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1.
Clin Radiol ; 78(4): 295-300, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36702708

RESUMEN

As interventional radiology (IR) treatments have evolved, they have become less invasive, enabling rapid recovery, which expedites ambulation and promotes same-day discharge. As a result of this, a significant proportion of IR elective work can be provided using a day-case service model. Reconfiguration of IR services to increase day-case procedures using a dedicated IR day-case unit (RDU) to facilitate the passage of patients is vital to ensure best medical practice. The aim of this review is to discuss the benefits of day-case IR procedures, the optimal structure of an RDU, and to inform radiologists how to introduce and/or improve day-case IR services in their IR practice.


Asunto(s)
Atención al Paciente , Radiología Intervencionista , Humanos , Radiología Intervencionista/métodos
2.
Clin Radiol ; 78(4): 288-294, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36707396

RESUMEN

This review describes the rationale in support of admitting rights for interventional radiologists and presents options for the management of interventional radiology (IR) inpatients. The manuscript also discusses wider aspects of IR involvement in inpatient treatment, such as income and funding for IR services, and the implications for IR as a clinical specialty.


Asunto(s)
Atención al Paciente , Radiología Intervencionista , Humanos , Hospitalización , Pacientes Internos , Radiólogos
3.
Cardiovasc Intervent Radiol ; 45(9): 1391-1398, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35790566

RESUMEN

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).


Asunto(s)
Embolización Terapéutica , Neoplasias Hepáticas , Acreditación , Embolización Terapéutica/métodos , Hepatectomía/métodos , Venas Hepáticas/patología , Hepatomegalia , Humanos , Hipertrofia/etiología , Hipertrofia/patología , Hipertrofia/cirugía , Hígado/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Estudios Multicéntricos como Asunto , Vena Porta/patología , Estudios Prospectivos , Resultado del Tratamiento
4.
Cardiovasc Intervent Radiol ; 45(8): 1152-1162, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35277726

RESUMEN

BACKGROUND: The COVID-19 pandemic had an unprecedented impact on clinical practice and healthcare professionals. We aimed to assess how interventional radiology services (IR services) were impacted by the pandemic and describe adaptations to services and working patterns across the first two waves. METHODS: An anonymous six-part survey created using an online service was distributed as a single-use web link to 7125 members of the Cardiovascular and Interventional Radiological Society of Europe via email. Out of 450 respondents, 327 who completed the survey at least partially including 278 who completed the full survey were included into the analysis. RESULTS: Interventional radiologists (IRs) reported that the overall workload decreased a lot (18%) or mildly (36%) or remained stable (29%), and research activities were often delayed (30% in most/all projects, 33% in some projects). Extreme concerns about the health of families, patients and general public were reported by 43%, 34% and 40%, respectively, and 29% reported having experienced significant stress (25% quite a bit; 23% somewhat). Compared to the first wave, significant differences were seen regarding changes to working patterns, effect on emergency work, outpatient and day-case services in the second wave. A total of 59% of respondents felt that their organisation was better prepared for a third wave. A total of 19% and 39% reported that the changes implemented would be continued or potentially continued on a long-term basis. CONCLUSION: While the COVID-19 pandemic has negatively affected IR services in terms of workload, research activity and emotional burden, IRs seem to have improved the own perception of adaptation and preparation for further waves of the pandemic.


Asunto(s)
COVID-19 , Humanos , Pandemias/prevención & control , Radiólogos , Radiología Intervencionista , Encuestas y Cuestionarios
5.
Ann R Coll Surg Engl ; 100(6): 480-484, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29658337

