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1.
Clin Radiol ; 78(5): e425-e432, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36849278

RESUMO

AIM: To evaluate the Prostate Imaging Reporting and Data System, version 2.1 (PIRADS V2.1) criteria for seminal vesicle invasion (SVI) and examine whether the timing of last ejaculation influences the detection of SVI. MATERIALS AND METHODS: The study population consisted of 68 patients (34 with SVI, 34 without SVI, matching groups by age and prostate volume) who underwent PIRADS V2.1-compliant multiparametric magnetic resonance imaging (MRI; 34 at 1.5 T, 34 at 3 T). Before the examination, the time of last ejaculation (38/68 ≤ 5 days, 30/68 > 5 days) was collected via a questionnaire. The five PIRADS V2.1 criteria for SVI with subsequent overall assessment were evaluated retrospectively by two independent examiners (examiner 1 with >10 years of experience, examiner 2 with 6 months of experience) in a single-blinded fashion for all patients using a questionnaire and a six-point scale (0 = no, 1 = very likely not, 2 = probably not, 3 = possible, 4 = probable, 5 = certain). RESULTS: E1 achieved high specificity (100%) and positive predictive value (PPV; 100%) in the overall assessment, independent of the time of last ejaculation (sensitivity = 76.5%, negative predictive value [NPV] = 81%). The area under the curve (AUC) value was 0.882; for E2, it was 0.765. At ≤5 days, the AUC values of E1 and E2 differed significantly (0.867 versus 0.681, p=0.016), as did the diffusion restriction criterion (0.833 versus 0.681, p=0.028). E1 showed high AUC values independent of time. E2 had better values for all criteria at >5 days than at ≤5 days. There were no significant differences between the examiners in all observations at >5 days. CONCLUSION: The PIRADS V2.1 criteria are well suited for an experienced examiner to detect SVI independent of time point. An inexperienced examiner will benefit from patients being abstinent >5 days prior to MRI.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/patologia , Glândulas Seminais/diagnóstico por imagem , Estudos Retrospectivos , Ejaculação , Neoplasias da Próstata/patologia , Invasividade Neoplásica/patologia , Imageamento por Ressonância Magnética/métodos , Estadiamento de Neoplasias
2.
Eur Heart J ; 43(25): 2407-2417, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35139192

RESUMO

AIMS: The most appropriate definition of perioperative myocardial infarction (pMI) after coronary artery bypass grafting (CABG) and its impact on clinically relevant long-term events is controversial. We aimed to (i) analyse the incidence of pMI depending on various current definitions in a 'real-life' setting of CABG surgery and (ii) determine the long-term prognosis of patients with pMI depending on current definitions. METHODS AND RESULTS: A consecutive cohort of 2829 coronary artery disease patients undergoing CABG from two tertiary university centres with the presence of serial perioperative cardiac biomarker measurements (cardiac troponin and creatine kinase-myocardial band) were retrospectively analysed. The incidence and prognostic impact of pMI were assessed according to (i) the 4th Universal Definition of Myocardial Infarction (4UD), (ii) the definition of the Society for Cardiovascular Angiography and Interventions (SCAI), and (iii) the Academic Research Consortium (ARC). The primary endpoint of this study was a composite of myocardial infarction, all-cause death, and repeat revascularization; secondary endpoints were mortality at 30 days and during 5-year follow-up. There was a significant difference in the occurrence of pMI (49.5% SCAI vs. 2.9% 4UD vs. 2.6% ARC). The 4th Universal Definition of Myocardial Infarction and ARC criteria remained strong independent predictors of all-cause mortality at 30 days [4UD: odds ratio (OR) 12.18; 95% confidence interval (CI) 5.00-29.67; P < 0.001; ARC: OR 13.16; 95% CI 5.41-32.00; P < 0.001] and 5 years [4UD: hazard ratio (HR) 2.13; 95% CI 1.19-3.81; P = 0.011; ARC: HR 2.23; 95% CI 1.21-4.09; P = 0.010]. Moreover, the occurrence of new perioperative electrocardiographic changes was prognostic of both primary and secondary endpoints. CONCLUSION: Incidence and prognosis of pMI differ markedly depending on the underlying definition of myocardial infarction for patients undergoing CABG. Isolated biomarker release-based definitions (such as troponin) were not associated with pMI relevant to prognosis. Additional signs of ischaemia detected by new electrocardiographic abnormalities, regional wall motion abnormalities, or coronary angiography should result in rapid action in everyday clinical practice.


