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1.
Wound Repair Regen ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656746

RESUMO

In the Netherlands the primary care (General Practitioner or homecare nurse) encounter a variety of wounds ranging from traumatic to diabetic foot ulcers. According to a recent study 82.4% of the patients with a wound can be treated in a primary setting with the GP as medical supervisor. The remaining 17.6% of patients need more extensive care including advice by a specialised doctor, diagnosis and treatment. Prompt analyses and treatment of underlying causes by specialised doctors in a multidisciplinary setting is necessary for treating patients with complicated wound. This article describes the impact of Electronic Health Consultation on all wounds treated in the primary care. And describes the effect on the duration until referral to the hospital and the influence on the amount of unnecessary referrals to the hospital. All data was collected prospectively from June 2020 until October 2021. The study involved a process where primary care could seek advice from a Wound Physician at the Alrijne Wound Centre through a specialised Electronic Health Consultation. A total of 118 patients were analysed. 41/118 (34.7%) patients required a physical consultation with analysis and treatment in the hospital, after teleconsultation. The remaining 77/118 (65.3%) could be treated in primary care after Electronic Health Consultation. The mean duration of wound existence until Electronic Health Consultation was 39.3 days (range 5-271, SD: 38.5). 3/41 (7.3%) of the referrals were unnecessary. Electronic Health Consultation serves as a valuable and efficient tool for enhancing wound care, ultimately contributing to improved patient management and resource allocation within the healthcare system. This article describes the impact of Electronic Health Consultation on all wounds treated in the primary care and the influence on the duration until referral to the hospital and the influence on the amount of unnecessary referrals to the hospital.

2.
Mil Med ; 189(3-4): e645-e651, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-37703048

RESUMO

INTRODUCTION: During tactical combat casualty care, life- and limb-saving procedures might also be performed by combat medics. This study assesses whether it is feasible to use a head-mounted display (HMD) to provide telemedicine (TM) support from a consulted senior surgeon for combat medics when performing a two-incision lower leg fasciotomy. MATERIALS AND METHODS: Nine combat medics were randomized into groups to perform a two-incision lower leg fasciotomy. One group used the Vuzix M400 and the second group used the RealWear HMT-1Z1. A third, control, group received no guidance. In the Vuzix M400 group and RealWear HMT-1Z1 group, a senior surgeon examined the results after the two-incision lower leg fasciotomy was finished to assess the release of compartments, possible collateral damage, and performance of the combat medics. In the control group, these results were examined by a surgical resident with expertise in two-incision lower leg fasciotomies. The resident's operative performance questionnaire was used to score the performance of the combat medics. The telehealth usability questionnaire was used to evaluate the usability of the HMDs as perceived by the combat medics. RESULTS: Combat medics using an HMD were considered competent in performing a two-incision lower leg fasciotomy (Vuzix: median 3 [range 0], RealWear: median 3 [range 1]). These combat medics had a significantly better score in their ability to adapt to anatomical variances compared to the control group (Vuzix: median 3 [range 0], RealWear: median 3 [range 0], control: median 1 [range 0]; P = .018). Combat medics using an HMD were faster than combat medics in the control group (Vuzix: mean 14:14 [SD 3:41], RealWear: mean 15:42 [SD 1:58], control: mean 17:45 [SD 2:02]; P = .340). The overall satisfaction with both HMDs was 5 out of 7 (Vuzix: median 5 [range 0], RealWear: median 5 [range 1]; P = .317). CONCLUSIONS: This study shows that it is feasible to use an HMD to provide TM support performance from a consulted senior surgeon for combat medics when performing a two-incision lower leg fasciotomy. The results of this study suggest that TM support might be useful for combat medics during tactical combat casualty care when performing life- and limb-saving procedures.