RESUMEN

Introduction Sporadic renal angiomyolipomas, although benign in natural can cause life-threatening spontaneous haemorrhage. Surveillance of smaller lesions is recommended but there is no guidance on the surveillance interval or modality. Our aim was to study our sporadic angiomyolipoma population to determine the growth rate, factors that were associated with a higher growth rate and design a surveillance programme. Materials and methods All sporadic renal angiomyolipomas diagnosed between September 2009 and March 2015 were included. Patients with a diagnosis of tuberous sclerosis were excluded. Results A total of 217 sporadic renal angiomyolipomas were diagnosed. The median follow-up was 24 months (range 10-118 months). The median size at diagnosis was 9.00 mm with a mean growth rate of 0.13 mm/year (standard deviation 0.88). One hundred and fifty angiomyolipomas (69%) were shown to have negative or zero growth. In the remaining 67, 59 had a growth rate of less than 2.00 mm/year. Size of angiomyolipoma, tumour burden and age were not associated with a higher growth rate on multivariate analysis. Conclusion The majority of sporadic angiomyolipomas are small and do not grow. Our practice is to perform surveillance for those greater than 20 mm, with five-yearly ultrasound scans for 21-29 mm, and two-yearly surveillance for 30-39 mm tumours.


Asunto(s)
Angiomiolipoma/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Angiomiolipoma/patología , Femenino , Estudios de Seguimiento , Hospitales de Distrito , Hospitales Generales , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía Computarizada por Rayos X , Carga Tumoral , Ultrasonografía , Espera Vigilante
6.
Frontline Gastroenterol ; 8(1): 26-28, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28839881

RESUMEN

Endoscopic ultrasound (EUS) is increasingly used in the management of hepatobiliary lesions, allowing staging and tissue acquisition. It is operator-dependent, and fine needle aspiration (FNA) of solid lesions provides an auditable standard; high-volume centres have shown excellent results for solid pancreatic lesion FNA with sensitivities of 92%-97%. The British Society of Gastroenterology guidelines stress that clinical quality should determine service provision, with geographical accessibility a secondary consideration. We set up the Wessex EUS network, working from a single hepatobiliary (HPB) pancreatic multidisciplinary team, with EUS provided in four local centres providing agreed standards and audit. Pancreatic solid lesion FNA results showed a pooled sensitivity of 94%, comparable with high-volume single centres. This demonstrates a network with good clinical governance is a plausible solution to providing a specialist service such as EUS and may be a roadmap that other specialist services under pressure could follow.

7.
Am J Transplant ; 15(11): 2940-6, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26153092

RESUMEN

In previous studies with different donor selection criteria and noncontemporary surgical techniques, graft arterial stenosis (GAS) has been reported to occur more frequently in adult recipients of pediatric en bloc renal allografts (EBKT) as compared to single adult donor allografts. The purpose of our study was to evaluate the incidence of GAS within our EBKT recipient population and to evaluate clinical and imaging features of those cases with GAS. In a retrospective cohort study, we analyzed 182 EBKT performed at a single institution. We identified cases of suspected GAS based on clinical factors, lab results, and noninvasive imaging. Diagnosis of GAS was confirmed by digital subtraction angiography. Two EBKT recipients (1.1% of 182) had angiographically confirmed GAS at 2.5 and 4.5 months after transplant. In both cases, the stenoses were short segment within the proximal (perianastomotic) donor aorta, color Doppler ultrasound demonstrated peak systolic velocities of >400 cm/s, and poststenotic parvus tardus waveforms were present. Both patients underwent angioplasty and demonstrated postintervention improvement in renal function and blood pressure. Restenosis did not occur during follow up. In conclusion, recipients of EBKT have a low incidence of GAS, similar to the lowest reported for adult single allografts.


Asunto(s)
Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Riñón/irrigación sanguínea , Donantes de Tejidos , Adolescente , Adulto , Factores de Edad , Anciano , Aloinjertos , Angiografía/métodos , Angioplastia de Balón/métodos , Niño , Estudios de Cohortes , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/terapia , Femenino , Estudios de Seguimiento , Rechazo de Injerto/epidemiología , Rechazo de Injerto/patología , Humanos , Lactante , Riñón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios/métodos , Estudios Retrospectivos , Medición de Riesgo , Rol , Factores de Tiempo , Obtención de Tejidos y Órganos , Resultado del Tratamiento , Ultrasonografía Doppler , Adulto Joven
8.
Am J Physiol Regul Integr Comp Physiol ; 301(4): R1132-42, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21795637

