between the 2 groups. However, among the AAC group, donors with an AAC score of >100 were associated with delayed renal function recovery (P = .035). Donors with AAC were more likely to have glomerulosclerosis (50.0% vs 29.1%; P = .022), tubular atrophy (62.5% vs 33.1%; P = .002), and a higher nephrosclerosis score (P = .002). CONCLUSIONS: Living donors with an AAC score of >100 require close observation because they have a higher probability of delayed renal function recovery after donation. AAC is associated with nephrosclerosis in healthy adults.
Assuntos
Aorta Abdominal/diagnóstico por imagem , Doadores Vivos , Nefrectomia/efeitos adversos , Coleta de Tecidos e Órgãos/efeitos adversos , Calcificação Vascular/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/patologia , Arteriosclerose/etiologia , Arteriosclerose/patologia , Biomarcadores/análise , Biópsia , Feminino , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nefroesclerose/diagnóstico por imagem , Nefroesclerose/etiologia , Recuperação de Função Fisiológica , Calcificação Vascular/diagnóstico por imagemRESUMO
PURPOSE Congenital hypertrophy of the retinal pigment epithelium (CHRPE) may simulate choroidal melanoma in certain cases. We report unique clinical features we have observed in cases of CHRPE in young myopic pigmented patients.METHODS Patients who were referred for evaluation of a suspicious choroidal lesion and found to have a CHRPE lesion with the clinical appearance of lesion elevation and a subretinal fluid-like 'shadow sign' were included. Patient and lesion characteristics were tabulated. Available images, including fundus photography, ultrasonography, optical coherence tomography (OCT), and fluorescein angiography (FA) were reviewed.ResultsSix patients were included. The 'shadow sign' was anterior to the CHRPE lesion in all cases. The mean age of the patients was 27.3 years. The ethnicities of the patients were Chinese (n=1), Hispanic (n=3), or African-American (n=2). Five of six patients were myopic.CONCLUSIONS Although most CHRPE lesions appear flat on ophthalmoscopy, lesions in young myopic patients of pigmented ethnicities may appear elevated with a 'shadow sign' due to 'dark without pressure.' This new finding may be related to the vitreoretinal interface in young myopic pigmented patients and must be distinguished from true subretinal fluid and lesion thickness, which are often observed in choroidal melanoma.
Assuntos
Miopia/diagnóstico , Doenças Retinianas/congênito , Doenças Retinianas/diagnóstico , Epitélio Pigmentado da Retina/patologia , Adolescente , Adulto , Criança , Feminino , Angiofluoresceinografia , Humanos , Hipertrofia , Masculino , Tomografia de Coerência Óptica , Adulto JovemRESUMO
Most solid tumors undergo hypoxia, leading to rapid cell division, metastasis and expansion of a cell population with hallmarks of cancer stem cells (CSCs). Tumor-selective replication of oncolytic adenoviruses may be hindered by oxygen deprivation in tumors. It is desirable to develop a potent oncolytic adenovirus, retaining its antitumor activity even in a hypoxic environment. We have previously generated an Oct4-dependent oncolytic adenovirus, namely Ad9OC, driven by nine copies of the Oct4 response element (ORE) for specifically killing Oct4-overexpressing bladder tumors. Here, we developed a novel Oct4 and hypoxia dual-regulated oncolytic adenovirus, designated AdLCY, driven by both hypoxia response element (HRE) and ORE. We showed that hypoxia-inducible factor (HIF)-2α and Oct4 were frequently overexpressed in hypoxic bladder cancer cells, and HIF-2α was involved in HRE-dependent and Oct4 transactivation. AdLCY exhibited higher cytolytic activities than Ad9OC against hypoxic bladder cancer cells, while sparing normal cells. AdLCY exerted potent antitumor effects in mice bearing human bladder tumor xenografts and syngeneic bladder tumors. It could target hypoxic CD44- and CD133-positive bladder tumor cells. Therefore, AdLCY may have therapeutic potential for targeting hypoxic bladder tumors and CSCs. As Oct4 is expressed in various cancers, AdLCY may be further explored as a broad-spectrum anticancer agent.
