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1.
Front Neurol ; 14: 1131322, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37114227

RESUMO

Introduction: Patients with cerebrovascular disease may suffer from other vascular morbidities, such as abdominal aortic aneurysm (AAA). Previously, a high prevalence of AAA has been demonstrated in men 60 years of age and older who have experienced TIA or stroke. This report evaluates the results of a decade's operation of a local screening program for AAA in this selected neurologic population. Methods: Men aged ≥60 years and admitted to the neurology ward of a community-based hospital in the Netherlands from 2006 to 2017 with a diagnosis of TIA or stroke were selected for screening. The diameter of the abdominal aorta was assessed by abdominal ultrasonography. Patients with detected AAA were referred for evaluation by a vascular surgeon. Results: AAA was detected in 72 of 1,035 screened patients (6.9%). AAAs with a diameter of 3.0-3.9 cm accounted for 61.1% of the total aneurysms found; AAAs with a diameter of 4.0-5.4 cm accounted for 20.8% of the total; and large aneurysms with a diameter of ≥5.5 cm accounted for 18.1% of all aneurysms discovered. A total of 18 patients (1.7%) underwent elective aneurysm repair. Discussion: The detection rate of AAA in older men with cerebrovascular disease was roughly 5-fold the detection rate in known European screening programs in older men from the general population. The proportion of large AAAs (≥5.5 cm) was also substantially higher. These findings reveal a previously unknown co-morbidity in patients with cerebrovascular disease and may be helpful for cardiovascular management of this large group of neurologic patients. Current and future AAA screening programs may also benefit from this knowledge.

2.
Neth Heart J ; 31(2): 52-60, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35976610

RESUMO

BACKGROUND: Coronary computed tomography angiography (CCTA) is widely used in the diagnostic work-up of patients with stable chest pain. CCTA has an excellent negative predictive value, but a moderate positive predictive value for detecting coronary stenosis. Computed tomography-derived fractional flow reserve (FFRct) is a non-invasive, well-validated technique that provides functional assessment of coronary stenosis, improving the positive predictive value of CCTA. However, to determine the value of FFRct in routine clinical practice, a pragmatic randomised, controlled trial (RCT) is required. We will conduct an RCT to investigate the impact of adding FFRct analysis in the diagnostic pathway of patients with a coronary stenosis on CCTA on the rate of unnecessary invasive coronary angiography, cost-effectiveness, quality of life and clinical outcome. METHODS: The FUSION trial is a prospective, multicentre RCT that will randomise 528 patients with stable chest pain and anatomical stenosis of ≥ 50% but < 90% in at least one coronary artery of ≥ 2 mm on CCTA, to FFRct-guided care or usual care in a 1:1 ratio. Follow-up will be 1 year. The primary endpoint is the rate of unnecessary invasive coronary angiography within 90 days. CONCLUSION: The FUSION trial will evaluate the use of FFRct in stable chest pain patients from the Dutch perspective. The trial is funded by the Dutch National Health Care Institute as part of the research programme 'Potentially Promising Care' and the results will be used to assess if FFRct reimbursement should be included in the standard health care package.

3.
Eur J Radiol Open ; 4: 118-122, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29034281

RESUMO

OBJECTIVE: To examine the safety and efficacy of contrast injection through a central venous catheter (CVC) for contrast-enhanced computed tomography (CECT). METHODS: A systematic literature search was performed using PubMed. Studies were deemed eligible if they reported on the use of CVCs for contrast administration. Selected articles were assessed for their relevance and risk of bias. Articles with low relevance and high risk of bias or both were excluded. Data from included articles was extracted. RESULTS: Seven studies reported on the use of CVCs for contrast administration. Catheter rupture did not occur in any study. The incidence of dislocation ranged from 2.2-15.4%. Quality of scans was described in three studies, with less contrast enhancement of pulmonary arteries and the thoracic aorta in two studies, and average or above average quality in one study. Four other studies used higher flowrates, but did not report quality of scans. CONCLUSION: Contrast injection via CVCs can be performed safely for CECT when using a strict protocol. Quality of scans depended on multiple factors like flow rate, indication of the scan, and cardiac output of the patient. In each patient, an individual evaluation whether to use the CVC as access for contrast media should be made, while bolus tracking may be mandatory in most cases.