RESUMEN

The crucian carp (Carassius carassius) seems unique among vertebrates in its ability to maintain cardiac performance during prolonged anoxia. We investigated whether this phenomenon arises in part from a myocardium tolerant to severe acidosis or because the anoxic crucian carp heart may not experience a severe extracellular acidosis due to the fish's ability to convert lactate to ethanol. Spontaneously contracting heart preparations from cold-acclimated (6-8°C) carp were exposed (at 6.5°C) to graded or ungraded levels of acidosis under normoxic or anoxic conditions and intrinsic contractile performance was assessed. Our results clearly show that the carp heart is tolerant of acidosis as long as oxygen is available. However, heart rate and contraction kinetics of anoxic hearts were severely impaired when extracellular pH was decreased below 7.4. Nevertheless, the crucian carp heart was capable of recovering intrinsic contractile performance upon reoxygenation regardless of the severity of the anoxic + acidotic insult. Finally, we show that increased adrenergic stimulation can ameliorate, to a degree, the negative effects of severe acidosis on the intrinsic contractile properties of the anoxic crucian carp heart. Combined, these findings indicate an avoidance of severe extracellular acidosis and adrenergic stimulation are two important factors protecting the intrinsic contractile properties of the crucian carp heart during prolonged anoxia, and thus likely facilitate the ability of the anoxic crucian carp to maintain cardiac pumping.


Asunto(s)
Acidosis/fisiopatología , Carpas/fisiología , Hipoxia/fisiopatología , Contracción Miocárdica/fisiología , Estrés Fisiológico/fisiología , Neuronas Adrenérgicas/fisiología , Animales , Etanol/metabolismo , Femenino , Frecuencia Cardíaca/fisiología , Concentración de Iones de Hidrógeno , Lactatos/metabolismo , Masculino , Modelos Animales
9.
Clin Radiol ; 66(10): 945-52, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21658691

RESUMEN

AIM: To assess the utility of 64 section multidetector computed tomography (MDCT) lower-limb angiography in the evaluation of patients with critical limb ischaemia (CLI) or severe intermittent claudication (IC) in grading disease before endovascular treatment. MATERIALS AND METHODS: Forty-one consecutive patients with CLI or severe IC were assessed using 64 section MDCT angiography. The MDCT examinations were compared with subsequent intra-arterial digital subtraction angiography (IADSA) examinations performed at the time of endovascular intervention. The MDCT and IADSA examinations were independently scrutinized by readers blinded to the results of the other imaging method. RESULTS: For arterial segments with haemodynamically significant disease (stenosis ≥50%), the overall sensitivity, specificity, and accuracy of MDCT in patients with severe claudication and CLI was 99% (95% CI: 98-100%), 98% (95% CI: 97-100%) and 98% (95% CI: 97-99%), respectively. The positive predictive value (PPV) was 97% and the negative predictive value (NPV) was 99%. CONCLUSIONS: MDCT angiography is a useful tool in the assessment of patients with severe claudication and CLI and can be reliably used to grade disease severity and plan treatment.


Asunto(s)
Angiografía de Substracción Digital , Arteriopatías Oclusivas/diagnóstico por imagen , Claudicación Intermitente/diagnóstico por imagen , Isquemia/diagnóstico por imagen , Extremidad Inferior/irrigación sanguínea , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Arteriopatías Oclusivas/fisiopatología , Enfermedad Crítica , Femenino , Humanos , Claudicación Intermitente/fisiopatología , Isquemia/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Interpretación de Imagen Radiográfica Asistida por Computador , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad
10.
Clin Radiol ; 66(1): 1-12, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21147293

RESUMEN

Patent vascular access is a prerequisite for adequate haemodialysis, and is a major determinant of quality of life and long-term survival of patients with end-stage renal disease. Autogenous haemodialysis fistulas (AVFs) have demonstrated superior clinical outcome when compared to synthetic grafts, but both types of access remain susceptible to venous stenoses, and consequent thrombotic occlusion. Recent publications have reported primary patency rates of up to 100% following percutaneous de-clotting of AVFs incorporating techniques such as pharmacological thrombolysis, mechanical thrombectomy, and thrombo-aspiration. Endovascular management also provides information regarding the underlying cause of access thrombosis, with option to treat. Consequently, there has been a paradigm shift in the management of fistula thrombosis, with interventional radiology assuming a lead role in initial salvage procedures. This article will attempt to provide the reader with an insight into the multiple radiological techniques that can be employed to salvage a thrombosed AVF based on current published literature.


