RESUMEN
PURPOSE: Retinal oxygen supply is a critical requirement in ocular function, and when inadequate can lead to retinopathy. Endothelial dysfunction is a leading pathophysiology in diabetes and cardiovascular disease and may be assessed by endothelial microparticles (EMPs). We hypothesised links between retinal vessel oxygenation and EMPs, expecting these indices to be more adverse in those with both DM and CVD. METHODS: Plasma from 34 patients with diabetes mellitus alone (DM), 40 with cardiovascular disease (CVD) alone and 36 with DM plus CVD was probed for EMPs by flow cytometry, but also for vascular markers soluble E-selectin (sEsel) and von Willebrand factor (vWf) (both ELISA). Retinal vessel fractal dimension, lacunarity, calibres and oxygen saturation were assessed from monochromatic and dual wavelength imaging respectively, intra-ocular pressure by was measured by rebound tonometry (I-CARE). RESULTS: There was no difference in oxygenation (arterial p = 0.725, venous p = 0.264, arterio-venous difference 0.375) between the groups, but there were differences in EMPs (p = 0.049), vWf (p = 0.004) and sEsel (p = 0.032). In the entire cohort, and in diabetes alone, EMPs correlated with venous oxygenation (r = 0.24, p = 0.009 and r = 0.43, p = 0.011 respectively), while in DM + CVD, sEsel correlated with venous oxygenation (r = 0.55, p = 0.002) and with the arterial-venous difference (r = -0.63, p = 0.001). In multivariate regression analysis of vascular markers against retinal oximetry indices in the entire group, EMPs were positively linked to venous oxygenation (p = 0.037). CONCLUSIONS: Despite differences in systemic markers of vascular function between DM, CVD and DM + CVD, there was no difference in arterial or venous retinal oxygenation, or their difference. However, EMPs were linked to venous oximetry, and may provide further insight into the mechanisms underlying diabetes and diabetic retinopathy.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Retinopatía Diabética , Biomarcadores , Retinopatía Diabética/diagnóstico , Humanos , Oxígeno , Saturación de Oxígeno , Vasos Retinianos , Factor de von Willebrand/análisisRESUMEN
BACKGROUND: Retinal vessel calibre and vascular dilation/constriction in response to flicker light provocation may provide a measure distinguishing patients suffering from diabetes mellitus and/or cardiovascular disease. METHODS: One hundred and sixteen age and sex matched patients with diabetes mellitus (DM), cardiovascular disease (CVD) and both DM and CVD (DM + CVD) underwent systemic and intraocular pressure measurements. Retinal vessel calibres were assessed using a validated computer-based program to compute central retinal artery and vein equivalents (CRVE) from monochromatic retinal images. Vessel dilation and constriction responses to flicker light provocation were assessed by continuous retinal vessel diameter recordings. Plasma endothelial markers von Willebrand factor (vWf) and soluble E selectin (sEsel) were measured by ELISA. RESULTS: Retinal vessel calibres were comparable across groups but CRVE correlated significantly with disease duration in DM patients (r = 0.57, p < 0.001). Patients suffering DM only exhibited reduced arterial vasomotion at rest and reduced arterial constriction following flicker light induced vessel dilation compared to patients with CVD and those suffering both CVD + DM (p = 0.030). Patients suffering from CVD + DM exhibited significant differences between each flicker cycle in regards to arterial maximum constriction (p = 0.006) and time needed to reach arterial maximum dilation (p = 0.004), whereas the other two groups did not show such inconsistencies between individual flicker cycles. vWf was raised in CVD + DM compared to the other two groups (p ≤ 0.02), whilst sEsel was raised in CVD + DM compared to DM alone (p = 0.044). CONCLUSIONS: Dynamic retinal vascular calibres as obtained by continuous diameter measurements using flicker light provocation can reveal subtle differences between groups suffering from CVD with and without DM. This difference in reaction pattern and lack of arterial constriction in DM may provide a suitable marker to monitor progression.