Assuntos
Fasciotomia , Telemedicina , Humanos , Médicos de Combate , Fasciotomia/métodos , Estudos de Viabilidade , Perna (Membro)
3.
Trials ; 23(1): 803, 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36153539

RESUMO

BACKGROUND: The Netherlands Armed Forces have been successfully using deep-frozen (- 80 °C) thrombocyte concentrate (DTC) for the treatment of (massive) bleeding trauma patients in austere environments since 2001. However, high-quality evidence for the effectiveness and safety of DTCs is currently lacking. Therefore, the MAssive transfusion of Frozen bloOD (MAFOD) trial is designed to compare the haemostatic effect of DTCs versus room temperature-stored platelets (RSP) in the treatment of surgical bleeding. METHODS: The MAFOD trial is a single-blinded, randomized controlled non-inferiority trial and will be conducted in three level 1 trauma centres in The Netherlands. Patients 12 years or older, alive at hospital presentation, requiring a massive transfusion including platelets and with signed (deferred) consent will be included. The primary outcome is the percentage of patients that have achieved haemostasis within 6 h and show signs of life. Haemostasis is defined as the time in minutes from arrival to the time of the last blood component transfusion (plasma/platelets or red blood cells), followed by a 2-h transfusion-free period. This is the first randomized controlled study investigating DTCs in trauma and vascular surgical bleeding. DISCUSSION: The hypothesis is that the percentage of patients that will achieve haemostasis in the DTC group is at least equal to the RSP group (85%). With a power of 80%, a significance level of 5% and a non-inferiority limit of 15%, a total of 71 patients in each arm are required, thus resulting in a total of 158 patients, including a 10% refusal rate. The data collected during the study could help improve the use of platelets during resuscitation management. If proven non-inferior in civilian settings, frozen platelets may be used in the future to optimize logistics and improve platelet availability in rural or remote areas for the treatment of (massive) bleeding trauma patients in civilian settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05502809. Registered on 16 August 2022.


Assuntos
Hemostáticos , Perda Sanguínea Cirúrgica , Plaquetas , Hemostasia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Temperatura
4.
Sports Med ; 52(12): 3055-3064, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35904751

RESUMO

AIM: Defining universally accepted guidelines for the diagnosis and treatment of chronic exertional compartment syndrome (CECS) is hampered by the absence of high-quality scientific research. The aim of this Delphi study was to establish consensus on practical issues guiding diagnosis and treatment of CECS of the leg in civilian and military patient populations. METHODS: An international expert group was queried using the Delphi technique with a traditional three-round electronic consultation. Results of previous rounds were anonymously disclosed in the questionnaire of rounds 2 and 3, if relevant. Consensus was defined as > 70% positive or negative agreement for a question or statement. RESULTS: The panel consisted of 27 civilian and military healthcare providers. Consensus was reached on five essential key characteristics of lower leg CECS. The panel achieved partial agreement regarding standardization of the diagnostic protocol, including muscle tissue pressure measurements. Consensus was reached on conservative and surgical treatment regimens. However, the experts did not attain consensus on their approach of postoperative rehabilitation and preferred treatment approach of recurrent or residual disease. A summary of best clinical practice for the diagnosis and management of CECS was formulated by experts working in civilian and military healthcare facilities. CONCLUSION: The Delphi panel reached consensus on key criteria for signs and symptoms of CECS and several aspects for conservative and surgical treatment. The panel did not agree on the role of ICP values in the diagnostic process, postoperative rehabilitation guidelines protocol, or the preferred treatment approach for recurrent or residual disease. These aspects serve as a first attempt to initiate simple guidelines for clinical practice.


Assuntos
Síndrome Compartimental Crônica do Esforço , Síndromes Compartimentais , Humanos , Consenso , Perna (Membro) , Síndromes Compartimentais/diagnóstico , Síndromes Compartimentais/cirurgia , Inquéritos e Questionários
5.
Eur J Vasc Endovasc Surg ; 60(1): 49-55, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32331994

RESUMO

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.


Assuntos
Aneurisma Ilíaco/cirurgia , Idoso , Idoso de 80 Anos ou mais , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/mortalidade , Procedimentos Endovasculares/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Aneurisma Ilíaco/epidemiologia , Aneurisma Ilíaco/mortalidade , Aneurisma Ilíaco/patologia , Artéria Ilíaca/patologia , Artéria Ilíaca/cirurgia , Masculino , Países Baixos/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento
6.
Injury ; 50(6): 1186-1191, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31047681

