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1.
Ann Oncol ; 29(4): 1004-1009, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29408977

RESUMO

Background: The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is combination treatment with platinum, 5-FU and cetuximab (PFE). However, this regimen requires hospitalization to ensure proper hydration and continuous infusion of 5-FU, and causes severe nausea and anorexia. We evaluated the efficacy and safety of paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with R/M SCCHN. Patients and methods: Eligibility criteria included recurrent and/or metastatic, histologically proven SCC of the oropharynx, oral cavity, hypopharynx or larynx; PS 0-1; adequate organ function; no suitable local therapy for R/M SCCHN; and no prior systemic chemotherapy for R/M SCCHN. Chemotherapy consisted of paclitaxel 100 mg/m2 on days 1, 8; carboplatin area under the blood concentration-time curve 2.5 on days 1, 8, repeated every 3 weeks for up to 6 cycles; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicities. Primary end point was overall response rate. Secondary end points were safety, treatment completion rate, progression-free survival, overall survival, and clinical benefit rate. Planned sample size was 45 patients. Results: Forty-seven subjects were accrued from July 2013 to October 2014. Of 45 evaluable, 40 were male; median age was 63 years; Eastern Cooperative Oncology Group Performance Status was 0/1 in 23/22 cases; site was the hypopharynx/oropharynx/oral cavity/larynx in 17/11/10/7 cases; and 36/9 cases were smokers/nonsmokers, respectively. Overall response rate, the primary end point, was 40%. Median overall survival was 14.7 months and progression-free survival was 5.2 months. Grade 3/4 adverse events included neutropenia (68%), skin reaction (15%), fatigue (9%) and febrile neutropenia (9%). A potentially treatment-related death occurred in one patient with intestinal pneumonia. Conclusions: The PCE regimen shows promising activity with acceptable toxicity in the outpatient clinic. Further studies are needed to compare PCE with PFE in this population. Registered clinical trial number: UMIN000010507.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Metástase Neoplásica , Paclitaxel/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
2.
Am J Transplant ; 16(2): 625-33, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26517570

RESUMO

We investigated the impact of polymorphisms in host innate immunoregulatory genes on the development of infectious complications after liver transplantation (LT). The single-nucleotide polymorphisms (SNPs) of C1QA [276A/G], FCGR2A [131H/R], and FCGR3A [158F/V], genes encoding the Fc gamma receptor (FcγR), were analyzed in 89 living donor LT recipients in relation to the occurrences of postoperative infectious complications within 30 days after LT. Consistent with a lower affinity of the isoform encoded by FCGR3A [158F] to both IgG1 and IgG3, a significantly higher incidence of bloodstream infections (BSI) was observed in the FCGR3A [158F/V or F/F] than in the FCGR3A [158V/V] individuals. The combination of FCGR2A and FCGR3A SNPs further stratified the incidence of BSI, regardless of C1QA SNP. The predominant causative pathogen of BSI in the FCGR3A [158F/F or F/V] patients was gram-positive cocci (73.3%), of which one third was methicillin-resistant Staphylococcus aureus. No differences were observed in the incidence of fungal infections or in cytomegalovirus infections with respect to the three gene polymorphisms. Our findings indicate that FcγR SNPs are predisposing factors for BSI and can predict mortality after LT. This study provides a foundation for further prospective studies on a larger scale.


Assuntos
Doenças Transmissíveis/diagnóstico , Rejeição de Enxerto/diagnóstico , Hepatopatias/complicações , Transplante de Fígado/efeitos adversos , Polimorfismo de Nucleotídeo Único/genética , Receptores de IgG/genética , Adulto , Idoso , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/etiologia , Feminino , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Hepatopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Cuidados Pré-Operatórios , Prognóstico , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
3.
ESMO Open ; 9(6): 103476, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38833968

