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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Inibidores da Aromatase/farmacologia , Inibidores da Aromatase/uso terapêutico , Receptores de Estrogênio/genética , Receptores Androgênicos/genética , Resistencia a Medicamentos Antineoplásicos/genéticaRESUMO
OBJECTIVES: Human age-dependent telomere attrition and telomere shortening are associated with several age-associated diseases and poorer overall survival. The aim of this study was to determine longitudinal leucocyte telomere length dynamics and identify factors associated with temporal changes in telomere length. DESIGN AND METHODS: Leucocyte telomere length was measured by quantitative polymerase chain reaction in 8074 participants from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, an ongoing community-based prospective cohort study initiated in 1997. Follow-up data were available at two time-points up to 2007. Leucocyte telomere length was measured, on between one and three separate occasions, in a total of 16 783 DNA samples. Multilevel growth models were created to identify the factors that influence leucocyte telomere dynamics. RESULTS: We observed an average attrition rate of 0.47 ± 0.16 relative telomere length units (RTLUs) per year in the study population aged 48 (range 39-60) years at baseline. Annual telomere attrition rate increased with age (P < 0.001) and was faster on average in men than in women (P for interaction 0.043). The major independent factors determining telomere attrition rate were active smoking (approximately tripled the loss of RTLU per year, P < 0.0001) and multiple traits of the metabolic syndrome (waist-hip ratio, P = 0.007; blood glucose level, P = 0.045, and HDL cholesterol level, P < 0.001). CONCLUSIONS: Smoking and variables linked to the metabolic syndrome are modifiable lifestyle factors that accelerate telomere attrition in humans. The higher rate of cellular ageing may mediate the link between smoking and the metabolic syndrome to an increased risk of several age-associated diseases.
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Senescência Celular/genética , Fumar/efeitos adversos , Encurtamento do Telômero , Adulto , Índice de Massa Corporal , Feminino , Humanos , Leucócitos , Masculino , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Fumar/genética , Fumar/mortalidade , Telômero/genética , Encurtamento do Telômero/genéticaRESUMO
Vesicoureteric reflux has been associated with paediatric urinary tract infection. Fluoroscopic micturating cystourethrography (MCU) has been the gold standard of diagnostic test for decades; however, it has been criticized owing to its lower detection rate and radiation dose to children. Therefore, new radiation-free reflux imaging modalities have been developed, in which ultrasound-based contrast-enhanced voiding urosonography (ceVUS) is a good example. However, ultrasonography has been considered as an operator-dependent examination. Therefore, our study aimed to examine the inter-observer agreement of this sonographic technique, which has not been evaluated before. Moreover, the second-generation ultrasound contrast SonoVue has been recently marketed, and the data on its efficacy on intravesical use in ceVUS is relatively scarce. Thus, we also aimed to investigate the diagnostic performance and safety profile of SonoVue-enhanced VUS in the diagnosis of vesicoureteric reflux. Our prospective comparative study compared the diagnostic performance of ceVUS with MCU in young children presenting with first episode of urinary tract infection. We performed sequential ceVUS and MCU examinations in 31 patients (62 pelvi-ureter units). Perfect inter-observer agreement (Cohen's kappa statistics = 1.0, p < 0.001) was achieved in ceVUS, suggesting its good reliability in reflux detection and grading. Using MCU as reference, ceVUS had 100 % sensitivity and 84 % specificity and carried higher reflux detection rate than MCU (p < 0.001). There was no complication encountered. Conclusion: Voiding urosonography is a reliable, sensitive, safe and radiation-free modality in the investigation of vesicoureteric reflux in children. It should be incorporated in the diagnostic algorithm in paediatric urinary tract infection.