Assuntos
Aorta Torácica , Infarto do Miocárdio , Biomarcadores , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Prognóstico , Estudos Retrospectivos , Troponina
3.
Ann Oncol ; 31(8): 1030-1039, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32339648

RESUMO

BACKGROUND: The phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We report updated efficacy data from the second interim analysis. PATIENTS AND METHODS: Treatment-naive patients with aRCC were randomized (1 : 1) to receive avelumab (10 mg/kg) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were PFS and overall survival (OS) among patients with programmed death ligand 1-positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population. RESULTS: Of 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm {PD-L1+ population: hazard ratio (HR) 0.62 [95% confidence interval (CI) 0.490-0.777]}; one-sided P < 0.0001; median 13.8 (95% CI 10.1-20.7) versus 7.0 months (95% CI 5.7-9.6); overall population: HR 0.69 (95% CI 0.574-0.825); one-sided P < 0.0001; median 13.3 (95% CI 11.1-15.3) versus 8.0 months (95% CI 6.7-9.8)]. OS data were immature [PD-L1+ population: HR 0.828 (95% CI 0.596-1.151); one-sided P = 0.1301; overall population: HR 0.796 (95% CI 0.616-1.027); one-sided P = 0.0392]. CONCLUSION: Among patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature. CLINICAL TRIAL NUMBER: NCT02684006.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Anticorpos Monoclonais Humanizados , Axitinibe , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Sunitinibe/uso terapêutico
4.
J Eur Acad Dermatol Venereol ; 33(6): 1177-1188, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30720896

RESUMO

BACKGROUND: Superficial cutaneous infection caused by the zoophilic dermatophyte Trichophyton benhamiae is often associated with a highly inflammatory immune response. As non-professional immune cells, epidermal keratinocytes and dermal fibroblasts contribute to the first line of defence by producing pro-inflammatory cytokines and antimicrobial peptides (AMP). OBJECTIVE: Purpose of this study was to gain a deeper understanding of the pathogenesis and the fungal-host interaction as not much is known about the innate immune response of these cutaneous cells against T. benhamiae. METHODS: Using a dermatophytosis model of fibroblasts and keratinocytes incubated with T. benhamiae DSM 6916, analyses included determination of cell viability and cytotoxicity, effects on the innate immune response including expression and secretion of pro-inflammatory cytokines/chemokines and expression of AMP, as well as alterations of genes involved in cell adhesion. RESULTS: Trichophyton benhamiae DSM 6916 infection led to severe cell damage and direct induction of a broad spectrum of pro-inflammatory cytokines and chemokines in both cutaneous cells. Only keratinocytes differentially up-regulated AMP genes expression after T. benhamiae DSM 6916 infection. Expression of AMPs in fibroblasts was not inducible by fungal infection, whereas their absences potentially contributed to a continuous increase in the fungal biomass on fibroblasts, which in turn was reduced in keratinocytes possibly due to the antimicrobial actions of induced AMPs. On mRNA level, T. benhamiae DSM 6916 infection altered cell-cell contact proteins in keratinocytes, indicating that targeting specific cell-cell adhesion proteins might be part of dermatophytes' virulence strategy. CONCLUSION: This study showed that in addition to immune cells, keratinocytes and fibroblasts could participate in antimicrobial defence against an exemplary infection with T. benhamiae DSM 6916.


Assuntos
Dermatomicoses/microbiologia , Epiderme/imunologia , Fibroblastos/imunologia , Imunidade Inata , Queratinócitos/imunologia , Trichophyton/patogenicidade , Humanos
5.
Phys Rev Lett ; 116(14): 147601, 2016 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-27104726

RESUMO

Electron-phonon coupling is one of the most fundamental effects in condensed matter physics. We here demonstrate that photoelectron momentum mapping can reveal and visualize the coupling between specific vibrational modes and electronic excitations. When imaging molecular orbitals with high energy resolution, the intensity patterns of photoelectrons of the vibronic sidebands of molecular states show characteristic changes due to the distortion of the molecular frame in the vibronically excited state. By comparison to simulations, an assignment of specific vibronic modes is possible, thus providing unique information on the coupling between electronic and vibronic excitation.