4.
Breast Cancer Res Treat ; 158(3): 535-41, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27444926

RESUMO

Ultrasound guidance (USG) during breast-conserving surgery improves tumor-free surgical resection margins. The objective of this study was to evaluate whether USG reduces resection volumes without compromising margin status. 134 patients with palpable or nonpalpable T1-2N0-1 invasive breast cancer were treated with USG and compared with a historical reference control group (CON) consisting of palpation-guided (PAG) or wire-guided localization (WIG) breast-conserving surgery. Primary outcomes were excess resection volume and clear margin status, and secondary outcome was re-excision rate. 66 patients underwent USG. In the CON group (n = 68), PAG was performed in 24 (35 %) and WIG in 44 (64 %) patients. Median excision volume [39 (IQR 20-66) vs 56 (38-94) cm(3); p = 0.001] and median calculated resection ratio [1.7 (1.0-2.9) vs 2.8 (1.4-4.6) (p = 0.005)] were significantly smaller in the USG than in the CON group. Median minimal distance to the resection margin [4 mm (IQR 2-5 mm) vs 2 mm (1-4 mm), p = 0.004] was significantly larger. Clear resection margins were achieved in 58 of the USG patients (88 %) and in 58 of the CON patients (86 %) (p = 0.91); this was true in patients with palpable as well as nonpalpable lesions. Reexcision was needed in 6.1 and 7.2 % respectively. Relative risk for re-excision in the USG group was 0.82 (95 % CI 0.23-2.93). In patients with palpable and nonpalpable breast cancers, USG allows for lower excision volume and reduced resection of healthy breast tissue, without increased re-excision rate.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia Segmentar/métodos , Ultrassonografia Mamária/métodos , Idoso , Feminino , Humanos , Margens de Excisão , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
5.
Br J Cancer ; 113(2): 226-31, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26042933

RESUMO

BACKGROUND: Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored their prognostic value in patients with recurrent glioblastoma. METHODS: In this side study of the BELOB trial, 141 patients with recurrent glioblastoma were randomised to receive single-agent bevacizumab or lomustine, or bevacizumab plus lomustine. Before treatment, after 4 weeks and after 6 weeks of treatment, CECs were enumerated. RESULTS: The number of CECs increased during treatment with bevacizumab plus lomustine, but not during treatment in the single-agent arms. In patients treated with lomustine single agent, higher absolute CEC numbers after 4 weeks (log10CEC hazard ratio (HR) 0.41, 95% CI 0.18-0.91) and 6 weeks (log10CEC HR 0.16, 95% CI 0.05-0.56) of treatment were associated with improved overall survival (OS). Absolute CEC numbers in patients receiving bevacizumab plus lomustine or bevacizumab single agent were not associated with OS. CONCLUSION: CEC numbers increased during treatment with bevacizumab plus lomustine but not during treatment with either agent alone, suggesting that this combination induced the greatest vascular damage. Although the absolute number of CECs was not associated with OS in patients treated with bevacizumab either alone or in combination, they could serve as a marker in glioblastoma patients receiving lomustine single agent.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Células Endoteliais/fisiologia , Glioblastoma/tratamento farmacológico , Lomustina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antígenos CD/análise , Bevacizumab , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Movimento Celular , Células Endoteliais/citologia , Feminino , Proteínas Ligadas por GPI/análise , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Cinética , Lomustina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos
6.
Br J Cancer ; 112(3): 556-61, 2015 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-25562435

RESUMO

BACKGROUND: Despite good outcomes for many, a substantial group of patients undergoing metastasectomy for isolated liver metastases from colorectal cancer (CRC) experience early recurrence. We have investigated whether circulating tumour cell (CTC) detection can identify patients developing disease recurrence within 1 year after liver metastasectomy. METHODS: In CRC patients undergoing liver metastasectomy, 30 ml peripheral blood was withdrawn preoperatively. CTCs were detected by the CellSearch system after a density-gradient-based enrichment step. RESULTS: One hundred and seventy-three samples from 151 individual patients were analysed. In 75 samples (43%), CTCs were detected, 16% had ⩾3 CTCs/7.5 ml of blood. Eighty-two patients (47%) experienced early disease recurrence (<1 year). The 1-year recurrence rate between patients with or without detectable CTCs were similar (47% vs 48%) or with a low or high CTC count (<3 or ⩾3 CTCs/7.5 ml of blood) (50% vs 47%). Also disease-free and overall survival were similar between patients with or without CTCs. CONCLUSIONS: The presence of CTCs in preoperative peripheral blood samples does not identify patients at risk for early disease recurrence after curative resection of colorectal liver metastases. Other parameters are needed to better identify patients at high risk to relapse after liver metastasectomy for CRC.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Separação Celular/métodos , Neoplasias Colorretais/cirurgia , Detecção Precoce de Câncer , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Recidiva
7.
Ann Oncol ; 26(3): 510-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25471333

