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1.
Head Neck ; 46(6): 1280-1293, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38562045

RESUMO

BACKGROUND: Although flexible laryngoscopy (FL) is the reference modality for diagnosing vocal cord paralysis (VCP), FL involves patient discomfort and insertion intolerance. Dynamic digital radiography (DDR) with high spatial and temporal resolution is easier to use and less invasive when evaluating VCP. METHODS: Seventy-eight patients underwent FL and DDR before and after neck surgery. Qualitative and quantitative vocal cord movement (VCM) evaluations were conducted. Patients with postoperative VCP were followed-up regularly. RESULTS: DDR exhibited diagnostic performance with 67% sensitivity and 100% specificity. The cutoff for VCM was 2.4 mm, with DDR exhibiting 100% sensitivity and 78% specificity. All cords with transient VCP had positive VCM at both 3 weeks and 2 months. Additionally, 50% and 75% of cords with permanent VCP had negative VCM at 3 weeks and 2 months, respectively. CONCLUSIONS: DDR is promising for the diagnosis of postoperative VCP and early prediction of permanent postoperative VCP.


Assuntos
Laringoscopia , Paralisia das Pregas Vocais , Humanos , Paralisia das Pregas Vocais/diagnóstico por imagem , Paralisia das Pregas Vocais/etiologia , Paralisia das Pregas Vocais/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Adulto , Prognóstico , Sensibilidade e Especificidade , Intensificação de Imagem Radiográfica/métodos , Idoso de 80 Anos ou mais
2.
Clin Case Rep ; 10(7): e6124, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35898737

RESUMO

Dynamic digital radiography (DDR) is a motion-detecting technique with high temporal resolution. Flexible laryngoscopy is a common modality for the observation of the larynx; however, it generates aerosol. DDR is an easy and less risky screening test for the diagnosis of recurrent laryngeal nerve paralysis during the COVID-19 pandemic.

3.
Anat Sci Int ; 97(4): 347-357, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35113344

RESUMO

Tissue-hardening effect and health-hazard issue of formaldehyde (FA) have long been a great disadvantage of this conventional fixative in anatomical research. We recently developed a FA-free embalming method for cadavers which utilizes N-vinyl-2-pyrrolidone (NVP) and enables assessment of motion kinetics by maintaining the softness of embalmed tissue. By assessing the feasibility of NVP-embalmed tissue to mimic vocalization, this study aimed to prove the potential of embalmed cadavers, which have previously been used only for the understanding of anatomical morphology, for the assessment of precise motion physiology in the human body. Ten cadavers embalmed in NVP (n = 6) and FA (n = 4) were incorporated in this study. Excised larynges underwent experimental phonation to mimic vocalization with fast and pliable vibration of vocal folds. High-speed digital imaging was utilized for the assessment of vocal fold vibration. Furthermore, acoustic analysis of the voiced sound, and reproducibility examination were also performed. Regular vocal fold vibrations successfully produced voiced sounds during experimental phonation using NVP-embalmed larynges. The vibratory frequency, vibration amplitude, and stretch rate of the vocal folds were comparable to those of living humans. Six months after the first experiment, the vocal parameters were reproduced, to suggest the long-term preservation potential of our NVP-embalming technique. On the other hand, neither voiced sound nor vocal fold vibration were observed in FA-embalmed larynges. This novel embalming technique could pioneer the next era to utilize embalmed cadavers for the examination of motion physiology in the human body.


Assuntos
Laringe , Prega Vocal , Cadáver , Embalsamamento , Humanos , Pirrolidinonas , Reprodutibilidade dos Testes , Vibração , Prega Vocal/fisiologia
5.
Laryngoscope Investig Otolaryngol ; 6(2): 252-260, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33869757