RESUMO

BACKGROUND: An important unmet need for new treatment options remains for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) previously treated with both platinum-based chemotherapy and anti-programmed cell death protein 1 (PD-1) antibody. Retrospective studies suggest that previous treatment with immune checkpoint inhibitor might augment the efficacy of subsequent chemotherapy. Here, we conducted a phase II trial aimed to evaluate the efficacy and safety of paclitaxel plus biweekly cetuximab for patients in this setting. PATIENTS AND METHODS: This was a single-arm, multicenter, phase II trial. Key eligibility criteria were R/M-HNSCC, and previous treatment with both platinum-based chemotherapy and PD-1 antibody. Paclitaxel plus biweekly cetuximab consisted of weekly paclitaxel 100 mg/m2 (days 1, 8, 15) and biweekly cetuximab 500 mg/m2 (days 1, 15) with a cycle of 28 days until progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs) (Common Terminology Criteria for Adverse Events version 5.0). RESULTS: Between August 2020 and August 2022, 35 patients were enrolled, of whom 33 were assessable for response. ORR was 69.6% (95% confidence interval 51.2% to 84.4%). With a median follow-up period for survivors of 16.6 months, median PFS and OS were 5.5 and 13.3 months, respectively. DCR was 93.7%. Twenty-three patients (65%) experienced grade 3 or 4 AEs, including neutropenia (34%), infection (14%), leukopenia (11%), mucositis (8%), and pneumonitis (8%). Eight patients discontinued study treatment due to treatment-related AEs, and no treatment-related death was observed. CONCLUSIONS: Paclitaxel plus biweekly cetuximab showed highly encouraging efficacy and manageable toxicities in R/M-HNSCC patients previously treated with both platinum-based chemotherapy and PD-1 antibody. This combination therapy warrants further investigation in this setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cetuximab , Neoplasias de Cabeça e Pescoço , Paclitaxel , Humanos , Cetuximab/administração & dosagem , Cetuximab/uso terapêutico , Cetuximab/farmacologia , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Paclitaxel/farmacologia , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Adulto , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem
4.
Clin Oncol (R Coll Radiol) ; 34(12): e505-e514, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35654667

RESUMO

AIMS: Although palliative radiotherapy for gastric cancer may improve some symptoms, it may also have a negative impact due to its toxicity. We investigated whether symptoms improved after radiotherapy with adjustment for the Palliative Prognostic Index (PPI) considering that patients with limited survival tend to experience deterioration of symptoms. MATERIALS AND METHODS: This study was an exploratory analysis of the Japanese Radiation Oncology Study Group study (JROSG 17-3). We assessed six symptom scores (nausea, anorexia, fatigue, shortness of breath, pain at the irradiated area and distress) at registration and 2, 4 and 8 weeks thereafter. We tested whether symptoms linearly improved after adjusting for the baseline PPI. Shared parameter models were used to adjust for potential bias in missing data. RESULTS: The present study analysed all 55 patients enrolled in JROSG 17-3. With time from registration as the only explanatory variable in the model, a significant linear decrease was observed in shortness of breath, pain and distress (slopes, -0.26, -0.22 and -0.19, respectively). Given that the interaction terms (i.e. PPI × time) were not significantly associated with symptom scores in any of the six symptoms, only PPI was included as the main effect in the final multivariable models. After adjusting for the PPI, shortness of breath, pain and distress significantly improved (slope, -0.25, -0.19 and -0.17; P < 0.001, 0.002 and 0.047, respectively). An improvement in fatigue and distress was observed only in patients treated with a biologically effective dose ≤14.4 Gy. CONCLUSION: Shortness of breath, pain and distress improved after radiotherapy. Moreover, a higher PPI was significantly associated with higher symptom scores at all time points, including baseline. In contrast, PPI did not seem to influence the improvement of these symptoms. Regardless of the expected survival, patients receiving radiotherapy for gastric cancer can expect an improvement in shortness of breath, pain and distress over 8 weeks. Multiple-fraction radiotherapy might hamper the improvement in fatigue and distress by its toxicity or treatment burden.