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Sistema Urinário/diagnóstico por imagem , Urografia/métodos , Refluxo Vesicoureteral/diagnóstico por imagem , Pré-Escolar , Meios de Contraste , Estudos Transversais , Feminino , Fluoroscopia , Humanos , Lactente , Masculino , Variações Dependentes do Observador , Estudos Prospectivos , Ultrassonografia , MicçãoRESUMO
Vesicoureteric reflux is an important association of paediatric urinary tract infection. Fluoroscopic micturating cystourethrography and radionuclide cystography have been employed for detecting and grading vesicoureteric reflux. However, both modalities involve ionising radiation, which can pose significant radiation risk to growing children. They also have a lower detection rate due to intermittent fluoroscopic technique in micturating cystourethrography, and lower spatial resolution in radionuclide cystography. Therefore, newer radiation-free ultrasound-based contrast-enhanced voiding urosonography has been developed in Europe for 15 years. This article aimed to summarise the current literature and discuss the first local pilot study in our institution on detection of vesicoureteric reflux by contrast-enhanced voiding urosonography. Contrast-enhanced voiding urosonography is a valid alternative to micturating cystourethrography in assessing vesicoureteric reflux, based on its superior diagnostic performance, reliability, safety, feasibility, and radiation safety for children. Therefore, it should be incorporated in the guideline for investigating paediatric urinary tract infection.
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Micção , Refluxo Vesicoureteral/diagnóstico por imagem , Criança , Pré-Escolar , Técnicas de Diagnóstico Urológico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Sensibilidade e Especificidade , UltrassonografiaRESUMO
Aim: With the characteristics such as low toxicity, high total surface, ability to inhibit the growth of pathogenic microorganisms, zinc oxide nanoparticles (ZnO NPs), as one of the metallic nanoparticles, have been chosen as an antibacterial agent to treat various skin infections. The present study was aimed to determine the antibacterial potential of ZnO NPs on Bacillus subtilis, the Gram-positive bacterium that can cause skin and wound infections. Methods: B. subtilis was exposed to 5 to 150 µg/mL of ZnO NPs for 24 h. The parameters employed to evaluate the antimicrobial potential of ZnO NPs were the growth inhibitory effect on B. subtilis, the surface interaction of ZnO NPs on the bacterial cell wall, and also the morphological alterations in B. subtilis induced by ZnO NPs. Results: The results demonstrated a significant (p <0.05) inhibition of ZnO NPs on B. subtilis growth and it was in a dose-dependent manner for all the tested concentrations of ZnO NPs from 5 to 150 µg/mL at 24 h. Fourier transformed infrared (FTIR) spectrum confirmed the involvement of polysaccharides and polypeptides of bacterial cell wall in surface binding of ZnO NPs on bacteria. The scanning electron microscopy (SEM) was used to visualize the morphological changes, B. subtilis illustrated several surface alterations such as distortion of cell membrane, roughening of cell surface, aggregation and bending of cells, as well as, the cell rupture upon interacting with ZnO NPs for 24 h. Conclusion: The results indicated the potential of ZnO NPs to be used as an antibacterial agent against B. subtilis. The findings of the present study might bring insights to incorporate ZnO NPs as an antibacterial agent in the topical applications against the infections caused by B. subtilis.
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Nanopartículas Metálicas , Óxido de Zinco , Humanos , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Óxido de Zinco/metabolismo , Bacillus subtilis/metabolismo , Testes de Sensibilidade Microbiana , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Antibacterianos/farmacologiaRESUMO
Date pits are agricultural waste byproducts and are available in tons yearly. Milk MUFAs are lipids beneficial for health and sorted out for food product development. This work is aimed at researching the effect of supplementing dairy goats with date pit powder (DPP) as a source of fatty acids (FA), an alternative to enhancing the unsaturated FA in milk and analysed via chemometrics in a 3-month supplementation-based study. Saanen-Boer crossed dairy goats were divided into six groups comprising of control, 10 g and 20 g both for Ajwa DPP (high-quality dates) and Mariami DPP (agricultural waste byproduct), and another 30 g for Mariami DPP only. The supplementation exercise was done daily on each dairy goat. The DPP and milk samples were analysed for its FA profile applying GC-FID and followed by chemometric techniques, namely, PCA and PLS. Results indicated that the n-6/n-3 ratio was the highest for the unsupplemented group compared to the DPP-treated goats with lower n-6/n-3 ratios. The M30 group showcased the most promising health-related class of FAs viewed by 3D PCA and PLS model clustering patterns, in particular monounsaturated FA (MUFA) (C18:1n9c or oleic acid). These results suggest that Mariami DPP supplementation at higher doses and time to lactating Saanen-Boer cross goats can be a means to milk FA quantity and quality enhancement and that chemometrics via pattern recognition can be useful statistical tools when dealing with overwhelming data.
