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OBJECTIVES: To investigate the natural history of men with low levels of baseline prostate-specific antigen in terms of risk of increased prostate-specific antigen, developing prostate cancer and also the likelihood of detecting clinically insignificant cancer in population-based screening. METHODS: A total of 10,653 men aged between 55 and 68 years with baseline prostate-specific antigen levels of 2.0 ng/mL or lower screened annually were enrolled. The cumulative risks of increased prostate-specific antigen and developing cancer were investigated. The relationships of baseline prostate-specific antigen with clinicopathological features of screening-detected cancer were also investigated. RESULTS: A total of 1405 men (13.2%) showed serum prostate-specific antigen above 2.0 ng/mL and 68 (0.6%) were diagnosed with prostate cancer during the observation period. Cumulative probabilities of increased prostate-specific antigen above 2.0 ng/mL over 10 years were 7.7%, 18.3%, 57.3%, and 88.7% in men with baseline prostate-specific antigen levels of 0.0-0.5, 0.6-1.0, 1.1-1.5, and 1.6-2.0 ng/mL, respectively. The cumulative probabilities of developing prostate cancer at 4 years in men with baseline prostate-specific antigen of 0.0-1.0 and 1.1-2.0 ng/mL were 0.05% and 1.10%, respectively. Patients with unfavorable clinicopathological features were diagnosed at 3 years, and at 1 year after the initial screening visit in men with baseline prostate-specific antigen levels of 0.0-1.0 and 1.1-2.0 ng/mL, respectively. CONCLUSIONS: The cumulative probabilities of increased prostate-specific antigen and developing prostate cancer significantly increase with higher baseline prostate-specific antigen ranges. Our database could contribute to the establishment of a natural history-adjusted screening system in the future.
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Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Idoso , Estudos de Coortes , Detecção Precoce de Câncer , Humanos , Japão/epidemiologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico , RiscoRESUMO
OBJECTIVES: To clarify the present status regarding repeat examination in the annual population screening system in Japan, and to analyze the clinical characteristics and prostate-specific antigen kinetics of prostate cancer detected in this setting. METHODS: We summarized the annual individual data of prostate-specific antigen-based population screening in Kanazawa, Japan, and analyzed the prostate cancer detection rates at first and repeat screening. The clinical characteristics were compared between patients detected at first and repeat screening. The patients were classified according to favorable or unfavorable clinical characteristics of cancer, and prostate-specific antigen kinetics were compared between the two groups. RESULTS: From 2000 to 2011, 19 620 men participated in this screening program, and a total of 59 019 screenings were carried out. The total annual numbers of examinees increased, and the annual rates of first examinees gradually decreased. The annual detection rates of cancer at total screening decreased in the second year. The annual detection rate at first screening was not different from that in the first year. The rate of patients with favorable cancer features was significantly higher among patients detected at repeat screening than at first screening. The rates of patients with high prostate-specific antigen velocity and low prostate-specific antigen doubling time were significantly higher in unfavorable than favorable cancer patients in repeat screening. CONCLUSIONS: Repeat population screening could contribute to early detection of prostate cancer, and it seems that prostate-specific antigen kinetics might predict the cancer characteristics in repeat screening.
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Detecção Precoce de Câncer , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Idoso , Humanos , Japão , Cinética , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVES: To investigate the age-specific reference range of prostate-specific antigen and clinical characteristics of screening-detected cancer in prostate-specific antigen-based screening, and to verify the age-specific prostate-specific antigen cut-offs in the Japanese Urological Association Guidelines. METHODS: Prostate-specific antigen distributions were estimated in a total of 69,028 screening tests according to the age of the participants in population screening from 2000 to 2013. The age-specific reference range of prostate-specific antigen for detection of cancer was investigated by analyzing the receiver operating characteristic curves. Furthermore, the clinicopathological features of screening-detected cancer with serum prostate-specific antigen levels below the age-specific prostate-specific antigen cut-off in the Japanese Urological Association Guidelines were also investigated. RESULTS: Of all 69,028 screens, 2053 prostate biopsies (2.97%) were carried out and 549 cases of cancer (0.79%) were diagnosed. The 95th percentiles in all participants aged 54-59, 60-64, 65-69 and 70-75 years old were 2.90, 3.60, 4.10, and 4.70 ng/mL, respectively. The optimal prostate-specific antigen cut-offs for cancer detection determined from the receiver operating characteristic curves were 2.3 and 2.6 for the age ranges 54-69 and 70-75 years, respectively. These values were lower than the age-specific cut-offs in the Japanese Urological Association Guidelines. Of all 137 patients with prostate-specific antigen levels below the age-specific cut-offs in the Japanese Urological Association Guidelines, 80 (58.4%) had unfavorable clinicopathological features as active surveillance criteria. CONCLUSIONS: The age-specific reference range of prostate-specific antigen might be lower than that recommended in the Japanese Urological Association Guidelines. An individualized and natural history-adjusted screening system should be established for screening participants with low prostate-specific antigen level.
