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1.
AJNR Am J Neuroradiol ; 38(5): 882-889, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28279985

RESUMO

BACKGROUND AND PURPOSE: ADC as a marker of tumor cellularity has been promising for evaluating the response to therapy in patients with glioblastoma but does not successfully stratify patients according to outcomes, especially in the upfront setting. Here we investigate whether restriction spectrum imaging, an advanced diffusion imaging model, performed after an operation but before radiation therapy, could improve risk stratification in patients with newly diagnosed glioblastoma relative to ADC. MATERIALS AND METHODS: Pre-radiation therapy diffusion-weighted and structural imaging of 40 patients with glioblastoma were examined retrospectively. Restriction spectrum imaging and ADC-based hypercellularity volume fraction (restriction spectrum imaging-FLAIR volume fraction, restriction spectrum imaging-contrast-enhanced volume fraction, ADC-FLAIR volume fraction, ADC-contrast-enhanced volume fraction) and intensities (restriction spectrum imaging-FLAIR 90th percentile, restriction spectrum imaging-contrast-enhanced 90th percentile, ADC-FLAIR 10th percentile, ADC-contrast-enhanced 10th percentile) within the contrast-enhanced and FLAIR hyperintensity VOIs were calculated. The association of diffusion imaging metrics, contrast-enhanced volume, and FLAIR hyperintensity volume with progression-free survival and overall survival was evaluated by using Cox proportional hazards models. RESULTS: Among the diffusion metrics, restriction spectrum imaging-FLAIR volume fraction was the strongest prognostic metric of progression-free survival (P = .036) and overall survival (P = .007) in a multivariate Cox proportional hazards analysis, with higher values indicating earlier progression and shorter survival. Restriction spectrum imaging-FLAIR 90th percentile was also associated with overall survival (P = .043), with higher intensities, indicating shorter survival. None of the ADC metrics were associated with progression-free survival/overall survival. Contrast-enhanced volume exhibited a trend toward significance for overall survival (P = .063). CONCLUSIONS: Restriction spectrum imaging-derived cellularity in FLAIR hyperintensity regions may be a more robust prognostic marker than ADC and conventional imaging for early progression and poorer survival in patients with glioblastoma. However, future studies with larger samples are needed to explore its predictive ability.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Glioblastoma/diagnóstico por imagem , Adulto , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Glioblastoma/classificação , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
2.
Prostate Cancer Prostatic Dis ; 19(2): 168-73, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26754261

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI) is emerging as a robust, noninvasive method for detecting and characterizing prostate cancer (PCa), but limitations remain in its ability to distinguish cancerous from non-cancerous tissue. We evaluated the performance of a novel MRI technique, restriction spectrum imaging (RSI-MRI), to quantitatively detect and grade PCa compared with current standard-of-care MRI. METHODS: In a retrospective evaluation of 33 patients with biopsy-proven PCa who underwent RSI-MRI and standard MRI before radical prostatectomy, receiver-operating characteristic (ROC) curves were performed for RSI-MRI and each quantitative MRI term, with area under the ROC curve (AUC) used to compare each term's ability to differentiate between PCa and normal prostate. Spearman rank-order correlations were performed to assess each term's ability to predict PCa grade in the radical prostatectomy specimens. RESULTS: RSI-MRI demonstrated superior differentiation of PCa from normal tissue, with AUC of 0.94 and 0.85 for RSI-MRI and conventional diffusion MRI, respectively (P=0.04). RSI-MRI also demonstrated superior performance in predicting PCa aggressiveness, with Spearman rank-order correlation coefficients of 0.53 (P=0.002) and -0.42 (P=0.01) for RSI-MRI and conventional diffusion MRI, respectively, with tumor grade. CONCLUSIONS: RSI-MRI significantly improves upon current noninvasive PCa imaging and may potentially enhance its diagnosis and characterization.


Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias da Próstata/cirurgia , Curva ROC , Estudos Retrospectivos , Carga Tumoral
3.
Prostate Cancer Prostatic Dis ; 18(1): 81-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25559097

RESUMO

BACKGROUND: Standard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI). METHODS: We compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique. RESULTS: 27 patients were evaluated, excluding one patient where distortion could not be performed. Preoperative standard MRI correctly identified extraprostatic the extension in two of the nine pT3 (22%) patients, whereas RSI-MRI identified EPE in eight of nine (89%) patients. RSI-MRI correctly identified pT2 disease in the remaining 18 patients. CONCLUSIONS: In this proof of principle study, we conclude that our novel RSI-MRI technology is feasible and shows promise for substantially improving PCa imaging. Further translational studies of prostate RSI-MRI in the diagnosis and staging of PCa are indicated.


Assuntos
Imageamento por Ressonância Magnética/métodos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Gadolínio , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Próstata/patologia , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Radiografia
5.
Artigo em Inglês | MEDLINE | ID: mdl-24066010

RESUMO

Purpose. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting side effect of cytostatic drugs. Since there are no proven therapeutic procedures against CIPN, we were interested to define the role of electroacupuncture (EA) from which preliminary data showed promising results. Methods. In a randomized trial with a group sequential adaptive design in patients with CIPN, we compared EA (LV3, SP9, GB41, GB34, LI4, LI11, SI3, and HT3; n = 14) with hydroelectric baths (HB, n = 14), vitamin B1/B6 capsules (300/300 mg daily; VitB, n = 15), and placebo capsules (n = 17). The statistical power in this trial was primarily calculated for proving EA only, so results of HB and VitB are pilot data. Results. CIPN complaints improved by 0.8 ± 1.2 (EA), 1.7 ± 1.7 (HB), 1.6 ± 2.0 (VitB), and 1.3 ± 1.3 points (placebo) on a 10-point numeric rating scale without significant difference between treatment groups or placebo. In addition no significant differences in sensory nerve conduction studies or quality of life (EORTC QLQ-C30) were found. Conclusions. The used EA concept, HB, and VitB were not superior to placebo. Since, contrary to our results, studies with different acupuncture concepts showed a positive effect on CIPN, the effect of acupuncture on CIPN remains unclear. Further randomized, placebo controlled studies seem necessary. This trial is registered with DRKS00004448.

6.
AJNR Am J Neuroradiol ; 34(6): 1157-63, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23275591

RESUMO

BACKGROUND AND PURPOSE: DTI is being increasingly used to visualize critical white matter tracts adjacent to brain tumors before neurosurgical resection. However, brain tumors, particularly high-grade gliomas, are typically surrounded by regions of FLAIR hyperintensity that include edema, which increase isotropic diffusion, degrading the ability of standard DTI to uncover orientation estimates within these regions. We introduce a new technique, RSI, which overcomes this limitation by removing the spherical, fast diffusion component introduced by edema, providing better analysis of white matter architecture. MATERIALS AND METHODS: A total of 10 patients with high-grade gliomas surrounded by FLAIR-HI that at least partially resolved on follow-up imaging were included. All patients underwent RSI and DTI at baseline (FLAIR-HI present) and at follow-up (FLAIR-HI partially resolved). FA values obtained with RSI and DTI were compared within regions of FLAIR-HI and NAWM at both time points. RESULTS: RSI showed higher FA in regions of FLAIR-HI and NAWM relative to DTI, reflecting the ability of RSI to specifically measure the slow, restricted volume fraction in regions of edema and NAWM. Furthermore, a method by time interaction revealed that FA estimates increased when the FLAIR-HI resolved by use of standard DTI but remained stable with RSI. Tractography performed within the region of FLAIR-HI revealed the superior ability of RSI to track fibers through severe edema relative to standard DTI. CONCLUSIONS: RSI improves the quantification and visualization of white matter tracts in regions of peritumoral FLAIR-HI associated with edema relative to standard DTI and may provide a valuable tool for neurosurgical planning.