RESUMO

BACKGROUND: A circulating tumor cell (CTC) count is an established prognostic factor in metastatic breast cancer (MBC). Besides enumeration, CTC characterization promises to improve outcome prediction and treatment guidance. Having shown the feasibility of quantifying clinically relevant mRNA transcripts in CTCs, we determined the prognostic value of CTC gene expression in MBC. PATIENTS AND METHODS: CTCs were isolated and enumerated from blood of 197 MBC patients who were about to start first-line systemic therapy. Of these, 180 were assessable for quantification of mRNA expression by RT-qPCR in relation to time-to-treatment failure (TTF). A prognostic CTC gene profile was generated by leave-one-out cross validation in a 103 patient discovery set and validated in 77 patients. Additionally, all 180 patients were randomly divided into two equal sets to discover and validate a second prognostic profile. RESULTS: CTC count predicted for TTF at baseline {≥5 versus <5 CTCs/7.5 ml blood, hazard ratio (HR) 2.92 [95% confidence interval (CI) 1.71-4.95] P < 0.0001}. A 16-gene CTC profile was generated in the first discovery set, which identified patients with death or TTF <9 months versus those with a better outcome. In multivariate analysis, the 16-gene profile was the only factor associated with TTF [HR 3.15 (95% CI 1.35-7.33) P 0.008]. Validation of this profile in the independent patient set pointed into the same direction, but was not statistically significant. A newly generated 8-gene profile showed similarly favorable test characteristics as the 16-gene profile, but did not significantly pass validation either. CONCLUSION: A 16-gene CTC profile was identified, which provided prognostic value on top of CTC count in MBC patients. However, validation of this profile in an independent cohort, nor of a second profile, reached statistical significance, underscoring the need to further fine-tune the still promising approach of CTC characterization.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Perfilação da Expressão Gênica/métodos , Células Neoplásicas Circulantes , Adulto , Bélgica/epidemiologia , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prognóstico , Estudos Prospectivos
8.
Br J Cancer ; 111(1): 149-56, 2014 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-24892449

RESUMO

BACKGROUND: Mature circulating endothelial cells (CEC) are surrogate markers of endothelial damage. CEC measured in patients with advanced cancer are thought not only to derive from damaged normal vasculature (n-CEC), but also from damaged (t-CEC). Therefore, assays that allow the discrimination between these two putative types of CEC are thought to improve the specificity of the enumeration of CEC in cancer. METHODS: Identification of tumour-associated endothelial markers (TEM) by comparing antigen expression on normal vs t-CEC and assess the presence of t-CEC in peripheral blood of cancer patients by incorporating TEM in our novel flow cytometry-based CEC detection assay. RESULTS: No difference in antigen expression between normal and malignant endothelial cells (ECs) was found for CD54, CD109, CD137, CD141, CD144 and CXCR7. In contrast, overexpression for CD105, CD146, CD276 and CD309 was observed in tumour ECs compared with normal ECs. CD276 was most differentially expressed and chosen as a marker for further investigation. CD276-expressing CEC were significantly higher in 15 patients with advanced colorectal cancer (median 9 (range 1-293 cell per 4 ml); P<0.005), in 83 patients with a glioblastoma multiforme (median 10 (range 0-804); P<0.0001) and in 14 patients with advanced breast cancer (median 14 (range 0-390) P<0.05) as compared with 24 healthy individuals (median 3 (range 0-11)). Of all patients with malignancies, 58% had CD276(+) CEC counts above the ULN (8 cell per 4 ml). CONCLUSIONS: The present study shows that CD276 can be used to discriminate ECs from malignant tissue from ECs from normal tissue. In addition, CD276(+) CEC do occur in higher frequencies in patients with advanced cancer.