Asunto(s)
Derivación Arteriovenosa Quirúrgica/efectos adversos , Fallo Renal Crónico/terapia , Radiología Intervencionista/métodos , Diálisis Renal/efectos adversos , Terapia Recuperativa/métodos , Trombosis/diagnóstico por imagen , Humanos , Radiografía , Diálisis Renal/métodos , Trombectomía/métodos , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Trombosis/prevención & control , Trombosis/cirugía
11.
Eur J Neurol ; 17(2): 280-8, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19845749

RESUMEN

BACKGROUND AND PURPOSE: Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder caused by an increased CAG repeat size in the huntingtin gene. Apart from neurological impairment, the disease is also accompanied by progressive weight loss, abnormalities in glucose homeostasis and a higher prevalence of diabetes mellitus, which may partly be caused by disturbed growth hormone (GH) and ghrelin secretion. Therefore, we aimed to perform a detailed analysis of GH and ghrelin secretion in HD patients in relation to clinical signs and symptoms. METHODS: In nine early-stage, medication-free HD patients and nine age-, gender- and body mass index-matched controls, we measured serum GH levels every 10 min for 24 h and assessed ghrelin response to food intake. Multi-parameter auto-deconvolution and approximate entropy analysis were applied to quantify basal, pulsatile, and total GH secretion rates as well as the regularity of GH secretion. RESULTS: We found no significant differences in GH and ghrelin secretion characteristics between HD patients and controls (total GH secretion: 137 +/- 36 vs. 181 +/- 43 mU/l/24 h, respectively; P = 0.439). However, in HD patients, both GH secretion and its irregularity as well as the degree of postprandial ghrelin suppression significantly increased with worsening motor and functional impairment (all P < 0.05). Moreover, postprandial ghrelin suppression also increased with decreasing body weight and higher CAG repeat number (both P < 0.05). CONCLUSIONS: These findings suggest changes in the regulation of GH and ghrelin secretion dynamics in early stage HD patients that could become more prominent in the later stages of the disease.


Asunto(s)
Ghrelina/sangre , Hormona de Crecimiento Humana/sangre , Enfermedad de Huntington/sangre , Composición Corporal , Índice de Masa Corporal , Peso Corporal , Estudios de Casos y Controles , Ingestión de Alimentos/fisiología , Femenino , Ghrelina/metabolismo , Hormona de Crecimiento Humana/metabolismo , Humanos , Proteína Huntingtina , Enfermedad de Huntington/genética , Enfermedad de Huntington/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares/genética , Fenotipo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Repeticiones de Trinucleótidos
12.
Med Dosim ; 34(3): 225-7, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19647633

RESUMEN

The purpose of this study was to determine the perceived and actual chin position(s) used for radiotherapy of head-and-neck cancers in a variety of clinical settings. Dosimetrists were asked to describe the external landmarks used to set the chin position. The lateral treatment planning radiographic figures in Ang's textbook, Radiotherapy for Head and Neck Cancers: Indications and Techniques, were analyzed for chin position by drawing a horizontal line from the tip of the chin to the cervical spine. The physicians at 7 departments were asked to rate the chin positions used in their departments for head-and-neck simulations. Choices included: (1) mildly flexed, (2) neutral, (3) mildly extended, and (4) hyperextended. In addition, each center was asked to select 2 representative cases to show routine chin position. The dosimetrists fixed the chin in neutral position by placing a virtual plane defined by 3 points (the base of the nasal septum [acanthus] and the external auditory canals) perpendicular to the table top. The type of head holder was irrelevant. Eighty-two percent (31/38) of the figures in Ang's text showed positioning in the neutral position (tip of the chin intersected the cervical spine between C2-3/C3-4). Most (71.4%) of the radiotherapists thought their patients were treated in the hyperextended neck position but, in fact, 85.7% (12/14) of the simulations showed a neural neck position. Reproducible chin positioning can be obtained by using the acanthiomeatal line. Consistent use of this technique will create a uniformly positioned set of axial co-images that have consistent appearance of avoidance and lymphatic areas. This will simplify contouring on axial computed tomography (CT) images of the neck. Standardizing the chin position is an important step to developing a standardized atlas and developing an information tool for automated contouring.