Assuntos
Edema Encefálico/patologia , Neoplasias Encefálicas/patologia , Imagem de Tensor de Difusão/métodos , Glioma/patologia , Fibras Nervosas Mielinizadas/patologia , Adulto , Idoso , Astrocitoma/patologia , Astrocitoma/cirurgia , Edema Encefálico/cirurgia , Neoplasias Encefálicas/cirurgia , Feminino , Seguimentos , Glioblastoma/patologia , Glioblastoma/cirurgia , Glioma/cirurgia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios
8.
Eur Respir J ; 35(2): 381-90, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19643940

RESUMO

The prognosis for lung cancer patients treated with chemotherapy is poor. Single nucleotide polymorphisms (SNPs) in matrix metalloproteinase (MMP) genes could influence treatment outcome by altering apoptotic pathways. Eight SNPs with known or suspected phenotypic effect in six genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) were investigated. For 349 Caucasian patients with primary lung cancer, receiving first-line chemotherapy, three different endpoints were analysed: response after the second cycle, progression free survival (PFS) and overall survival (OS). The prognostic value of the SNPs was analysed using multiple logistic regression for all patients and histology-, stage- and treatment-specific subgroups. Hazard ratio estimates for PFS and OS were calculated using Cox regression methods. None of the investigated polymorphisms modified response significantly in the whole patient population. However, tumour stage IIIB variant allele carriers of MMP2 C-735T showed a significantly worse response. PFS was significantly prolonged in MMP1 G-1607GG variant allele carriers and OS in small cell lung cancer patients carrying the MMP12 A-82G variant allele. In conclusion, this study identified SNPs in MMP1, MMP2, MMP7 and MMP12 for further investigation as possible predictors of chemotherapy outcome in lung cancer patients.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Antineoplásicos/farmacologia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , Pessoa de Meia-Idade , Polimorfismo Genético , Prognóstico
9.
Ann Oncol ; 21(5): 1094-9, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19858085

RESUMO

BACKGROUND: There are only few studies on cancer patients who are treated in complementary and alternative medicine clinics and comparing them with patients in conventional care. We will present the comparison of characteristics of two patient cohorts: one was treated in a homeopathic cancer care clinic and one was treated in a conventional oncology care (CC) outpatient clinic. PATIENTS AND METHODS: Six-hundred and forty-seven patients were included in this cross-sectional cohort study and had to fill in questionnaires [health-related quality of life (QoL) (Functional Assessment of Cancer Therapy-General Scale), depression and anxiety (Hospital Anxiety and Depression Scale), fatigue (Multidimensional Fatigue Inventory) and expectancies toward treatment]. Clinical data were extracted from medical records. This study presents the comparison of both cohorts. RESULTS: Patients in the homeopathy cohort are younger, better educated and more often employed than patients in the CC cohort. The most pronounced differences indicate longer disease histories and different diagnostic and clinical pretreatment variables. Despite the clinical differences, QoL as well as anxiety, depression and fatigue was similar in both the groups. CONCLUSIONS: Homeopathic treatment is sought by cancer patients at a different phase during the course of the disease, which has particular implications for research. However, expectancies toward the benefit of the treatment as well as QoL data are similar.


Assuntos
Homeopatia , Neoplasias/terapia , Qualidade de Vida , Sintomas Afetivos/etiologia , Sintomas Afetivos/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Terapia Combinada , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Pacientes Ambulatoriais/estatística & dados numéricos , Dor/etiologia , Manejo da Dor , Satisfação do Paciente , Padrões de Prática Médica , Dosagem Radioterapêutica , Inquéritos e Questionários , Taxa de Sobrevida , Resultado do Tratamento
10.
Scand J Immunol ; 69(6): 563-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19439018

RESUMO

It is well known that sera of patients with systemic autoimmunity contain autoantibodies to nuclear antigens. It is also known that patients with systemic autoimmunity have an increased risk for the development of tumours. Interestingly, tumour patients frequently develop autoantibodies and there is a growing list of potential tumour-associated antigens. It is, however, not known whether or not patients with systemic autoimmunity also develop antibodies to tumour-associated antigens. Here we describe the development of a novel multiprotein array allowing us to screen for autoantibodies to 30 different tumour-associated antigens in parallel. Using this novel assay, we found that the frequency of autoantibodies to the selected tumour-associated antigens is increased between 2- and 14-fold in patients with systemic autoimmunity compared with an age-matched control group.