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Enfermedades Cardiovasculares/fisiopatología , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Retinopatía Diabética/fisiopatología , Arteria Retiniana/fisiopatología , Vena Retiniana/fisiopatología , Vasoconstricción , Vasodilatación , Anciano , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Retinopatía Diabética/sangre , Retinopatía Diabética/diagnóstico , Progresión de la Enfermedad , Selectina E/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Presión Intraocular , Luz , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , Factor de von Willebrand/análisisRESUMEN
As heart failure, coronary artery disease and atrial fibrillation all bring a risk of thrombosis, anti-thrombotic therapy is recommended. Despite such treatment, major cardiovascular events such as myocardial infarction and stroke still occur, implying inadequate suppression of thrombus formation. Accordingly, identification of patients whose haemostasis remains unimpaired by treatment is valuable. We compared indices for assessing thrombogenesis and fibrinolysis by two different techniques in patients on different anti-thrombotic agents, i.e. aspirin or warfarin. We determined fibrin clot formation and fibrinolysis by a microplate assay and thromboelastography, and platelet marker soluble P selectin in 181 patients with acute or chronic heart failure, coronary artery disease who were taking either aspirin or warfarin. Five thromboelastograph indices and four microplate assay indices were different on aspirin versus warfarin (p < 0.05). In multivariate regression analysis, only microplate assay indices rate of clot formation and rate of clot dissolution were independently related to aspirin or warfarin use (p ≤ 0.001). Five microplate assay indices, but no thrombelastograph index, were different (p < 0.001) in aspirin users. Three microplate assay indices were different (p ≤ 0.002) in warfarin users. The microplate assay indices of lag time and rate of clot formation were abnormal in chronic heart failure patients on aspirin, suggesting increased risk of thrombosis despite anti-platelet use. Soluble P selectin was lower in patients on aspirin (p = 0.0175) but failed to correlate with any other index of haemostasis. The microplate assay shows promise as a tool for dissecting thrombogenesis and fibrinolysis in cardiovascular disease, and the impact of antithrombotic therapy. Prospective studies are required to determine a role in predicting thrombotic risk.
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Técnicas de Laboratorio Clínico/métodos , Fibrinolíticos/uso terapéutico , Cardiopatías/tratamiento farmacológico , Tromboelastografía/normas , Análisis de Matrices Tisulares/normas , Aspirina/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Técnicas de Laboratorio Clínico/normas , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Fibrinólisis/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Trombosis/tratamiento farmacológico , Warfarina/uso terapéuticoRESUMEN
PURPOSE: To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease. METHODS: Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index. RESULTS: Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p < 0.05). Arterial reaction time was linked to serum creatinine (p = 0.036) and eGFR (p = 0.039); venous reaction time was linked to creatinine clearance (p = 0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p < 0.001 and p = 0.003, respectively) and the dilatation amplitude (p = 0.038 and p = 0.048, respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p = 0.004) and dilatation amplitude (p = 0.017), vWf was linked to the maximum constriction response (p = 0.016), and creatinine clearance to the baseline diameter fluctuation (p = 0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p = 0.022). CONCLUSIONS: Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses.
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Biomarcadores/metabolismo , Diabetes Mellitus/sangre , Tasa de Filtración Glomerular/fisiología , Riñón/fisiopatología , Microcirculación/fisiología , Vasos Retinianos/fisiopatología , Vasodilatación/fisiología , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Creatinina/metabolismo , Diabetes Mellitus/fisiopatología , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Estimulación LuminosaRESUMEN
INTRODUCTION: The endothelium and angiogenesis are therapeutic targets in cancer. Response to treatment may be assessed by laboratory plasma markers such as circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), von Willebrand factor (vWf), soluble E selectin, vascular endothelial growth factor (VEGF) and angiogenin. We hypothesised that these markers, obtained before surgery, would predict 2-year outcome after surgery with or without anti-angiogenic therapy for colorectal cancer (CRC). METHODS: We recruited 154 patients with CRC, of whom 51 were treated with surgery alone, 74 were treated with standard chemotherapy (5-fluorouracil) and 29 were treated with standard chemotherapy plus anti-VEGF therapy (Avastin). Peripheral blood was taken before surgery. CD34(+)/CD45(-)/CD146(+) CECs and CD34(+)/CD45(-)/CD309 [KDR](+) EPCs were measured by flow cytometry and plasma markers by ELISA. RESULTS: After a mean of 2.1 years follow-up (range 1.9-2.3 years), 52 of the patients (33.7 %) experienced a poor outcome (radiological and/or histological evidence of tumour spread or recurrence, or death [n = 26]). In univariate analysis, poor outcome was linked to Dukes' stage (p < 0.001), American Joint Committee on Cancer (AJCC) stage (p < 0.001), type of treatment (surgery alone, standard chemotherapy with or without anti-antigenic therapy) (p = 0.047), CECs (p < 0.02) and EPCs (p < 0.01). In subsequent binary logistic regression analysis, only Dukes' stage (hazard ratio 2.3, 95 % confidence interval 1.0-5.3, p = 0.047) and modified AJCC stage (4.62, 1.88-11.33, p < 0.001) predicted a poor outcome. CONCLUSION: Endothelial cell markers (CECs, EPCs, vWf, soluble E selectin) and growth factors (VEGF and angiogenin), measured before surgery, have nothing extra to offer in predicting 2-year outcome in colorectal cancer when compared to Dukes' or AJCC stage.