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INTRODUCTION: An involved circumferential resection margin (CRM) following surgery for rectal cancer is the strongest predictor of local recurrence and may represent a failure of the multidisciplinary team (MDT) process. AIM OF STUDY: The study analyses the causes of positive CRM in patients undergoing elective surgery for rectal cancer with respect to the decision-making process of the MDT, preoperative rectal cancer staging and surgical technique. METHOD: From March 2002 to September 2005, data were collected prospectively on all patients undergoing elective rectal cancer surgery with curative intent. The data on all patients identified with positive CRM were analysed. RESULTS: Of 158 patients (male:female = 2.2:1) who underwent potentially curative surgery, 16 (10%) patients had a positive CRM on postoperative histology. Four were due to failure of the pelvic magnetic resonance imaging (MRI) staging scans to predict an involved margin, two with an equivocal CRM on MRI did not have preoperative radiotherapy, one had an inaccurate assessment of the site of primary tumour and in one intra-operative difficulty was encountered. No failure of staging or surgery was identified in the remaining eight of the 16 patients. Abdominoperineal resection (APR) was associated with a 26% positive CRM, compared with 5% for anterior resection. CONCLUSION: No single consistent cause was found for a positive CRM. The current MDT process and/or surgical technique may be inadequate for low rectal tumours requiring APR.
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Colectomia/métodos , Neoplasias Retais/patologia , Reto/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Estudos Prospectivos , Neoplasias Retais/cirurgia , Reto/cirurgiaRESUMO
BACKGROUND: To evaluate whether the risk of methotrexate (MTX) exposure through skin contamination using parenteral doses of 25 mg warrants special oncology handling precautions during administration. METHODS: We conducted a study with six human volunteers deliberately exposed to an entire dose of 25 mg MTX solution on their skin for 30 min. Serum levels of MTX were measured at baseline, 2, 4, 8, 12 and 24 h as well as serum homocysteine at baseline and 24 h after clinical exposure. Twenty-four-hour urinary excretion of MTX and possible local or systemic signs of toxicity were also recorded. RESULTS: All MTX serum concentrations were less than 0.02 micromol/L within the 24-h period. This is 500 times below the recommended serum concentration for which folinic acid supplementation is recommended. There was also no significant increase in homocysteine level to suggest MTX toxicity. The only adverse effects were mild local dermal reactions in three female volunteers. CONCLUSION: Deliberate skin contamination and possible inhalation of a 25 mg MTX solution failed to show significant or quantifiable serum and urine concentrations to suggest MTX toxicity. Precautions to prevent contact with MTX designed for oncology protocols are unnecessary for our rheumatology patients or their carers using these much lower immunosuppressant doses for autoimmune diseases.
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Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Adulto , Feminino , Humanos , Infusões Parenterais/efeitos adversos , Infusões Parenterais/métodos , Masculino , Metotrexato/sangue , Pessoa de Meia-Idade , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologiaRESUMO
BACKGROUND: Renal failure aggravates pathological cardiac remodelling induced by myocardial infarction (MI). Cardiac remodelling is associated with telomere shortening, a marker for biological ageing. We investigated whether mild and severe renal failure shorten cardiac telomeres and excessively shorten telomeres after MI. METHODS: Rats were subjected to sham, unilateral (UNX) or 5/6th nephrectomy (5/6NX) to induce none, mild or severe renal failure. MI was induced by left coronary artery ligation. Renal function parameters and blood pressure were measured. DNA was isolated from non-infarcted cardiac tissue. Telomere length was assessed by quantitative polymerase chain reaction (PCR). RESULTS: Proteinuria was unchanged in UNX and MI compared with control, but strongly increased in 5/6NX, UNX+MI and 5/6NX+MI. Serum creatinine levels were increased fourfold in 5/6NX and tenfold in 5/6NX+MI. 5/6NX and groups with both renal failure and MI showed an approximate 20% reduction of telomere length, similar to the MI group. No excess telomere shortening was observed in hearts from rats with renal ablation after MI. CONCLUSION: Severe renal failure, but not mild renal failure, leads to shortening of cardiac telomeres to a similar extent as found after MI. Renal failure did not induce excessive telomere shortening after MI. (Neth Heart J 2009;17:190-4.).