Assuntos
Radioterapia (Especialidade) , Neoplasias Gástricas , Humanos , Prognóstico , Neoplasias Gástricas/complicações , Neoplasias Gástricas/radioterapia , Cuidados Paliativos , Fadiga/etiologia , Dor/etiologia , Dor/radioterapia , Dor/diagnóstico , Dispneia/etiologia , Dispneia/radioterapia
6.
J Natl Cancer Inst ; 67(2): 407-12, 1981 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-6115080

RESUMO

Spontaneous hepatic changes in old male rats of Wistar and F344 inbred strains were studied histochemically. gamma-Glutamyl transpeptidase-positive hepatocytic foci and cholangiolar proliferation associated with fibrosis and inflammatory infiltration were common findings in the old rats of both strains. Histochemical properties of the hepatocytes of the foci were similar to those of hyperplastic foci seen in early stages of liver carcinogenesis due to various chemical carcinogens. The incidence of the foci was 2.52/cm2 of the histochemically stained sections in 105-week-old male Wistar and F344 rats, and the presence of other spontaneous neoplastic and nonneoplastic changes was revealed.


Assuntos
Neoplasias Hepáticas/veterinária , Fígado/patologia , Lesões Pré-Cancerosas/veterinária , Doenças dos Roedores/patologia , gama-Glutamiltransferase , Fatores Etários , Animais , Animais de Laboratório , Ductos Biliares/patologia , Peso Corporal , Histocitoquímica , Neoplasias Hepáticas/patologia , Pneumopatias/veterinária , Masculino , Tamanho do Órgão , Lesões Pré-Cancerosas/patologia , Ratos , Ratos Endogâmicos
7.
J Natl Cancer Inst ; 62(6): 1489-95, 1979 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-286121

RESUMO

A microsomal butyrylesterase (L-I) was purified from the livers of male W rats treated with phenobarbital, and an antiserum against this purified L-I was raised in a rabbit. By the Ouchteriony double-diffusion test, a precipitin line was observed between the anti-L-I antiserum and each Triton X-100 extract of livers during development, regeneration after partial hepatectomy, and carcinogenesis and of hyperplastic nodules and hepatomas, all of which revealed L-I in their esterase isoenzyme patterns. These precipitin lines exhibited esterase activity. The fusion of the lines of these tissue extracts and that of the purified L-I indicated the presence of an antigen site common to their esterases. The extracts of adult and fetal livers and also of hepatomas resembling fetal liver in the esterase isoenzyme pattern did not produce a precipitin line with anti-L-I antiserum.


Assuntos
Hidrolases de Éster Carboxílico/metabolismo , Isoenzimas/metabolismo , Neoplasias Hepáticas Experimentais/enzimologia , Regeneração Hepática , Microssomos Hepáticos/enzimologia , Fenobarbital/farmacologia , Animais , Butiratos , Hidrolases de Éster Carboxílico/imunologia , Feto/enzimologia , Isoenzimas/imunologia , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Lesões Pré-Cancerosas/enzimologia , Ratos , Fatores de Tempo
8.
Cancer Res ; 40(6): 1769-73, 1980 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7371007

RESUMO

Using an immunofluorescent technique, we demonstrated the production of rat embryonic-type hemoglobin in extra-medullary hematopoietic cells, which appeared in the liver of adult Wistar rats fed a diet containing 0.06% 3'-methyl-4=dimethylaminoazobenzene. Specific anti-rat embryonic hemoglobin serum was prepared by immunizing a rabbit with hemoglobin from a 15- or 16-day-old Wistar rat fetus and absorbing with adult rat liver hemogenate and red blood cells. The appearance of hematopoietic foci was observed at both precancerous and cancerous stages during 3'-methyl-4-dimethylaminoazobenzene-induced liver carcinogenesis. At the cancerous stage, almost all these foci were observed in poorly differentiated hepatocellular carcinomas. The hematopoietic cells seen at both stages were stained positively with antiembryonic hemoglobin serum, but red blood cells and other types of cells in the liver did not show this specific fluorescence. These results together with earlier observations on the appearance of fetal characteristics strongly suggest that a fetal environment prevails in the adult rat liver during hepatic carcinogenesis.


