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1.
Rom J Intern Med ; 59(2): 166-173, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33826812

RESUMO

Introduction. An on-going coronavirus disease 2019 (COVID-19) has become a challenge all over the world. Since an endoscopy unit and its staff are at potentially high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we conducted a survey for the management of the gastrointestinal endoscopic practice, personal protective equipment (PPE), and risk assessment for COVID-19 during the pandemic at multiple facilities.Methods. The 11-item survey questionnaire was sent to representative respondent of Department of Gastroenterology, Osaka City University Hospital, and its 19 related facilities.Results. A total of 18 facilities submitted valid responses and a total of 373 health care professionals (HCPs) participated. All facilities (18/18: 100%) were screening patients at risk for SARS-CoV-2 infection before endoscopy. During the pandemic, we found that the total volume of endoscopic procedures decreased by 44%. Eleven facilities (11/18: 61%) followed recommendations of the Japan Gastroenterological Endoscopy Society (JGES); consequently, about 35%-50% of esophagogastroduodenoscopy and colonoscopy were canceled. Mask (surgical mask or N95 mask), face shield/goggle, gloves (one or two sets), and gown (with long or short sleeves) were being used by endoscopists, nurses, endoscopy technicians, and endoscope cleaning staff in all the facilities (18/18: 100%). SARS-CoV-2 infection risk assessment of HCPs was conducted daily in all the facilities (18/18: 100%), resulting in no subsequent SARS-CoV-2 infection in HCPs.Conclusion. COVID-19 has had a dramatic impact on the gastrointestinal endoscopic practice. The recommendations of the JGES were appropriate as preventive measures for the SARSCoV-2 infection in the endoscopy unit and its staff.


Assuntos
COVID-19 , Endoscopia Gastrointestinal , Controle de Infecções , Exposição Ocupacional/prevenção & controle , Medição de Risco , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/transmissão , Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/normas , Pesquisas sobre Atenção à Saúde , Humanos , Controle de Infecções/instrumentação , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Japão/epidemiologia , Equipamento de Proteção Individual/classificação , Equipamento de Proteção Individual/normas , Equipamento de Proteção Individual/provisão & distribuição , SARS-CoV-2 , Gestão da Segurança/tendências
2.
Cancer Discov ; 11(1): 158-175, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32847940

RESUMO

Agonistic antibodies targeting CD137 have been clinically unsuccessful due to systemic toxicity. Because conferring tumor selectivity through tumor-associated antigen limits its clinical use to cancers that highly express such antigens, we exploited extracellular adenosine triphosphate (exATP), which is a hallmark of the tumor microenvironment and highly elevated in solid tumors, as a broadly tumor-selective switch. We generated a novel anti-CD137 switch antibody, STA551, which exerts agonistic activity only in the presence of exATP. STA551 demonstrated potent and broad antitumor efficacy against all mouse and human tumors tested and a wide therapeutic window without systemic immune activation in mice. STA551 was well tolerated even at 150 mg/kg/week in cynomolgus monkeys. These results provide a strong rationale for the clinical testing of STA551 against a broad variety of cancers regardless of antigen expression, and for the further application of this novel platform to other targets in cancer therapy. SIGNIFICANCE: Reported CD137 agonists suffer from either systemic toxicity or limited efficacy against antigen-specific cancers. STA551, an antibody designed to agonize CD137 only in the presence of extracellular ATP, inhibited tumor growth in a broad variety of cancer models without any systemic toxicity or dependence on antigen expression.See related commentary by Keenan and Fong, p. 20.This article is highlighted in the In This Issue feature, p. 1.