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Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Células Endoteliales/metabolismo , Células Progenitoras Endoteliales/patología , Anciano , Anciano de 80 o más Años , Recuento de Células , Colon/irrigación sanguínea , Colon/patología , Neoplasias Colorrectales/sangre , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neovascularización Patológica , Periodo Preoperatorio , Recto/irrigación sanguínea , Recto/patología , Resultado del TratamientoRESUMEN
Cardiopulmonary bypass (CPB) causes reperfusion injury that when most severe is clinically manifested as a systemic inflammatory response syndrome. The anaesthetic propofol may have anti-inflammatory properties that may reduce such a response. We hypothesised differing effects of propofol and isoflurane on inflammatory markers in patients having CBR Forty patients undergoing elective CPB were randomised to receive either propofol or isoflurane for maintenance of anaesthesia. CRP, IL-6, IL-8, HIF-1α (ELISA), CD11 and CD18 expression (flow cytometry), and haemoxygenase (HO-1) promoter polymorphisms (PCR/electrophoresis) were measured before anaesthetic induction, 4 hours post-CPB, and 24 hours later. There were no differences in the 4 hours changes in CRP, IL-6, IL-8 or CD18 between the two groups, but those in the propofol group had higher HIF-1α (P = 0.016) and lower CD11 expression (P = 0.026). After 24 hours, compared to the isoflurane group, the propofol group had significantly lower levels of CRP (P < 0.001), IL-6 (P < 0.001) and IL-8 (P < 0.001), with higher levels CD11 (P = 0.009) and CD18 (P = 0.002) expression. After 24 hours, patients on propofol had increased expression of shorter HO-1 GT(n) repeats than patients on isoflurane (P = 0.001). Use of propofol in CPB is associated with a less adverse inflammatory profile than is isofluorane, and an increased up-regulation of HO-1. This supports the hypothesis that propofol has anti-inflammatory activity.
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Anestésicos Intravenosos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Puente Cardiopulmonar , Propofol/uso terapéutico , Síndrome de Respuesta Inflamatoria Sistémica/prevención & control , Adulto , Anestésicos por Inhalación , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Antígenos CD18/sangre , Femenino , Hemo-Oxigenasa 1/sangre , Hemo-Oxigenasa 1/genética , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Isoflurano , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Regiones Promotoras Genéticas , Receptores de Complemento 3d/sangre , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/genética , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Resultado del TratamientoRESUMEN
INTRODUCTION: The importance of the endothelium in angiogenesis and cancer is undisputed, and its integrity may be assessed by laboratory markers such as circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), plasma von Willebrand factor (vWf), soluble E selectin, vascular endothelial growth factor (VEGF) and angiogenin. Antiantigenic therapy may be added to standard cytotoxic chemotherapy as a new treatment modality. We hypothesised that additional antiangiogenic therapy acts in a contrasting manner to that of standard chemotherapy on the laboratory markers. METHODS: We recruited 68 patients with CRC, of whom 16 were treated with surgery alone, 32 were treated with surgery followed by standard chemotherapy (5-flurouracil), and 20 were treated with surgery followed by standard chemotherapy plus anti-VEGF therapy (Avastin). Peripheral blood was taken before surgery, and again 3 months and 6 months later. CD34(+)/CD45(-)/CD146(+) CECs and CD34(+)/CD45(-)/CD309[KDR](+) EPCs were measured by flow cytometry, plasma markers by ELISA. RESULTS: In each of the three groups, CECs and EPCs fell at 3 months but were back at pre-surgery levels at 6 months (P<0.05). VEGF was lower in both 3-and 6-month samples in the surgery-only and surgery plus standard chemotherapy groups (P<0.05), but in those on surgery followed by standard chemotherapy plus anti-VEGF therapy, low levels at 3 months (P<0.01) increased to pre-surgery levels at 6 months. In those having surgery and standard chemotherapy, soluble E selectin was lower, whereas angiogenin was higher at 6 months than at baseline (both P<0.05). CONCLUSIONS: We found disturbances in endotheliod cells regardless of treatment, whereas VEGF returned to levels before surgery in those on antiangiogenic therapy. These observations may have clinical and pathophysiological implications.