Assuntos
Células-Tronco Hematopoéticas/metabolismo , Hemoglobina E/biossíntese , Hemoglobinas Anormais/biossíntese , Neoplasias Hepáticas Experimentais/metabolismo , Fígado/metabolismo , Animais , Medula Óssea/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Metildimetilaminoazobenzeno , Ratos
9.
Cancer Res ; 38(9): 2753-8, 1978 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-209888

RESUMO

Carcinoma tissues induced by 3'-methyl-4-dimethylaminoazobenzene were investigated both morphologically and biochemically. The most prominent histological pattern was an undifferentiated carcinomatous one. While this type of carcinoma, histologically, appeared to be due to a uniform population of cells, electron microscopic examination revealed that the carcinoma tissue was composed of many types of cells including cells that contained either the brush border or the mucous droplets seen in goblet cells. In addition, tumor cells that contain serotonin-like granules were noticed. An electrophoretogram of alkaline phosphatase in the tissue extract of this type of carcinoma revealed distinctly the presence of its intestinal isozyme. These findings evidently show that carcinoma induced by 3'-methyl-4-dimethylaminoazobenzene includes in addition to the cells differentiated toward hepatocytes or cholangiolar cells, those differentiated toward intestinal epithelial cells.


Assuntos
Carcinoma Hepatocelular/patologia , Intestinos/patologia , Neoplasias Hepáticas/patologia , Metildimetilaminoazobenzeno , p-Dimetilaminoazobenzeno , Fosfatase Alcalina/metabolismo , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/enzimologia , Grânulos Citoplasmáticos/ultraestrutura , Intestinos/enzimologia , Isoenzimas/metabolismo , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/enzimologia , Masculino , Microscopia Eletrônica , Microvilosidades/enzimologia , Microvilosidades/ultraestrutura , Neoplasias Experimentais/patologia , Ratos , p-Dimetilaminoazobenzeno/análogos & derivados
10.
Cancer Res ; 42(10): 4158-63, 1982 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7105011

RESUMO

The activity of butyrylcholinesterase (BCHE), a liver fetal isozyme (Zone L-V) of a nonspecific esterase, was studied histochemically and cytochemically in rat hepatocellular carcinomas induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). In normal adult rats, BCHE activity was very prominent in cells of the intestinal mucosa but was not detectable in the liver. On the other hand, in fetal rat liver, a few cells scattered throughout the organ were BCHE positive. 3'-Me-DAB induced poorly differentiated hepatocellular carcinomas showing an intense BCHE activity, especially in areas consisting of small tumoral cells proliferating in a sheet-like pattern. Surrounding noncancerous liver tissue was completely devoid of reaction products. Less-differentiated trabecular hepatocellular carcinomas also showed a positive reaction. On the other hand, well-differentiated hepatocellular carcinoma and hepatocellular carcinoma with an adenomatous pattern were barely stained, while areas of cholangiofibrosis were usually negative. Thus, in confirmation of a previous report, BCHE appears to be a positive marker of poorly differentiated hepatocellular carcinomas induced by 3'-Me-DAB. By electron microscopy, reaction products were demonstrated in the cisternae of the endoplasmic reticulum, in the nuclear envelopes, and sometimes on the cell surface of undifferentiated tumoral cells. The significance of the appearance of BCHE activity in hepatocellular carcinomas induced by 3'-Me-DAB is discussed.


Assuntos
Butirilcolinesterase/metabolismo , Colinesterases/metabolismo , Neoplasias Hepáticas Experimentais/enzimologia , Animais , Histocitoquímica , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Metildimetilaminoazobenzeno , Microscopia Eletrônica , Ratos , Ratos Endogâmicos
11.
Cancer Res ; 35(5): 1282-7, 1975 May.
Artigo em Inglês | MEDLINE | ID: mdl-47267