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OBJECTIVE: The English arm of the UK Bowel Cancer Screening Pilot has recently concluded its third round. The primary aim of this study was to assess the effects of this programme on the emergency and elective cancer workload at University Hospitals Coventry and Warwickshire NHS Trust; the largest trust within the screened region. The secondary aim was to assess its effect upon Dukes staging, mortality and stoma formation for emergency colorectal cancer (CRC) admissions. DESIGN: A retrospective analysis of validated data for CRC admissions over a period of 6 years from 1999 to 2004 was performed. The first year, 1999, represented the pre-screening year (PSY) which was taken as a baseline. Data for the next 5 years, screening years 1-5 (SY1-SY5), were recorded for the mode of admission, occurrence of emergency surgery, 30-day mortality and Dukes staging. RESULTS: In the PSY (1999), 29.4% of CRCs were admitted as an emergency, decreasing to 15.8% by 2004 (p = 0.001). As a consequence, there was a significant decrease in the number of emergency CRC procedures performed over the same period (p<0.05). There was also a significant reduction in the 30-day mortality from 48% in 1999 to 13% in 2004 (p<0.05). Dukes stage C carcinomas, however, remained the predominant stage presenting as emergencies throughout the studied period (SY3, 53%; SY4, 38%; SY5, 50%). CONCLUSION: Following commencement of the UK Bowel Cancer Screening Pilot, there has been a significant decline in emergency CRC workload with a marked improvement in 30-day mortality and decreased stoma formation, in Coventry and North Warwickshire. It is postulated that the witnessed and notable positive impact over such a short time period is the result of increased detection of asymptomatic malignancies within the screening programme, increased public awareness of the symptoms of CRC, together with a change in attitudes and referral patterns of general practitioners within Coventry and North Warwickshire.
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Neoplasias Colorretais/prevenção & controle , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Serviços Médicos de Emergência/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Sangue Oculto , Idoso , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Colostomia/estatística & dados numéricos , Emergências , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Projetos PilotoRESUMO
The surgical approach for the correction of residual velopharyngeal insufficiency requiring secondary surgery at Chang Gung Memorial Hospital is the modified Furlow palatoplasty with pharyngeal flap (mFP-PF). The aim of this study was to describe the mFP-PF technique and to determine the results obtained with regard to improvements in velopharyngeal function in patients undergoing this surgery. This retrospective analysis included 58 non-syndromic patients treated during the period 1992-2015 who complained of hypernasal speech after primary cleft palate repair and failed postoperative speech therapy. All of them underwent mFP-PF surgery. Preoperative and postoperative perceptual speech assessment results were obtained. The male to female ratio in the study group was 1.2:1, and the mean patient age at the time of surgery was 8.27 years. The patients underwent nasoendoscopic examination and the velar closing ratio was categorized as 0.1-0.4 in 53.4% and 0.5-0.7 in 46.6%. The assessment of speech after mFP-PF showed statistically significant changes for all perceptual speech outcomes. The incidence of repeat surgery was 3.4%. This study revealed that 96.6% of patients did not require second surgery for velopharyngeal insufficiency. Further studies on obstructive sleep apnoea in post-mFP-PF patients and improvements to the surgical technique should be considered.
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Fissura Palatina , Insuficiência Velofaríngea , Feminino , Humanos , Masculino , Palato Mole , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: This paper reports on a non-conventional method for the management of facial carbuncles, highlighting its superiority over conventional surgical treatment in terms of cosmetic outcome and shorter duration of wound healing. BACKGROUND: The mainstay of treatment for carbuncles involves the early administration of antibiotics in combination with surgical intervention. The conventional saucerisation, or incision and drainage, under normal circumstances results in moderate to large wounds, which may need secondary surgery such as skin grafting, resulting in a longer duration of wound healing and jeopardising cosmetic outcome. CASE REPORTS: The reported three cases presented with extensive carbuncles over the chin, face and lips region. In addition to early commencement of intravenous antibiotics, the pus was drained, with minimal incision and conservative wound debridement, with the aim of maximal skin conservation. This was followed by thrice-daily irrigation with antibiotic-containing solution for a minimum of 2 consecutive days. The wounds healed within two to four weeks, without major cosmetic compromise. CONCLUSION: The new method showed superior cosmetic outcomes, with a shorter duration of wound healing. Conservative surgical management can be performed under regional anaesthesia, which may reduce morbidity and mortality; patients with facial carbuncles often have higher risks with general anaesthesia.