RESUMO

BACKGROUND: To further strengthen the evidence base on the use of Resuscitative Endovascular Balloon occlusion of the Aorta (REBOA) we performed a Delphi consensus. The aim of this paper is to establish consensus on the indications and contraindications for the use of REBOA in trauma and non-trauma patients based on the existing evidence and expertise. STUDY DESIGN: A literature review facilitated the design of a three-round Delphi questionnaire. Delphi panelists were identified by the investigators. Consensus was reached when at least 70% of the panelists responded to the survey and more than 70% of respondents reached agreement or disagreement. RESULTS: Panel members reached consensus on potential indications, contra-indications and settings for use of REBOA (excluding the pre hospital environment), physiological parameters for patient selection and indications for early femoral access. Panel members failed to reach consensus on the use of REBOA in patients in extremis (no pulse, no blood pressure) and the use of REBOA in patients with two major bleeding sites. CONCLUSIONS: Consensus was reached on indications, contra indications, physiological parameters for patient selection for REBOA and early femoral access. The panel did not reach consensus on the use of REBOA in patients in pre-hospital settings, patients in extremis (no pulse, no blood pressure) and in patients with 2 or more major bleeding sites. Further research should focus on the indications of REBOA in pre hospital settings, patients in near cardiac arrest and REBOA inflation times.


Assuntos
Traumatismos Abdominais/terapia , Aorta Abdominal/lesões , Oclusão com Balão , Consenso , Técnica Delphi , Hemorragia/prevenção & controle , Ressuscitação , Traumatismos Abdominais/complicações , Procedimentos Endovasculares , Humanos , Guias de Prática Clínica como Assunto , Ressuscitação/métodos
7.
Injury ; 50(2): 286-291, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30594315

RESUMO

BACKGROUND: Aortic Occlusion Balloons (AOB) are used for hemorrhage control in hemodynamically unstable patients. Stability of an AOB is essential for reliable aortic occlusion. The primary aim of this study is to determine whether different types of AOB migrate after total, intermittent or partial occlusion in a porcine aorta positioned in an in vitro model. MATERIALS AND METHODS: A porcine thoracic aortic section was positioned in a model of the human circulation. Primary and secondary migration was tested in Cook Coda™ 2-9.0-35-120-32 and 2-10-35-140-46, Cook Medical, USA; Rescue balloon™ Tokai RB-167080-E, Tokai Medical Products, Japan; Reliant™ AB46, Medtronic, USA; Russian prototype AOB; ER-REBOA™, Prytime Medical Devices, USA; LeMaitre™ 28 and 45 Aortic Occlusion Catheter, LeMaitre Vascular, USA. These AOB were tested in hypotensive, normotensive and hypertensive scenarios. Migration in total occlusion, intermittent occlusion and partial occlusion was recorded for all AOB. RESULTS: Limited primary migration occurred in all AOB after total occlusion. The Cook Coda™ 2-9.0-35-120-32 balloon showed maximal migration in 1 test cycle. No migration occurred during intermittent occlusion. Kinking occurs in various degrees but does not seem to prevent a successful occlusion of the aorta. No migration occurred during partial occlusion except in the Russian prototype AOB. In a partial occlusion scenario, distal perfusion occurred only with 5 ml remaining in all balloon types. CONCLUSIONS: All AOB were successful in full aortic occlusion. Limited primary migration occurred in all AOB after total occlusion only the Cook Coda™ 2-9.0-35-120-32 balloon showed maximal migration once. No migration occurred during intermittent occlusion, during partial occlusion only the Russian prototype AOB migrated. Stiffness and size of the catheter are important factors in preventing migration and kinking.


Assuntos
Aorta Torácica/patologia , Oclusão com Balão/efeitos adversos , Migração de Corpo Estranho , Hemorragia/prevenção & controle , Teste de Materiais/métodos , Animais , Aorta Torácica/anatomia & histologia , Oclusão com Balão/instrumentação , Modelos Animais de Doenças , Migração de Corpo Estranho/prevenção & controle , Humanos , Técnicas In Vitro , Masculino , Suínos
8.
Eur J Trauma Emerg Surg ; 44(4): 535-550, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29785654