Asunto(s)
Neoplasias de Cabeza y Cuello/radioterapia , Cabeza/diagnóstico por imagen , Cuello/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Radioterapia Conformacional/normas , Tomografía Computarizada por Rayos X/métodos , Humanos , Valores de Referencia , Estados Unidos
13.
Clin Radiol ; 64(4): 430-8, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19264189

RESUMEN

This review was performed to describe the range of magnetic resonance imaging (MRI) appearances of borderline ovarian tumours. The MRI findings in 26 patients with 31 borderline ovarian tumours (mean age: 40.1 years, range: 14-85 years) were retrospectively reviewed. For each tumour, site, size, MRI characteristics, and enhancement following gadolinium administration were recorded. There were 20 serous and 11 mucinous borderline ovarian subtypes. Nine of 26 patients demonstrated bilateral disease on MRI; synchronous contralateral ovarian disease included three benign, five serous borderline, and one serous invasive tumour. A history of a metachronous mucinous borderline tumour was identified in one patient. MRI appearances were classified into four morphological categories: group 1 (6/31, 19%), unilocular cysts; group 2 (6/31, 19%), minimally septate cysts with papillary projections; group 3 (14/31, 45%), markedly septate lesions with plaque-like excrescences; and group 4 (5/31, 16%), predominantly solid with exophytic papillary projections, all of serous subtype. There was a significant difference in mean volume between serous (841.5 cm(3)) and mucinous (6358.2 cm(3)) subtypes (p=0.009). All tumours demonstrated at least one MRI feature suggestive of malignancy. The present review demonstrates the variable MRI appearances of borderline ovarian tumours along with imaging features suggestive of tumour subtype. In patients in whom the clinical features are suggestive of a borderline ovarian tumour (young age and normal or minimally elevated CA125), the ability to predict a borderline disease using morphological features observed on MRI would be extremely helpful in surgical planning, with the potential to offer fertility or ovary-preserving surgery. Future studies are required to further this aim.


Asunto(s)
Imagen por Resonancia Magnética , Neoplasias Ováricas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Gadolinio , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Neoplasias Ováricas/clasificación , Neoplasias Ováricas/diagnóstico , Radioisótopos , Estudios Retrospectivos , Adulto Joven
14.
Clin Radiol ; 63(12): 1361-71, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18996268

RESUMEN

Blunt renal trauma is the third most common injury in abdominal trauma following splenic and hepatic injuries, respectively. In the majority, such injuries are associated with other abdominal organ injuries. As urological injuries are not usually life-threatening, and clinical signs and symptoms are non-specific, diagnosis is often delayed. We present a practical approach to the diagnosis and management of these injuries based on our experience in a busy inner city trauma hospital with a review of the current evidence-based practice. Diagnostic imaging signs are illustrated.


Asunto(s)
Diagnóstico por Imagen/métodos , Riñón/lesiones , Uretra/lesiones , Vejiga Urinaria/lesiones , Heridas no Penetrantes/diagnóstico , Accidentes de Tránsito , Traumatismos en Atletas , Femenino , Hematuria/patología , Humanos , Masculino , Guías de Práctica Clínica como Asunto , Índices de Gravedad del Trauma , Heridas no Penetrantes/complicaciones
15.
Rev Sci Tech ; 23(1): 319-30; discussion 391-401, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15200106

RESUMEN

Clinical veterinary services were privatised in Jamaica in September 1992. Using the limited official data, the authors briefly examine the premise and logistics behind transferring the responsibility for clinical services, which may be regarded as 'a private good', to private veterinary practitioners. There are indications that this privatisation model can work for farmers, despite financial problems in the livestock industry and a decline in production, caused by trade liberalisation policies and the substitution of cheaper imports. In addition, other national fiscal problems, such as a downturn in the economy, have left veterinarians attempting to boost production in a livestock industry which lacks adequate financial structuring and resources. The authors express concern that various unpublished projections since the last official agricultural survey in 1996 indicate that the livestock industry in Jamaica is diminishing. It is possible that valuable genetic breeding stock may never recover. A comprehensive study of the future of the livestock industry and its associated services is strongly urged. Ten years after the event, the authors reflect on the privatisation of clinical veterinary services in Jamaica and offer some suggestions to improve on the quality of the services offered by private veterinary practitioners.