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Calicreínas/sangue , Guias de Prática Clínica como Assunto , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Fatores Etários , Idoso , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/sangue , Valores de Referência , Estudos RetrospectivosRESUMO
BACKGROUND: This study evaluated the effect of exercise training on body temperature and clarified the relationship between body temperature and body composition in the elderly. METHODS: In this retrospective cohort study, a total of 91 elderly participants performed aerobic and anaerobic exercise training twice a week for 2 years. Non-contact infrared thermometer and bioelectrical impedance analysis were performed at baseline and at 2 years. RESULTS: Mean age of study participants was 81.0 years. The participants were divided into two groups by baseline body temperature of 36.3 °C; lower body temperature group (n = 67) and normal body temperature group (n = 24). Body temperature rose significantly after exercise training in the lower body temperature group (36.04 ± 0.11 °C to 36.30 ± 0.13 °C, p < 0.0001), whereas there was no significant difference in the normal body temperature group (36.35 ± 0.07 °C to 36.36 ± 0.13 °C, p = 0.39). A positive correlation was observed between the amount of change in body temperature and baseline body temperature (r = -0.68, p < 0.0001). Increase in skeletal muscle mass was an independent variable related to the rise in body temperature by the multivariate logistic regression analysis (odds ratio: 4.77, 95% confidence interval: 1.29-17.70, p = 0.02). CONCLUSIONS: Exercise training raised body temperature in the elderly, especially those with lower baseline body temperature.
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Emergence of malignant ureteral obstruction (MUO) has been reported as a sign of poor prognosis; however, the distribution of survival time in patients with MUO is considerably wide, and no risk classification score has been constructed. To evaluate whether a novel risk classification score for overall survival that we previously developed, is effective in a large cohort. Investigator-initiated, prospective, multicenter diagnostic/prognostic study was conducted. Patients with MUO were divided into three risk groups based on the score calculated using four prognostic factors (PLaCT: Primary site, Laterality, serum Creatinine level, and Treatment for primary site) at the first visit, and prospective follow-up was performed. Overall survival and ureteral stent failure-free survival of each risk group were compared. In total, 300 patients with 21 different primary sites were enrolled. The numbers of patients in good, intermediate, and poor risk groups were 105, 106, and 89, respectively. Median survival times of patients in good, intermediate, and poor risk groups were 406, 221, and 77 days, respectively (P < 0.0001). In 217 patients with ureteral stenting, median ureteral stent failure-free survival times of good, intermediate, and poor risk groups were 385, 183, and 57 days, respectively (P < 0.0001). Limitations include the limited ethnicity and the extended duration of study enrollment. The novel PLaCT risk classification score could divide MUO patients into three risk groups with distinct survival times and ureteral stent patencies. This score will aid in establishing prognosis and treatment strategy for all physicians engaged in cancer treatment.
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Ureter/patologia , Obstrução Ureteral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Stents/efeitos adversos , Obstrução Ureteral/etiologia , Neoplasias da Bexiga Urinária/etiologia , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVES: To analyze the clinical effects of flutamide as a second-line anti-androgen for combined androgen blockade in patients with castration-resistant prostate cancer (CRPC) initially treated with bicalutamide as a first-line anti-androgen. METHODS: Our study population consisted of 16 patients with CRPC who were treated with flutamide (375 mg daily) as second-line hormonal therapy. Dehydroepiandrosterone (DHEA), androstenedione, androstenediol, testosterone and dihydrotestosterone were measured to investigate the relationship between plasma androgens and outcome following treatment. Furthermore, adrenal androgen levels in a medium of adrenal cancer cell line were also measured. RESULTS: Second-line hormonal therapy using flutamide resulted in a reduction of the prostate-specific antigen (PSA) level in 14 (87.5%) of 16 patients. A PSA decline greater than 50% was observed in 8 (50%) of the 16 patients. The duration of median responsiveness was 6.25 months. PSA elevation of baseline androstenediol level was a predictive factor of PSA responsiveness. The lower DHEA group improved the duration of responsiveness to flutamide. In vitro, 3 micromol/L flutamide suppressed DHEA, androstenedione and androstenediol synthesis compared with bicalutamide in a medium of adrenal cancer cell line. CONCLUSIONS: Our data show that flutamide suppresses the adrenal androgens in comparison with bicalutamide. The responsiveness and response duration of flutamide can be predicted in patients with a higher baseline androstenediol level and a lower DHEA level. Metabolites from adrenal androgens contribute to the progression of prostate cancer.