Assuntos
Antígenos de Neoplasias/imunologia , Autoanticorpos/sangue , Doenças Autoimunes/sangue , Immunoblotting/métodos , Autoantígenos/sangue , Doenças Autoimunes/imunologia , Humanos , Proteínas Recombinantes/imunologia
11.
J Psychosoc Oncol ; 27(2): 274-96, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19337933

RESUMO

Neuropsychological deficits are among the negative side effects of adjuvant chemotherapy for breast cancer. We compared the effects of two types of neuropsychological interventions against a control group with no specific training in a total of 96 female in-patients undergoing oncological rehabilitation. Most results of a comprehensive neuropsychological test battery improved significantly during the patients' oncological rehabilitation in all three groups; we identified no specific intervention effects. We observed little overall correlation between the neuropsychological test results and the patients' own appraisals of their mental capacity. Clinically relevant neuropsychological deficits were still evident 6 months later in a small subgroup of patients.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/reabilitação , Instrução por Computador , Testes Neuropsicológicos/estatística & dados numéricos , Terapia Ocupacional , Prática Psicológica , Adulto , Antineoplásicos/uso terapêutico , Atenção/efeitos dos fármacos , Neoplasias da Mama/psicologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Transtornos Cognitivos/psicologia , Feminino , Alemanha , Humanos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/psicologia , Transtornos da Memória/reabilitação , Memória de Curto Prazo/efeitos dos fármacos , Pessoa de Meia-Idade , Psicometria , Qualidade de Vida/psicologia , Tempo de Reação/efeitos dos fármacos , Software
12.
J Med Food ; 12(6): 1316-20, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20041787

RESUMO

Consumption of certain fruits and vegetables is now widely associated with chemoprevention of degenerative diseases like cancer and cardiovacsular disorders because of their antioxidant components. Polyphenols, a heterogeneous group of compounds, are one of these constituents. Hibiscus esculentus L. (Family Malvaceae), commonly referred to as okro, okra, or lady's finger, is an important component of diet in Nigeria and other countries in sub-Saharan Africa. In this article, we describe the polyphenol composition and antioxidant potential of H. esculentus of Nigerian origin. Quercetin glucoside (quercetrin) and an unidentified flavonoid were detected. In vitro antioxidant assay of methanol extract of the fruits showed potent antioxidant/radical scavenging activities with 50% inhibitory concentration values of 25 and 43 microL when analyzed by the xanthine oxidase and 2-deoxyguanosine methods, respectively. These data suggest that H. esculentus, popular especially during the rainy season in Nigeria and many tropical West, Central, and Eastern African countries, is a good contributor to the antioxidant status and disease chemoprevention of people in these countries.


Assuntos
Antioxidantes/química , Flavonoides/química , Frutas/química , Hibiscus/química , Fenóis/química , Extratos Vegetais/química , Sequestradores de Radicais Livres/química , Nigéria , Polifenóis
13.
J Med Food ; 12(6): 1321-5, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20041788