Asunto(s)
Crianza de Animales Domésticos/tendencias , Privatización , Medicina Veterinaria , Crianza de Animales Domésticos/economía , Animales , Atención a la Salud , Humanos , Jamaica
16.
Am J Pathol ; 159(3): 971-82, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11549590

RESUMEN

Interactions between specific cell-surface molecules, which include the urokinase receptor (uPAR) and integrins, are crucial to processes of tumor invasion and metastasis. Here we demonstrate that uPAR and beta1-integrins may cluster at distinct sites at the cell surface of metastatic MDA-MB-231 breast cancer cells and form functional complexes. Attachment assays performed in the presence of a synthetic peptide (p25), which interferes with the formation of uPAR-integrin complexes, reveal that uPAR is able to regulate the adhesive function of integrins in breast cancer cells. On dissociation of the uPAR-integrin complexes by p25, tumor cell attachment to the extracellular matrix was either decreased (vitronectin) or increased (fibronectin). Moreover, the tumor cells display remarkable morphological changes when cultured on fibronectin in the continuous presence of p25, leading to increased cell spreading and attachment. In marked contrast to control conditions, increased cellular adhesion to fibronectin after p25 treatment was entirely beta1-integrin-mediated. The role of uPAR-integrin complexes in tumor progression was studied in an in vivo bone xenograft model. Stably transfected MDA-MB-231 cells that overexpress p25 showed a significant reduction in tumor progression in bone (P < or = 0.0001 versus mock-control). In line with these observations, continuous administration of p25 (25 microg/mouse/day, osmotic minipumps) for 28 days resulted in significantly reduced tumor progression of MDA-MB-231 cells in bone (P < or = 0.005) when compared to scrambled control peptide. In conclusion, our data demonstrate that uPAR can act as an adhesion receptor in breast cancer and is capable of regulating integrin function. Our findings strongly suggest that adhesive and proteolytic events are tightly associated in metastatic breast cancer cells and that functional integrin-uPAR complexes are involved in tumor progression in vivo.


Asunto(s)
Neoplasias de la Mama/fisiopatología , Integrinas/metabolismo , Receptores de Superficie Celular/fisiología , Neoplasias Óseas/metabolismo , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Adhesión Celular/fisiología , Progresión de la Enfermedad , Femenino , Fibrinolisina/metabolismo , Humanos , Persona de Mediana Edad , Activadores Plasminogénicos/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores del Activador de Plasminógeno Tipo Uroquinasa
17.
Endocrinology ; 141(5): 1667-74, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10803575

RESUMEN

Endochondral bone formation is regulated by systemically and locally acting growth factors. A role for vascular endothelial growth factor (VEGF) in this process has recently been proposed, because inactivation of VEGF inhibits endochondral bone formation via inhibition of angiogenesis. Despite the known effect of VEGF as specific endothelial growth factor, its effects on osteoblast differentiation have not been studied. We, therefore, examined the expression of VEGF-A, -B, -C, and -D and their receptors in a model of osteoblast differentiation using the mouse preosteoblast-like cell line KS483. Early in differentiation, KS483 cells express low levels VEGF-A, -B, and -D messenger RNA, whereas during mineralization, KS483 cells express high levels. In addition, expression of the VEGF receptors, VEGFR1, VEGFR2, and VEGF165R/neuropilin, coincided with expression of their ligands, being maximally expressed during mineralization. VEGF-A production during osteoblast differentiation was stimulated by insulin-like growth factor I that enhances osteoblast differentiation and was inhibited by PTH-related peptide that inhibits osteoblast differentiation. Furthermore, continuous treatment of KS483 cells with recombinant human VEGF-A stimulated nodule formation. Although treatment of KS483 cells with soluble FLT1, an agent that blocks binding of VEGF-A and -B to VEGFR1, did not inhibit nodule formation, this observation does not exclude involvement of VEGFR2 in the regulation of osteoblast differentiation. As it is known that VEGF-A, -C, and -D can act through activation of VEGFR2, other isoforms might compensate for VEGF-A loss. The expression pattern of VEGFs and their receptors shown here suggests that VEGFs play an important role in the regulation of bone remodeling by attracting endothelial cells and osteoclasts and by stimulating osteoblast differentiation.