6.
J Oral Pathol Med ; 45(5): 346-55, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26403591

RESUMO

OBJECTIVES: Monitoring surgical removal of oral squamous cell carcinomas (OSCC) is being routinely performed through clinical and imaging follow-up. We analyzed the potential use of serum lactate, lactate dehydrogenase (LDH), and LDH isoenzymes (LDH 1-5) as biomarkers in blood for the monitoring of surgical removal of OSCC. MATERIALS AND METHODS: Serum lactate, LDH, and LDH isoenzymes (LDH 1-5) have been prospectively assessed in healthy individuals (n = 19), patients with OSCC (n = 34: primary OSCC, n = 32 and recurrent OSCC, n = 2) before surgery and after curative tumor resection (n = 26). LDHA and LDHB expressions were analyzed by immunohistochemistry (IHC) in the same OSCC tumor specimen. RESULTS: Positive LDHA tumor tissue expression measured by IHC (n = 34/34, 100%) was significantly associated with increased serum LDH-5 (n = 24/34, 71%, P = 0.0258) but weak significantly associated with increased total serum LDH (n = 23/34, 68%, P = 0.0592). Positive LDHB tumor tissue expression measured by IHC (n = 25/34, 74%) was significantly associated with increased total serum LDH (P = 0.0172). After surgery, serum LDH and LDH-5 isoenzyme significantly decreased and LDH-1 significantly increased in the aftercare. A significantly inverse correlation of LDHA with LDHB IHC scores was found (P < 0.0001). CONCLUSIONS: The association of LDHA and LDHB measured by IHC with serum LDH indicates that analyzing this enzyme could serve as a favorable 'liquid biopsy' (non-invasive diagnostic tool) for OSCC.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/enzimologia , Neoplasias de Cabeça e Pescoço/cirurgia , L-Lactato Desidrogenase/sangue , Neoplasias Bucais/enzimologia , Neoplasias Bucais/cirurgia , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/sangue , Biópsia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Isoenzimas/biossíntese , Isoenzimas/sangue , L-Lactato Desidrogenase/biossíntese , Ácido Láctico/sangue , Masculino , Neoplasias Bucais/sangue , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/enzimologia , Recidiva Local de Neoplasia/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço
7.
Med Oral Patol Oral Cir Bucal ; 21(5): e554-8, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27475696

RESUMO

BACKGROUND: Recent studies have shown an increase in the incidence of oral squamous cell carcinoma (OSCC) in younger patients. The hypothesis that tumors could be hormonally induced during pregnancy or in young female patients without the well-known risk factors alcohol or tobacco abuse seems to be plausible. MATERIAL AND METHODS: Estrogen Receptor alpha (ERα) and Progesterone Receptor (PR) expression were analyzed in normal oral mucosa (n=5), oral precursor lesions (simple hyperplasia, n=11; squamous intraepithelial neoplasia, SIN I-III, n=35), and OSCC specimen. OSCCs were stratified in a young female (n=7) study cohort and older patients (n=46). In the young female study cohort three patients (n=3/7) developed OSCC during or shortly after pregnancy. Breast cancer tissues were used as positive control for ERα and PR expression. RESULTS: ERα expression was found in four oral precursor lesions (squamous intraepithelial neoplasia, SIN I-III, n=4/35, 11%) and in five OSCC specimen (n=5/46, 11%). The five ERα positive OSCC samples were older male patients. All patients within the young female study cohort were negatively stained for both ERα and PR. CONCLUSIONS: ER expression could be regarded as a seldom risk factor for OSCC. PR expression seems to be not relevant for the development of OSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Estrogênios , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal , Gravidez , Progesterona , Adulto Jovem
8.
Br J Cancer ; 110(10): 2537-43, 2014 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-24667645

RESUMO

BACKGROUND: The aim of this study was to examine the prognostic value of four significant aberrations based on our previous studies by array-CGH to develop a prognostic Fluorescence-in situ-hybridisation (FISH) assay for clear cell renal cell carcinomas (ccRCC). METHODS: Fluorescence-in situ-hybridisation experiments were performed on 100 ccRCCs (52 metastasised out of 48 non-metastasised). The mean/median follow up of patients was 59/54 months. Commercially available FISH probes were used for each critical chromosomal region (1q21.3, 7q36.3, 9p21.3p24.1 and 20q11.21q13.32). The total number of specific aberrations (TNSA) was calculated for each tumour based on the specific genomic alterations. RESULTS: Total number of specific aberrations was the best predictor of metastasis (area under the curve (AUC)=0.814) compared with single aberrations (AUC: 0.619-0.708) and to 11 different combinations of these 4 aberrations in the receiver operating characteristic curve analysis. Total number of specific aberrations, tumour grade and tumour size were independent predictors of metastasis in the multivariate analysis (P<0.001) for the whole cohort as well as for organ-confined tumours. Total number of specific aberrations and grade could also independently predict cancer-specific mortality (CSM). Total number of specific aberrations demonstrated the highest significance in COX proportional hazard models of overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). CONCLUSIONS: We identified TNSA as an independent prognostic factor which is associated with metastasis occurrence, CSM, OS, CSS and PFS in patients with ccRCCs.