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Inhibidores de la Angiogénesis/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores/análisis , Neoplasias Colorrectales/metabolismo , Células Endoteliales/metabolismo , Neovascularización Patológica/diagnóstico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bevacizumab , Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/tratamiento farmacológico , Células Endoteliales/efectos de los fármacos , Células Endoteliales/patología , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Leucovorina/administración & dosificación , Masculino , Estadificación de Neoplasias , Neovascularización Patológica/sangre , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Pronóstico , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
AIMS: The response to glucagon-like peptide 1 receptor agonist treatment may be influenced by endogenous ß-cell function. We investigated whether urinary C-peptide creatinine ratio assessed before or during liraglutide treatment was associated with treatment response. METHODS: A single, outpatient urine sample for urinary C-peptide creatinine ratio was collected 2 h after the largest meal of the day among two separate groups: (1) subjects initiating liraglutide (0.6 â 1.2 mg daily) or (2) subjects already treated with liraglutide for 20-32 weeks. The associations between pretreatment and on-treatment urinary C-peptide creatinine ratio and HbA1c change at 32 weeks were assessed using univariate and multivariate analyses (the ratio was logarithm transformed for multivariate analyses). Changes in HbA1c according to pretreatment urinary C-peptide creatinine ratio quartiles are shown. RESULTS: One hundred and sixteen subjects (70 pretreatment, 46 on treatment) with Type 2 diabetes from 10 diabetes centres were studied. In univariate analyses, neither pretreatment nor on-treatment urinary C-peptide creatinine ratio correlated with HbA1c change (Spearman rank correlation coefficient, r = -0.17, P = 0.17 and r = -0.20, P = 0.19, respectively). In multi-linear regression analyses, entering baseline HbA1c and log urinary C-peptide creatinine ratio, pretreatment and on-treatment log urinary C-peptide creatinine ratio became significantly associated with HbA1c change (P = 0.048 and P = 0.040, respectively). Mean (sd) HbA1c changes from baseline in quartiles 1 to 4 of pretreatment urinary C-peptide creatinine ratio were -3 ± 17 mmol/mol (-0.3 ± 1.6%) (P = 0.52), -12 ± 15 mmol/mol (-1.1 ± 1.4%) (P = 0.003), -11 ± 13 mmol/mol (-1.0 ± 1.2%) (P = 0.002) and -12±17 mmol/mol (-1.1±1.6%) (P=0.016), respectively. CONCLUSIONS: Postprandial urinary C-peptide creatinine ratios before and during liraglutide treatment were weakly associated with the glycaemic response to treatment. Low pretreatment urinary C-peptide creatinine ratio may be more useful than higher values by predicting poorer glycaemic response.
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Péptido C/orina , Creatinina/orina , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Incretinas/uso terapéutico , Periodo Posprandial , Anciano , Diabetes Mellitus Tipo 2/orina , Femenino , Péptido 1 Similar al Glucagón/uso terapéutico , Hemoglobina Glucada/análisis , Humanos , Liraglutida , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Disadvantages with traditional anticoagulants (vitamin K antagonists and heparinoids) have led to the development on non-vitamin K antagonist oral anticoagulants (NOACs). These agents are set to replace the traditional anticoagulants in situations such as following orthopaedic surgery, in atrial fibrillation, and in the prevention and treatment of venous thromboembolism. Although superior to vitamin K antagonists and heparinoids in several aspects, NOACs retain the ability to cause haemorrhage and, despite claims to the contrary, may need monitoring. This review aims to summarise key aspects of the NOACs of relevance to the laboratory.