RESUMO

Polyphenols are abundant micronutrients in our diet that have been credited with chemoprevention of diseases associated with oxidative stress. In this study, we investigated the whole ripened fruit of Dacryodes edulis (G.Don) H.J Lam, a multipurpose tree growing in West and Central Africa and other countries bordering the Gulf of Guinea, for polyphenol content as well as its antioxidant/radical scavenging capacity. Analysis of the methanol extract of the fruit by high-performance liquid chromatography coupled to an ultraviolet dual-array detector and mass-selective detector revealed the presence of catechol (9.27 mg/kg), gallate (10.40 mg/kg), methylgallate (0.88 mg/kg), ellagic acid (3.10 mg/kg), quercetin (0.21 mg/kg), and quercetin rhamnoside (0.76 mg/kg). The extract showed very high antioxidant potential (50% inhibitory concentration [IC(50)] = 14 microL), but a rather weak radical scavenging activity (IC(50) = 357 microL), when tested in vitro with the xanthine oxidase and 2-deoxyguanosine assay model systems, respectively. These results suggest that consumption of D. edulis could contribute to prevention of diseases that are related to oxidative stress.


Assuntos
Antioxidantes/química , Burseraceae/química , Flavonoides/química , Frutas/química , Fenóis/química , Extratos Vegetais/química , África Central , Sequestradores de Radicais Livres/química , Polifenóis
14.
Carcinogenesis ; 30(2): 282-5, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19037091

RESUMO

The impact of DNA damage commonly thought to be involved in chronic degenerative disease causation is particularly detrimental during fetal development. Within a multicenter study, we analyzed 77 white blood cell (WBC) samples from mother-newborn child pairs to see if imprinting of DNA damage in mother and newborn shows a similar pattern. Two adducts 1,N(6)-ethenodeoxyadenosine (epsilondA) and 3,N(4)-ethenodeoxycytidine (epsilondC) were measured by our ultrasensitive immunoaffinity (32)P-post-labeling method. These miscoding etheno-DNA adducts are generated by the reaction of lipid peroxidation (LPO) end products such as 4-hydroxy-2-nonenal with DNA bases. Mean epsilondA and epsilondC levels when expressed per 10(9) parent nucleotides in WBC-DNA from cord blood were 138 and 354, respectively; in maternal WBC-DNA, the respective values were 317 and 916. Thus, the DNA-etheno adduct levels were reliably detectable and about two times lower in child cord blood, the difference being significant at P < 0.0004. Analysis of epsilondA and epsilondC levels in cord versus maternal blood WBC showed strong positive correlations (R(2) approximately 0.9, P < 0.00001). In conclusion, LPO-induced DNA damage arising from endogenous reactive aldehydes in WBC of both mother and newborn can be reliably assessed by epsilondA and epsilondC as biomarkers. The high correlation of etheno adduct levels in mother and child WBC suggests that a typical signature of DNA damage is induced similarly in fetus and mother. Prospective cohort studies have to reveal whether these two WBC-DNA adducts could serve as risk indicator for developing hematopoietic cancers and other disorders later in life.


Assuntos
Adutos de DNA/química , Dano ao DNA/fisiologia , Desoxiadenosinas/sangue , Desoxicitidina/análogos & derivados , Leucócitos/metabolismo , Aldeídos/metabolismo , Criança , Desoxicitidina/sangue , Feminino , Sangue Fetal , Humanos , Recém-Nascido , Peroxidação de Lipídeos , Projetos Piloto , Gravidez
15.
Psychooncology ; 18(7): 775-82, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19061196

RESUMO

OBJECTIVE: Various studies have demonstrated that neuropsychological deficits are potential side-effects of adjuvant therapy in breast cancer patients. To date, little is known about the long-term development of these deficits and their implications for patients' everyday life. METHODS: Within the framework of an intervention study, 90 breast cancer patients after adjuvant chemotherapy were examined at three measurement points. The focus of this article is on the cognitive status at the last measurement point (on average, 9 months after the end of oncological therapy) and, in particular, on the correlations between subjective self-appraisal and neuropsychological test results. RESULTS: Although the prevalence of neuropsychological deficits significantly decreased as time elapsed after the end of oncological therapy, 21% of our sample group still displayed indications of clinically relevant long-term cognitive deficits. A sub-group of severely affected patients showed specific deficits in verbal-semantic memory and judged their everyday cognitive performance as being extremely poor. CONCLUSION: The identification of verbal-semantic memory as a specific problem area has important implications on the planning of future studies with regard to both the examination of underlying pathophysiological mechanisms and the specific effects of these deficits on patients' self-appraisal.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Transtornos Cognitivos/induzido quimicamente , Testes Neuropsicológicos/estatística & dados numéricos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/epidemiologia , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/psicologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Inventário de Personalidade/estatística & dados numéricos , Psicometria , Autoimagem , Papel do Doente
16.
Regul Toxicol Pharmacol ; 53(2): 107-20, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19027814