Assuntos
Carcinoma de Células Renais/genética , Hibridização in Situ Fluorescente , Neoplasias Renais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Aberrações Cromossômicas , Intervalo Livre de Doença , Feminino , Humanos , Interfase , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Medição de Risco
9.
Clin Exp Immunol ; 175(2): 316-22, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24666024

RESUMO

Appendicitis followed by appendectomy (AA) at a young age protects against inflammatory bowel disease (IBD). We wanted to characterize the role of the T helper type 17 (Th17) system involved in this protective effect. AA was performed on 5-week-old male BALB/c mice and distal-colon samples were harvested. Mice with two laparotomies each served as sham-sham (SS) controls. RNA was extracted from four individual colonic samples per group (AA and SS groups) and each sample microarray-analysed and reverse transcription-polymerase chain reaction (RT-PCR)-validated. Gene-set enrichment analysis (GSEA) showed that the Th17 recruitment factor gene CCL20 was significantly suppressed at both 3 days post-AA and 28 days post-AA. Although Th17 cell development differentiation factor genes TGF-ß2 and TGF-ß3 were significantly up-regulated 3 days post-AA, GSEA 28 days post-AA showed that AA down-regulated 29 gene-sets associated with TGF-ß1, TGF-ß2 and TGF-ß3 in contrast to none up-regulated with any of these genes. GSEA showed substantial down-regulation of gene-sets associated with Th17 lymphocyte recruitment, differentiation, activation and cytokine expression in the AA group 28 days post-AA. We conclude that Th17-system cytokines are kept under control by AA via down-regulation of proinflammatory CCL20, a rapid down-regulation of pro-Th17 cell differentiation genes TGF-ß2 and TGF-ß3, suppression of RORC-associated gene-sets, increased protective STAT1 expression and suppression of 81 'pro-Th17' system gene-sets. AA suppresses the Th17 pathway leading to colitis amelioration. Further characterization of Th17-associated genes and biological pathways will assist in the development of better therapeutic approaches in IBD management.


Assuntos
Apendicectomia , Apendicite/cirurgia , Colite/prevenção & controle , Células Th17/metabolismo , Animais , Apendicite/imunologia , Apendicite/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Quimiocina CCL20/metabolismo , Colite/cirurgia , Colo/imunologia , Regulação para Baixo , Expressão Gênica , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Fator de Transcrição STAT1/metabolismo , Células Th17/imunologia , Fator de Crescimento Transformador beta2/metabolismo , Fator de Crescimento Transformador beta3/metabolismo , Regulação para Cima
10.
Infection ; 42(6): 1061-4, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25234200

RESUMO

Schistosomiasis is a widespread helminthic infection which sometimes may affect travelers to endemic areas. We report on a case of urogenital and placental schistosomiasis in a 28-year-old German woman who had been exposed to schistosomiasis in Lake Malawi one year earlier. She experienced painless macrohaematuria in her 21st week of pregnancy. Cystoscopy revealed vesical lesions typical for urogenital schistosomiasis. Histopathology confirmed ova of Schistosoma (S.) haematobium. The patient was treated with praziquantel 40 mg/kg/body weight/day for 3 days. After 285 days of gestation and 18 weeks post treatment, the patient delivered a healthy girl. Histopathology of placenta revealed eggs of S. haematobium in placental stroma. The infant proved negative for anti-Schistosoma spp. antibodies at the age of 15 months. This is the first report on placental schistosomiasis since 1980 and the first case occurring in a traveler.


Assuntos
Doenças Placentárias/parasitologia , Complicações Parasitárias na Gravidez/parasitologia , Schistosoma haematobium/isolamento & purificação , Esquistossomose Urinária/diagnóstico , Adulto , Animais , Feminino , Alemanha , Humanos , Malaui , Gravidez , Viagem
11.
Allergy ; 68(4): 472-80, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23452076

RESUMO

BACKGROUND: Extracellular Adenosine-5'-Triphosphate (ATP) is known to accumulate in the lung, following allergen challenge, and contributes via activation of purinergic receptors on dendritic cells (DC), to the development of allergic airway inflammation (AAI). Extracellular ATP levels in the airways are normally tightly regulated by CD39. This ectonucleotidase is highly expressed by DC purified from skin (Langerhans cells) and bone marrow, and has been shown to modulate DC adaptive/haptenic immune responses. In this study, we have evaluated the impact of Cd39 deletion and associated perturbation of purinergic signaling in AAI. METHODS: Standard ovalbumin (OVA)-alum and house dust mite (HDM) bone marrow-derived DC (BMDC)-dependent models of AAI were used to study effects of Cd39. Migration assays, time lapse microscopy, and T-cell priming assays were further used to determine functional relevance of Cd39 expression on BMDC in the setting of immune and Th2-mediated responses in these models. RESULTS: Cd39(-/-) mice exhibited marked increases in BALF ATP levels but paradoxically exhibited limited AAI in both OVA-alum and HDM models. These pathophysiological abnormalities were associated with decreased myeloid DC activation and chemotaxis toward ATP, and were linked to purinergic receptor desensitization responses. Further, Cd39(-/-) DCs exhibited limited capacity to both prime Th2 responses and form stable immune synaptic interactions with OVA-transgenic naïve T cells. CONCLUSIONS: Cd39-deficient DCs exhibit limited capacity to induce Th2 immunity in a DC-driven model of AAI in vivo. Our data demonstrate a role of CD39 and perturbed purinergic signaling in models of AAI.