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Anticoagulantes/administración & dosificación , Bencimidazoles/administración & dosificación , Hemorragia/prevención & control , Morfolinas/administración & dosificación , Pirazoles/administración & dosificación , Piridinas/administración & dosificación , Piridonas/administración & dosificación , Tiazoles/administración & dosificación , Tiofenos/administración & dosificación , Trombosis/prevención & control , beta-Alanina/análogos & derivados , Administración Oral , Anticoagulantes/efectos adversos , Bencimidazoles/efectos adversos , Dabigatrán , Relación Dosis-Respuesta a Droga , Hemorragia/etiología , Humanos , Morfolinas/efectos adversos , Pirazoles/efectos adversos , Piridinas/efectos adversos , Piridonas/efectos adversos , Rivaroxabán , Tiazoles/efectos adversos , Tiofenos/efectos adversos , Trombosis/tratamiento farmacológico , Resultado del Tratamiento , Vitamina K/antagonistas & inhibidores , beta-Alanina/administración & dosificación , beta-Alanina/efectos adversosRESUMEN
The World Health Organisation has reported that the viral disease known as COVID-19, caused by SARS-CoV-2, is the leading cause of death by a single infectious agent. This narrative review examines certain components of the pandemic: its origins, early clinical data, global and UK-focussed epidemiology, vaccination, variants, and long COVID.
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COVID-19 , SARS-CoV-2 , COVID-19/complicaciones , Humanos , Pandemias/prevención & control , Síndrome Post Agudo de COVID-19RESUMEN
Introduction: Diabetes is a leading risk factor for cardiovascular disease (CVD), the pathophysiology of both being linked to metabolic, endothelial, renal, angiogenic and platelet abnormalities. We hypothesised that abnormalities in these systems are more adverse in those whose CVD is compounded by diabetes, compared to those with diabetes or CVD alone. Materials and methods: Serum or plasma from 66 patients with diabetes alone, 76 with CVD alone, and 70 with both diabetes and CVD i.e. diabetic cardiovascular disease, was probed for markers of angiogenesis [angiopoietin 1 and 2, vascular endothelial growth factor (VEGF) and endoglin], metabolic [soluble receptor for advanced glycation products (sRAGE), leptin, lipocalin-2, interleukin-8, and cystatin-C], the endothelium (von Willebrand factor, endothelial microparticles and soluble E selectin)], and the platelet (platelet microparticles and soluble P selectin) by ELISA, Luminex or flow cytometry. Results: VEGF (p = 0.04), von Willebrand factor (p = 0.001) and endothelial microparticles (p = 0.042) were all higher in diabetic cardiovascular disease than in diabetes alone and cardiovascular disease alone. Soluble E selectin was higher in diabetic cardiovascular disease than in diabetes alone (p = 0.045), whilst cystatin-C (p = 0.004) and soluble P selectin (p < 0.001) were higher in diabetes and diabetic cardiovascular disease than in cardiovascular disease alone. There were no differences in angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, or interleukin-8. Conclusion: Angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, interleukin-8, and cystatin-c cannot differentiate diabetes from cardiovascular disease, or both conditions combined. Our data point to a more adverse endothelial (von Willebrand factor, endothelial microparticles), and angiogenic profile (VEGF) in those with diabetic cardiovascular disease, supporting the view that this group should be targeted more aggressively.