RESUMO

OBJECTIVES: Recent technology manufactured a nasopharyngeal videoscope with pistol-shaped grip (PG). This study aimed to assess the ergonomic feasibility of this novel device in daily ENT practice. METHODS: To assess the ergonomic impact of grip shape on ENT physicians, conventional grip videoscope (CG) and PG were utilized in this study. Surface electromyography (sEMG) was recorded to assess the muscle activity in the upper limb during endoscopy on a training model. Bilateral sEMG recordings were performed including thenar muscle, pronator teres muscle, brachioradialis muscle, and biceps brachii muscle. Mean value of the mean sEMG amplitude throughout the task in triplicated examinations (mMA) with each electrode, total values of four mMAs in both of the grip-side and the insertion tube-side limb muscles, and total value of all eight mMAs were calculated, and compared between CG and PG. Subgroup analyses were also performed in the experienced ENT physicians and the residents. RESULTS: PG provided significantly lower mMA values in thenar muscle and brachioradialis muscle of the grip-side limb compared with CG. Total value of four mMAs in PG was significantly lower compared with that in CG in the grip-side limb, and total value of all eight mMAs in PG was significantly lower compared with that in CG. Furthermore, total value of four mMAs in PG was significantly lower compared with that in CG in the grip-side limb, in both of the subgroups. CONCLUSION: This is the first study to support the idea that the newly designed pistol-grip endoscope may have an ergonomic advantage over conventional endoscope for otolaryngologists in daily practice. LEVEL OF EVIDENCE: 4.

6.
Am J Otolaryngol ; 41(6): 102727, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32979665

RESUMO

PURPOSE: In cases of unilateral vocal fold paralysis (UVFP), voice disorders caused by glottic insufficiency can lead to a considerable reduction in the patient's quality of life. Voice therapy (VT) is an effective treatment that must be started early after the onset of vocal fold paralysis. This study examined the effect of early VT for patients with UVFP occurring after esophagectomy. MATERIALS AND METHODS: Patients who had residual UVFP at 1 month postoperatively after esophagectomy for esophageal cancer between November 2014 and March 2017 were evaluated. Seventeen patients were divided into the VT group (n = 6) and non-VT group (n = 11). We compared these two groups and retrospectively examined the effect of early VT. The study endpoints included aerodynamic tests, laryngeal endoscopy, laryngeal stroboscopy, and glottal closure. All of these evaluations were performed at preoperatively and at 1 and 3 months postoperatively. RESULTS: Subglottal pressure reduced notably in the VT group, and both the mean flow rate and maximum phonation time tended to improve after VT. Conversely, there were no significant differences in MFR and MPT in the non-VT group. Furthermore, although UVFP remained after VT, we achieved glottal closure for all three patients. Conversely, only two of the six patients with glottic insufficiency in the non-VT group achieved glottal closure. CONCLUSION: VT may be effective for improving impaired vocal function in patients with UVFP. It is reasonable to expect that VT can be initiated 1 month after the onset of vocal fold paralysis.


Assuntos
Glote/fisiopatologia , Complicações Pós-Operatórias/terapia , Pressão , Paralisia das Pregas Vocais/terapia , Treinamento da Voz , Idoso , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fonação , Complicações Pós-Operatórias/etiologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Tempo , Paralisia das Pregas Vocais/diagnóstico , Paralisia das Pregas Vocais/etiologia , Paralisia das Pregas Vocais/fisiopatologia
7.
Gan To Kagaku Ryoho ; 47(4): 709-711, 2020 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-32389992

RESUMO

The present case pertained to a 70-year-old woman. The fecal occult blood test was positive. Colonoscopyrevealed rectal cancer. She underwent the first operation of low anterior resection. Pathological diagnosis was carcinoid, se, ly2, v0, n1. Approximately2 months later, multiple liver metastases were found. Because of strong enhancement at angiography, transarterial chemoembolization(TACE)was selected. After 3 rounds of TACE, we operated the residual liver metastasis approximately1 year and 7 months after the first operation. However, approximately8 years and 9 months after the first operation, multiple liver metastases were found again. Hepatic arterial infusion(HAI)was chosen because tumors showed weak en- hancement on CT. First, we tried high-dose HAI(5-FU 1 g/dayat 1-3 and 5-7, amount: 6 g/week), and liver metastases was almost in CR. However, extrahepatic metastasis was found on PET-CT. Because of rapid growth, we operated the growing lymph node. Pathological diagnosis was diffuse large-cell type B-cell malignant lymphoma. Thus, we extended the interval of HAI(weekly, biweekly, and monthly)and simultaneously4 courses of R-THP-COP(R: rituximab, THP: pirarubicin, C: cyclophosphamide, O: vincristine, P: prednisolone)therapyfor malignant lymphoma was administered. She is now an outpatient. Liver metastases continue to be in CR at approximately1 year and the IL-2R value is almost within normal range.