RESUMO

In response to a Hazard Notice by the Medical Devices Agency of the UK in 2000 regarding the Trilucent breast implant (TBI), an expert panel was convened to implement a research program to determine whether genotoxic compounds were formed in the soybean oil filler (SOF) of TBIs and whether these could be released to produce local or systemic genotoxicity. The panel established a research program involving six laboratories. The program recruited 47 patients who had received TBIs (9 patients had received silicone implants previously). A reference group (REBI) of 34 patients who had exchanged either silicone (17 patients) implants (REBI-E) or patients (17) who were to receive primary implantation augmentation with silicone (REBI-PIA), and who were included as needed to increase either the pre- or post-explantation sample number. Of the 17 REBI-E patients, 5 had silicone implants and 12 had saline implants previously (prior to the last exchange). Investigation was undertaken before and after replacement surgery in the TBI patients and before and after replacement or augmentation surgery in the REBI patients. The pre- to post-operative sample interval was 8-12 weeks. Pre-operative samples were collected within 7 days prior to the operation. Information on a variety of demographic and behavioral features was collected. Biochemical and biological endpoints relating to genotoxic lipid peroxidation (LPO) products potentially formed in the SOF, and released locally or distributed systemically, were measured. The SOF of explanted TBIs was found to have substantial levels of LPO products, particularly malondialdehyde (MDA), and low levels of trans-4-hydroxy-2-nonenal (HNE) not found in unused implants. Mutagenicity of the SOF was related to the levels of MDA. Capsules that formed around TBIs were microscopically similar to those of reference implants, but MDA-DNA adducts were observed in capsular macrophages and fibroblasts of only TBI capsules. These cell types are not progenitors of breast carcinoma (BCa) and the location of the implants precludes LPO products reaching the mammary epithelial cells which are progenitors of BCa. Blood levels of LPO products were not increased in TBI patients compared to REBI patients and did not change with explantation. In TBI patients, white blood cells did not show evidence of increased levels of LPO-related aldehyde DNA adducts. In conclusion, based on a number of measured parameters, there was no evident effect that would contribute to breast or systemic cancer risk in the TBI patients, and the recommended treatment of TBI patients involving explantation was judged appropriate.


Assuntos
Implantes de Mama/efeitos adversos , Peroxidação de Lipídeos , Testes de Mutagenicidade , Óleo de Soja/efeitos adversos , Adulto , Aldeídos/metabolismo , Remoção de Dispositivo , Feminino , Fibroblastos/metabolismo , Humanos , Macrófagos/metabolismo , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Falha de Prótese , Géis de Silicone , Cloreto de Sódio/química
17.
Bone Marrow Transplant ; 41(1): 79-90, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17934527

RESUMO

Neuropsychological deficits are potential side effects of hematopoietic stem cell therapy (HSCT). Systematic data on the long-term course of and therapeutic options for these consequences are limited. One hundred fifty-seven patients were screened for cognitive deficits following HSCT for malignant diseases at an in-patient oncologic rehabilitation clinic. Patients showing evidence of impairment were randomly assigned to one of two training groups: individualized PC-supported training or neuropsychological group therapy. The control group consisted of patients who received no specific training. During in-patient rehabilitation, the results of a comprehensive neuropsychological test battery improved significantly in all three groups, and no specific intervention effects were identified. Neuropsychological deficits were still evident in a subgroup of patients 6 months later. Correlation between neuropsychological testing and patients' self-evaluation of cognitive functioning in daily life was generally low. Sustained attention and verbal-semantic memory played the main role for self-appraisal and in the designation as 'neuropsychologically impaired'. In conclusion, a substantial number of patients revealed evidence of cognitive deficits a long time after HSCT. There is a need for more studies and for the development of differentiated rehabilitative measures for such therapeutic consequences.