Assuntos
Antineoplásicos/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Vírus Oncolíticos/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Xenoenxertos , Humanos , CamundongosRESUMO
The University of Washington Quality of Life (UW-QOL) questionnaire is often used to assess health-related quality of life (HRQOL) of head and neck cancer patients. The aim of this study was to translate the UW-QOL version 4 into the Korean language and to carry out an initial validation study. A recognized methodology for translation of questionnaires was used. The validation study used the final Korean version between March and September 2009. Adult patients were recruited, with a confirmed diagnosis of head and neck cancer, therapy completed and disease-free for at least 1 year. The UW-QOL was successfully translated into Korean. 56 patients completed Korean versions of UW-QOL, the Beck Depression Inventory and the World Health Organization Quality of Life-BREF and various expected correlations were confirmed first between the two UW-QOL subscales (Spearman 0.54 p<0.001) and then of these subscales with the other concurrent measures. Lower (worse) UW-QOL scores were seen for later stage patients in all 12 domains. The Korean version of UW-QOL is ready for use in the assessment of HRQOL for Korean patients. Validation work needs to be continued to further establish psychometric properties of the questionnaire for use in this population.
Assuntos
Neoplasias de Cabeça e Pescoço/psicologia , Qualidade de Vida , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Depressão/diagnóstico , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Psicometria , Reprodutibilidade dos Testes , República da Coreia , Estatísticas não Paramétricas , Traduções , Reino Unido , WashingtonRESUMO
Chronic inflammation underlies the basis for development and progression of cancers and a variety of other disorders, but what specifically defines its pathogenic nature remains largely undefined. Recent genetic and pharmacological studies in the mouse suggest that the immune modulatory enzyme indoleamine 2,3-dioxygenase (IDO), identified as an important mediator of immune escape in cancer, can also contribute to the development of pathology in the context of chronic inflammatory models of arthritis and allergic airway disease. IDO-deficient mice do not display spontaneous disorders of classical inflammation and small molecule inhibitors of IDO do not elicit generalized inflammatory reactions. Rather, in the context of a classical model of skin cancer that is promoted by chronic inflammation, or in models of inflammation-associated arthritis and allergic airway disease, IDO impairment can alleviate disease severity. Here we offer a survey of preclinical literature suggesting that IDO functions as a modifier of inflammatory states rather than simply as a suppressor of immune function. We propose that IDO induction in a chronically inflamed tissue may shape the inflammatory state to support, or in some cases retard, pathogenesis and disease severity.
Assuntos
Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Inflamação/enzimologia , Inflamação/imunologia , Neoplasias/enzimologia , Neoplasias/imunologia , Animais , Artrite Reumatoide/enzimologia , Artrite Reumatoide/imunologia , Asma/enzimologia , Asma/imunologia , Humanos , Doenças Inflamatórias Intestinais/enzimologia , Doenças Inflamatórias Intestinais/imunologiaRESUMO
Cortical precursor cells secrete soluble factors for their own survival and self-renewal. We show here that neural precursor cells isolated from embryonic rat cortices abundantly secrete leukemia inhibitory factor (LIF) and express its receptor components, gp130 and LIF receptor. LIF signaling is responsible for cortical precursor cell survival. As described previously, LIF caused astrocytic differentiation of cultured embryonic cortical precursor cells. LIF-mediated survival and astrocytic differentiation of cortical precursor cells were differentially regulated, depending on the developmental ages of embryos from which cortical precursors were isolated. LIF did not enhance the survival of cortical precursor cells isolated from later embryos (embryonic day 16, E16). Moreover, LIF-mediated astrocytic differentiation was not observed in early (E12) cortical precursors. Inhibition studies revealed that Janus-activated kinase/signal transducer and activator of transcription and phosphatidylinositol 3 kinase/Akt pathways participate in both the LIF-mediated effects. However, mitogen-activated protein kinase, another signal pathway activated by LIF, was specifically responsible for astrocytic differentiation. These findings collectively indicate that precursor cells self-regulate the sequential processes of brain development, such as early maintenance of the precursor cell population and later differentiation into astrocytes, via common LIF signaling.