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Antibacterianos/uso terapêutico , Carbúnculo/terapia , Desbridamento/métodos , Adulto , Terapia Combinada , Tratamento Conservador , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , CicatrizaçãoRESUMO
Among most patients attending a rectal clinic, rectal bleeding is a common presenting feature. In most patients, the cause is attributed to a benign lesion. In a small percentage, the cause is neoplastic, and for this reason, rectal bleeding merits further study. Left-sided tumors account for the majority of these tumors and are within the reach of a flexible sigmoidoscopy. This study aimed at examining the diagnostic performance of the one stop rectal clinic in Coventry. Between November 2001 and May 2002, 250 consecutive patients were seen in the one stop rectal bleeding clinic of a tertiary referral hospital. Patients were asked of the nature of rectal bleed and altered bowel habits and were examined by digital rectal examination, with a proctoscopy and rigid sigmoidoscopy before either a full colonoscopic examination or flexible sigmoidoscopy with a completion Barium enema. During the study period, colorectal cancer was detected in 4 patients (1.6%), adenomatous polyps in 36 patients (14.4%), and ulcerative colitis in 8 patients (3.2%). In 98 patients (39.2%), no abnormality was present, and in the remaining patients, diverticulosis (n = 60; 24%) and hemorrhoids were present (n = 44; 17.6%).
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Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS: We studied if post-radiation plasma Epstein-Barr virus (EBV) DNA predicted local clinical remission after radical intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma. MATERIALS AND METHODS: Patients with non-metastatic nasopharyngeal carcinoma with baseline and serial plasma EBV DNA were treated with radical IMRT ± adjunct chemotherapy. Eight weeks after IMRT, they had plasma EBV DNA and routine six-site random nasopharyngeal biopsies on the same day. A repeat biopsy was carried out every 2 weeks if residual tumours were noted in previous biopsies until 12 weeks after IMRT when local persistence was defined. Correlation of undetectable plasma EBV DNA with local clinical remission was carried out. RESULTS: Two hundred and sixty patients with serial plasma EBV DNA completed IMRT, after a median follow-up of 3.1 years. Only one (0.4%) suffered from local persistence. Area under the curve values of receiver operating characteristics of undetectable plasma EBV DNA for negative biopsy at 8 weeks and local persistence were 0.642 and 0.439, respectively. They increased to 0.856 (P = 0.007) and 0.952 (P = 0.119), respectively, when combined with age <65 years and T1/T2 stage. CONCLUSIONS: Post-treatment plasma EBV DNA was not useful to predict local clinical remission in this study, probably because of excellent local control after IMRT. However, it may serve as a reference for high-risk patients treated with older radiation techniques.
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DNA Viral/sangue , Infecções por Vírus Epstein-Barr/complicações , Neoplasias Nasofaríngeas/virologia , Adulto , Idoso , Área Sob a Curva , Carcinoma , Quimioterapia Adjuvante , Terapia Combinada , Infecções por Vírus Epstein-Barr/sangue , Feminino , Herpesvirus Humano 4/genética , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/radioterapia , Prognóstico , Curva ROC , Radioterapia de Intensidade ModuladaRESUMO
OBJECTIVES: This study was designed to investigate the changes in regional distensibility of the ischemic segment and of a remote nonischemic segment brought about by graded myocardial ischemia. BACKGROUND: Ventricular distensibility is a major determinant of left ventricular end-diastolic pressure. The effects of graded myocardial ischemia on the regional distensibility of the ischemic area have not been studied. Moreover, there are few data on the effects of myocardial ischemia on the regional distensibility of the nonischemic myocardium. METHODS: Nine anesthetized open chest mongrel dogs were fitted with instruments to measure left ventricular pressure and circumferential length (sonomicrometry) in the ischemic segment and in a nonischemic segment. The pressure-length relation was modified by stepwise infusion and withdrawal of 200 ml of each dog's own blood over 30 min in five consecutive stages of regional ischemia. Unstressed dimensions were obtained by repeated inferior vena cava occlusions. In both segments, regional distensibility was assessed at end-diastole by means of the constants of the pressure-length (chamber stiffness), the pressure-strain and the force-strain (myocardial stiffness) relations. RESULTS: In the ischemic segment, partial and complete coronary occlusions were associated with a twofold increase in the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant, whereas in the nonischemic segment the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant increased by 50%. CONCLUSIONS: Regional myocardial ischemia is associated with a decrease in distensibility of both the ischemic and the remote nonischemic myocardium.