Assuntos
Trifosfato de Adenosina , Neoplasias , Animais , Anticorpos Monoclonais/farmacologia , Antígenos de Neoplasias , Imunoterapia , Camundongos , Neoplasias/tratamento farmacológico , Microambiente Tumoral , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral
3.
J Med Econ ; 20(2): 204-212, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27701921

RESUMO

OBJECTIVE: This analysis estimated the cost-effectiveness of intravitreal aflibercept injection(s) (IAI) for wet age-related macular degeneration (wAMD) compared with other treatments in Japan. METHODS: This was a cost-utility analysis based on published data. A state-transition cohort model was constructed with six health states based on best-corrected visual acuity in the better-seeing eye. The cycle time was 4 weeks, and the time horizon was 12 years. The model compared IAI 2 mg every 8 weeks (2q8) for 2 years after three initial monthly injections, ranibizumab as needed, ranibizumab 0.5 mg every 4 weeks (0.5q4), pegaptanib sodium 0.3 mg every 6 weeks, verteporfin photodynamic therapy (PDT), and best supportive care, assumed to include medical management and monitoring, but no active therapy. Costs (expressed as Japanese yen [JPY]) and quality-adjusted life years (QALYs) gained were estimated for each treatment and discounted at 2.0%. Input data were obtained from clinical studies, the Japanese drug tariff and social insurance reimbursement schedule, and expert opinion. The analysis was conducted from the societal perspective, including medical costs as well as costs of blindness. RESULTS: IAI 2q8 was dominant (i.e. more effective in terms of QALYs and less costly) to all other comparators (ranibizumab as needed, ranibizumab 0.5q4, pegaptanib sodium, PDT, and best supportive care), as shown by the incremental cost-utility ratio (i.e. cost per QALY gained). LIMITATIONS: The strengths of the analysis include the wide range of comparators evaluated and the use of Japanese-specific utility data. The limitations include the use of one eye, inclusion of published data up to 2 years only, and assumptions on disease course over 5 years. CONCLUSIONS: IAI 2q8 was more effective in terms of QALYs and less costly compared with other treatments for wAMD in Japan.


Assuntos
Análise Custo-Benefício , Injeções Intravítreas , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/economia , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/economia , Custos de Medicamentos/estatística & dados numéricos , Feminino , Gastos em Saúde , Humanos , Japão , Masculino , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/economia , Anos de Vida Ajustados por Qualidade de Vida , Triazenos/administração & dosagem , Triazenos/economia
4.
J Toxicol Pathol ; 28(1): 43-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26023261

RESUMO

Recently, large-scale gene expression profiling is often performed using RNA extracted from unfixed frozen or formalin-fixed paraffin embedded (FFPE) samples. However, both types of samples have drawbacks in terms of the morphological preservation and RNA quality. In the present study, we investigated 30 human prostate tissues using the PFA-AMeX method (fixation using paraformaldehyde (PFA) followed by embedding in paraffin by AMeX) with a DNA microarray combined with laser-capture microdissection. Morphologically, in contrast to the case of atypical adenomatous hyperplasia, loss of basal cells in prostate adenocarcinomas was as obvious in PFA-AMeX samples as in FFPE samples. As for quality, the loss of rRNA peaks 18S and 28S on the capillary electropherograms from both FFPE and PFA-AMeX samples showed that the RNA was degraded equally during processing. However, qRT-PCR with 3' and 5' primer sets designed against human beta-actin revealed that, although RNA degradation occurred in both methods, it occurred more mildly in the PFA-AMeX samples. In conclusion, the PFA-AMeX method is good with respect to morphology and RNA quality, which makes it a promising tool for DNA microarrays combined with laser-capture microdissection, and if the appropriate RNA quality criteria are used, the capture of credible GeneChip data is well over 80% efficient, at least in human prostate specimens.