Assuntos
Antígenos B7/biossíntese , Biomarcadores Tumorais/metabolismo , Células Endoteliais/metabolismo , Neoplasias/metabolismo , Células Neoplásicas Circulantes/metabolismo , Estudos de Casos e Controles , Diferenciação Celular/fisiologia , Citometria de Fluxo , Humanos , Imunofenotipagem , Neoplasias/sangue , Neoplasias/genética , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia
9.
Cytometry B Clin Cytom ; 86(1): 3-14, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24151248

RESUMO

Detection of minimal residual disease is recognized as an important post-therapy risk factor in acute myeloid leukemia patients. Two most commonly used methods for residual disease monitoring are real-time quantitative polymerase chain reaction and multiparameter flow cytometry. The results so far are very promising, whereby it is likely that minimal residual disease results will enable to guide future post-remission treatment strategies. However, the leukemic clone may change between diagnosis and relapse due to the instability of the tumor cells. This instability may already be evident at diagnosis if different subpopulations of tumor cells coexist. Such tumor heterogeneity, which may be reflected by immunophenotypic, molecular, and/or cytogenetic changes, can have important consequences for minimal residual disease detection, since false-negative results can be expected to be the result of losses of aberrancies used as minimal residual disease markers. In this review the role of such changes in minimal residual disease monitoring is explored. Furthermore, possible causes of tumor instability are discussed, whereby the concept of clonal selection and expansion of a chemotherapy-resistant subpopulation is highlighted. Accordingly, detailed knowledge of the process of clonal evolution is required to improve both minimal residual disease risk stratification and patient outcome.


Assuntos
Leucemia Mieloide Aguda/patologia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/prevenção & controle , Neoplasia Residual/diagnóstico , Neoplasia Residual/prevenção & controle , Adulto , Biomarcadores Tumorais , Evolução Clonal , Resistencia a Medicamentos Antineoplásicos/genética , Citometria de Fluxo , Variação Genética , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/tratamento farmacológico , Reação em Cadeia da Polimerase em Tempo Real , Resultado do Tratamento
10.
Artigo em Inglês | MEDLINE | ID: mdl-24123710

RESUMO

Detection of minimal residual disease is recognized as an important post-therapy risk factor in acute myeloid leukemia patients. Two most commonly used methods for residual disease monitoring are real time quantitative polymerase chain reaction and multiparameter flow cytometry. Results so far are very promising, whereby it is likely that minimal residual disease results will enable to guide future post-remission treatment strategies. However, the leukemic clone may change between diagnosis and relapse due to instability of the tumor cells. This instability may already be evident at diagnosis if different subpopulations of tumor cells coexist. Such tumor heterogeneity, which may be reflected by immunophenotypic, molecular and/or cytogenetic changes, can have important consequences for minimal residual disease detection, since false-negative results can be expected to be the result of losses of aberrancies used as minimal residual disease markers. In this review the role of such changes in minimal residual disease monitoring is explored. Furthermore, possible causes of tumor instability are discussed, whereby the concept of clonal selection and expansion of a chemotherapy resistant subpopulation is highlighted. Accordingly, detailed knowledge of the process of clonal evolution is required to improve both minimal residual disease risk stratification and patient outcome. © 2013 Clinical Cytometry Society.

11.
Blood Cancer J ; 3: e129, 2013 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-23912609

RESUMO

Flow-cytometric detection of minimal residual disease (MRD) has proven in several single-institute studies to have an independent prognostic impact. We studied whether this relatively complex approach could be performed in a multicenter clinical setting. Five centers developed common protocols to accurately define leukemia-associated (immuno)phenotypes (LAPs) at diagnosis required to establish MRD during/after treatment. List mode data files were exchanged, and LAPs were designed by each center. One center, with extensive MRD experience, served as the reference center and coordinator. In quarterly meetings, consensus LAPs were defined, with the performance of centers compared with these. In a learning (29 patients) and a test phase (35 patients), a mean of 2.2 aberrancies/patient was detected, and only 1/63 patients (1.6%) had no consensus LAP(s). For the four centers without (extensive) MRD experience, clear improvement could be shown: in the learning phase, 39-63% of all consensus LAPs were missed, resulting in a median 30% of patients (range 21-33%) for whom no consensus LAP was reported; in the test phase, 27-40% missed consensus LAPs, resulting in a median 16% (range 7-18%) of 'missed' patients. The quality of LAPs was extensively described. Immunophenotypic MRD assessment in its current setting needs extensive experience and should be limited to experienced centers.