Assuntos
Tumor Carcinoide , Quimioembolização Terapêutica , Neoplasias Hepáticas , Linfoma , Neoplasias Retais , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Tumor Carcinoide/secundário , Tumor Carcinoide/terapia , Feminino , Fluoruracila , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Linfoma/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Retais/terapia
8.
Nat Commun ; 11(1): 2362, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398673

RESUMO

Due to their bacterial ancestry, many components of mitochondria share structural similarities with bacteria. Release of molecular danger signals from injured cell mitochondria (mitochondria-derived damage-associated molecular patterns, mito-DAMPs) triggers a potent inflammatory response, but their role in fibrosis is unknown. Using liver fibrosis resistant/susceptible mouse strain system, we demonstrate that mito-DAMPs released from injured hepatocyte mitochondria (with mtDNA as major active component) directly activate hepatic stellate cells, the fibrogenic cell in the liver, and drive liver scarring. The release of mito-DAMPs is controlled by efferocytosis of dying hepatocytes by phagocytic resident liver macrophages and infiltrating Gr-1(+) myeloid cells. Circulating mito-DAMPs are markedly increased in human patients with non-alcoholic steatohepatitis (NASH) and significant liver fibrosis. Our study identifies specific pathway driving liver fibrosis, with important diagnostic and therapeutic implications. Targeting mito-DAMP release from hepatocytes and/or modulating the phagocytic function of macrophages represents a promising antifibrotic strategy.


Assuntos
Alarminas/imunologia , Células Estreladas do Fígado/imunologia , Hepatócitos/metabolismo , Cirrose Hepática/imunologia , Hepatopatia Gordurosa não Alcoólica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alarminas/metabolismo , Animais , Apoptose/imunologia , Modelos Animais de Doenças , Progressão da Doença , Feminino , Hepatócitos/citologia , Hepatócitos/imunologia , Humanos , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Macrófagos/imunologia , Masculino , Camundongos , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/imunologia , Fagocitose/imunologia , Tioacetamida/toxicidade , Adulto Jovem
9.
Chem Res Toxicol ; 33(1): 154-161, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31461269

RESUMO

Despite the recent advances in the life sciences and the remarkable investment in drug discovery research, the success rate of small-molecule drug development remains low. Safety is the second most influential factor of drug attrition in clinical studies; thus, the selection of compounds with fewer toxicity concerns is crucial to increase the success rate of drug discovery. Compounds that promiscuously bind to multiple targets are likely to cause unexpected pharmacological activity that may lead to adverse effects. Therefore, avoiding such compounds during early research stages would contribute to identifying compounds with a higher chance of success in the clinic. To evaluate the interaction profile against a wide variety of targets, we constructed a small-scale promiscuity panel (PP) consisting of eight targets (ROCK1, PDE4D2, GR, PPARγ, 5-HT2B, adenosine A3, M1, and GABAA) that were selected from diverse gene families. The validity of this panel was confirmed by comparison with the promiscuity index evaluated from larger-scale panels. Analysis of data from the PP revealed that both lipophilicity and basicity are likely to increase promiscuity, while the molecular weight does not significantly contribute. Additionally, the promiscuity assessed using our PP correlated with the occurrence of both in vitro cytotoxicity and in vivo toxicity, suggesting that the PP is useful to identify compounds with fewer toxicity concerns. In summary, this small-scale and cost-effective PP can contribute to the identification of safer compounds that would lead to a reduction in drug attrition due to safety issues.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Animais , Sobrevivência Celular , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Células Hep G2 , Humanos , Camundongos , PPAR gama/genética , Ratos , Receptor A3 de Adenosina/genética , Receptor Muscarínico M1/genética , Receptor 5-HT2B de Serotonina/genética , Receptores de GABA-A/genética , Receptores de Glucocorticoides/genética , Quinases Associadas a rho/genética
10.
Gan To Kagaku Ryoho ; 47(13): 2317-2319, 2020 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-33468946