RESUMO

BACKGROUND: Circulatory collapse is a leading cause of mortality among traumatic major exsanguination and in ruptured aortic aneurysm patients. Approximately 40% of patients die before hemorrhage control is achieved. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct designed to sustain the circulation until definitive surgical or endovascular repair. A systematic review was conducted for the current clinical use of REBOA in patients with hemodynamic instability and to discuss its potential role in improving prehospital and in-hospital outcome. METHODS: Systematic review and meta-analysis (1900-2017) using MEDLINE, Cochrane, EMBASE, Web of Science and Central and Emcare using the keywords "aortic balloon occlusion", "aortic balloon tamponade", "REBOA", and "Resuscitative Endovascular Balloon Occlusion" in combination with hemorrhage control, hemorrhage, resuscitation, shock, ruptured abdominal or thoracic aorta, endovascular repair, and open repair. Original published studies on human subjects were considered. RESULTS: A total of 490 studies were identified; 89 met criteria for inclusion. Of the 1436 patients, overall reported mortality was 49.2% (613/1246) with significant differences (p < 0.001) between clinical indications. Hemodynamic shock was evident in 79.3%, values between clinical indications showed significant difference (p < 0.001). REBOA was favored as treatment in trauma patients in terms of mortality. Pooled analysis demonstrated an increase in mean systolic pressure by almost 50 mmHg following REBOA use. CONCLUSION: REBOA has been used in trauma patients and ruptured aortic aneurysm patients with improvement of hemodynamic parameters and outcomes for several decades. Formal, prospective study is warranted to clarify the role of this adjunct in all hemodynamic unstable patients.


Assuntos
Aorta , Oclusão com Balão/métodos , Exsanguinação/complicações , Ressuscitação/métodos , Choque Hemorrágico/etiologia , Choque Hemorrágico/prevenção & controle , Hemodinâmica , Humanos
9.
Open Cardiovasc Med J ; 10: 44-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27053966

RESUMO

PURPOSE: To show a complication of the use of an Angio-Seal™ closure device. CASE: We present a patient with a systolic murmur in his femoral artery after PCI. The murmur was caused by a dislocated Angio-Seal™, a vascular closure device. This was diagnosed by Doppler Ultrasound. The device was surgically removed. CONCLUSION: Vascular complications, such as lower limb ischemia, requiring surgical intervention tend to be higher after use of a vascular closure device. We advise routine physical examination of the puncture site after percutaneous closure with a vascular closure device, such as an Angio-Seal™. The removal of the device can be performed via an open or endoscopic approach, based on available experience.

10.
Environ Sci Pollut Res Int ; 22(19): 14442-54, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26022396

RESUMO

A combined chemical and biological analysis of samples from a major obsolete pesticide and persistent organic pollutant (POP) dumpsite in Northern Tajikistan was carried out. The chemical analytical screening focused on a range of prioritized compounds and compounds known to be present locally. Since chemical analytics does not allow measurements of hazards in complex mixtures, we tested the use of a novel effect-based approach using a panel of quantitative high-throughput CALUX reporter assays measuring distinct biological effects relevant in hazard assessment. Assays were included for assessing effects related to estrogen, androgen, and progestin signaling, aryl hydrocarbon receptor-mediated signaling, AP1 signaling, genotoxicity, oxidative stress, chemical hypoxia, and ER stress. With this panel of assays, we first quantified the biological activities of the individual chemicals measured in chemical analytics. Next, we calculated the expected sum activity by these chemicals in the samples of the pesticide dump site and compared the results with the measured CALUX bioactivity of the total extracts of these samples. The results showed that particularly endocrine disruption-related effects were common among the samples. This was consistent with the toxicological profiles of the individual chemicals that dominated these samples. However, large discrepancies between chemical and biological analysis were found in a sample from a burn place present in this site, with biological activities that could not be explained by chemical analysis. This is likely to be caused by toxic combustion products or by spills of compounds that were not targeted in the chemical analysis.


Assuntos
Misturas Complexas/análise , Disruptores Endócrinos/análise , Monitoramento Ambiental/métodos , Substâncias Perigosas/análise , Praguicidas/análise , Instalações de Eliminação de Resíduos , Bioensaio/métodos , Linhagem Celular Tumoral , Misturas Complexas/química , Misturas Complexas/toxicidade , Disruptores Endócrinos/toxicidade , Genes Reporter , Substâncias Perigosas/toxicidade , Humanos , Luciferases/genética , Praguicidas/toxicidade , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Medição de Risco , Tadjiquistão , Transcrição Gênica/efeitos dos fármacos
11.
BMJ Case Rep ; 20142014 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-24789153

RESUMO

The current case presents a patient who was admitted to our hospital with the diagnosis of cellulitis of the right groin. In the following days, the patient's condition deteriorated and developed a septic shock. Exploration in the operating room showed a necrotising fasciitis of the adductor muscles, with an infected sebaceous cyst in the inguinal crest as port d'entrée. After extensive surgical debridement, antibiotic therapy, haemodynamic and respiratory support, the patient recovered. Necrotising fasciitis is a rare but very lethal condition, which necessitates aggressive surgical therapy and antibiotic support. The current case report is the first report to show a necrotising fasciitis due to an infected sebaceous cyst.