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Contração Miocárdica , Isquemia Miocárdica/fisiopatologia , Análise de Variância , Anestesia , Animais , Diástole , Modelos Animais de Doenças , Cães , Feminino , Halotano , Hemodinâmica , Masculino , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/etiologia , Sístole , TiopentalRESUMO
Aim of this explorative study was to determine the prognostic value of protein expression of the DNA damage repair enzymes ERCC1, hRad51, and BRCA1 for tumour response and survival of non-small-cell lung cancer patients treated with chemotherapy. Patients with either a short or long overall survival were selected from a randomized phase III trial comparing cisplatin-gemcitabine and epirubicin-gemcitabine. Tumour biopsies were assessed for differences in immunohistochemical staining using antibodies against ERCC1, hRad51, and BRCA1. A total of 33 patients were included. A positive nuclear staining for ERCC1, hRad51, and BRCA1 was observed in 44, 12, and 90% of biopsies, respectively. In large cell carcinoma nuclear hRad51 staining was absent. In five biopsies stained for hRad51 an unexpected membrane-like staining was observed; these biopsies showed no nuclear staining. DNA damage repair protein expressions were not significantly different in responders versus non-responders, or in patients with a short or long overall survival. In conclusion, immunohistochemical staining of ERCC1, hRad51, and BRCA1, in tumour biopsies from non-small-cell lung cancer patients was not predictive for tumour response and survival after chemotherapy.
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Proteína BRCA1/biossíntese , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Ligação a DNA/biossíntese , Endonucleases/biossíntese , Neoplasias Pulmonares/genética , Rad51 Recombinase/biossíntese , Adulto , Idoso , Biópsia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Dano ao DNA , Reparo do DNA , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise de SobrevidaRESUMO
This study aimed to determine the effect of streptozotocin (STZ)-induced diabetes on pulsatile LH secretion in the mature male rat. LH pulse frequency was reduced by 56% and pulse amplitude by 54%, with a consequential decrease of 72% in mean LH levels 8 days after i.v. administration of STZ (55 mg/kg) to castrated Wistar rats compared with castrated non-diabetic controls. Twice daily insulin treatment completely reversed all parameters of pulsatile LH secretion to control values. Food-restricted non-diabetic controls, studied to distinguish the metabolic effect of diabetes from that of concurrent weight loss, demonstrated a 34% reduction in LH pulse frequency but no significant changes in LH pulse amplitude or mean LH levels compared with non-diabetic controls given free access to food. To distinguish whether the decreased LH pulse amplitude in diabetes was due to a reduction in either the quantity of hypothalamic gonadotrophin-releasing hormone (GnRH) released per secretory episode or to decreased pituitary responsiveness to GnRH, the responsiveness of the pituitary to exogenous GnRH (1-1000 ng/kg body weight) was tested in diabetic rats after castration, using a full Latin square experimental design. The net LH response (total area under response curve over 40 min following GnRH) was decreased by 33% (P = 0.001) in diabetic compared with control rats. The decreased LH pulse frequency in STZ-induced diabetes therefore suggests that the metabolic effect of diabetes is to decelerate directly the firing rate of the hypothalamic GnRH pulse generator independent of testicular feedback. These effects were fully reversed by insulin treatment and were only partly due to the associated weight loss.(ABSTRACT TRUNCATED AT 250 WORDS)
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Diabetes Mellitus Experimental/fisiopatologia , Hormônio Luteinizante/metabolismo , Hipófise/metabolismo , Animais , Peso Corporal , Diabetes Mellitus Experimental/sangue , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Luteinizante/sangue , Masculino , Orquiectomia , Hipófise/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Taxa Secretória/fisiologia , Fatores de TempoRESUMO