Assuntos
Antígenos CD/genética , Apirase/genética , Asma/genética , Asma/imunologia , Trifosfato de Adenosina/biossíntese , Compostos de Alúmen , Animais , Antígenos CD/metabolismo , Apirase/deficiência , Apirase/metabolismo , Movimento Celular/genética , Movimento Celular/imunologia , Citocinas/biossíntese , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Pulmão/imunologia , Pulmão/metabolismo , Camundongos , Camundongos Knockout , Ovalbumina/imunologia , Pyroglyphidae/imunologia , Células Th2/imunologia , Células Th2/metabolismo
12.
Diabetes Obes Metab ; 15(10): 871-81, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23425609

RESUMO

Exenatide once weekly is the first glucose-lowering agent available to patients with type 2 diabetes mellitus (T2DM) which is administered once per week. This long-acting formulation contains the same active ingredient as exenatide twice daily, except that the exenatide is encapsulated in dissolvable microspheres. Following subcutaneous injection, exenatide once weekly microspheres remain in place under the skin and slowly degrade, releasing active exenatide continuously into circulation. In randomized clinical trials, exenatide once weekly was associated with significant glycaemic improvement and moderate weight loss in patients with T2DM when administered as monotherapy or in combination with a variety of oral antidiabetic agents. Exenatide once weekly also lowered blood glucose more effectively than titrated basal insulin in patients on metformin or metformin plus sulphonylurea background therapy. Gastrointestinal side effects (nausea, vomiting and diarrhoea) were the most common tolerability issues associated with exenatide once weekly administration, but they occurred at lower rates than in patients on other glucagon-like peptide receptor agonists (i.e., exenatide twice daily or liraglutide). Issues regarding the place of exenatide once weekly in T2DM pharmacotherapy are discussed.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Peptídeos/administração & dosagem , Peçonhas/administração & dosagem , Redução de Peso/efeitos dos fármacos , Glicemia/metabolismo , Preparações de Ação Retardada/administração & dosagem , Diabetes Mellitus Tipo 2/sangue , Diarreia/induzido quimicamente , Esquema de Medicação , Quimioterapia Combinada , Exenatida , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Injeções Subcutâneas , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Peptídeos/farmacocinética , Peptídeos/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Peçonhas/farmacocinética , Peçonhas/farmacologia , Vômito/induzido quimicamente
13.
Pulmonology ; 29(5): 385-391, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36964122

RESUMO

INTRODUCTION: Among adults, sleep apnea is more common in highlanders than in lowlanders. We evaluated the sleep apnea prevalence in children living at high altitude compared to age-matched low-altitude controls. METHODS: Healthy children, 7-14 y of age, living at 2500-3800m in the Tien Shan mountains, Kyrgyzstan, were prospectively studied in a health post at 3250m. Healthy controls of similar age living at 700-800m were studied in a University Hospital at 760m in Bishkek. Assessments included respiratory sleep studies scored according to pediatric standards, clinical examination, medical history, and the pediatric sleep questionnaire (PSQ, range 0 to 1 with increasing symptoms). RESULTS: In children living at high altitude (n = 37, 17 girls, median [quartiles] age 10.8y [9.6;13.0]), sleep studies revealed: mean nocturnal pulse oximetry 90% (89;91), oxygen desaturation index (ODI, >3% dips in pulse oximetry) 4.3/h (2.5;6.7), apnea/hypopnea index (AHI) total 1.7/h (1.0;3.6), central 1.6/h (1.0;3.3), PSQ 0.27 (0.18;0.45). In low-altitude controls (n=41, 17 girls, age 11.6y [9.5;13.0], between-groups comparison of age P=0.69) sleep studies revealed: pulse oximetry 97% (96;97), ODI 0.7/h (0.2;1.2), AHI total 0.4/h (0.1;1.0), central 0.3/h (0.1;0.7), PSQ 0.18 (0.14;0.31); P<0.05, all corresponding between-group comparisons. CONCLUSIONS: In school-age children living at high altitude, nocturnal oxygen saturation was lower, and the total and central AHI were higher compared to children living at low altitude. The greater score of sleep symptoms in children residing at high altitude suggests a potential clinical relevance of the nocturnal hypoxemia and subtle sleep-related breathing disturbances.