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Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Androgênios/sangue , Flutamida/uso terapêutico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico , Glândulas Suprarrenais/metabolismo , Idoso , Idoso de 80 Anos ou mais , Androgênios/metabolismo , Linhagem Celular Tumoral , Humanos , Masculino , Orquiectomia , Prognóstico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Terapia de SalvaçãoRESUMO
The H-1 NMR spectra of a series of linear poly(ethylene oxides) compounds (POE compounds) were measured in dichloromethane-d2 at 25 degrees C, where the POE compounds (HO-(CH2CH2O-)n-R) were unsubstituted POE, HEOn (R=H, n=3, 4, 6), and alkyl-substituted POE, DEOn (R=C12H25, n=4, 6, 8) and MeEO6 (R=CH3, n=6). All the peaks of H-1 NMR signals were assigned to each methylene proton of POE. The chemical shifts and coupling constant between vicinal protons were evaluated by a complete spin analysis. The spectral changes of POE compounds by the addition of potassium ion were measured at various metal-to-POE ratios. The chemical shift change of each methylene proton by the formation of the complex was evaluated. The downfield shift of methylene protons caused by the complex formation indicates that the ethylene oxide that the ethylene oxide moiety is coordinating to surround the potassium ion in the same manner as the cyclic crown ether complexes. The results of spin lattice relaxation time measurements of DEO6 suggest that all the methylenes of the ethylene oxides are immobilized by the coordination to the metal ion. Thus, it was confirmed that all oxygens of POE are participating in the complex formation.
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Solvent sublation has been studied for the separation and determination of trace iron(II) in various kinds of water samples. A strongly magenta-colored anionic [Fe(FZ)3](4-) complex was formed at pH 5.0 upon adding 3-(2-pyridyl)-5,6-bis(4-phenylsulfonic acid)-1,2,4-triazine (ferrozine, FZ) to the sample solution. Tetrabutylammonium bromide (TBAB) was added in the solution to form the (TBA)4[Fe(FZ)3)] ion pair, and an oleic acid (HOL) surfactant was added. Then, the (TBA)4[Fe(FZ)3] ion pairs were floated by vigorous shaking in the flotation cell and extracted into methyl isobutyl ketone (MIBK) on the surface of the aqueous solution. The iron collected in the MIBK layer was measured directly by spectrophotometry and/or flame atomic-absorption spectrophotometry. Different experimental variables that may affect the sublation efficiency were thoroughly investigated. The molar absorptivity of the (TBA)4[Fe(FZ)3] ion pair was 2.8 x 10(4) l mol(-1) cm(-1) in the aqueous layer. Beer's law held up to 1.0 mg L(-1) Fe(II) in the aqueous as well as in the organic layers. The adopted solvent sublation method was successfully applied for the determination of Fe(II) in natural water samples with a preconcentration factor of 200. The application was extended to determine iron in pharmaceutical samples.
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Ferrozina/química , Ferro/análise , Compostos de Amônio Quaternário/análise , Solventes , Espectrofotometria/métodos , Relação Dose-Resposta a Droga , Concentração de Íons de Hidrogênio , Íons , Modelos Químicos , Modelos Estatísticos , Ácido Oleico/química , Espectrofotometria/instrumentação , Tensoativos , Temperatura , Triazinas/química , Água/análiseRESUMO
BACKGROUND: To investigate the cumulative probability of developing prostate cancer according to prostate-specific antigen (PSA) velocity (PSAV) from first-to second-round PSA-based population screening in men with low baseline serum PSA levels. PATIENTS AND METHODS: A total of 11,913 men aged between 54 and 69 years with baseline PSA levels of ≤2.0 ng/ml at the first population screening and who underwent population screening at least twice, were enrolled. The cumulative probability of developing prostate cancer according to age, baseline PSA and PSAV was investigated. The clinicopathological features of screen-detected cancer were also investigated. RESULTS: Out of the 11,913 men, 110 (0.92%) were pathologically diagnosed with prostate cancer during the observation period. The cumulative probability of developing prostate cancer in all participants after 5 and 10 years was 0.64% and 1.79%, respectively. Univariate and multivariate analyses determined that baseline PSA levels and PSAVs were significant predictors of developing cancer and the hazard ratio increased with increasing baseline PSA levels and PSAVs. The optimal PSAV cut-off levels for prostate cancer development were 0.069, 0.106 and 0.285 for the baseline PSA ranges of 0.0-1.0, 1.1-1.5 and 1.6-2.0 ng/ml, respectively. There were no significant differences in baseline PSA levels and PSAVs according to the clinical characteristics of the screen-detected prostate cancer patients. CONCLUSION: The present study demonstrated that serum PSA levels at second round screening were a strong predictor of cancer development in men with baseline PSA levels≤2.0 ng/ml at the first population screening.