12.
Neth J Med ; 71(3): 139, 143, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23712812
13.
Cancer Treat Rev ; 39(7): 691-700, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23683721

RESUMO

Circulating tumor cells (CTCs) can be found in the peripheral blood of patients with different solid tumors, including breast cancer. A CTC count is a strong established prognostic factor in various stages in several tumor types. Besides that, characterization of CTCs is expected to become an invaluable tool to predict treatment response and personalize cancer treatments. Likely, CTCs are shed by different tumor lesions and may therefore provide a comprehensive view of tumor characteristics at a certain time-point, including inter- and intratumoral heterogeneity. Obtained through a simple venipuncture, CTCs could this way serve as a "liquid biopsy". However, isolation and subsequent characterization of CTCs is technically extremely challenging, mainly due to the small number of cells amidst a large majority of leukocytes. A wide range of assays has been developed, but only the CellSearch System(®) (Veridex, Raritan, NJ, USA) has obtained FDA approval for CTC enumeration so far. For characterization purposes, no assay has been validated at all. Nevertheless, the first studies investigating the clinical value of CTC characteristics have been performed. Here, we review these clinical studies. The various techniques used to interrogate CTCs are briefly described and an overview of the clinical relevance of CTC characterization in breast cancer is given.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Células Neoplásicas Circulantes , Medicina de Precisão , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Humanos , Células Neoplásicas Circulantes/metabolismo , Prognóstico
15.
J Thromb Haemost ; 10(5): 931-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22385979

RESUMO

BACKGROUND: Mature circulating endothelial cells (CECs) are surrogate markers of endothelial damage/dysfunction. A lack of standardized assays and consensus on CEC phenotype has resulted in a wide variation of reported CEC numbers (4-1300 per mL). OBJECTIVES: Given the need for a quick, reliable, robust and validated CEC assay at an affordable price, we present a novel approach to enumerate CECs using a multi-parameter flow cytometric (FCM) method without immunological pre-enrichment. METHODS: CECs were defined as CD34+, CD45neg, CD146+ and DNA+ events based on the immunophenotype of endothelial cells from vein-wall dissections. As CECs express high levels of CD34, we based our assay on absolute CD34 counts after analyzing all CD34 positive events in a total blood volume of 4 mL needed for a precise enumeration of CECs at a frequency of < 1 cell µL(-1). RESULTS: The endothelial origin of CECs was confirmed by morphology, immunohistochemistry and gene expression. The new FCM assay was tested in parallel with a validated assay (i.e. CellSearch). CEC levels ranged from 4 to 79 CEC mL(-1) in healthy individuals and were significantly higher in patients with advanced solid malignancies (P = 0.0008) and in patients with hematological malignancies (P < 0.0001). CONCLUSIONS: This flow cytometric method should be useful as a fast and economical assay to enumerate and characterize CECs.


Assuntos
Contagem de Células/métodos , Células Endoteliais/patologia , Citometria de Fluxo , Imunofenotipagem , Neoplasias/patologia , Antígenos CD34/análise , Biomarcadores/análise , Antígeno CD146/análise , Estudos de Casos e Controles , Células Endoteliais/imunologia , Regulação da Expressão Gênica , Genótipo , Humanos , Imuno-Histoquímica , Antígenos Comuns de Leucócito/análise , Neoplasias/sangue , Neoplasias/genética , Neoplasias/imunologia , Países Baixos , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
J Neurol Neurosurg Psychiatry ; 81(12): 1341-4, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20667866