5.
Ophthalmology ; 122(3): 571-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25439429

RESUMO

PURPOSE: To evaluate the effect of intravitreal aflibercept injection on visual function in wet age-related macular degeneration (AMD). DESIGN: Prospective, multicenter, double-masked, active-controlled, parallel-group, randomized phase 3 clinical studies (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD [VIEW] 1 and 2 [clinicaltrials.gov identifiers, NCT00509795 and NCT00637377, respectively]). PARTICIPANTS: Patients (n=2419) with active, treatment-naïve, exudative AMD. This analysis included patients who received intravitreal aflibercept 2.0 mg every 8 weeks (2q8; n=607) or ranibizumab 0.5 mg every 4 weeks (0.5q4; n=595). INTERVENTION: Patients were randomized 1:1:1:1 to receive intravitreal aflibercept 2q8 (after 3 initial monthly doses), intravitreal aflibercept 2q4, intravitreal aflibercept 0.5q4, or ranibizumab 0.5q4 in the study eye. Patients in the intravitreal aflibercept 2q8 group received a sham injection alternating with active treatment. MAIN OUTCOME MEASURES: The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was administered at baseline and at weeks 12, 24, 36, and 52. The NEI VFQ-25 subscale scores were compared between intravitreal aflibercept 2q8 and ranibizumab 0.5q4 treatment arms, the approved dosing for each agent worldwide. Change in composite NEI VFQ-25 score was evaluated based on categorical change in visual acuity (worsened, unchanged, improved). RESULTS: Baseline NEI VFQ-25 scores were similar for both treatments in both studies. Mean change from baseline to 52 weeks was similar for ranibizumab 0.5q4 and intravitreal aflibercept 2q8 across all 12 subscales, with the greatest improvements noted for mental health and general vision (9.0-11.6 points, both treatments, both studies). Improvement of 4 points or more (both treatments, both studies) also was observed for subscales near vision, distance vision, role difficulties, and dependency. Mean change from baseline to 52 weeks in NEI VFQ-25 composite score (pooled data) stratified by clinical response showed meaningful improvement only in patients who gained 5 Early Treatment Diabetic Retinopathy letters or more (7.3 and 7.8 points for intravitreal aflibercept 2q8 and ranibizumab 0.5q4, respectively). CONCLUSIONS: Visual function outcomes were similar across all NEI VFQ-25 subscales over 52 weeks for intravitreal aflibercept 2q8 and ranibizumab 0.5q4, with clinically meaningful improvement recorded in 6 of 12 subscales.


Assuntos
Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Injeções Intravítreas , Masculino , Estudos Prospectivos , Ranibizumab , Perfil de Impacto da Doença , Inquéritos e Questionários , Degeneração Macular Exsudativa/fisiopatologia
6.
Clin Infect Dis ; 58(1): 11-21, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24014735

RESUMO

BACKGROUND: Pretravel health consultations help international travelers manage travel-related illness risks through education, vaccination, and medication. This study evaluated costs and benefits of that portion of the health consultation associated with malaria prevention provided to US travelers bound for West Africa. METHODS: The estimated change in disease risk and associated costs and benefits resulting from traveler adherence to malaria chemoprophylaxis were calculated from 2 perspectives: the healthcare payer's and the traveler's. We used data from the Global TravEpiNet network of US travel clinics that collect de-identified pretravel data for international travelers. Disease risk and chemoprophylaxis effectiveness were estimated from published medical reports. Direct medical costs were obtained from the Nationwide Inpatient Sample and published literature. RESULTS: We analyzed 1029 records from January 2009 to January 2011. Assuming full adherence to chemoprophylaxis regimens, consultations saved healthcare payers a per-traveler average of $14 (9-day trip) to $372 (30-day trip). For travelers, consultations resulted in a range of net cost of $20 (9-day trip) to a net savings of $32 (30-day trip). Differences were mostly driven by risk of malaria in the destination country. CONCLUSIONS: Our model suggests that healthcare payers save money for short- and longer-term trips, and that travelers save money for longer trips when travelers adhere to malaria recommendations and prophylactic regimens in West Africa. This is a potential incentive to healthcare payers to offer consistent pretravel preventive care to travelers. This financial benefit complements the medical benefit of reducing the risk of malaria.