Assuntos
Desbridamento/métodos , Cisto Epidérmico/complicações , Fasciite Necrosante/etiologia , Fasciite Necrosante/cirurgia , Choque Séptico/terapia , Idoso , Antibacterianos/uso terapêutico , Celulite (Flegmão)/diagnóstico , Celulite (Flegmão)/etiologia , Progressão da Doença , Serviço Hospitalar de Emergência , Tratamento de Emergência/métodos , Cisto Epidérmico/diagnóstico por imagem , Cisto Epidérmico/cirurgia , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/tratamento farmacológico , Feminino , Seguimentos , Bactérias Gram-Positivas/isolamento & purificação , Virilha , Humanos , Tratamento de Ferimentos com Pressão Negativa/métodos , Índice de Gravidade de Doença , Choque Séptico/etiologia , Choque Séptico/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
12.
Eur J Vasc Endovasc Surg ; 47(1): 87-99, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24239103

RESUMO

OBJECTIVE: The objective of the paper is to present a case of an infected bare metal stent in the left common iliac artery that was removed by an urgent operation, and to review the literature on diagnosis and outcome of infected coronary and non-coronary metal stents. METHODS: A systematic search of the Medline database was performed with the purpose of identifying risk factors, signs and symptoms, imaging strategies, and treatment modalities of bare metal stent infections, both coronary and peripheral. RESULTS: In total, 76 additional studies/case reports (48 non-coronary; 29 coronary) were included and analyzed. Intravascular bare metal stent infections are a rare but serious complication, often leading to emergency surgery (overall: 75.3%; non-coronary cases: 83.3%; coronary cases: 62.1%). In 25.0% of the non-coronary cases, infection led to amputation of an extremity or removal of viscera. Reported mortality was up to 32.5% of the cases (non-coronary: 22.9%; coronary 48.3%). Physicians should always be suspicious of a stent infection when patients present with aspecific symptoms such as fever and chills after stent placement. Additional imaging can be used to detect the presence of a pseudoaneurysm. A PET-CT is an ideal medium for identification of a stent infection. CONCLUSIONS: Intravascular stent infection is associated with a high risk of morbidity and mortality. Surgery is the preferred treatment option, but not always possible, especially in patients with a coronary stent. In selected cases, bare metal stent infections may be prevented by the use of prophylactic antibiotics at stent placement.


Assuntos
Falso Aneurisma/etiologia , Aneurisma Infectado/etiologia , Arteriopatias Oclusivas/terapia , Procedimentos Endovasculares/efeitos adversos , Artéria Ilíaca , Artéria Poplítea , Infecções Relacionadas à Prótese/etiologia , Infecções Estafilocócicas/etiologia , Stents/efeitos adversos , Tromboembolia/terapia , Falso Aneurisma/diagnóstico , Falso Aneurisma/microbiologia , Falso Aneurisma/terapia , Aneurisma Infectado/diagnóstico , Aneurisma Infectado/microbiologia , Aneurisma Infectado/terapia , Arteriopatias Oclusivas/diagnóstico por imagem , Constrição Patológica , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Pessoa de Meia-Idade , Artéria Poplítea/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/terapia , Fatores de Risco , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/terapia , Tromboembolia/diagnóstico por imagem , Terapia Trombolítica , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Environ Sci Technol ; 47(20): 11651-9, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23987121