Propylthiouracil (PTU) has been demonstrated to reduce alcohol-induced hepatocyte damage and severe alcoholic liver disease. Although the mechanism by which the drug operates is yet to be elucidated, there is evidence that PTU may act as an antioxidant. The present study examines the reaction of PTU with oxygen free radicals and the ability of PTU to directly inhibit peroxidation of a model membrane system. PTU reacted directly with hydroxyl radicals produced by gamma-radiolysis. The rate constant for the PTU/hydroxyl radical reaction as determined by steady state competition kinetics with p-nitrosodimethylaniline was 8 x 10(9) L/mol/sec. PTU was less reactive towards superoxide generated by the xanthine/xanthine oxidase system, having a small but significant inhibitory effect on superoxide-induced reduction of cytochrome c only at a concentration of 200 microM. The ability of PTU to protect lipids from peroxidative changes was tested in membranes prepared from linoleic acid. The rate of peroxidation induced by 40 degrees heat decreased from 0.078 to 0.024 mM hydroperoxide/hr in the presence of 0-50 microM PTU. However, this trend was reversed at PTU concentrations above 50 microM. These data suggest that the protective effects of PTU against liver damage may be due to scavenging reactions with hydroxyl radicals in particular and/or its antioxidant potential.
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Antioxidantes/farmacologia , Propiltiouracila/farmacologia , Animais , Antioxidantes/química , Sequestradores de Radicais Livres , Temperatura Alta , Hidróxidos/química , Radical Hidroxila , Cinética , Peroxidação de Lipídeos , Fígado/efeitos dos fármacos , Modelos Biológicos , Propiltiouracila/química , Superóxidos/químicaRESUMO
Aggressive angiomyxoma (AAM) is a rare, locally infiltrative but nonmetastasizing tumor of the pelvic and perineal soft tissues that occurs almost exclusively in adult females. The authors describe four cases of AAM in adult males that arose in the scrotum. There was some histologic variation among the tumors. One case was focally hypercellular around the blood vessels, two were more densely cellular throughout, and one had cystic degeneration. Three of the tumors were widely infiltrative, and one of the four tumors recurred locally. The clinicopathologic features of these cases are similar to those of AAM occurring in females. In either sex, AAM should be distinguished from benign myxoid tumors with a low risk of local recurrence and fully malignant myxoid tumors with distant metastatic potential.
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Neoplasias dos Genitais Masculinos/patologia , Mixoma/patologia , Escroto , Adolescente , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade NeoplásicaRESUMO
In this study, Sprague-Dawley rats were exposed in a TEM chamber to 20-MHz (HF-band) continuous-wave radiofrequency radiation (RFR) for 6 hr/day, 5 days/week up to 6 weeks. The average E-field intensity was 2686 +/- 164 V/m (mean +/- SD) and the calculated specific absorption rate was 0.3 W/kg. Randomly sampled rats killed on Days 8, 22, 39, and 42 after initiation of exposure showed no statistically significant differences from controls for body mass, spleen cell density, erythrocyte and leukocyte counts, hematocrit, hemoglobin, methemoglobin, erythrocyte fragility, bilirubin, creatinine, SGPT, alkaline phosphatase, calcium, sodium, potassium, and spleen cell chemiluminescence. Splenic mass differences were statistically significant (p less than 0.05) only on Day 22. Spleen to body mass ratios differed significantly between exposed and control groups on Days 22 and 39 (P less than 0.05 and P less than 0.025, respectively). Histologic examination of the rats revealed the successive accumulation of phagocytic cells, lymphoid proliferation, development of lesions, and tissue necrosis characteristic of respiratory mycoplasmosis. In a followup experiment, a separate set of rats was exposed for 6 weeks to identical levels of RFR. No significant differences were found in splenic parameters and spleen cell peroxidative activity. Histologic examination of these animals revealed no evidence of mycoplasma infection. The observed differences between exposed and control animals of the first experiment appear to have resulted from subclinical respiratory mycoplasmosis rather than exposure to RFR.