Assuntos
Antimaláricos/economia , Antimaláricos/uso terapêutico , Quimioprevenção/economia , Quimioprevenção/métodos , Malária/economia , Malária/prevenção & controle , Viagem , África Ocidental , Análise Custo-Benefício , Humanos , Modelos Estatísticos , Fatores de Tempo , Estados Unidos
7.
J Toxicol Pathol ; 26(2): 223-6, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23914066

RESUMO

Some anticancer therapeutic antibodies are designed to act through complement-dependent cytotoxicity (CDC). It has been reported that there are many membrane complement regulatory proteins (mCRPs) that inhibit CDC. In the present study, we examined the expression of two mCRPs, the complement receptor 1-related gene/protein Y (Crry) and the decay-accelerating factor CD55, in three normal rats by immunohistochemistry. Crry and CD55 were detected widely in rat organs and tissues. Crry was found mainly in the urinary, digestive, respiratory, immunohematopoietic, circulatory and neuroendocrine systems. CD55 was found in the urinary, digestive and neuroendocrine systems. However, the two molecules were expressed in separate cells within the same organ. These results suggest that the distribution of mCRPs is related to the strict regulation of CDC activation in these organs and tissues and that the two molecules have a nonoverlapping expression pattern, a fact indicating specific roles in CDC regulation.

8.
J Toxicol Pathol ; 26(1): 41-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23723567

RESUMO

Some therapeutic antibodies as anticancer agents exert their effects through the host immune system, but the factors that predict their cytotoxicity, including complement-dependent cytotoxicity (CDC), are unclear. In the present study, we attempted to elucidate some of these factors in a preclinical model. CDC-related mesangiolysis caused by administration of the anti-Thy-1.1 antibody can be studied in the rat anti-Thy-1 glomerulonephritis model, so the model was used in this study. Three animals each were sacrificed at 0.5, 1, 8, 24 and 48 hours after i.v. administration of the anti-Thy-1.1 antibody at 1mg/kg. The distribution of the Thy-1.1 antigen and 2 membrane complement regulatory proteins (mCRPs), Crry and CD55, in three non-treated animals and the distribution of the injected antibody and C3 in the model was studied by immunohistochemistry. In the mesangial cells of the kidney, both expression of the antigen and distribution of the antibody with C3 deposition were observed with weak expression of mCRPs. There was also antigen and antibody distribution in the medullary cells of the adrenal gland and in the lymphocytes of the thymus but no C3 deposition, which was thought to be related to high expression of mCRPs. The antigen was observed in several other organs and tissues without distribution of the antibody. Cell death was only observed in the mesangial cells. These results clearly demonstrate that activation of CDC is regulated by several factors, such as distribution of the target molecule, antibody distribution and the balance among the molecules of the CDC cascade and mCRPs.

9.
J Toxicol Pathol ; 25(4): 281-5, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23345932

RESUMO

Increased incidence of adrenal pheochromocytoma is frequently encountered in rat carcinogenicity studies. In some of the studies, the finding is judged to be due to a rat-specific mechanism of carcinogenesis caused by a disturbance of calcium homeostasis. However, direct evidence that the proliferation of chromaffin cells in the adrenal medulla is induced solely by hypercalcemia is not available. In this study, calcium gluconate was intravenously infused for 7 days to rat chromaffin cells by a tail cuff method, and cumulative labeling with bromodeoxyuridine (BrdU) was carried out to evaluate the proliferative activity. The serum calcium concentration was dose-dependently increased, and a high calcium concentration was stably sustained from day 2 to 7. In the adrenal medulla, BrdU-positive chromaffin cells increased in the calcium gluconate-treated animals, and the BrdU-labeling index increased in a dose-dependent manner. In addition, an increased BrdU-labeling index of chromaffin cells was shown to correlate with the serum calcium concentration. Our results demonstrate that hypercalcemia directly enhances the proliferative activity of chromaffin cells and that the proliferative activity is correlated with the serum calcium concentration.

10.
Nihon Shokakibyo Gakkai Zasshi ; 107(10): 1630-4, 2010 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-20938113

RESUMO

A 20-year-old man had suffered from dysphagia since primary school. Upper gastrointestinal and endoscopy examinations revealed severe circumferential stenosis of the upper intra-thoracic esophagus. Secondary stenosis due to factors such as inflammation did not appear present, so congenital esophageal stenosis (CES) was diagnosed. Dysphagia improved after two endoscopic balloon dilatations. Almost all cases of CES are treated in baby-hood, and individuals who remain untreated until adulthood are rare. Check ups and diagnoses should be made taking CES into consideration, even in adults.