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) represent a class of ubiquitously occurring environmental compounds that are implicated in a wide range of toxicological effects. Routine measurement of PAH contamination generally involves chemical analytical analysis of a selected group of representatives, for example, EPA-16, which may result in underestimation of the PAH-related toxicity of a sample. Many high molecular weight PAHs are known ligands of the aryl hydrocarbon receptor (AhR), a nuclear receptor that mediates toxic effects related to these compounds. Making use of this property we developed a PAH CALUX assay, a mammalian, H4IIe- cell-based reporter assay for the hazard identification of total PAH mixtures. The PAH CALUX reporter cell line allows for specific, rapid (4 h exposure time) and reliable quantification of AhR-induced luciferase induction relative to benzo[a]pyrene (BaP), which is used as a positive reference PAH congener. Full dose response relationships with inductions over 100-fold were reached within only 2 h of exposure to BaP. The PAH CALUX is highly sensitive, that is, using a 4 h exposure time, a limit of detection (LOD) of 5.2 × 10(-11) M BaP was achieved, and highly accurate, that is, a repeatability of 5.9% and a reproducibility of 6.6% were established. Screening of a selection of PAHs that were prioritized by the European Union and/or the U.S. Environmental Protection Agency showed that the PAH CALUX bioassay has a high predictability, particularly for carcinogenic PAHs. Experiments with synthetic mixtures and reference materials containing complex PAH mixtures show the suitability of the assay for these types of applications. Moreover, the presented results suggest that application of the PAH CALUX will result in a lower risk of underestimation of the toxicity of a sample than chemical analytical approaches that focus on a limited set of prioritized compounds.


Assuntos
Bioensaio/métodos , Misturas Complexas/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Benzo(a)pireno/análise , Linhagem Celular , Poluentes Ambientais/análise , Genes Reporter , Luciferases/metabolismo , Camundongos , Fatores de Tempo
14.
Toxicol In Vitro ; 27(5): 1425-32, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23563205

RESUMO

The present study shows significant correlations between the EC50 for PPARγ activation in a reporter gene cell line and resistin downregulation in mouse adipocytes, and between the IC50 for resistin downregulation and the already published minimum effective dose for antihyperglycemic activity in a mouse model. These correlations indicate that PPARγ mediated downregulation of resistin might promote insulin sensitivity and that downregulation of resistin in mouse adipocytes provides an adequate and possibly more direct bioassay for screening of newly developed antihyperglycemic compounds. Because of the higher throughput of the PPARγ the resistin downregulation assays seems most suitable to be used as a second tier in a tiered screening strategy.


Assuntos
Adipócitos/efeitos dos fármacos , PPAR gama/metabolismo , Resistina/genética , Tiazolidinedionas/farmacologia , Células 3T3-L1 , Adipócitos/citologia , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Regulação para Baixo , Camundongos , RNA Mensageiro/metabolismo
15.
Reprod Toxicol ; 38: 53-64, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23511061

RESUMO

The application of alternative methods in developmental and reproductive toxicology is challenging in view of the complexity of mechanisms involved. A battery of complementary test systems may provide a better prediction of developmental and reproductive toxicity than single assays. We tested twelve compounds with varying mechanisms of toxic action in an assay battery including 24 CALUX transcriptional activation assays, mouse cardiac embryonic stem cell test, ReProGlo assay, zebrafish embryotoxicity assay, and two CYP17 and two CYP19 activity assays. The battery correctly detected 11/12 compounds tested, with one false negative occurring, which could be explained by the absence of the specific mechanism of action of this compound in the battery. Toxicokinetic modeling revealed that toxic concentrations were in the range expected from in vivo reproductive toxicity data. This study illustrates added value of combining assays that contain complementary biological processes and mechanisms, increasing predictive value of the battery over individual assays.


Assuntos
Alternativas aos Testes com Animais , Teratogênicos/toxicidade , Testes de Toxicidade/métodos , Animais , Aromatase/metabolismo , Bioensaio , Linhagem Celular , Células Cultivadas , Embrião não Mamífero/efeitos dos fármacos , Células-Tronco Embrionárias/efeitos dos fármacos , Humanos , Camundongos , Ratos , Receptores de Esteroides/metabolismo , Reprodutibilidade dos Testes , Reprodução , Esteroide 17-alfa-Hidroxilase/metabolismo , Peixe-Zebra
16.
Phlebology ; 26(5): 209-12, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21357621