RESUMO

OBJECTIVE: Paraneoplastic neurological syndromes associated with anti-Hu antibodies (Hu-PNS) are mediated by a T-cell immune response that is directed against the Hu antigens. In pregnancy, many Th1-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis regress. We hypothesised that this decreased disease activity during pregnancy may be related to high human chorionic gonadotropin (hCG) levels. METHODS: 15 Hu-PNS patients were treated in a prospective, uncontrolled and unblinded trial with 10,000 IU daily of hCG administered by intramuscular injection during 12 weeks. Primary outcome measures were functional improvement defined as a decrease of one or more points on the modified Rankin Scale (mRS) or stabilisation in patients with mRS score ≤3 and improvement of neurological impairment assessed with the Edinburgh Functional Impairment Tests (EFIT). Secondary end points included the change in activities of daily living as evaluated using the Barthel Index. RESULTS: Seven of 15 patients (47%) improved on the mRS or stabilised at mRS score ≤3. Four patients (27%) showed significant improvement of neurological impairment as indicated by an overall Edinburgh Functional Impairment Tests score of ≥1 point. Five patients improved on the Barthel Index (33%). CONCLUSION: Comparison with previous studies suggests that hCG may have immunomodulatory activity and may modify the course of Hu-PNS, although well-established confounding factors may have contributed in this uncontrolled trial.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/tratamento farmacológico , Gonadotropina Coriônica/administração & dosagem , Síndromes Paraneoplásicas do Sistema Nervoso/tratamento farmacológico , Atividades Cotidianas/classificação , Idoso , Animais , Doenças Autoimunes/imunologia , Gonadotropina Coriônica/sangue , Avaliação da Deficiência , Feminino , Humanos , Injeções Intramusculares , Masculino , Camundongos , Camundongos Endogâmicos NOD , Pessoa de Meia-Idade , Limitação da Mobilidade , Exame Neurológico , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Estudos Prospectivos , Células Th1/efeitos dos fármacos , Células Th1/imunologia
17.
Eur J Cancer ; 46(11): 2027-35, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20399640

RESUMO

PURPOSE: We investigated whether serum markers of angiogenesis endothelin-1 (ET-1) and tissue factor (TF), and/or markers of vascular damage such as circulating endothelial cells (CECs), or their relative changes during treatment, were prognostic for overall survival (OS) in castration resistant prostate cancer (CRPC) patients. Additionally, we combined these markers with circulating tumour cells (CTCs) to construct a predictive nomogram for treatment outcome. PATIENTS AND METHODS: One hundred and sixty two CRPC patients treated with a docetaxel containing regimen had blood drawn before and at 2-5 weeks and 6-8 weeks after treatment start. Prospectively determined CTC and CEC levels, and retrospectively measured serum concentrations of ET-1 (pg/mL) and TF (pg/mL) were evaluated to determine their prognostic value for OS. RESULTS: Baseline CEC, TF and ET-1 were not prognostic for OS. A > or = 3.8-fold increase in CEC 2-5 weeks after treatment initiation was associated with decreased OS (median 10.9 versus 16.8 months; P=0.015), as was any decrease in TF levels compared to baseline levels (median 11.9 versus 21.5 months; P=0.0005). As previously published, baseline and CTC counts > or = 5 at 2-5 weeks were also predictive of decreased OS. Combining CTC with changes in TF and CEC 2-5 weeks after treatment initiation yielded four groups differing in OS (median OS 24.2 versus 16.0 versus 11.4 versus 6.1 months; P<0.0001). CONCLUSION: CEC, CTC and TF levels alone and combined can predict early on OS in CRPC patients treated with docetaxel-based therapy. A prospective study to confirm the use of these markers for patient management is needed.


Assuntos
Antineoplásicos/uso terapêutico , Endotelina-1/metabolismo , Células Neoplásicas Circulantes , Neoplasias da Próstata/tratamento farmacológico , Taxoides/uso terapêutico , Tromboplastina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Biomarcadores Tumorais/metabolismo , Docetaxel , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Orquiectomia , Estudos Prospectivos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Análise de Sobrevida , Resultado do Tratamento
18.
Eur J Neurol ; 16(5): 602-7, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19236464

RESUMO

BACKGROUND AND PURPOSE: Population screening for aneurysms of the abdominal aorta (AAA) is still not implemented in any country, despite proven benefit both in decreased mortality and in cost effectiveness. Detecting a subpopulation with higher prevalence of AAA may alter this situation. METHODS: Between 2002 and 2005, all patients with a stroke or transient ischaemic attack (TIA) admitted to the department of Neurology of a community-based hospital were classified according to the Toast criteria and enrolled in a prospective study to assess the diameter of the abdominal aorta. The diameter was assessed by ultrasonography. A written questionnaire and blood tests were used to assess risk factors. RESULTS: The prevalence of AAA amongst the 499 screened patients in the study was 5.8% [95% confidence interval (CI) 5.6-6.0%]. Of the risk factors or Toast criteria, only male gender and age over 59 years correlated significantly with AAA. In the subgroup of 235 men aged over 59 years, the prevalence of AAA was 11.1% (95% CI 10.4-11.8%). CONCLUSION: The prevalence of AAA in men over 59 years of age presenting with a stroke or TIA is nearly twofold increased (11.1%) compared with all patients. Therefore, screening for AAA in this subgroup of patients seems beneficial. However, further studies are needed to confirm this finding and to explore the clinical benefit and cost effectiveness.