Assuntos
Altitude , Síndromes da Apneia do Sono , Adulto , Feminino , Humanos , Criança , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Sono , Oxigênio , Oximetria
14.
ESMO Open ; 8(6): 102050, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37976999

RESUMO

The JAVELIN Bladder 100 phase III trial led to the incorporation of avelumab first-line (1L) maintenance treatment into international guidelines as a standard of care for patients with advanced urothelial carcinoma (UC) without progression after 1L platinum-based chemotherapy. JAVELIN Bladder 100 showed that avelumab 1L maintenance significantly prolonged overall survival (OS) and progression-free survival in this population compared with a 'watch-and-wait' approach. The aim of this manuscript is to review clinical studies of avelumab 1L maintenance in patients with advanced UC, including long-term efficacy and safety data from JAVELIN Bladder 100, subgroup analyses in clinically relevant subpopulations, and 'real-world' data obtained outside of clinical trials, providing a comprehensive resource to support patient management. Extended follow-up from JAVELIN Bladder 100 has shown that avelumab provides a long-term efficacy benefit, with a median OS of 23.8 months measured from start of maintenance treatment, and 29.7 months measured from start of 1L chemotherapy. Longer OS was observed across subgroups, including patients who received 1L cisplatin + gemcitabine, patients who received four or six cycles of 1L chemotherapy, and patients with complete response, partial response, or stable disease as best response to 1L induction chemotherapy. No new safety signals were seen in patients who received ≥1 year of avelumab treatment, and toxicity was similar in those who had received cisplatin or carboplatin with gemcitabine. Other clinical datasets, including noninterventional studies conducted in Europe, USA, and Asia, have confirmed the efficacy of avelumab 1L maintenance. Potential subsequent treatment options after avelumab maintenance include antibody-drug conjugates (enfortumab vedotin or sacituzumab govitecan), erdafitinib in biomarker-selected patients, platinum rechallenge in suitable patients, nonplatinum chemotherapy, and clinical trial participation; however, evidence to determine optimal treatment sequences is needed. Ongoing trials of avelumab-based combination regimens as maintenance treatment have the potential to evolve the treatment landscape for patients with advanced UC.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Cisplatino , Carcinoma de Células de Transição/tratamento farmacológico , Gencitabina , Neoplasias da Bexiga Urinária/tratamento farmacológico , Desoxicitidina
15.
Endoscopy ; 44(2): 154-60, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22271026

RESUMO

BACKGROUND AND STUDY AIMS: Endoscopic submucosal injection of epinephrine may cause systemic effects on the cardiovascular system. The aim of this experimental study was to assess systemic hemodynamic changes after submucosal injection of epinephrine during upper gastrointestinal endoscopy in a porcine model. METHODS: Measurements were taken from 12 pigs under general anesthesia. During gastroscopy 5 mL of normal saline, and 2.5 mL and 5 mL of epinephrine (1:10,000) were injected into the submucosal layers of the gastric antrum, corpus, and distal esophagus. After each injection, the cardiac index and global end diastolic volume index (GEDVI, reflecting preload) were measured every 3 minutes by transpulmonary thermodilution for a minimum of 12 minutes. The following parameters were also recorded: heart rate, mean arterial pressure (MAP), and systemic vascular resistance index (SVRI, reflecting afterload). RESULTS: Significant hemodynamic changes were observed after submucosal injection of epinephrine into the esophagus, including heart rate (maximum + 4 %) and MAP (maximum - 4%) after injection of 2.5 mL epinephrine, and stronger changes in heart rate (maximum +13%), cardiac index (maximum +21%), MAP (maximum -4%), and SVRI (maximum -12%) after the injection of 5 mL epinephrine. After submucosal injection of epinephrine into the gastric antrum and corpus, hemodynamic effects were less evident. Here significant changes were observed in heart rate (maximum +3%), MAP (maximum -2%), cardiac index (maximum +7%), and SVRI (maximum -8%) only after the injection of 5 mL epinephrine into the antrum. CONCLUSION: Endoscopic submucosal injection of epinephrine is associated with changes in systemic hemodynamic parameters, especially when performed in the esophagus, and the procedure might therefore induce harmful side effects.