Assuntos
Transtornos Cognitivos/reabilitação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias/terapia , Adolescente , Adulto , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Testes Neuropsicológicos
18.
Food Chem Toxicol ; 45(3): 472-85, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17084499

RESUMO

The root bark of Anisophyllea dichostyla R. Br. is traditionally used in the Democratic Republic Congo for the treatment of several conditions such as anorexia, fatigue and intestinal infections. We have identified and quantitated several polyphenol antioxidants in the methanol extract of the root bark (120g). The polyphenol content (3.32g/kg) was predominantly ellagitannins (25%) and polyhydroxyflavan-3-ols (catechins and procyanidins, 75%) with 3'-O-methyl-3,4-methylenedioxo ellagic acid 4'-O-beta-d-glucopyranoside and (-)-epicatechin as the major species in each class. These two compounds and the following species were identified unequivocally by NMR spectroscopy: (+)-catechin, (-)-epicatechin 3-O-gallate, 3-O-methyl ellagic acid, 3,3'-di-O-methyl ellagic acid, 3'-O-methyl-3,4-methylenedioxo ellagic acid, 3'-O-methyl-3,4-methylenedioxo ellagic acid 4'-O-beta-d-glucopyranoside, and 3'-O-methyl ellagic acid 4-O-beta-d-xylopyranoside. The following additional compounds were purified by semi-preparative HPLC and tentatively identified on the basis of UV spectra, HPLC-ESI-MS and nano-ESI-MS-MS: (+)-catechin-3-O-beta-d-glucopyranoside, epicatechin-(4beta-->8)-catechin (procyanidin B(1)), epicatechin-(4beta-->8)-epicatechin (procyanidin B(2)), an (epi)catechin trimer, 3-O-methyl ellagic acid 4-O-beta-d-glucopyranoside, (-)-epicatechin 3-O-vanillate, 3,4-methylenedioxo ellagic acid 4'-O- beta-d-glucopyranoside, and 3,3'-di-O-methyl ellagic acid 4-O-beta-d-xylopyranoside. Fractionation of the raw extract by column chromatography on silicic acid yielded 10 fractions. In the hypoxanthine/xanthine oxidase antioxidant assay system, CC-9 which contained a range of polyphenols dominated by (-)-epicatechin-O-gallate proved to be the most potent antioxidant fraction (IC(50)=52 micro g/mL) in terms of ROS scavenging. In terms of XO inhibition CC-8, dominated by (epi)catechin trimer and which also contained appreciable amounts of 3'-O-methyl ellagic acid 4'-O-beta-d-xylopyranoside, as well as the catechins (+)-catechin-3-O-beta-d-glucopyranoside, epicatechin-(4beta-->8)-catechin (procyanidin B(1)), and (-)-epicatechin 3-O-gallate, proved to be the most potent (IC(50)=36 micro g/mL).


Assuntos
Catequina/química , Cucurbitaceae , Ácido Elágico/química , Fitoterapia , Proantocianidinas/química , República Democrática do Congo , Humanos , Medicinas Tradicionais Africanas , Extratos Vegetais/química , Raízes de Plantas
19.
Biomarkers ; 11(4): 329-40, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16908440