RESUMO

An 89-year-old woman with complete blindness presented with a right lower abdominal tumor and weight loss. The CT scan showed a huge mass approximately 9 cm in diameter in the ileocecum, invading the right urinary tract and right iliac artery and vein. Findings of the TCS biopsy led to the suspicion of ileocecal carcinoid. Another punch biopsy specimen acquired under general anesthesia indicated mucinous cell carcinoma. When she suffered from right leg pain approximately 3 months later, we provided radiation therapy(50 Gy)because of intolerance to UFT. Consequently, pain disappeared, and the tumor size decreased significantly. We administered TS-1 but discontinued it because of intolerance. Further, 2.8 years after the first medical examination, the tumor recurred, and she developed ileus. We performed ileocolectomy, and pathological findings indicated that the adenocarcinoma in the appendix had progressed from goblet cell carcinoid(sig, si[right ovary], ly1b, v1a, n0). Four years after the first medical examination, CEA had elevated rapidly, and lung metastases were found. She died approximately 4.2 years after the first medical examination. The last measured CEA level had been 596.7 ng/mL. Starting from the lowest level at the first examination, the CEA level had slowly elevated until before the operation and rapidly elevated postoperatively. Immunopathological findings showed that the operated specimen stained diffusely for CEA, without any mucinous component. We suspected that radiation therapy modified goblet cell carcinoid to adenocarcinoma.


Assuntos
Neoplasias Abdominais , Adenocarcinoma , Neoplasias do Apêndice , Tumor Carcinoide , Hidronefrose , Adenocarcinoma/complicações , Idoso de 80 Anos ou mais , Neoplasias do Apêndice/complicações , Neoplasias do Apêndice/cirurgia , Tumor Carcinoide/complicações , Feminino , Humanos , Hidronefrose/etiologia , Recidiva Local de Neoplasia
11.
J Med Chem ; 62(20): 9175-9187, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31550153

RESUMO

Dysferlinopathies, which are muscular diseases caused by mutations in the dysferlin gene, remain serious medical problems due to the lack of therapeutic agents. Herein, we report the design, synthesis, and structure-activity relationships of a 2,6-disubstituted 3H-imidazo[4,5-b]pyridine series, which was identified from the phenotypic screening of chemicals that increase the level of dysferlin in myocytes differentiated from patient-derived induced pluripotent stem cells (iPSCs). Optimization studies with cell-based phenotypic assay led to the identification of a highly potent compound, 19, with dysferlin elevation effects at double-digit nanomolar concentrations. In addition, the molecular target of our chemical series was identified as tubulin, through a tubulin polymerization assay and a competitive binding assay using a photoaffinity labeling probe.


Assuntos
Imidazóis/química , Distrofia Muscular do Cíngulo dos Membros/tratamento farmacológico , Piridinas/química , Moduladores de Tubulina/uso terapêutico , Sítios de Ligação , Diferenciação Celular , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Disferlina/metabolismo , Células Hep G2 , Humanos , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Simulação de Acoplamento Molecular , Distrofia Muscular do Cíngulo dos Membros/patologia , Proteína MyoD/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Estrutura Terciária de Proteína , Piridinas/farmacologia , Piridinas/uso terapêutico , Relação Estrutura-Atividade , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologia
12.
Eur Arch Otorhinolaryngol ; 276(11): 3159-3164, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31485732