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Enfermedades Cardiovasculares , Cistatinas , Diabetes Mellitus , Angiopoyetina 1/metabolismo , Biomarcadores , Cistatinas/metabolismo , Selectina E/metabolismo , Endoglina/metabolismo , Endotelio/química , Endotelio/metabolismo , Humanos , Interleucina-8 , Leptina , Lipocalina 2 , Selectina-P/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de von Willebrand/análisis , Factor de von Willebrand/metabolismoRESUMEN
BACKGROUND: Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial. METHODS: Patients with advanced cancer received oral cyclophosphamide 50 mg o.d., celecoxib 400 mg b.d. and methotrexate 2.5 mg b.d. for two consecutive days each week. Response was determined every 8 weeks; toxicity was evaluated according to CTC version 2.0. Plasma markers of inflammation, coagulation and angiogenesis were measured. RESULTS: Sixty-seven of 69 patients were evaluable for response. Twenty-three patients had stable disease (SD) after 8 weeks, but there were no objective responses to therapy. Median time to progression was 57 days. There was a low incidence of toxicities. Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only. There were no changes in other plasma markers. CONCLUSION: This metronomic approach has negligible activity in advanced cancer albeit with minimal toxicity. Analysis of plasma markers indicates minimal effects on endothelium in this trial. These data for this particular regimen do not support basic tenets of metronomic chemotherapy, such as the ability to overcome resistant tumours by targeting the endothelium.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Metotrexato/uso terapéutico , Neoplasias/tratamiento farmacológico , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Angiopoyetina 1/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Celecoxib , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/sangre , Metotrexato/administración & dosificación , Persona de Mediana Edad , Neoplasias/sangre , Pirazoles/administración & dosificación , Sulfonamidas/administración & dosificaciónRESUMEN
OBJECTIVES: To compare the safety and efficacy of thalidomide in combination with carboplatin to carboplatin alone as a first-line therapy in women with ovarian cancer and to evaluate the anti-angiogenic effects of thalidomide by measurement of surrogate markers of angiogenesis. METHODS: Forty patients with Stage IC-IV ovarian cancer were randomly assigned to receive either carboplatin (AUC 7) intravenously every four weeks for up to six doses (n = 20) or carboplatin at the same dose and schedule, plus thalidomide 100 mg orally daily for six months (n = 20). RESULTS: After median follow-up of 1.95 years, there was no difference in the overall response rate (90% in carboplatin arm, 75% in combination arm; p = 0.41). Increased incidence of symptoms of constipation, dizziness, tiredness and peripheral neuropathy was observed in the combination arm. There was a significant fall in CA-125 and E-selectin in both arms after treatment and VCAM-1 in the carboplatin arm. No significant difference between the two arms was observed in any of the markers analysed. CONCLUSIONS: In our trial the addition of thalidomide to carboplatin was well tolerated with no increased efficacy. The fall in some of the angiogenic markers in both groups may reflect tumour response rather than any specific anti-angiogenic effect of thalidomide.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Talidomida/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores/sangre , Antígeno Ca-125/sangre , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carcinoma/irrigación sanguínea , Selectina E/sangre , Femenino , Humanos , Persona de Mediana Edad , Neovascularización Patológica/sangre , Neoplasias Ováricas/irrigación sanguínea , Talidomida/administración & dosificación , Talidomida/efectos adversos , Resultado del Tratamiento , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
BACKGROUND: Cardiovascular disease (CVD) remains a major cause of morbidity and mortality, especially in the presence of diabetes, possibly because of endothelial damage. Increased circulating progenitor cells (CPCs) and increased plasma markers of angiogenesis [vascular endothelial growth factor (VEGF) and the angiopoietins (Ang-1 and -2)] may be evidence of this damage. Treatment with hydroxy-methyl-glutaryl (HMG-CoA) reductase inhibitors ('statins') improves outcomes in patients with vascular disease, including diabetic patients. We hypothesized that 80 mg per day atorvastatin influences CPC counts of VEGF and the angiopoietins in patients with atherosclerotic CVD with or without diabetes mellitus. METHODS: Cardiovascular disease patients with diabetes mellitus (Group A, n = 14) and nondiabetic patients with CVD only (Group B, n = 10) took atorvastatin 80 mg per day for a period of 8-10 weeks. CPCs (CD34+/CD133+/CD45-) were defined by flow cytometry, plasma levels VEGF and Ang-1 and Ang-2 by ELISA). RESULTS: Circulating progenitor cell counts increased (P < 0.001) in Group A compared with a nonsignificant change in Group B (P = 0.37). VEGF levels fell significantly in Group A (P = 0.04) but no significant change was seen in Group B (P = 0.16). Whilst Ang-1 remained unchanged (P = 0.41), Ang-2 levels increased markedly in both groups (P < 0.05). These effects were independent of LDL and total cholesterol changes but were associated with HDL changes. CONCLUSION: High-dose atorvastatin increased circulating CPCs, reduced VEGF and increased Ang-2 in patients with diabetes and CVD, providing another possible pathophysiological mechanism for the beneficial effects of statins in CVD.