Assuntos
Epinefrina/farmacologia , Gastroscopia , Hemodinâmica/efeitos dos fármacos , Vasoconstritores/farmacologia , Animais , Relação Dose-Resposta a Droga , Epinefrina/administração & dosagem , Esôfago , Feminino , Mucosa Gástrica , Injeções , Estudos Prospectivos , Suínos , Vasoconstritores/administração & dosagem
16.
Colorectal Dis ; 14(10): 1276-86, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22309286

RESUMO

AIM: Immunosuppression and steroid medication have been identified as risk factors for complicated sigmoid diverticulitis. The underlying molecular mechanisms have not yet been elucidated. We hypothesized that glucocorticoid-induced tumour necrosis factor receptor (GITR) and matrix metalloproteinase-9 (MMP-9) might play a role. METHOD: GITR and MMP-9 were analysed at protein [immunohistochemistry/immunofluorescence (IF)] and messenger RNA level (real-time polymerase chain reaction) in surgical specimens with complicated and non-complicated diverticulitis (n=101). IF double staining and regression analysis were performed for both markers. GITR expression was correlated with clinical data and its usefulness as a diagnostic test was investigated. RESULTS: High GITR expression (≥41%) was observed in the inflammatory infiltrate in complicated diverticulitis, in contrast to non-complicated diverticulitis where GITR expression was low (P<0.001). High GITR expression was significantly associated with steroid use and pulmonary diseases (both P<0.001). MMP-9 expression correlated with GITR expression (R(2) =0.7268, P<0.0001, r=0.85) as demonstrated with IF double-staining experiments. Co-labelling of GITR with CD68, but not CD15, suggested that GITR-expressing cells in diverticulitis are macrophages. GITR expression was superior to C-reactive protein (CRP), white cell count and temperature in distinguishing complicated and non-complicated diverticulitis. CONCLUSIONS: Our results suggest that GITR expression in inflammatory cells might potentially indicate a molecular link between steroid use and complicated forms of acute sigmoid diverticulitis. Increased MMP-9 expression by GITR signalling might explain the morphological changes in the colonic wall of perforated and phlegmonous diverticulitis. Analysis of soluble GITR might be a promising strategy for future research.


Assuntos
Doença Diverticular do Colo/metabolismo , Proteína Relacionada a TNFR Induzida por Glucocorticoide/metabolismo , Imunossupressores/efeitos adversos , Metaloproteinase 9 da Matriz/metabolismo , Doenças do Colo Sigmoide/metabolismo , Esteroides/efeitos adversos , Idoso , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Doença Diverticular do Colo/induzido quimicamente , Doença Diverticular do Colo/complicações , Doença Diverticular do Colo/diagnóstico , Feminino , Fucosiltransferases/metabolismo , Humanos , Imuno-Histoquímica , Antígenos CD15/metabolismo , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Doenças do Colo Sigmoide/induzido quimicamente , Doenças do Colo Sigmoide/complicações , Doenças do Colo Sigmoide/diagnóstico
17.
Appl Microbiol Biotechnol ; 94(4): 931-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22258642

RESUMO

The influence of glucose release on growth and biotransformation of yeasts was examined by using the medium EnBase® Flo in shake flasks. The medium contains a polysaccharide acting as substrate, which is degraded to glucose by the addition of an enzyme. In the present paper, this medium was adapted for the cultivation of yeasts by increasing the complex components (booster) and the enzyme concentrations to guarantee a higher glucose release rate. Important changes were an increase of the complex component booster to 10-15% and an increased glucose release by increasing the enzyme content to 15 U L(-1). The 20 yeasts investigated in the present work showed an improvement of growth and biomass production when cultivated with the EnBase medium in comparison to yeast extract dextrose (YED) medium. Values of optical densities (OD(600)) of approximately 40 AU (corresponding to over 60 g L(-1) wet cell weight) were achieved for all 20 yeast strains tested. During the following screening of the yeasts in whole-cell biotransformation, an improvement of the conversion for 19 out of the 20 yeasts cultivated with the EnBase Flo medium could be observed. The biomass from the EnBase Flo cultivation showed a higher conversion activity in the reduction of 2-butanone to (R/S)-2-butanol. The enantioselectivity (ee) of 15 yeast strains showed an improvement by using the EnBase medium. The number of yeasts with an ee >97% increased from zero with YED to six with EnBase medium. Thus, the use of a glucose release cultivation strategy in the screening process for transformation approaches provides significant benefits compared to standard batch approaches.