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Córtex Cerebral/embriologia , Embrião de Mamíferos/citologia , Interleucina-6/fisiologia , Animais , Antígenos CD/metabolismo , Astrócitos/metabolismo , Western Blotting , Bromodesoxiuridina/farmacologia , Diferenciação Celular , Linhagem da Célula , Sobrevivência Celular , Células Cultivadas , Receptor gp130 de Citocina , Relação Dose-Resposta a Droga , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , L-Lactato Desidrogenase/metabolismo , Fator Inibidor de Leucemia , Ligantes , Glicoproteínas de Membrana/metabolismo , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Fatores de TempoRESUMO
Plantago major L., a popular traditional Chinese medicine, has long been used for treating various diseases varying from cold to viral hepatitis. The aim of present study was to examine the antiviral activity of aqueous extract and pure compounds of P. major. Studies were conducted on a series of viruses, namely herpesviruses (HSV-1, HSV-2) and adenoviruses (ADV-3, ADV-8, ADV-11). The antiviral activity of EC50 was defined as the concentration achieved 50% cyto-protection against virus infection and the selectivity index (SI) was determined by the ratio of CC50 (concentration of 50% cellular cytotoxicity) to EC50. Results showed that aqueous extract of P. major possessed only a slight anti-herpes virus activity. In contrast, certain pure compounds belonging to the five different classes of chemicals found in extracts of this plant exhibited potent antiviral activity. Among them, caffeic acid exhibited the strongest activity against HSV-1 (EC50=15.3 microg/ml, SI=671), HSV-2 (EC50=87.3 microg/ml, SI=118) and ADV-3 (EC50=14.2 microg/ml, SI=727), whereas chlorogenic acid possessed the strongest anti-ADV-11 (EC50=13.3 microg/ml, SI=301) activity. The present study concludes that pure compounds of P. major, which possess antiviral activities are mainly derived from the phenolic compounds, especially caffeic acid. Its mode of action against HSV-2 and ADV-3 was found to be at multiplication stages (postinfection of HSV-1: 0-12 h; ADV-3: 0-2 h), and with SI values greater than 400, suggesting the potential use of this compound for treatment of the infection by these two viruses.
Assuntos
Adenoviridae/efeitos dos fármacos , Antivirais/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Plantago , Adenoviridae/fisiologia , Ácidos Cafeicos/farmacologia , Linhagem Celular , Ácido Clorogênico/farmacologia , Efeito Citopatogênico Viral/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 2/fisiologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fatores de Tempo , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND/AIM: Management of renal anemia in end-stage renal disease requires careful evaluation of the iron status before and in particular during erythropoietin treatment. However, there is no simple and practical iron index accurately predictive of functional iron deficiency in these patients till now. The purpose of this prospective study, therefore, is to evaluate whether a short course of low-dose intravenous iron challenge can detect functional iron deficiency in hemodialysis patients. METHODS: Twenty-four patients with baseline serum ferritin levels between 100 and 500 ng/ml were treated with intravenous saccharated ferric oxide, 960 mg over 24 hemodialysis treatments, and the hemoglobin level was checked every week. RESULTS: Patients whose hemoglobin value increased at least by 1 g/dl within the 8-week period were classified as having functional iron deficiency or as responders (n = 26; 81.2%). All other subjects were classified as having adequate iron levels or as nonresponders (n = 6; 18.8%). There were no significant differences in age, sex, dialysis years, Kt/V, dialyzers, hemoglobin, and basal and final transferrin saturation and ferritin between responders and nonresponders. In addition, there were no iron indices with acceptable levels of sensitivity and specificity. On the contrary, the cutoff value of increments of hemoglobin of at least 0.2 g/dl after a 2-week intravenous iron trial had a sensitivity of 96.2% and a specificity of 100% in all patients (n = 32) and a sensitivity of 100% and a specificity of 100% after patients with transferrin saturation <20% were excluded (n = 24). These values had the greatest utility of the tests studied in this work. CONCLUSION: A 240-mg intravenous iron challenge during a 2-week period may be a simple, accurate, and straightforward method to detect a functional iron deficiency status in hemodialysis patients undergoing erythropoietin therapy.