RESUMO

PURPOSE: Ultra-high-resolution computed tomography (UHRCT) is an emerging imaging technology that is able to achieve simultaneous 160 slices with super-thin 0.25 mm thickness. The purpose of this study was to assess the feasibility of UHRCT to visualize laryngeal structure and kinetics. METHODS: Three normal volunteers and three patients with unilateral vocal fold paralysis (UVFP) were incorporated in this case series. First, images were taken under five conditions in normal volunteers. Five tasks consisted of (1) air inspiration through the nose (IN), (2) breath holding (BH), (3) sustained vowel /i:/ phonation (IP), (4) humming phonation (HP), and (5) forced glottic closure during exhalation (FC). Three-dimensional CT images of arytenoid and cricoid cartilages, as well as virtual laryngoscopic images, were reconstructed using UHRCT data. Reconstructed images were compared among five conditions to assess the best tasks to picture laryngeal kinetics. Second, pre- and post-phonosurgical images were examined in UVFP patients to evaluate potential role of UHRCT to assess laryngeal pathology in hoarse patients. RESULTS: Among the five conditions, IN and IP conditions were considered suitable to visualize laryngeal structure at rest and during phonation, respectively. Kinetic abnormalities including asymmetric motion of arytenoid cartilages were elucidated in UVFP patients, and virtual endoscopy visualized the clinically invisible posterior three-dimensional glottic chinks. Furthermore, UHRCT was useful to understand changes in laryngeal structure achieved by phonosurgery. CONCLUSIONS: UHRCT is an emerging imaging technology that can be used for minimally invasive visualization and assessment of laryngeal structure and kinetics. Future studies to assess more number of patients with laryngeal dysfunction are warranted.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Laringe , Tomografia Computadorizada Multidetectores/métodos , Paralisia das Pregas Vocais , Adulto , Cartilagem Aritenoide/diagnóstico por imagem , Feminino , Humanos , Cinética , Laringoplastia/métodos , Laringoscopia/métodos , Laringe/diagnóstico por imagem , Laringe/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fonação/fisiologia , Reprodutibilidade dos Testes , Paralisia das Pregas Vocais/diagnóstico , Paralisia das Pregas Vocais/fisiopatologia , Paralisia das Pregas Vocais/cirurgia
13.
Toxicol Sci ; 170(1): 223-233, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31020312

RESUMO

Accumulation of toxic endogenous and/or exogenous substances can trigger tissue injury. Multidrug and toxin extrusion proteins (MATEs) are transporters at renal proximal tubules involved in the secretion of hydrophilic substances into urine. Multidrug and toxin extrusion protein inhibition can lead to nephrotoxicity via accumulation of toxic substances; however, case studies demonstrating causality are rare, except for drug-drug interaction studies. To explore the involvement of MATE inhibition in nephrotoxicity, MATE1 inhibition, cytotoxicity, and mitochondrial toxicity (MT) of 38 in-house compounds that showed toxicity were assessed in in vivo safety evaluations using rats, dogs, and monkeys and compared considering unbound exposures at minimal steady-state concentration (C24h,u) between nephrotoxicity positive and negative compounds. Logarithmic-corrected means of C24h,u normalized by MATE1 IC50 or cytotoxicity EC50 (C24h,u/IC50 and C24h,u/EC50) were higher for nephrotoxic compounds. An exposure cutoff of C24h,u/IC50 > 0.01 filtered nephrotoxicity with a 54% positive predictive value. Of 7 cases filtered with this cutoff, all the cases showed pathological changes at renal proximal tubules expressing MATE1. Furthermore, all cases with > 0.01 reliable exposure for MATE1 inhibition and cytotoxicity exhibited nephrotoxicity. Although compounds potent for MATE1 inhibition and cytotoxicity without and with MT (potentials of 10, 30, and 40 µM, respectively) were correctly classified as nephrotoxic by evaluation of in vitro potency alone, without considering exposures, these results suggest that MATE1 inhibition potency and cytotoxicity can be used to assess nephrotoxicity, especially at proximal tubules, and could be used for safety assessment in early drug discovery.