RESUMO

The study was carried out to identify alpha-fetoprotein (AFP)-producing cells in the hepatic tissue by immunofluorescent antibody techniques during the early stage of 3'-methyl-4-dimethylaminoazobenzene ingestion. After 1 to 3 weeks, cells fluorescent to AFP were undetectable in cholangiolar cells ("oval cells") and also in degenerated megalocytic hepatocytes. After 4 to 7 weeks AFP appeared in rat sera, and "transitional cells" and small hepatocytes proliferated markedly in the periportal areas of hepatic lobules. AFP was exclusively detected in the majority of the transitional cells and a small portion of the small hepatocytes. Some fluorescent cells appeared in small groups, and others were randomly distributed in the periportal areas. The typical oval cells and the megalocytic hepatocytes were not fluorescent. When AFP in sera became undetectable, the regenerated hepatocytes matured considerably and were not brightly fluorescent. In the hepatic tissue, where AFP-producing cells were observed by fluorescent antibody technique, hematopoietic cells were frequently observed but they were not fluorescent.


Assuntos
alfa-Globulinas/metabolismo , Proteínas Fetais/metabolismo , Neoplasias Hepáticas/metabolismo , Animais , Imunofluorescência , Fígado/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/induzido quimicamente , Masculino , Neoplasias Experimentais/sangue , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/metabolismo , Ratos , p-Dimetilaminoazobenzeno
12.
Biochim Biophys Acta ; 582(2): 185-95, 1979 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-760821

RESUMO

A carboxylesterase (carboxylic-ester hydrolase, EC 3.1.1.1) was induced in the liver of rats after repeated administration of phenobarbital. This enzyme migrated most rapidly towards the anode among Triton X-100-solubilized liver esterases by electrophoresis on the cellulose acetate membrane and it was tentatively designated as L-I. L-I increased in the microsomal fraction and was mainly concentrated in the fraction of smooth endoplasmic reticulum that proliferated after phenobarbital treatment. L-I- was separated from other liver esterases and purified about 800-fold. The purified L-I was homogeneous as judged by polyacrylamide gel electrophoresis and exhibited a molecular weight of about 55 000 as determined by gel filtration. L-I split the 1-naphthyl ester of butyric acid faster than esters of acetic, propionic or valeric acids; it therefore seemed to be a butyrylesterase.


Assuntos
Hidrolases de Éster Carboxílico/biossíntese , Microssomos Hepáticos/efeitos dos fármacos , Fenobarbital/farmacologia , Animais , Hidrolases de Éster Carboxílico/isolamento & purificação , Retículo Endoplasmático/enzimologia , Indução Enzimática/efeitos dos fármacos , Masculino , Microssomos Hepáticos/enzimologia , Ratos
13.
J Histochem Cytochem ; 24(8): 926-32, 1976 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-60440

RESUMO

When the immunofluroscent study on the distribution and the incidence of albumin-producing hepatocytes in the rat liver was performed by the method of Sainte-Marie, the number of positive cells showed various values (10-60%). It was surmised that when the permeability of the fixative was delayed, albumin had flowed out from the cytoplasm of the unfixed hepatocytes. By the simple means of constant stirring of the fixative using a magnetic stirrer, we accomplished rapid fixation and achieved results in which positive cells attained 100%. On the other hand, the incidence of positive cells decreased markedly when rats were fed a protein-free diet.


Assuntos
Imunofluorescência/métodos , Fígado/metabolismo , Albumina Sérica/biossíntese , Animais , Eletroforese Descontínua/métodos , Imunodifusão , Fígado/citologia , Masculino , Ratos , Albumina Sérica/análise , Coloração e Rotulagem
14.
Am J Kidney Dis ; 37(1): 113-118, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11136175