Asunto(s)
Factores de Crecimiento Endotelial/biosíntesis , Linfocinas/biosíntesis , Osteoblastos/fisiología , Proteínas Tirosina Quinasas Receptoras/biosíntesis , Receptores de Factores de Crecimiento/biosíntesis , Animales , Diferenciación Celular , Línea Celular , Electroforesis en Gel de Poliacrilamida , Factores de Crecimiento Endotelial/genética , Ensayo de Inmunoadsorción Enzimática , Humanos , Factor I del Crecimiento Similar a la Insulina/farmacología , Ratones , Proteína Relacionada con la Hormona Paratiroidea , Reacción en Cadena de la Polimerasa , Proteínas/farmacología , ARN Mensajero/metabolismo , Receptores de Superficie Celular/biosíntesis , Receptores de Factores de Crecimiento Endotelial Vascular , Factor A de Crecimiento Endotelial Vascular , Factor B de Crecimiento Endotelial Vascular , Factor C de Crecimiento Endotelial Vascular , Factor D de Crecimiento Endotelial Vascular , Receptor 3 de Factores de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular
18.
J Pharm Pharmacol ; 51(12): 1409-14, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10678496

RESUMEN

Nitric oxide (NO) is a mediator of bone metabolism with effects on both bone resorption and formation. Its production by both the constitutive and inducible isoforms of nitric oxide synthase (NOS) is affected by oestrogen in several types of cell and in tissues other than bone cells. Recently, oestrogens were found to increase basal NO production by osteoblasts via enhanced activity or expression, or both, of NOS-3. Inflammatory cytokines, however, increase NO by increasing the expression of NOS-2. In this study we have examined whether cytokine-induced NO production by osteoblastic cells was affected by oestrogenic compounds by studying the effect of 17beta-oestradiol and the anti-oestrogens ICI164,384 and 4-hydroxytamoxifen on cytokine-induced NO production in oestrogen receptor positive MC3T3-E1 osteoblast-like cells. Combinations of the inflammatory cytokines interleukin-1beta, tumour necrosis factor-alpha, and interferon-gamma with lipopolysaccharide stimulated NO production up to 11-fold. This cytokine-induced NO production was further increased dose-dependently by the anti-oestrogens ICI164,384 and 4-hydroxytamoxifen (133.3 +/- 3.2% and 146.0 +/- 13.2%, respectively). 17Beta-oestradiol either had no effect on or slightly inhibited cytokine-induced NO production. It did, however, dose-dependently counteract the stimulatory effect of the anti-oestrogens. Concentrations of 17beta-oestradiol needed to prevent the stimulatory effect of 4-hydroxytamoxifen were ca tenfold that of ICI164,384. These findings show that, in addition to the stimulatory effect of oestrogen on basal NO production by NOS-3, cytokine-induced NO production is also affected by oestrogenic compounds in osteoblasts.


Asunto(s)
Citocinas/farmacología , Estrógenos/farmacología , Óxido Nítrico/biosíntesis , Osteoblastos/efectos de los fármacos , Animales , Células Cultivadas , Citocinas/fisiología , Estradiol/análogos & derivados , Estradiol/farmacología , Antagonistas de Estrógenos/farmacología , Estrógenos/fisiología , Interferón gamma/farmacología , Interleucina-1/farmacología , Lipopolisacáridos/farmacología , Ratones , Osteoblastos/metabolismo , Alcamidas Poliinsaturadas , Tamoxifeno/análogos & derivados , Tamoxifeno/farmacología , Factor de Necrosis Tumoral alfa/farmacología
19.
Eur J Endocrinol ; 136(3): 324-9, 1997 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9100559