Assuntos
Cateterismo/métodos , Estenose Esofágica/congênito , Estenose Esofágica/terapia , Esofagoscopia , Humanos , Masculino , Adulto Jovem
11.
J Toxicol Sci ; 35(4): 503-14, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20686337

RESUMO

Interstitial lung disease has been reported in cancer patients treated with epidermal growth factor receptor tyrosine kinase inhibitors, erlotinib and gefitinib. Preclinical safety studies with erlotinib did not show any evidence for an induction of injury on intact lungs in rats and dogs. In the present study, we investigated the effects of erlotinib on lung injury induced by intratracheal administration of bleomycin (BLM) in rats. In Experiment 1, we examined the effects of short-term (7- and 21-day) administration of erlotinib (10 mg/kg/day, p.o.; subtoxic dose) on the BLM (0.1 or 0.6 mg/rat)-induced lung injury of slight and moderate severity. In Experiment 2, we examined the effects of long term (up to 63-day) administration of higher-dose (up to 20 mg/kg/day; toxic dose; accompanied with decreased body weight gain and severe skin lesions) erlotinib on the BLM-induced lung injury. In rats receiving erlotinib alone, no lung lesions were noted. In rats receiving BLM alone, diffuse alveolar damage (DAD) and, subsequently, pulmonary fibrosis of slight or moderate severity was observed. The administration of erlotinib to BLM-treated rats showed no exacerbation of lung injuries in indices such as macroscopic findings, lung weights, histopathological scores (lung lesion density and lung fibrosis score), and pulmonary hydroxyproline (HyP) level. These results suggest that erlotinib does not have any exacerbating effects on lung injuries induced by BLM in rats.


Assuntos
Lesão Pulmonar/induzido quimicamente , Inibidores de Proteínas Quinases/toxicidade , Fibrose Pulmonar/induzido quimicamente , Quinazolinas/toxicidade , Animais , Bleomicina , Cães , Cloridrato de Erlotinib , Humanos , Hidroxiprolina/análise , Injeções , Pulmão/efeitos dos fármacos , Lesão Pulmonar/patologia , Neutrófilos/efeitos dos fármacos , Fibrose Pulmonar/patologia , Ratos , Traqueia
12.
Gan To Kagaku Ryoho ; 37(6): 1139-43, 2010 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-20567124

RESUMO

A 65-year-old woman who had diffuse hepatocellular carcinoma(HCC)with tumor thrombus of right portalvein(Vp3) and lung metastases(Stage IVB)was treated by single-agent therapy with tegafur/uracil(UFT). As a result, primary and metastatic tumors were not recognized by diagnostic imaging, with a noted decrease of AFP, AFP-L3 and PIVKA-II. Generally, oral chemotherapy for HCC is not recommended because of the low response rate. However, there have been some reports including the present case which have showed a marked response with UFT. We thus conclude that UFT can be an option with low risk of crucial adverse effects in the treatment of selected HCC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Tegafur/uso terapêutico , Trombose/etiologia , Uracila/uso terapêutico , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/secundário , Estadiamento de Neoplasias , Veia Porta/patologia , Indução de Remissão , Tegafur/administração & dosagem , Trombose/patologia , Tomografia Computadorizada por Raios X , Uracila/administração & dosagem
13.
J Toxicol Sci ; 34(1): 39-52, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19182434

RESUMO

Totally implantable catheter animal models are considered useful for pharmacological and toxicological studies. In this report, we assessed the feasibility of using an indwelling vascular access port (VAP) in rats for long-term evaluation of repeated and intermittent dose toxicity studies. In Experiment 1, the VAP devices were implanted in male and female rats and a saline solution administered intravenously via the posterior vena cava for 2 weeks (4 ml/kg, 2 ml/min, 5 times/week, 10 times total). General conditions, body weight and blood chemistry showed no toxicological changes compared with the rats in the non-implanted, non-treated group. Hematology changes such as transient increases in peripheral blood reticulocytes and eosinophils were noted post-implantation. In pathology, proliferation of the endothelium at the site of VAP implantation and perivascular inflammatory cell infiltration including eosinophils in lung were noted at the end of the treatment period. Moreover, we found that the lumbar area is more suitable for VAP implantation than the back of neck for young, still growing rats. Experiment 2 included a 1-month intravenous intermittent dose (4 ml/kg, 2 ml/min, 1 time/week, 5 times total) toxicity study in VAP-implanted rats followed by a 1-month recovery period conducted under Good Laboratory Practice (GLP) regulations. The results suggested that an animal model with implanted VAP is useful for intermittent intravenous dosing of drugs. Moreover, VAP implantation in animals is expected to be extrapolated to use VAP in humans in clinical studies.