RESUMO

Polycystic kidney disease (PKD) is one of the most common genetic disorders and a major cause of renal death or end-stage renal disease (ESRD) requiring regular hemodialysis. The responsible genes recently have been cloned; however, genetic factors influencing the rate of progression to ESRD in patients with PKD have yet to be defined. Several studies have shown increased activity of the renin-angiotensin system (RAS) in patients with PKD. In addition, genetic polymorphisms of the RAS have been associated with the development of cardiovascular diseases. Therefore, these polymorphisms are good candidates for disease-modifying genetic factors or markers in PKD. In two previous reports of white subjects with a cumulative survival analysis, it was suggested that patients with P:KD1 homozygous for the deletion allele of the angiotensin-converting enzyme (ACE) gene are at increased risk for early renal death. To confirm this hypothesis in Japanese subjects, 103 individuals with PKD were genotyped for several components of the RAS, ie, ACE insertion/deletion (I/D) polymorphism, angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT1) A1166C. Seventy-six of the 103 patients (73.8%) reached ESRD at an average age of 52.1 +/- 11.3 years. The frequencies of each genotype of the genes were similar to those expected from Hardy-Weinberg equilibrium. There was a tendency to an excess of patients homozygous for the D allele in patients with ESRD (DD in patients with ESRD, 11.8%; DD in patients without ESRD, 3.7%; chi-square, 1.505; P: = 0.22). Cumulative renal survival was significantly less in those with the DD genotype compared with ID/II genotypes. Estimated mean renal survival was 46.4 years (95% confidence interval, 39.5 to 53.3) in subjects with the DD genotype and 57.2 years (95% confidence interval, 54.2 to 60.2) in ID/II genotypes (chi-square, 7.76; P: = 0.0053). There was no association between age at onset of ESRD and either M235T or A1166C polymorphism. These findings suggest that Japanese patients with PKD homozygous for the D allele of the ACE gene are at increased risk for developing ESRD at an early age.


Assuntos
Peptidil Dipeptidase A/genética , Doenças Renais Policísticas/genética , Adulto , Feminino , Frequência do Gene , Genes ras/genética , Genótipo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Doenças Renais Policísticas/etnologia , Polimorfismo Genético
15.
Clin Nephrol ; 59(6): 406-14, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12834171

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited renal disorders in the world. Mutations in PKD1 are responsible for 80-95% of all autosomal dominant polycystic kidney disease (ADPKD). Although the need for linkage analysis of ADPKD is decreasing after the success of mutation detection at whole exons of PKD1, linkage analysis still has some advantages in detecting non-PKD1 families, thereby avoiding hopeless mutation analysis. METHODS: We evaluated ten microsatellite markers beside or inside PKD1 on chromosome 16p. Allele frequency and heterozygosity of each marker were calculated based on the 100 genotypes obtained from 50 normal Japanese. Automated microsatellite genotyping using ABI Prism 377 and GeneScan software was applied. Markers were mapped using radiation hybrid mapping. Finally, this strategy was applied in the linkage analysis of 6 independent Japanese ADPKD families. RESULTS: D16S3024, D16S3082, D16S3027 and D16S423 showed high heterozygosity (> 0.80) in a normal Japanese population and sufficient proximity to the PKD1 gene for linkage analysis. We could successfully analyze 144 genotypes within 7 hours. This strategy produced theoretically near-maximum LOD scores in 4 independent Japanese families inheriting ADPKD. CONCLUSIONS: Automated genotyping using microsatellite markers, D16S3024, D16S3082, D16S3027 and D16S423 are very useful in the linkage analysis of ADPKD.


Assuntos
Ligação Genética , Repetições de Microssatélites , Rim Policístico Autossômico Dominante/genética , Mapeamento Cromossômico , Análise Mutacional de DNA/métodos , Genótipo , Humanos , Linhagem , Proteínas/genética , Canais de Cátion TRPP
16.
Clin Nephrol ; 52(5): 329-32, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10584998

RESUMO

The patient, a female, aged 65 years, developed diffuse peritoneal calcification nine years after commencing CAPD therapy. No abdominal symptoms or evidence of peritonitis were discovered during this period. Before peritoneal calcification was detected, a dialysate with a high glucose concentration (3.86%) had been used once daily for 16 months. In the case of this patient, it was not possible to discover any of the previous indicated etiologies of peritoneal calcification such as significantly elevated values for the product Ca x P, overt secondary hyperparathyroidism, or relapsing peritonitis. It was realized that the use of a high-glucose dialysate in a patient on long-term CAPD treatment had been one causative factor. After peritoneal calcification had been confirmed, the calcium concentration of the dialysate changed from 3.5 mEq/l to 2.5 mEq/l and the patient was put on a regime of 2.0 g alumigel (aluminum-containing phosphate binders) a day. Eight months later, a CT scan was taken. The peritoneal calcification has clearly been mitigated. At present, CAPD therapy is being continued in the absence of any abdominal symptoms.