Assuntos
Descoberta de Drogas/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Rim/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Animais , Sobrevivência Celular/efeitos dos fármacos , Simulação por Computador , Cães , Avaliação Pré-Clínica de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Haplorrinos , Células Hep G2 , Humanos , Rim/metabolismo , Rim/patologia , Células Madin Darby de Rim Canino , Proteínas de Transporte de Cátions Orgânicos/genética , Preparações Farmacêuticas/administração & dosagem , Ratos , Toxicocinética , Transfecção
14.
Gan To Kagaku Ryoho ; 45(1): 127-129, 2018 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-29362330

RESUMO

We treated 2 cases ofcolon metastasis ofgastric cancer considered to be caused by different pathway. Case 1 was a 55- year-old male with gastric cancer associated with metastases for lymph node, gallbladder, and liver. Curative surgical treatment of distal gastrectomy, partial hepatectomy, cholecystectomy and lymph node dissection was performed. The final find- ing was, L, Less, Type 3, pT4b(GB), tub2, pN3a(10/20), sP0, CY0, pH1, pM1, Stage IV , R0. Ten months after, ileocecal resection was performed, as a tumor was detected in the cecum. It was a submucosal tumor of well to moderately differentiated adenocarcinoma, and diagnosed as a metastasis ofgastric cancer. Case 2 was a 59-year-old male who received total gastrectomy. The final finding was UE, Less, Type 4, tub2-por2, pT4a, pN2(5/19), cM0, sP0, CY0, Stage III B, R1. One year and 10 months later, unevenness and redness in the mucosal membrane ofthe transverse colon occurred. Signet-ring cells were observed by the endoscopic biopsy, and colon metastasis ofstomach cancer was diagnosed. Consequently, transverse colectomy was performed. Diffused invasion of cancer cells was observed in all layers of the wall, which was considered as metastasis via gastrocolic ligament. Although colon metastasis ofstomach cancer is rare, its pathway varies, such as infiltration, direct invasion, hematogenous, and lymphogenous. Form oflesion also varies. For diagnosis ofcolon lesion occurring during follow-up after gastric cancer, these points should be noted.


Assuntos
Neoplasias do Colo/cirurgia , Neoplasias Gástricas/patologia , Biópsia , Quimioterapia Adjuvante , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Neoplasias do Colo/secundário , Evolução Fatal , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/cirurgia
15.
J Pharmacol Toxicol Methods ; 88(Pt 1): 46-55, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28688881

RESUMO

In vivo phototoxicity studies are important to predict drug-induced phototoxicity in humans; however, a standard methodology has not established. To determine differences in sensitivity to drug-induced phototoxicity among various skin sites, we evaluated phototoxic reactions in the back and abdominal skin of female Sprague-Dawley rats orally dosed with phototoxic drugs (pirfenidone, 8-methoxysoraren, doxycycline, and lomefloxacin) or a non-phototoxic drug (gatifloxacin) followed by solar-simulated light irradiation comprising 18J/cm2 ultraviolet A. Tissue reactions were evaluated by macroscopic and microscopic examination and immunohistochemistry for γ-H2AX, and tissue concentrations of pirfenidone, doxycycline, and lomefloxacin were measured by tandem mass spectrometry. In addition, the thicknesses of the skin layers at both sites were measured in drug-naïve rats. The abdominal skin showed more severe reactions to all phototoxic drugs than the back skin, whereas the minimal erythema dose in drug-naïve rats and skin concentrations of each drug were comparable between the sites. Furthermore, histopathological lesions and γ-H2AX-positive cells in the abdominal skin were detected in deeper layers than in the back skin. The stratum corneum and dermis in the abdominal skin were significantly thinner than in the back skin, indicating a difference in the depth of light penetration and potentially contributing to the site differences observed in sensitivity to phototoxicity. Gatifloxacin did not induce any phototoxic reactions at either site. In conclusion, the abdominal skin is more sensitive to drug-induced phototoxicity than the back skin and may represent a preferable site for irradiation in this rat phototoxicity model.