RESUMEN

Treatment of rats with phenytoin (DPH), an anti-epileptic drug, results in lower tissue thyroid hormone (TH) levels and interferes with the metabolic pathway of TH. To test the hypothesis that DPH affects the enterohepatic cycle of TH and, thus, the kinetics of TH turnover, we performed a kinetic experiment (three-compartment analysis) and a steady-state, double-isotope equilibrium experiment in rats treated for 3 weeks with DPH (50 mg/kg body weight per day) and in untreated controls. This included measurements of TH and TH metabolite levels, as well as the activities of enzymes involved in the TH metabolic pathway. DPH treatment resulted in a decrease in the production of thyroxine (T4) (by 25%) and tri-iodothyronine (T3) (by 37%), a decrease in the T3 concentration in all three pools, and a redistribution of T4 from the fast to the slow pool. The amount of T4 increased in intestinal contents and feces by 66% and 71% respectively. Expressed as a fraction of daily TH disposal, fecal loss of T4 was enhanced from 10 to 23% and that of T3 from 16 to 21%. An increase in T4 and T3 UDP-glucuronyltransferase activities was observed, suggesting that the increased fecal loss of T4 and T3 is secondary to an increased biliary output of their glucuronides. The reduced secretion of TH and increased fecal clearance during DPH treatment can lead in the long run to depletion of TH stores.


Asunto(s)
Fenitoína/farmacología , Tiroxina/metabolismo , Triyodotironina/metabolismo , Animales , Heces/química , Mucosa Intestinal/metabolismo , Cinética , Masculino , Ratas , Ratas Wistar , Tiroxina/análisis , Triyodotironina/análisis
20.
Eur J Endocrinol ; 134(2): 221-4, 1996 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8630523

RESUMEN

Treatment of rats with phenytoin (DPH), an anti-epileptic drug, results in lower tissue thyroid hormone (TH) levels. To investigate if this is accompanied by tissue hypothyroidism, rats were treated for 3 weeks with DPH (50 mg/kg body wt in food). Thyroid hormone-dependent parameters were measured, and the results were compared to those of control rats and to those of athyreotic rats substituted with thyroxine + triiodothyronine (Tx + TH) to reach the same plasma TH levels as DPH-treated rats. These rats were mildly hypothyroid with regard to their TH and TSH levels and TH-dependent parameters. Both DPH and Tx + TH led to a decrease in plasma thyroxine (T4) and triiodothyronine (T3) (+/-70% of the control). The percentage free T4 was unchanged. Plasma thyrotropin (TSH) was increased only in the Tx + TH rats (sixfold). For DPH rats, pituitary hormone content was not different from the control; growth hormone was lower and TSH was higher in Tx + TH rats. In DPH and Tx + TH rats, an increase in hepatic T4 and T3 uridine-diphosphate glucuronyltransferase activity was found, likewise indicating a change in the metabolic pathway of TH. Hepatic iodothyronine deiodinase (ID) type I activity decreased in Tx + TH rats but did not alter in DPH rats. Hepatic alpha-glycerophosphate dehydrogenase (alpha-GPD) decreased in DPH and Tx + TH rats. Malic enzyme in liver was enhanced in DPH rats. In the brains of DPH rats the level of alpha-GPD activity was raised; in Tx + TH it was lowered. The ID type II activity in the brain was reduced in DPH rats, but ID type III did not change for either group. Total body oxygen consumption increased in DPH rats (13%); it decreased in Tx + TH rats (9%). Our results show that DPH causes changes comparable to mild hypothyroidism. The lack of or a diminished hypothyroid response can be explained as the attenuating agonistic effect of DPH, which is supported by O2 consumption, brain ID type II and alpha-GPD activities. The T4 content was reduced by 30% in thyroid digests; this, together with a reduced T4 secretion, can lead to serious hypothyroxinemia during prolonged DPH treatment.


Asunto(s)
Anticonvulsivantes/farmacología , Fenitoína/farmacología , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/fisiología , Animales , Hormona del Crecimiento/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Consumo de Oxígeno , Hipófisis/metabolismo , Ratas , Ratas Wistar , Tirotropina/metabolismo , Tiroxina/metabolismo , Tiroxina/farmacología , Triyodotironina/metabolismo , Triyodotironina/farmacología
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