Assuntos
Calcinose/etiologia , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Doenças Peritoneais/etiologia , Idoso , Calcinose/diagnóstico , Calcinose/terapia , Feminino , Humanos , Doenças Peritoneais/diagnóstico , Doenças Peritoneais/terapia
17.
Artigo em Inglês | MEDLINE | ID: mdl-9927086

RESUMO

OBJECTIVE: The purposes of this study were to examine the time-related changes in pH, oxidation-reduction potential, and concentration of chlorine of electrolyzed neutral water and to evaluate the bactericidal effect of electrolyzed neutral water against bacteria from infected root canals. STUDY DESIGN: Various properties of electrolyzed neutral water--pH value, oxidation-reduction potential, and concentration of chlorine--were measured at different times after storage of the water in the open state, the closed state, or the closed-and-dark state. The bactericidal effect of the various electrolyzed neutral water samples was then tested against 17 strains of bacteria, including 15 strains isolated from infected canals, as well as against 1 strain of fungus. Each bacterial or fungal suspension was mixed with electrolyzed neutral water, and the 2 substances were reacted together for 1 minute. After incubation for 1 to 7 days, the bactericidal effect of the electrolyzed neutral water was determined. RESULTS: The pH value and oxidation-reduction potential of electrolyzed neutral water remained almost unchanged when the water was stored in a dark, closed container. However, the concentration of chlorine decreased from 18.4 ppm to 10.6 ppm. Electrolyzed neutral water showed a bactericidal or growth-inhibitory effect against the bacteria. CONCLUSIONS: The results indicate that electrolyzed neutral water maintains a constant pH and oxidation-reduction potential when kept in a closed container without light and that it exhibits a bacteriostatic/bactericidal action against isolates obtained from infected root canals.


Assuntos
Anti-Infecciosos Locais/farmacologia , Bactérias Anaeróbias/efeitos dos fármacos , Cavidade Pulpar/microbiologia , Irrigantes do Canal Radicular/farmacologia , Água/química , Água/farmacologia , Candida albicans/efeitos dos fármacos , Cloro/análise , Contagem de Colônia Microbiana , Escuridão , Armazenamento de Medicamentos , Eletrólise , Concentração de Íons de Hidrogênio , Ácido Hipocloroso/farmacologia , Testes de Sensibilidade Microbiana , Oxirredução , Fatores de Tempo
18.
Transplant Proc ; 46(3): 865-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24767367

RESUMO

BACKGROUND: New-onset diabetes mellitus (NODM) has a negative impact on graft and patient survivals. Hepatitis C virus (HCV) infection, high body mass index, increased donor and recipient ages, and calcineurin inhibitor (CNI) type have been identified as risk factors for the development of NODM. We aimed to elucidate the risk factors for the development of NODM and those for progressive glucose intolerance in adult living-donor liver transplant (LDLT) recipients. METHODS: We collected data from 188 primary liver transplant recipients (age > 16 years) who underwent LDLT from June 1991 to December 2011 at Hiroshima University Hospital. Risk factors for NODM and progressive impairment of glucose metabolism in pre-transplantation diabetes mellitus (DM) recipients were examined. RESULTS: Pre-transplantation DM was diagnosed in 32 recipients (19.3%). The overall incidence of NODM was 6.0% (8/134 recipients). Multivariate analysis revealed that old recipient age (≥55 years) is a unique predictive risk factor for developing NODM. The incident of pre-transplantation DM was significantly higher in recipients with HCV infection than in those without HCV. A high pre-transplantation triglyceride level was an independent risk factor for progressive impairment of glucose tolerance among 32 LDLT recipients with pre-transplantation DM. All of the NODM patients were being treated with tacrolimus at the time of diagnosis. Switching the CNI from tacrolimus to cyclosporine allowed one-half of the patients (4/8) to withdraw from insulin-dependent therapy. NODM and post-transplantation glucose intolerance had no negative impact on patient and graft outcomes. CONCLUSIONS: Older age of the recipient (≥55 years) was a significant risk factor for NODM. Hypertriglyceridemia in the recipients with DM is an independent risk factor for post-transplantation progressive impairment of glucose metabolism. NODM had no negative impact on outcomes in the LDLT recipients.