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Antígenos CD/sangre , Aterosclerosis/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Pirroles/uso terapéutico , Células Madre , Anciano , Angiopoyetina 1/sangre , Angiopoyetina 2/sangre , Antígenos CD34/sangre , Aterosclerosis/sangre , Aterosclerosis/patología , Atorvastatina , Diabetes Mellitus/sangre , Diabetes Mellitus/patología , Femenino , Humanos , Antígenos Comunes de Leucocito/sangre , Masculino , Persona de Mediana Edad , Neovascularización Patológica/sangre , Estudios Prospectivos , Factor A de Crecimiento Endotelial Vascular/metabolismoAsunto(s)
Aspirina/farmacología , Aspirina/uso terapéutico , Plaquetas/metabolismo , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/metabolismo , Monocitos/metabolismo , Selectina-P/metabolismo , Adhesividad Plaquetaria/efectos de los fármacos , Humanos , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéuticoRESUMEN
Biomedical scientists are bombarded daily by information, almost all of which refers to the health status of an individual or groups of individuals. This article is the second of a two-part review written to explain some of the issues related to presentation and analysis of data. In the first part (Br J Biomed Sci 2008; 65: 209-17) we focused on types of data, and how to analyse and present the data from an individual or from two groups of persons. Here, we will continue with an examination of data from three or more sets of persons, what methods are available to allow this analysis (i.e., statistical software packages), and will conclude with a statement on appropriate descriptors of data, their analyses and presentation, for authors considering submitting their data to this journal.
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Investigación Biomédica/estadística & datos numéricos , Estadística como Asunto/métodos , Interpretación Estadística de Datos , Políticas Editoriales , Humanos , Publicaciones Periódicas como Asunto , Programas InformáticosRESUMEN
Advances in molecular genetics have identified several species of RNA that fail to translate - hence the non-coding RNAs. The two major groups within this class of nucleic acids are microRNAs (miRNA) and long non-coding RNAs (lncRNA). There is growing body of evidence supporting the view that these molecules have regulatory effect on both DNA and RNA. The objective of this brief review is to explain the molecular genetic of these molecules, to summarize their potential as mediators of disease, and to highlight their value as diagnostic markers and as tools in disease management.
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Artritis Reumatoide/genética , Enfermedades Cardiovasculares/genética , Diabetes Mellitus Tipo 2/genética , Genoma Humano , Neoplasias/genética , ARN Largo no Codificante/genética , Animales , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Biomarcadores/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Hematopoyesis/genética , Humanos , Personal de Laboratorio/educación , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias/diagnóstico , Neoplasias/metabolismo , Neoplasias/patología , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Índice de Severidad de la EnfermedadRESUMEN
The biomedical scientist is bombarded on a daily basis by information, almost all of which refers to the health status of an individual or groups of individuals. This review is the first of a two-part article written to explain some of the issues related to the presentation and analysis of data. The first part focuses on types of data and how to present and analyse data from an individual or from one or two groups of persons. The second part will examine data from three or more sets of persons, what methods are available to allow this analysis (i.e., statistical software packages), and will conclude with a statement on appropriate descriptors of data, their analyses, and presentation for authors considering submission of their data to this journal.
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Investigación Biomédica/métodos , Estadística como Asunto , Terminología como Asunto , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Investigación Biomédica/normas , Investigación Biomédica/estadística & datos numéricos , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Three documents from government-sponsored bodies have recently provided new guidance on the diagnosis, treatment and management of venous thromboembolism. The Report of the Independent Expert Working Group to the Chief Medical Officer makes recommendations on general administrative arrangements, and provides a strategy for thromboprophylaxis. Among the recommendations of Guideline 46 from the National Institute for Health and Clinical Excellence are that all patients about to undergo surgery should be assessed to identify their risk factors for developing veno-thromboembolic disease, and be offered graduated compression/anti-embolism stockings and/or pharmacoprophylaxis. The National Patient Safety Agency document focuses principally on the management of, and education in, the use of oral anticoagulants. The impact and implications of these three documents for haematology-based biomedical scientists, such as in leading a thrombosis team, directing clinical management, training of healthcare professions, and in patient education, will be discussed.