RESUMO

Etheno-DNA adducts are generated from exogenous carcinogens such as vinyl chloride and urethane and also from endogenous lipid peroxidation products such as trans-4-hydroxy-2-nonenal (HNE). The present authors and others have established that 1,N6-ethenodeoxyadenosine (epsilondA) and 3,N4-ethenodeoxycytidine (epsilondC) are present in human urine and could be explored as biomarkers for monitoring whole-body oxidative stress. The present study reports on a new ultrasensitive 32P-postlabelling/thin-layer chromatography (TLC) method for the analysis of epsilondC as deoxynucleoside in human urine. The urine samples were purified and enriched on a solid-phase silica C-18 column followed by a semi-preparative reverse-phase high-performance liquid chromatography. The purified sample was labelled with a multisubstrate deoxyribonucleoside kinase from Drosophila melanogaster (Dm-dNK) in the presence of 5'-bromo-2'-deoxyuridine (BrdU) as internal standard. The absolute sensitivity of the method was 0.1 fmol epsilondC detectable in 500 microl of human urine. The analysis of human urine samples from 15 healthy volunteers revealed a mean epsilondC level of 2.49+/-1.76 (SD) fmol micromol-1 creatinine (range 0.66-6.42). By this non-invasive method, epsilondC in human urine could be explored as a biomarker for oxidative stress-related human diseases.


Assuntos
Biomarcadores/química , Técnicas de Química Analítica/métodos , Química Clínica/métodos , Desoxicitidina/urina , Animais , Cromatografia em Camada Fina/métodos , Adutos de DNA , Desoxicitidina/análogos & derivados , Desoxicitidina/química , Drosophila melanogaster/metabolismo , Humanos , Peroxidação de Lipídeos , Espectrometria de Massas , Modelos Químicos , Fosfotransferases (Aceptor do Grupo Álcool)/química , Fatores de Tempo , Raios Ultravioleta
20.
Food Chem Toxicol ; 44(2): 188-97, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16095792

RESUMO

In this study the content of anacardic acids, cardanols and cardols in cashew apple, nut (raw and roasted) and cashew nut shell liquid (CNSL) were analysed. The higher amounts (353.6 g/kg) of the major alkyl phenols, anacardic acids were detected in CNSL followed by cashew fibre 6.1 g/kg) while the lowest (0.65 g/kg) amounts were detected in roasted cashew nut. Cashew apple and fibre contained anacardic acids exclusively, whereas CNSL also contained an abundance of cardanols and cardols. Cashew nut (raw and roasted) also contained low amounts of hydroxy alkyl phenols. Cashew nut shell liquid was used for a basic fractionation of the alkyl phenol classes and the individual anacardic acids, major cardanols and cardols were purified to homogeneity from these fractions by semi-preparative HPLC and definitively identified by nano-ESI-MS-MS, GC-MS and NMR analyses. The hexane extracts (10 mg/ml) of all cashew products tested plus CNSL, displayed significant antioxidant capacity. Cashew nut shell liquid was the more efficient (inhibition=100%) followed by the hexane extract of cashew fibre (94%) and apple (53%). The antioxidant capacity correlated significantly (P<0.05) with the concentration of alkyl phenols in the extracts. A mixture of anacardic acids (10.0 mg/ml) showed the higher antioxidant capacity (IC50=0.60 mM) compared to cardols and cardanols (IC50>4.0 mM). The data shows that of these substances, anacardic-1 was by far the more potent antioxidant (IC50=0.27 mM) compared to cardol-1 (IC50=1.71 mM) and cardanol-1 (IC50>4.0 mM). The antioxidant capacity of anacardic acid-1 is more related to inhibition of superoxide generation (IC50=0.04 mM) and xanthine oxidase (IC50=0.30 mM) than to scavenging of hydroxyl radicals. At present a substantial amount of cashew fibre is mostly used in formulations of animal or poultry feeds. The data presented in this study, indicates that this waste product along with CNSL, both of which contain high contents of anacardic acids, could be better utilized in functional food formulations and may represent a cheap source of cancer chemopreventive agents.


Assuntos
Anacardium/química , Antioxidantes/química , Fenóis/química , Ácidos Anacárdicos/química , Ácidos Anacárdicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Desoxiguanosina/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Fenóis/isolamento & purificação , Resorcinóis/química , Resorcinóis/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray , Superóxidos/química , Xantina Oxidase/antagonistas & inibidores
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