Assuntos
Diabetes Mellitus/etiologia , Glucose/metabolismo , Transplante de Fígado/efeitos adversos , Doadores Vivos , Índice de Massa Corporal , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tacrolimo/administração & dosagem
19.
Transplant Proc ; 46(3): 982-5, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24767397

RESUMO

Maintaining hepatic inflow and appropriate venous drainage is important for maximizing the capacity of the retrieved graft in liver transplantation. Here, we report a successful case of multiple hepatic vein (HV) reconstruction using an all-in-one sleeve patch graft of the autologous great saphenous vein to ensure adequate blood flow through the HV. A patient with hepatocellular carcinoma caused by hepatitis C virus-induced cirrhosis underwent living donor liver transplantation using a right lobe graft. A preoperative dynamic computed tomography scan and intraoperative findings revealed that the graft had three middle HV tributaries, a superficial vein, segment VIII HV (V8), and segment V HV (V5). The openings of the superficial vein and V8 were located very close to that of the right hepatic vein (RHV) in the cutting surface. Each HV had significant diameter and drainage territory requiring reconstruction. An autologous great saphenous vein was used to create a sleeve patch to incorporate the close-packed HV openings. The autologous sleeve patch graft was sutured to the openings of the RHV and the superficial vein and the hole created on the sleeve patch graft was anastomosed to the openings of V8 directly on the back table to create an all-in-one sleeve patch. For the V5 reconstruction, the recipient's intrahepatic portal vein graft was used to create an interpositional conduit from the recipient's V5 to the inferior vena cava. The postoperative course was uneventful and postoperative studies revealed good graft function with excellent blood flow in the HV.


Assuntos
Veias Hepáticas/cirurgia , Transplante de Fígado/métodos , Doadores Vivos , Procedimentos Cirúrgicos Vasculares , Idoso , Humanos , Masculino
20.
Med Phys ; 39(6Part9): 3694-3695, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28519058

RESUMO

PURPOSE: 131 I radionuclide therapy is widely performed in a thyroid cancer treatment, but there has been almost no evaluation of the dose distribution. The aim of this work is to develop the calculation system using the data of SPECT-CT and to examine the effects of their image resolutions on the dose distribution. METHODS: We designed and constructed an acrylic phantom for measurement. A radioactive iodine capsule and glass dosimeters can be set in the layer structure of the phantom. We put iodine capsules (37MBq, 111MBq, 185MBq) in the middle of the phantom and acquired SPECT-CT (Infinia Hawkeye4 (GE)) images. Both the CT value data (image resolution: 1.1 mm) and the intensity map data of SPECT (image resolution: 4.4 mm) were independently used for the estimation of the cumulative dose distribution generated from the radioactive iodine in the phantom. We adopted Monte Carlo program PHITS2.0 as the simulation of the dose calculation. The absolute dose was measured by glass dosimeters. RESULTS: The measurement result by glass dosimeters was very similar to the Monte Carlo simulation result, in which the difference was about 0.3 %. We obtained the dose distributions reconstructed by the radioactive iodine distribution using CT value data and SPECT data, respectively. The iodine distribution from CT could be finer than that of SPECT data because of its higher image resolution. As a result, the difference was found to be factor two in the middle of the iodine distribution. On the other hand, both of the dose distribution was almost same above 2.2 cm distance from the center. CONCLUSIONS: We can reconstruct the 131I dose distribution using SPECT-CT data. For more accurate calculation of the dose distribution, it would be crucial to increase the resolution of SPECT data.

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