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Anemia Ferropriva/etiologia , Ferro/administração & dosagem , Falência Renal Crônica/complicações , Diálise Renal , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
To explore the potential use of prothymosin alpha(ProT), a putative thymic hormone, in gene therapy for bladder cancer, we generated a replication-defective recombinant retroviral vector encoding ProT and tested its antitumor effect on the MBT-2 murine bladder cancer. C3H/HeN mice injected with MBT-2 cells in conjunction with retroviruses encoding ProT exhibited smaller tumor mass, lower tumor incidence and higher survival rate, as well as higher antitumor cytotoxic activities compared with those injected with control viruses. However, such effects were not observed in severe combined immunodeficiency mice, suggesting that ProT exerts antitumor effects through its immunomodulatory activities. Cell growth in monolayer culture and colony formation in soft agar were enhanced in ProT gene-modified MBT-2 clones, and such growth-promoting activities of ProT could be reversed if its nuclear localization signal (NLS) was deleted. To circumvent the proliferation-promoting effect of ProT on tumor cells, a retroviral vector encoding ProT lacking NLS was constructed. Our results showed that retroviruses encoding NLS-deleted ProT was more efficacious than those encoding wild-type ProT in prolonging survival of tumor-bearing mice. This is the first report indicating that ProT, in particular NLS-deleted ProT, delivered by retroviral vectors may be further explored for the treatment of bladder cancer.
Assuntos
Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Precursores de Proteínas/genética , Retroviridae/genética , Timosina/análogos & derivados , Timosina/genética , Neoplasias da Bexiga Urinária/terapia , Animais , Divisão Celular , Feminino , Camundongos , Camundongos Endogâmicos , Camundongos SCID , Transplante de Neoplasias , Neoplasias da Bexiga Urinária/metabolismoRESUMO
PURPOSE: The purpose was to determine the effect of basal uterine perfusion on the pregnancy rates of in vitro fertilization and embryo transfer (IVF-ET) in women aged 40 and above. METHODS: A total of 47 patient aged 40 and over underwent IVF-ET. The conception cycles and the nonconception cycles were compared. RESULTS: Of the 47 patients, 4 patients were pregnant (8.5%). The mean age, basal follicle stimulating hormone (FSH), basal estradiol (E2) level, antral follicle count (AFC), number of ampoules of gonadotropin used, E2 levels and endometrial thickness on the day of human chorionic gonadotropin (hCG) administration, number of retrieved and fertilized oocytes, and number of transferred embryos were not statistically significant between the conception and nonconception cycles. However, the basal uterine artery pulsatility index (UA PI) was significantly lower in the conception cycles (P < 0.001). The receiver operating characteristics (ROC) curve analysis for basal FSH, AFC, and basal UA PI in predicting the pregnancy rate of IVF in patients aged > or = 40 were demonstrated. The best prediction rate was achieved by a pulsatility index cutoff of < 2.0 for a receptive uterus. CONCLUSIONS: Increased uterine perfusion in the early follicular phase enhanced the pregnancy rate of IVF in women aged 40 and above. It is therefore essential that patients aged > or = 40 with poor basal uterine perfusion should be identified early in the early follicular phase of the menstrual cycle to apply appropriate intervention to improve the uterine circulation for the subsequent chance of pregnancy.
Assuntos
Transferência Embrionária/métodos , Fertilização in vitro/métodos , Taxa de Gravidez , Útero/irrigação sanguínea , Adulto , Artérias/diagnóstico por imagem , Artérias/fisiologia , Blastocisto/fisiologia , Velocidade do Fluxo Sanguíneo , Meios de Cultura Livres de Soro , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Idade Materna , Folículo Ovariano/citologia , Gravidez , Gravidez de Alto Risco , Estudos Prospectivos , Fluxo Pulsátil , Fluxo Sanguíneo Regional , Sensibilidade e Especificidade , Ultrassonografia , Útero/diagnóstico por imagem , Resistência VascularRESUMO
PROBLEM: Neonatal estradiol injections in mice lead to follicular cystic ovaries that are similar to ovaries in patients with polycystic ovarian syndrome (PCOS). The present study examined ovarian cytokine production following neonatal estradiol injection. METHOD OF STUDY: Female (C3H,HeJ x 129/HeJ)F1 mice were injected daily with 20 microg 17beta-estradiol from 0-3 days postpartum. At intervals, animals were sacrificed to determine ovarian architecture, circulating levels of estradiol, ovarian and peritoneal macrophage cytokine production, and ovarian P450 aromatase enzyme mRNA levels. RESULTS: Similar to PCOS, our results show that neonatally estradiol-injected mice have lower levels of circulating estrogen that are correlated with decreased mRNA levels of P450 aromatase enzyme. Our data also show that follicular cystic ovaries have increased tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production. This increase in TNF-alpha and IL-6 production is also observed in peritoneal macrophages of estradiol-injected mice. CONCLUSION: The present study showed that neonatal estrogen injection in mice has an overall systemic effect on cytokine production. We speculate that increased cytokine production may alter certain important steps in follicular maturation, ultimately contributing to ovarian dysfunction.