Assuntos
Meios de Cultura/química , Enzimas/metabolismo , Glucose/análise , Programas de Rastreamento/métodos , Polissacarídeos/metabolismo , Leveduras/crescimento & desenvolvimento , Leveduras/metabolismo , Biocatálise , Biomassa , Biotransformação
18.
Bull Entomol Res ; 102(1): 17-28, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21749736

RESUMO

To date, a molecular phylogenetic approach has not been used to investigate the evolutionary structure of Trogoderma and closely related genera. Using two mitochondrial genes, Cytochrome Oxidase I and Cytochrome B, and the nuclear gene, 18S, the reported polyphyletic positioning of Trogoderma was examined. Paraphyly in Trogoderma was observed, with one Australian Trogoderma species reconciled as sister to all Dermestidae and the Anthrenocerus genus deeply nested within the Australian Trogoderma clade. In addition, time to most recent common ancestor for a number of Dermestidae was calculated. Based on these estimations, the Dermestidae origin exceeded 175 million years, placing the origins of this family in Pangaea.


Assuntos
Besouros/classificação , Besouros/genética , Animais , Austrália , Teorema de Bayes , Núcleo Celular/genética , Sequência Conservada , Citocromos b/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Evolução Molecular , Mitocôndrias/genética , Filogenia , Reação em Cadeia da Polimerase , RNA Ribossômico 18S/genética , Estações do Ano , Análise de Sequência de DNA
19.
Klin Padiatr ; 224(6): 382-5, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22915449

RESUMO

A child was admitted to our hospital for repair of a ventricular septal defect (VSD) characterized by a predominantly right-to-left shunt and a severe stenosis of the right ventricular outflow tract (Tetralogy of Fallot). Severe congenital anemia (hemoglobin 72 g/L), thrombocytopenia (42×G/L) and profound platelet dysfunction led a stem cell defect to be suspected. X-linked thrombocytopenia (GATA-1 mutation) was diagnosed. GATA-1 defect may complicate medical interventions due to excessive bleeding and partial or complete bone marrow failure. Maintaining a platelet count of 100 G/L and a maximal clot firmness (EXTEM-MCF) >50 mm allowed repair of the congenital heart defect without bleeding or hematological complications. Anemia and thrombocytopenia persisted after cardiac surgery, while the spontaneous bleeding tendency improved.


Assuntos
Anemia Diseritropoética Congênita/complicações , Anemia Diseritropoética Congênita/genética , Fator de Transcrição GATA1/genética , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/genética , Tetralogia de Fallot/complicações , Tetralogia de Fallot/genética , Tetralogia de Fallot/cirurgia , Trombocitopenia/complicações , Trombocitopenia/genética , Transcrição Gênica/genética , Áustria , Biópsia por Agulha , Medula Óssea/patologia , Criança , Seguimentos , Hemostasia Cirúrgica/métodos , Humanos , Masculino , Turismo Médico , Agulhas , Testes de Função Plaquetária , Cuidados Pós-Operatórios
20.
Int Endod J ; 45(12): 1156-64, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22712721

RESUMO

AIM: Adenoid cystic carcinoma (ACC) is a relatively rare epithelial tumour of the salivary glands in the maxillofacial region. About 40-60% of the patients develop distant metastases, which have been documented most commonly in the lung but also in brain, bone, liver, thyroid, spleen and pancreatic gland. SUMMARY: A 55-year-old women with intraosseous ACC in the mandible mimicking apical periodontitis following curative resection and radiotherapy is presented. Three years later, multiple lung metastases were observed followed by chemotherapy. Five years after curative resection, the patient presented simultaneously with new expansive soft tissue in the pancreas and mammary gland as well as in the kidney found to be metastatic ACC. No case has been reported to date on the manifestation of distant metastases of intraosseous ACC in the breast and the kidney as described by these observations. Metastatic mammary gland ACC stained positive for epithelial growth factor receptor (EGFR) but was negative for HER-2/neu and Cyclooxygenase-2 (COX-2) expression.


Assuntos
Perda do Osso Alveolar/diagnóstico , Carcinoma Adenoide Cístico/secundário , Erros de Diagnóstico , Neoplasias Mandibulares/patologia , Periodontite Periapical/diagnóstico , Neoplasias das Glândulas Salivares/patologia , Perda do Osso Alveolar/etiologia , Neoplasias da Mama/secundário , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Ciclo-Oxigenase 2/biossíntese , Diagnóstico Diferencial , Fator de Crescimento Epidérmico/química , Feminino , Humanos , Oxigenoterapia Hiperbárica , Neoplasias Renais/secundário , Neoplasias Mandibulares/cirurgia , Pessoa de Meia-Idade , Osteomielite/diagnóstico , Osteomielite/terapia , Neoplasias Pancreáticas/secundário , Receptor ErbB-2/análise , Neoplasias das Glândulas Salivares/cirurgia
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