Assuntos
Cateteres de Demora/efeitos adversos , Testes de Toxicidade/métodos , Animais , Autopsia/métodos , Análise Química do Sangue/métodos , Análise Química do Sangue/veterinária , Peso Corporal/fisiologia , Cateteres de Demora/veterinária , Esquema de Medicação , Eutanásia Animal , Feminino , Testes Hematológicos/métodos , Testes Hematológicos/veterinária , Infusões Intravenosas , Masculino , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Ratos , Ratos Sprague-Dawley , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade
14.
J Toxicol Pathol ; 22(4): 289-92, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22272004

RESUMO

Emphysematous cystitis is a rare disorder caused by bacterial infection and characterized by gas accumulation within the bladder wall with cyst formation. This report describes the histopathological characteristics of emphysematous cystitis found in a diabetic female beagle induced by streptozotocin and alloxan. Macroscopically, multiple cyst-like structures were observed on the cut surface of the urinary mucosa. During fixation, small specimens cut from the mucosa floated on the surface of the fixative solution. Histopathologically, multiple cysts were lined with a single layer of flattened cells found to be immunohistochemically positive for vimentin, partially positive for α-smooth muscle actin or macrophage scavenger receptor, class A, and thought to be myofibroblasts, fibroblasts or macrophages. Multinucleated giant cells were observed around the cysts, and gram-negative short bacilli were observed in the lumen of the urinary bladder. From these findings, this case was diagnosed as emphysematous cystitis.

15.
Gan To Kagaku Ryoho ; 35(10): 1769-74, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18931586

RESUMO

AIM: In this study, we investigated the efficacy and toxicity of fluorouracil(FU)+Leucovorin(LV)with oxaliplatin (FOLFOX)and irinotecan(FOLFIRI)for patients with advanced or metastatic colorectal cancer. METHODS: Eleven patients with advanced or metastatic colorectal cancer underwent chemotherapy, such as FOLFOX4, mFOLFOX6, and FOLFIRI. Four and 7 patients underwent FOLFOX4 and mFOLFOX6 as a first-line therapy, respectively. Five patients underwent FOLFIRI as a second-line therapy. RESULTS: The response rate(RR)for FOLFOX4 and mFOLFOX6 as a firstline therapy was 0%(0 of 4 patients)and 71%(5 of 7 patients), respectively. The RR for FOLFIRI as a second-line therapy was 40%(2 of 5 patients). The survival time of the eight patients experiencing CR, PR or SD in the firstline FOLFOX4/mFOLFOX6 or the second-line FOLFIRI is 7 to 27 months. That of the three patients not showing CR, PR or SD is 4 to 8 months. The former is significantly longer than the latter(p=0.0023). Toxicities were paresthesia, neutropenia, thrombocytopenia and general fatigue in FOLFOX4, paresthesia, neutropenia, thrombocytopenia, diarrhea and anaphylaxis in mFOLFOX6, while those were neutropenia, thrombocytopenia, stomatitis and general fatigue in the second-line FOLFIRI. CONCLUSION: For advanced or metastatic colorectal cancer, FOLFOX4/mFOLFOX6 followed by FOLFIRI may be effective and comparatively safe treatments.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Idoso , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Neoplasias Colorretais/diagnóstico por imagem , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/tratamento farmacológico , Estadiamento de Neoplasias , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Terapia de Salvação , Tomografia Computadorizada por Raios X
16.
Pathol Int ; 58(9): 559-67, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18801070