Assuntos
Estradiol/farmacologia , Interleucina-6/biossíntese , Ovário/metabolismo , Síndrome do Ovário Policístico/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Animais , Animais Recém-Nascidos , Aromatase/genética , Estradiol/sangue , Feminino , Interleucina-6/genética , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C3H , RNA Mensageiro/análise , Fator de Necrose Tumoral alfa/genéticaRESUMO
Previous studies with a mycobacterial heat shock protein (hsp-65) have demonstrated some efficacy using cationic liposome-mediated gene transfer in murine i.p. sarcoma models. To further analyze the efficacy of hsp-65 immunotherapy in clinically relevant models of localized cancer, immunocompetent mice bearing i.p. murine mesothelioma were treated with four i.p. doses of a cationic lipid complexed with plasmid DNA (pDNA) containing hsp65, LacZ, or a null plasmid. We observed >90% long-term survival (median survival, 150 days versus approximately 25 days, treated versus saline control, respectively) in a syngeneic, i.p. murine mesothelioma model (AC29). Long-term survivors were observed in all groups treated with lipid complexed with any pDNA. Lipid alone or DNA alone provided no demonstrable survival advantage. In a more aggressive i.p. model of mesothelioma (AB12), we observed >40% long-term survival in groups treated with lipid:pDNA complexes, again irrespective of the transgene. To ask whether these antitumor effects had led to an adaptive immune response against the tumor cell, we rechallenged long-term survivors in both murine models s.c. with the parental tumor cell line. Specific, long-lasting systemic immunity against the tumor was readily demonstrated in both models (AB12 and AC29). Consistent with these results, splenocytes from long-term survivors specifically lysed the parental tumor cell lines. Depleting the CD8+ T-cells from the splenocyte pool eliminated this lytic activity. Lipid:pDNA treatment of athymic, SCID, and SCID/Beige mice bearing a murine i.p. mesothelioma (AC29) resulted in only a slight survival advantage, but there were no long-term survivors. Treatment of immunocompetent mice depleted of specific immune effector cells demonstrated roles for CD8+ and natural killer cells. Although the exact mechanism(s) responsible for these antitumor effects is unclear, the results are consistent with roles for both innate and adaptive immune responses. An initial tumor cell killing stimulated by cationic lipid:pDNA complexes appears to be translated into long-term, systemic immunity against the tumor cell. These results are the first to demonstrate that adaptive immunity against a tumor cell can be induced by the administration of lipid:pDNA complexes. Multiple administrations of cationic lipid complexed with pDNA lacking an expressed transgene could provide a promising generalized immune-mediated modality for treating cancer.
Assuntos
Proteínas de Bactérias , DNA Bacteriano/genética , Vetores Genéticos , Imunoterapia Adotiva , Lipídeos/genética , Mesotelioma/terapia , Animais , Linfócitos T CD8-Positivos/fisiologia , Chaperonina 60 , Chaperoninas/genética , Ilhas de CpG , Intervalo Livre de Doença , Feminino , Técnicas de Transferência de Genes , Células Matadoras Naturais/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Camundongos SCID , Plasmídeos , Baço/efeitos dos fármacos , Fatores de Tempo , Células Tumorais CultivadasRESUMO
A 31-year-old woman had secondary infertility of 4 years' duration. Hysterosalpingography revealed bilateral distal tubal occlusion with bilateral hydrosalpinx-like appearance. At laparoscopy, both oviducts were occluded with marked hydropic change. Salpingoplasty was performed to correct bilateral hydrosalpinges and reform the fimbriated tubal ends. The procedure was performed uneventfully by an experienced surgeon in 45 minutes. Nine hours after the operation an emergency exploratory laparotomy was performed due to massive intraabdominal bleeding. The cause was a small tear, 3 cm long and 1 cm deep, with active bleeding in the inferior splenic tail. The laceration was repaired successfully with 1-0 chromic suture. The etiology of splenic laceration during laparoscopic surgery is uncertain. Many complications of laparoscopy are physiologic, and this one might have occurred while establishing pneumoperitoneum. Distortion and stretching of small vascular adhesions of the spleen with the abdominal wall also may have played a role. Gynecologists must be aware of the physiologic insult to patients during laparoscopy.