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Biomarcadores Tumorais/análise , Detecção Precoce de Câncer , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Idoso , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/sangue , Índice de Gravidade de DoençaRESUMO
The synergistic extraction of 14 trivalent lanthanoids (Ln(3+)) into 1,2-dichloroethane with a linear polyether (DEO6), HO(C(2)H(4)O)(6)C(12)H(25), and ß-diketones (HA) having different substituents was investigated at 25.0°C. The HAs used were trifluoroacetylacetone (Htfa), thenoyltrifluoroacetone (Htta), benzoyltrifluoroacetone (Hbta), naphthoyltrifluoroacetone (Hnta), and pivaloyltrifluoroacetone (Hpta). By the extraction of Ln(3+) with ß-diketone alone, the extraction constants of the neutral LnA(3) complex, [Formula: see text] , were determined. The intrinsic extraction constants, [Formula: see text] , were evaluated by employing the regular solution theory. Results indicate that the extractability of LnA(3) is dependent on the lipophilicity of the ligand, and the planar aromatic rings do not cause steric hindrance in the formation of the binary complex. Addition of DEO6 significantly enhanced the extraction of Ln(3+) by the formation of LnA(3)(DEO6). The ternary complex formation constants, ß(add), were determined for all the Ln(3+) and HA. The ß(add) of bta(-) and nta(-) complexes is similar with those of tfa(-) complexes, indicating that planar aromatic rings do not sterically hinder even the formation of the ternary complex. The higher values of ß(add) for the complexes of tta(-), which has a slightly dipolar thenoyl moiety, can be accounted for the presence of ligand-ligand interaction. The formation constants of the ternary complexes of pta(-) were lower compared to complexes of other ß-diketones because of steric hindrance due to the bulky t-butyl moiety. The detailed structures of the ternary complexes in solution were elucidated by NMR spectroscopy. Estimated structures sufficiently explain the variation in stability constants of LnA(3)(DEO6) among HAs and across the series of Ln(3+). The structures thus obtained were ascertained by the molecular models created by MM2 calculation.
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The structures of the ternary complexes of lanthanoid and yttrium (Ln3+)-thenoyltrifluoroacetonates (tta-) with polyether (POE) in organic phase were investigated by 1H-NMR spectroscopy, where the POEs are crown ethers (18-crown-6 and benzo-18-crown-6) and monodispersed linear polyethers (DEOn: HO-(CH2CH2O-)nC12H25, where n=4, 6, 8). The changes in chemical shift of methylene protons of POE by addition of the adduct complex [Ln(tta)3(POE)] were measured at various Ln3+-to-POE concentration ratios. Chemical shift changes for each proton of POE by the formation of [Ln(tta)3(POE)] were determined. Results revealed that oxygen atoms at the hydroxyl terminal of linear POE have higher tendency to coordinate to the metal ion in [Ln(tta)3] complex. Three (for La3+) or two (for Lu3+ or Y3+) oxygen atoms of the POE coordinate to the metal ion without substitution of tta- ligands to satisfy the metal ion's coordination number of nine or eight, respectively. In the case of 18-membered crown ether complexes, La3+ is incorporated inside the cavity of the POE, displacing one of the three tta- from the inner coordination sphere while the other two remain coordinated to the metal ion. On the other hand, for the adduct of Y3+ complex with crown ether, all three tta- ligands are directly coordinating to the metal ion.
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Éteres/química , Espectroscopia de Ressonância Magnética/métodos , Metais Terras Raras/química , Cloreto de Metileno/química , Tenoiltrifluoracetona/química , Cátions , PrótonsRESUMO
The equilibrium and structure of the complex formed by Al(III) and ethylenediamine-N,N'-bis(3-hydroxy-2-propionate) (EDBHP2-) have been studied using pH-potentiometry, 1H and 27Al NMR, ESI MS and single crystal X-ray diffraction methods. The EDBHP ligand is a strong Al-binder in aqueous solution for pH between 4 and 8 and for c(Al) = c(EDBHP)> or = 0.1 mmol dm(-3). The dominating complex identified by ESI MS and potentiometry is a neutral dimer, Al2L2(OH)2, with logbeta(22-2) = 14.16 +/- 0.03. In the solid Al2(EDBHP)2(OH)2.2H2O the Al(III) ions are connected through a double hydroxo bridge. Both four-dentate organic ligands are coordinated terminally through two carboxylate groups and two N-donors forming three five-membered chelate rings. The hydroxyl groups of the ligand EDBHP remain protonated and are not coordinated to the aluminium ions. The structure and composition of the dimer are very likely the same in solution and the solid state.