RESUMO

Immunodeficient mice are widely used for xenografts of human cells and tissue. The purpose of the present study was to investigate the characteristics of xenograft human tumor models using engraftment of various non-hematopoietic tumors in the NOD/SCID/gamma(c) (null) mouse. For tumor models, human solid tumor tissues were serially passaged three or more times to establish tissue lines. A total of 326 fresh tumor specimens, mainly gastrointestinal and female genital tissue, were engrafted with 54 established tissue lines. The types of tissue lines varied and included tumor tissue of both epithelial and mesenchymal origin. In some cases the original surgical specimen was replaced with large mononuclear cells. In the established tumor tissue lines, differentiation and tumor structure were similar to that of the original surgical specimen. The interstitium of the xenograft tissue in the tissue lines was relatively well preserved although slightly decreased and replaced by host tissue. These results indicate that human solid tumors can be successfully engrafted into the NOD/SCID/gamma(c) (null) mouse and that tissue lines with the characteristics of the original tumors can be established. Investigators in the field of tumor research will benefit from the availability of tissue lines that allow the establishment of more relevant in vivo human tissue models.


Assuntos
Modelos Animais de Doenças , Neoplasias/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Feminino , Humanos , Hospedeiro Imunocomprometido , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Transplante de Neoplasias/métodos , Transplante Heterólogo
17.
Gan To Kagaku Ryoho ; 35(9): 1563-7, 2008 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-18799912

RESUMO

A 70-year-old woman with pulmonary carcinomatous lymphangitis and paraaortic lymph node metastases due to gastric cancer, was treated by combination chemotherapy of S-1 and irinotecan (CPT-11). After one course of the chemotherapy, pulmonary carcinomatous lymphangitis and paraaortic lymph node metastases were remarkably improved. Diet intake was improving and cancer pain remarkably declined. Because the origin of gastric cancer was not improved, total gastrectomy, distal pancreatectomy and splenectomy were performed. After surgery, relapse of pulmonary carcinomatous lymphangitis caused death of the patient. The combination chemotherapy of S-1 and CPT-11 was effective for pulmonary carcinomatous lymphangitis and paraaortic lymph nodes metastases due to gastric cancer. However, careful consideration is required since surgery is performed on a patient who had suffered pulmonary carcinomatous lymphangitis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aorta/efeitos dos fármacos , Camptotecina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Linfangite/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Idoso , Camptotecina/uso terapêutico , Combinação de Medicamentos , Feminino , Gastroscopia , Humanos , Irinotecano , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Linfangite/diagnóstico por imagem , Linfangite/etiologia , Metástase Linfática/diagnóstico por imagem , Estadiamento de Neoplasias , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X , Falha de Tratamento
18.
World J Gastroenterol ; 11(10): 1532-4, 2005 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-15770732

RESUMO

AIM: To determine the efficacy of multislice CT for gastroenteric and hepatic surgery. METHODS: Dual-phase helical computed tomography was performed in 50 of 51 patients who underwent gastroenteric and hepatic surgeries. Twenty-eight, eighteen and four patients suffering from colorectal cancer, gastric cancer, and liver cancer respectively underwent colorectal surgery (laparoscopic surgery: 6 cases), gastrectomy, and hepatectomy. Three-dimensional computed tomography imaging of the inferior mesenteric artery, celiac artery and hepatic artery was performed. And in the follow-up examination of postoperative patients, multiplanar reconstruction image was made in case of need. RESULTS: Scans in 50 patients were technically satisfactory and included in the analysis. Depiction of major visceral arteries, which were important for surgery and other treatments, could be done in all patients. Preoperative visualization of the left colic artery and sigmoidal arteries, the celiac artery and its branches, and hepatic artery was very useful to lymph node dissection, the planning of a reservoir and hepatectomy. And multiplanar reconstruction image was helpful to diagnosis for the postoperative follow-up of patients. CONCLUSION: Three-dimensional volume rendering or multiplanar reconstruction imaging performed by multislice computed tomography was very useful for gastroenteric and hepatic surgeries.


Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada Espiral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Trato Gastrointestinal/diagnóstico por imagem , Trato Gastrointestinal/cirurgia , Humanos , Imageamento Tridimensional , Fígado/diagnóstico por imagem , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade
19.
World J Gastroenterol ; 11(44): 6932-5, 2005 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-16437595

RESUMO

AIM: To evaluate the usefulness of three-dimensional computed tomography (3DCT) in laparoscopic surgery for colorectal carcinoma. METHODS: Seventy-two patients with colorectal cancer who underwent curative operation at our hospital were enrolled in this study. They were classified into two groups by operative procedures. Sixteen patients underwent laparoscopic surgery, laparoscopic group (LG), while 56 patients underwent conventional open surgery, open group (OG). At our institution, contrast-enhanced CT is routinely performed as part of intra-abdominal screening and the 3D images of the major regional vessels are described. We have previously described about the preoperative visualization of the inferior mesenteric artery (IMA) by 3DCT. This time we newly acquired 3D images of the superior mesenteric artery (SMA)/superior mesenteric vein (SMV), ileocecal artery (ICA), middle colic artery (MCA), and inferior mesenteric vein (IMV). We have compared our two study groups with regard to five items, including clinical anastomotic leakage. We have discussed here the role of 3DCT in laparoscopic surgery for colorectal carcinoma. RESULTS: The mean length of the incision in LG was 4.625+/-0.89 cm, which was significantly shorter than that in OG (P<0.001). The association between ICA and SMV and SMA was described in the right-sided colectomy. The preoperative imaging of IMA and IMV was created in the rectosigmoidectomy. There was no significant difference in anastomotic leakage between the two groups, but no patients in LG experienced anastomotic leakage. CONCLUSION: Most of the patients are satisfied with the shorter incisional length following laparoscopic surgery. Preoperative visualization of the major regional vessels may be helpful for the secure treatment of the anastomosis in laparoscopic surgery for colorectal carcinoma.


Assuntos
Neoplasias Colorretais/cirurgia , Imageamento Tridimensional , Laparoscopia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Int J Mol Med ; 11(2): 175-9, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12525873

RESUMO

Although the cytokine network plays a key role in the inflammatory responses in inflammatory bowel disease, no comprehensive analysis of the intestinal cytokine network has been reported. We analyzed messenger RNA levels for various cytokines in human intestine by real-time quantitative polymerase chain reaction to clarify the cytokine profiles involved in the pathogenesis of inflammatory bowel disease. Biopsy specimens were obtained from 23 patients with ulcerative colitis (15 men, 8 women, mean age of 44.1 years), 17 patients with Crohn's disease (15 men, 2 women, mean age of 21.6 years), and 8 normal controls (6 men, 2 women, mean age of 62.7 years) who underwent colonoscopy for suspected colonic disease. Messenger RNA was isolated from two biopsy samples and reverse-transcribed to obtain cDNA. Mucosal mRNA levels for IL-1beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-gamma and TNF-alpha were simultaneously analyzed by real-time quantitative polymerase chain reaction. In patients with active ulcerative colitis, IL-1beta, IL-4, IL-5, IL-8, IL-12p40, IFN-gamma and TNF-alpha mRNA levels were significantly higher than those in controls. In patients with active Crohn's disease, IL-1beta, IL-8, and IL-12p40 mRNA levels were significantly higher than those in controls. Mucosal level of IL-12p40 mRNA was significantly higher in patients with inactive Crohn's disease than in controls. Both Th1 and Th2 cytokine mRNA levels were increased in colonic mucosa of patients with ulcerative colitis suggesting the possibility that cellular and humoral immunity play roles in the pathogenesis of this disease. In patients with Crohn's disease, Th1 cytokine mRNA levels were increased in colonic mucosa, suggesting predominance of cellular immunity in the pathogenesis of this disease.


Assuntos
Colo/metabolismo , Citocinas/genética , Doenças Inflamatórias Intestinais/metabolismo , RNA Mensageiro/metabolismo , Perfilação da Expressão Gênica , Humanos , Reação em Cadeia da Polimerase
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