Assuntos
Laparoscopia/efeitos adversos , Baço/lesões , Adulto , Doenças das Tubas Uterinas/cirurgia , Feminino , Humanos , Doença Iatrogênica , Baço/cirurgiaRESUMO
We set out to evaluate salivary cotinine concentrations to judge tobacco smoke exposure among infants and children, and to examine the results in relation to age and wheezing. This was a case-control study of wheezing children (n = 165) and children without respiratory tract symptoms (n = 106) who were enrolled in the Pediatric Emergency Department at the University of Virginia. The age range of both wheezing and control patients was 2 months to 16 years. Questionnaires were combined with cotinine assays in saliva to evaluate exposure to environmental tobacco smoke (ETS) for each child. The prevalence of exposure to one or more smokers at home was high (68%); and 43% of the children enrolled were exposed to ETS from their mothers. According to the questionnaires, and after adjusting for age and race, a wheezing child in this study was more likely than a control to be exposed to at least one smoker at home (odds ratio = 1.9; 95% CI = 1.1-3.4). However, the odds of exposure to ETS from smoking mothers did not differ significantly between wheezing and control patients, and no significant association was found between the presence of wheezing and salivary cotinine levels. Among children exposed to ETS at home, cotinine levels were significantly higher in saliva from those under the age of two years, and from toddlers aged 2 and 3 years, compared to values from children over age 4 years. Moreover, the number of smokers in the home strongly influenced cotinine levels from children under age 4 years. In addition, higher cotinine levels were observed in saliva from children under age 2 years who were exposed to ETS from their mothers. Cotinine levels were similar and significantly correlated in paired samples of saliva and serum from children under 4 years of age (n = 54), (r = 0.92, P < 0.001). Based on information gathered from questionnaires, the results indicate that wheezing children were more likely than controls to be exposed to ETS at home. However, significant differences in ETS exposure between wheezing and control groups with respect to maternal smoke exposure or comparisons of salivary cotinine levels were not apparent. It was clear that determinations of salivary cotinine for monitoring the prevalence and intensity of household smoke exposure in this study were most valuable during the first 4 years of life.
Assuntos
Cotinina/análise , Sons Respiratórios , Saliva/química , Poluição por Fumaça de Tabaco , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Feminino , Humanos , Lactente , Masculino , Sons Respiratórios/etiologiaRESUMO
PURPOSE: Our objective was to study the effect of a sonographically diffusely enlarged uterus without distinct uterine masses on the outcome of in vitro fertilization-embryo transfer (IVF-ET). METHODS: Nineteen primary infertility patients undergoing IVF-ET who had a sonographically diffusely enlarged uterus without distinct uterine masses were enrolled. An age-controlled group of 144 primary infertility patients undergoing IVF-ET with a normal uterus and no history of uterine surgery was included. RESULTS: The age, day 3 follicle stimulating hormone, antral follicle count, ovarian response, endometrial thickness, number of retrieved and fertilized oocytes, number of transferred embryos, clinical pregnancy rate, and total delivery rate were not statistically different between the two groups (P < 0.05). Patients with a sonographically diffused enlarged uterus without distinct uterine masses had a higher spontaneous abortion rate (66.7%) than controls (P < 0.04; odds ratio = 7.5; 95% confidence interval, 1.16-48.56). CONCLUSIONS: A high spontaneous abortion rate was found in patients with a sonographically diffusely enlarged uterus without distinct uterine masses undergoing IVF-ET. Enhanced luteal support was required.