Assuntos
Abdome/patologia , Dorso/patologia , Dermatite Fototóxica/patologia , Pele/patologia , Luz Solar/efeitos adversos , Testes de Toxicidade Aguda/métodos , Abdome/efeitos da radiação , Administração Oral , Animais , Dorso/efeitos da radiação , Dermatite Fototóxica/etiologia , Modelos Animais de Doenças , Doxiciclina/farmacologia , Feminino , Fluoroquinolonas/farmacologia , Gatifloxacina , Histonas/metabolismo , Metoxaleno/farmacologia , Fosfoproteínas/metabolismo , Piridonas/farmacologia , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Pele/efeitos da radiação , Espectrometria de Massas em Tandem , Testes de Toxicidade Aguda/instrumentação
16.
Dysphagia ; 32(4): 520-525, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28439670

RESUMO

Esophagectomy for esophageal cancer is invasive thoracic surgery with a high incidence rate of postoperative complications and prolongation of hospitalization, even if the standardized clinical pathway improves the outcome (mortality and morbidity). Postoperative recurrent nerve paralysis (RNP) is related to respiratory complications concomitant with prolonged hospitalization. However, it has not been elucidated which factors affect the incidence and recovery of RNP. To detect the predictive factor for postoperative RNP, we focused on preoperative serum albumin. Patients who had esophageal cancer with standard esophagectomy were evaluated. In total, 94 patients were divided into three groups depending on the presence of RNP (46 in patients without RNP, 29 in those with transient RNP who recovered within 6 months follow-up and 19 in those with residual RNP). We retrospectively investigated factors associated with residual RNP. Preoperative lower serum albumin was associated with residual RNP. In addition, days to the resumption of oral intake and duration of stay in the hospita postoperatively were delayed in the group of residual RNP. Multiple regression analysis indicated that preoperative serum albumin was a predictive factor for residual RNP. Preoperative lower serum albumin level might be linked to residual RNP which could prolong the resumption of postoperative oral intake and shorten the period of stay at the hospital after esophagectomy, leading to unfavorable outcomes for patients.


Assuntos
Doenças dos Nervos Cranianos/etiologia , Neoplasias Esofágicas/sangue , Esofagectomia/efeitos adversos , Paralisia/etiologia , Complicações Pós-Operatórias/etiologia , Nervo Laríngeo Recorrente , Albumina Sérica/análise , Idoso , Doenças dos Nervos Cranianos/epidemiologia , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Paralisia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Período Pré-Operatório , Estudos Retrospectivos
17.
Gan To Kagaku Ryoho ; 44(12): 1535-1537, 2017 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-29394693

RESUMO

We report a CR case of huge ovarian cancer with peritoneal and liver metastases who was operated bilateral ovaries, uterus and peritoneal metastases at first, followed by systemic chemotherapy and performed 4 times of radiofrequency ablation (RFA)and 2 times of liver resection(LR). The case was a 50-year-old woman. She suffered with bowel enlargement from over 1 year ago. Preoperative MRI finding was huge ovarian serous cyst with partial solid tumor inside. The major axis was about 30 cm. CA125 and CA19-9 levels were elevated. Tumor reduction surgery was performed with bilateral salpingooophorectomy and hysterectomy with resecting peritoneal metastatic lesions. Postoperative systemic chemotherapy(carbo- platin 550mg/day 1 plus paclitaxel 130mg/day 1, 8, 15)(CBDCA plus PTX)were performed amount 6 courses. Unfortu- nately liver metastases at S3, S4, S6, S7 and S8/5 appeared about 7months after operation.We restarted the CBDCA plus PTX therapy from 15 months after operation when the tumor maker elevated. After 18 courses of CBDCA plus PTX therapy liver metastases remained only at S3. But gradually tumors grew up and size of tumors increased in spite of 3 more courses of CBDCA plus PTX therapy. So we challenged 2 times of RFA at S8/5 metastases that grew most rapidly and the values of increasing tumor makers stopped elevating. Then we performed LR at S3 and S4 metastases and the values of tumor makers returned to the normal level. But next S6 and S7 metastases appeared, we chose the RFA at first. At last recurrence of S7 was resected and all of liver metastases were treated. We checked no peritoneal metastases twice at the time of operation. The values of tumor makers became the normal level. Now she is alive well without metastases over 6 years after first operation. RFA and LR were effective at liver metastases from ovarian cancer that became resistant to systemic chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas , Neoplasias Ovarianas/patologia , Carboplatina/administração & dosagem , Ablação por Cateter , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Paclitaxel/administração & dosagem
18.
Biomarkers ; 21(4): 353-62, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26901698