Assuntos
Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/epidemiologia , Ataque Isquêmico Transitório/complicações , Acidente Vascular Cerebral/complicações , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Humanos , Masculino , Programas de Rastreamento , Prevalência , Ultrassonografia
19.
Cytometry B Clin Cytom ; 76(1): 18-26, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18942105

RESUMO

BACKGROUND: Availability of immunophenotypic reference values for the various leukocyte populations distributed in bone marrow may be helpful to recognize abnormal bone marrow development and, therefore, useful as first screening of individuals with suspected hematological malignancies or other hematopoietic disorders. METHODS: A single tube four-color staining panel (CD66abce/CD14/CD45/CD34) together with a predefined gating strategy was utilized to immunologically differentiate the distribution of the major leukocyte populations in bone marrow aspirates of healthy donors. The sample-blood erythrocyte ratio was applied to assess the amount of blood contamination of marrow and account for this in the marrow value estimates. RESULTS: The frequency of the major leukocyte populations in bone marrow of 134 normal donors were for granulocytes: mean, 69.4%; SD, 10.3%; monocytes: mean, 4.7%; SD, 2.3%; lymphocytes: mean, 18.3%; SD, 8.7%. The frequency of the immature cell population that included precursor cells of each of the cell lineages among other cell types were mean 5.0%; SD 2.2%. The mean percentage of CD34 positive cells was 1.5%; SD 0.7%. Our results showed further that the frequency of cell populations, of which the presence is restricted to the bone marrow (e.g., CD34+ progenitor cells), is influenced by the degree of peripheral blood admixture. Between the total immature cells and purity of the bone marrow, there was a significant positive correlation demonstrated, whereas a negative correlation was found between the percentages of both lymphocytes as monocytes and the purity of the bone marrow. CONCLUSIONS: With a single tube-staining panel, we obtained reference values for flow cytometric assessment of all relevant leukocyte populations present in bone marrow that can be used as a frame of reference for better recognition of individuals with abnormal hematopoiesis. In addition, we have demonstrated the influence of the degree of peripheral blood admixture in the bone marrow aspirates on those reference values.


Assuntos
Células da Medula Óssea/fisiologia , Granulócitos/fisiologia , Linfócitos/fisiologia , Monócitos/fisiologia , Antígenos CD/metabolismo , Células da Medula Óssea/metabolismo , Citometria de Fluxo , Granulócitos/metabolismo , Humanos , Contagem de Leucócitos , Linfócitos/metabolismo , Monócitos/metabolismo , Valores de Referência
20.
Ned Tijdschr Geneeskd ; 152(31): 1705-9, 2008 Aug 02.
Artigo em Holandês | MEDLINE | ID: mdl-18727598

RESUMO

In three patients, men aged 77, 83 and 69 years, pneumatosis intestinalis was detected during CT for abdominal pain occurring in the first patient after an aortic stent had been placed, and during laparotomy because of ileus in the latter two patients. The first patient underwent removal of an ischaemic intestinal segment but died later due to infection around the prosthesis. The other two patients recovered after conservative therapy. Pneumatosis intestinalis is defined as the presence of gas in the wall of the gastrointestinal tract. Often it is detected by accident during abdominal radiographic examination or laparotomy. Pneumatosis intestinalis is a symptom and has been found in a wide variety of diseases. The clinical condition of the patient and the underlying disease determine the clinical significance of pneumatosis intestinalis and the therapy. The main issue is whether surgical intervention is necessary because of intestinal ischaemia or perforation.


Assuntos
Antibacterianos/uso terapêutico , Laparotomia , Pneumatose Cistoide Intestinal/diagnóstico , Pneumatose Cistoide Intestinal/etiologia , Dor Abdominal/etiologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pneumatose Cistoide Intestinal/diagnóstico por imagem , Pneumatose Cistoide Intestinal/cirurgia , Complicações Pós-Operatórias , Radiografia , Resultado do Tratamento
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