RESUMO

The objective of the study was first to quantify the level of pain that patients experience during VNUS ClosureFAST™ and in the first week following treatment. Secondly, to investigate the use of pain medication. Thirdly, to identify after how many days patients return to daily activities and whether pain is a factor of influence. A prospective descriptive cohort study was carried out. In all, 104 consecutive VNUS ClosureFAST procedures for greater saphenous vein (GSV) incompetence between 18 May and 28 August 2009 in the HagaZiekenhuis were included. A visual analogue score (VAS) was recorded immediately after the procedure. These patients were asked to register pain scores during the week following the procedure, the amount of pain medication if used and the time elapsed between the procedures and resuming daily activities. The average VAS score during the VNUS Closure procedure was four. The first three days after the procedure the VAS score was 2. After four days, the average score was 1. The average return to daily activities was on day two after the procedure. In total, 24% of all patients used paracetamol after the procedure. In summary, VNUS ClosureFAST procedure for GSV incompetence is not a painless treatment. After an average of two days, patients return to their daily activities. Pain does not seem to be a major factor in the resumption. Seventy-six percent of patients do not use any pain medication.


Assuntos
Ablação por Cateter/efeitos adversos , Dor/diagnóstico , Varizes/cirurgia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Acetaminofen/farmacologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Percepção , Estudos Prospectivos , Resultado do Tratamento
17.
Curr Drug Metab ; 9(8): 796-826, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18855613

RESUMO

Legislation and prospective legislative proposals in for instance the USA, Europe, and Japan require, or may require that chemicals are tested for their ability to disrupt the hormonal systems of mammals. Chemicals found to test positive are considered to be endocrine active substances (EAS) and may be putative endocrine disruptors (EDs). To date, there is still little or no experience with incorporating metabolic and toxicokinetic aspects into in vitro tests for EAS. This is a situation in sharp contrast to genotoxicity testing, where in vitro tests are routinely conducted with and without metabolic capacity. Originally prepared for the Organisation of Economic Cooperation and Development (OECD), this detailed review paper reviews why in vitro assays for EAS should incorporate mammalian systems of metabolism and metabolic enzyme systems, and indicates how this could be done. The background to ED testing, the available test methods, and the role of mammalian metabolism in the activation and the inactivation of both endogenous and exogenous steroids are described. The available types of systems are compared, and the potential problems in incorporating systems in in vitro tests for EAS, and how these might be overcome, are discussed. Lastly, some recommendations for future activities are made.


Assuntos
Disruptores Endócrinos/farmacologia , Animais , Biotransformação , Proliferação de Células/efeitos dos fármacos , Disruptores Endócrinos/metabolismo , Sistema Endócrino/efeitos dos fármacos , Indução Enzimática , Humanos , Metoxicloro/metabolismo , Metoxicloro/farmacologia , Pele/metabolismo , Esteroides/metabolismo , Ativação Transcricional/efeitos dos fármacos
20.
J Mol Endocrinol ; 32(3): 689-701, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15171709

RESUMO

With the aim of developing an in vivo model that directly detects activation of estrogen receptors (ERs), transgenic mice carrying a luciferase reporter gene were generated. The luciferase reporter gene was under the control of three consensus estrogen-responsive elements (EREs) coupled to a minimal TATA-box, with or without flanking chick beta-globin insulators. By using this model in combination with the IVIS imaging system, in vivo ER activation was measured. Dose- and time-dependent luciferase activity was induced in various organs of adult transgenic male mice exposed to diethylstilbestrol (DES) (10-1000 micro g/kg) and 17beta-estradiol dipropionate (EP) (10-1000 micro g/kg), when luciferase activity was measured ex vivo. The highest (>10 000-fold) induction of luciferase was measured in bone and kidney 24 h after exposure to 1000 micro g/kg EP. Other highly responsive organs include liver, testis, pituitary, brain, prostate and colon, which show different activity profiles. This in vivo model for detecting estrogenic activity can be used to assess tissue-specific action of ER agonists and antagonists. These could include selective ER modulators and environmental estrogens. In combination with the IVIS imaging system, this in vivo model is a powerful tool for assessing the kinetics of gene activation by estrogenic compounds.


Assuntos
Regulação da Expressão Gênica , Genes Reporter , Camundongos Transgênicos , Receptores de Estrogênio/metabolismo , Animais , Dietilestilbestrol/metabolismo , Estradiol/metabolismo , Estrogênios não Esteroides/metabolismo , Feminino , Humanos , Luciferases/genética , Luciferases/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Receptores de Estrogênio/genética , Elementos de Resposta , Fatores de Tempo , Distribuição Tecidual , Ativação Transcricional
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