RESUMO

CONTEXT: Plasma liver-specific mRNAs are useful biomarkers of hepatotoxicity in rats. OBJECTIVE: To investigate the potential application of liver-specific mRNAs as biomarkers for liver injury in humans. METHODS: We determined the plasma levels of liver-specific mRNAs by real-time qRT-PCR in healthy donors and patients with liver injury. RESULTS: Plasma levels of albumin (ALB) and apolipoprotein H (APOH) mRNAs increased in patients with elevated serum alanine aminotransferase. These mRNAs also increased in plasma after transcatheter arterial chemoembolization, which induces specific injury to liver. CONCLUSIONS: We demonstrated the potential application of plasma ALB and APOH mRNAs as clinical biomarkers for liver injury.


Assuntos
Biomarcadores/metabolismo , Fígado/lesões , RNA Mensageiro/genética , Albumina Sérica/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Ferimentos e Lesões/sangue
19.
Gan To Kagaku Ryoho ; 43(12): 2353-2355, 2016 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-28133319

RESUMO

The patient was a 73-year-old woman who underwent distalpancreatectomy for pancreas tailcancer (T3, N0, M0, stage III ). Hepatic arterialinfusion(HAI)using high-dose 5-fluorouracil(5-FU)(6,000mg/week)was performed 35 days after curative resection to prevent liver metastases. Although chemotherapy with gemcitabine(GEM)was administered for 2 weeks, the patient was aware of a nodule(1 cm in diameter)on the right lower quadrant of the abdomen. Resection of the cutaneous mass was performed and histological findings revealed metastatic adenocarcinoma from the pancreas cancer. Six courses of chemotherapy with GEM were administered as adjuvant therapy. Two years after the treatment with GEM, neurological symptoms appeared, and computed tomography(CT)and magnetic resonance imaging(MRI)revealed a solitary metastatic thalamus tumor(2 cm in diameter). After stereotactic radiotherapy, the patient was transferred to a different hospitalfor physicaltherapy. Herein, we report on a case of 2 year recurrence free survivalafter the resection of a cutaneous metastasis from pancreatic cancer.


Assuntos
Adenocarcinoma/secundário , Adenocarcinoma/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Neoplasias Cutâneas/secundário , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Humanos , Recidiva , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/cirurgia , Tálamo/patologia , Fatores de Tempo , Gencitabina
20.
Nihon Jibiinkoka Gakkai Kaiho ; 118(5): 643-50, 2015 May.
Artigo em Japonês | MEDLINE | ID: mdl-26349276

RESUMO

We retrospectively examined the records of patients treated for cervical tuberculous lymphadenitis in our department and analyzed the effectiveness of the various diagnostic methods. From January 2006 to December 2013, we treated 19 cases of cervical tuberculous lymphadenitis. The ages of patients with cervical tuberculous lymphadenitis ranged from 28 to 87 years old (mean, 61.4 years), and the male-to-female ratio was 8: 11. Two of the 19 patients with cervical tuberculous lymphadenitis presented with the comorbid condition of pulmonary tuberculosis. The sensitivity of cytological examination, smears, cultures and PCR (polymerase chain reaction) technique using an aspiration procedure for cervical tuberculous lymphadenitis were 13.3%, 50%, 60% and 71.4%, respectively: Although the detection ratio of fine needle aspiration cytology alone was low, the aspiration procedure could permit a definitive diagnosis by a combination of smear, culture and PCR. The QuantiFERON test (QFT) was positive in seven of seven cases, and T-SPOT was positive in two of two cases. Thus, QFT and T-SPOT were useful as aids in the diagnosis of cervical tuberculous lymphadenitis. For early diagnosis of cervical tuberculous lymphadenitis, it is important to consider a combined multimodal approach.


Assuntos
Pescoço/patologia , Tuberculose dos Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Diagnóstico Precoce , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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