Two-stage bone and meniscus allograft and autologous chondrocytes implant for unicompartmental osteoarthritis: midterm results.

BACKGROUND: We analyzed the clinical and radiographic evolution of patients with knee unicompartmental osteoarthritis and axis alteration and osteochondral lesions in the femoral condyle, treated with tibial plateau and meniscus allograft and cultured autologous chondrocyte implantation in the femur in two steps. PURPOSE: To analyze the clinical results with the first patients treated with this two-stage technique to avoid knee prosthesis in patients with unicompartmental osteoarthritis. MATERIAL AND METHODOLOGY: Sixteen patients, average age 56 years, were included in a cohort study. We performed an osteotomy with tibia plateau allograft, including the meniscus. In a second surgery, the chondrocyte fibrin scaffold was placed in the femur. Clinical symptoms and function were measured using KSSR and KOOS scores. Wilcoxon's test was performed to compare the results over the 2-year follow-up period. RESULTS: Mean KSSR before surgery was 35.69 (SD: 3.75) points, rising to 67 (SD: 15.42) at 3 months, 95.88 at 12 months (SD: 2.68) and 96.31 at 24 months (SD: 2.24). The KOOS before surgery was 65.14 (SD: 16.34), rising to 72.68 after 3 months (SD: 19.15), 76.68 at 12 months (SD: 18.92) and 64.28 at 24 months (SD: 11.79). Four of 5 patients returned to engaging in the activity that they had stopped practicing. Three patients experienced collapse of the tibia allograft, and they needed later a prosthesis. CONCLUSIONS: Simultaneous tibia plateau allograft and autologous chondrocyte implantation in the femur, after correction of the angular deformity, were performed, restoring the anatomy of the medial compartment and knee function in 82% of the patients 2 years after the operation. LEVEL OF EVIDENCE: IV.

Clinical-radiological correlations in a de novo cavernous angioma with pseudotumor-like behavior. / Correlato clínico-radiológico de un angioma cavernoso de novo con comportamiento seudotumoral.

Cavernous angiomas are cerebral vascular malformations that are usually congenital. These lesions are characterized as dynamic. The most common phenomenon in the course of these lesions is bleeding, which can result in significant fluctuations in their size and even lead to their disappearance. This article aims to describe the behavior of a cavernous angioma in its natural history, documenting: a) its de novo appearance, a very uncommon observation, and b) its changes on imaging studies, where it grew progressively like an expanding lesion but had no clinical repercussions. On magnetic resonance imaging, atypical signs can orient the etiological diagnosis of cavernous angioma versus other alternatives: de novo appearance, fluid-fluid or air-fluid level, incomplete hypointense ring due to hemosiderin deposition, pseudotumor-like growth, pseudocyst-like or multiloculated shape, vasogenic edema, mass effect, and size greater than 3cm.

Extracellular NK histones promote immune cell anti-tumor activity by inducing cell clusters through binding to CD138 receptor.

BACKGROUND: Natural killer (NK) cells are important anti-tumor cells of our innate immune system. Their anti-cancer activity is mediated through interaction of a wide array of activating and inhibitory receptors with their ligands on tumor cells. After activation, NK cells also secrete a variety of pro-inflammatory molecules that contribute to the final immune response by modulating other innate and adaptive immune cells. In this regard, external proteins from NK cell secretome and the mechanisms by which they mediate these responses are poorly defined. METHODS: TRANS-stable-isotope labeling of amino acids in cell culture (TRANS-SILAC) combined with proteomic was undertaken to identify early materials transferred between cord blood-derived NK cells (CB-NK) and multiple myeloma (MM) cells. Further in vitro and in vivo studies with knock-down of histones and CD138, overexpression of histones and addition of exogenous histones were undertaken to confirm TRANS-SILAC results and to determine functional roles of this material transferred. RESULTS: We describe a novel mechanism by which histones are actively released by NK cells early after contact with MM cells. We show that extracellular histones bind to the heparan sulfate proteoglycan CD138 on the surface of MM cells to promote the creation of immune-tumor cell clusters bringing immune and MM cells into close proximity, and thus facilitating not only NK but also T lymphocyte anti-MM activity. CONCLUSION: This study demonstrates a novel immunoregulatory role of NK cells against MM cells mediated by histones, and an additional role of NK cells modulating T lymphocytes activity that will open up new avenues to design future immunotherapy clinical strategies.

[Knowledge and attitude among general practitioners in Andalusia (Spain) on the identification of subjects at high risk of breast and colorectal cancer]. / Conocimientos y actitudes de los médicos de Atención Primaria de Andalucía (España) sobre la detección de personas con riesgo elevado de cáncer de mama y colorrectal.

AIMS: To assess the knowledge and attitude among general practitioners in Andalusia on the identification of subjects with elevated risk for breast cancer, colorectal cancer, and hereditary cancers, as well as to detect barriers to accessibility to the screening programs. METHODS: A descriptive, cross-sectional study was conducted based on an online survey of 24 questions. Data are shown as frequencies, and association tests were statistically used. The level of significance was set at<.05. RESULTS: Survey response rate was 32%, of which 224 were valid, and included 56% men, and a mean age±DE of 46±12 years. Established criteria for high risk breast cancer were already known by 71.4% [95% CI 65-76], being worst in those living in big cities (P<.014). Among general practitioners, 86% were allowed to order mammography in women with lumps or at moderate to high risk for breast cancer. As regards colorectal cancer, 87.9% of general practitioners knew the risk factors. Among general practitioners, 58.2% [95% CI 49-62] were allowed to order a colonoscopy if clinical suspicion was present, especially if they lived in large cities (P<.0001). CONCLUSIONS: The screening program for breast cancer is well-known by general practitioners, and the access to mammography is successful. Most of the general practitioners consider the follow-up program for persons at high risk for colorectal cancer appropriate, although half of those surveyed had some barriers to ordering colonoscopy. Knowledge on hereditary cancer is limited, and varies among areas. There is also a general lack of awareness on hereditary cancer and genetic counselling units.

Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated. METHODS: FXR and TGR5 expression was determined in human CCA tissues and cell lines. An orthotopic model of CCA was established in immunodeficient mice and tumor volume was monitored by magnetic resonance imaging under chronic administration of the specific FXR or TGR5 agonists, obeticholic acid (OCA) or INT-777 (0,03% in chow; Intercept Pharmaceuticals), respectively. Functional effects of FXR or TGR5 activation were evaluated on CCA cells in vitro. RESULTS: FXR was downregulated whereas TGR5 was upregulated in human CCA tissues compared to surrounding normal liver tissue. FXR expression correlated with tumor differentiation and TGR5 correlated with perineural invasion. TGR5 expression was higher in perihilar than in intrahepatic CCAs. In vitro, FXR was downregulated and TGR5 was upregulated in human CCA cells compared to normal human cholangiocytes. OCA halted CCA growth in vivo, whereas INT-777 showed no effect. In vitro, OCA inhibited CCA cell proliferation and migration which was associated with decreased mitochondrial energy metabolism. INT-777, by contrast, stimulated CCA cell proliferation and migration, linked to increased mitochondrial energy metabolism. CONCLUSION: Activation of FXR inhibits, whereas TGR5 activation may promote, CCA progression by regulating proliferation, migration and mitochondrial energy metabolism. Modulation of FXR or TGR5 activities may represent potential therapeutic strategies for CCA.

[Shared decision making from the perspective of the cancer patient: participatory roles and evaluation of the process]. / La toma de decisiones compartidas desde la perspectiva del paciente oncológico: roles de participación y valoración del proceso.

BACKGROUND: In Spain there is no clear knowledge about the degree to which Shared Decision Making (SDM) is carried out in the normal practice of oncology. Our article analyses the preferred role and the perceived role of oncological patients and measures the SDM process from their perspective. MATERIAL AND METHODS: Descriptive transversal study using a self-conducted questionnaire with patients with different types of cancer. To evaluate the role preferred and perceived by the patient we used The Control Preference Scales (CPS) and to measure SDM we used The nine-item Shared Decision Making Questionnaire (SDM-Q-9). RESULTS: Out of the 132 patients surveyed, only 118 provided analysable data. No evidence was found that sex, age, educational level or type of tumour affected the preferred role or the perceived role. Only 59.3% was in agreement with the role exercised. All of those who preferred a passive role achieved this (21.2%), while out of those who wanted a shared role (78.8%), this was achieved by only 48.39% while the remaining 51.61% played a passive role. None preferred or played an active role. The set of patients evaluated the SDM process with a score of 41.07±5.94, on a scale of 0 to 100, with the highest score of 61.39 ± 13.24 reached by urological patients. CONCLUSIONS: Our study found no evidence that, from the point of view of the oncological patient, the SDM model is being implemented in practice.

[Barriers and facilitators to implementing shared decision-making in oncology: Patient perceptions]. / Barreras y facilitadores para la implementación de la toma de decisiones compartidas en oncología: percepciones de los pacientes.

OBJECTIVE: To determine, from the point of view of the oncological patient, who made the decision about their treatment, as well as the major barriers and facilitators that enabled Shared Decision Making to be implemented. MATERIAL AND METHODS: A cross-sectional, descriptive, sand association study using a self-report questionnaire to selected cancer patients, with casual sampling in different oncology clinics and random time periods. A total of 108 patients provided analysable data. The information was collected on sociodemographic and clinical variables, who made the decision about treatment, and level of agreement or disagreement with various barriers and facilitators. RESULTS: More than one-third (38.1%) of patients claimed to have participated in shared decision making with their doctor. Barriers such as, time, the difficulty of understanding, the paternalism, lack of fluid communication, and having preliminary and often erroneous information influenced the involvement in decision-making. However, to have or not have sufficient tools to aid decision making or the patient's interest to participate had no effect. As regards facilitators, physician motivation, their perception of improvement, and the interest of the patient had a positive influence. The exception was the possibility of financial incentives to doctors. CONCLUSIONS: The little, or no participation perceived by cancer patients in decisions about their health makes it necessary to introduce improvements in the health care model to overcome barriers and promote a more participatory attitude in the patient.

Mechanisms of Resistance to Chemotherapy in Gastric Cancer.

Although surgical resection is the standard curative therapy for gastric cancer, these tumors are often diagnosed at an advanced stage, when surgery is not recommended. Alternative treatments such as radiotherapy and chemotherapy achieve only very modest results. There is therefore an urgent need to advance in this field of oncologic gastroenterology. The poor response of gastric cancer to chemotherapy is usually due to a combination of mechanisms of chemoresistance (MOC), which may include a reduction in drug uptake (MOC-1a), enhanced drug efflux (MOC-1b), a reduced proportion of active agents in tumor cells due to a reduction in pro-drug activation or an enhancement in drug inactivation (MOC-2), changes in the expression/function of the molecular targets of anticancer drugs (MOC-3), an enhanced ability of cancer cells to repair anticancer drug-induced DNA damage (MOC-4), and decreased expression/function of pro-apoptotic factors or up-regulation of anti-apoptotic genes (MOC-5). Two major goals of modern pharmacology aimed at overcoming this situation are the prediction of a lack of response to chemotherapy and the identification of the underlying mechanisms accounting for primary or acquired refractoriness to anticancer drugs. These are important issues if we are to select the best pharmacological regime for each patient and develop novel strategies to overcome chemoresistance. The present review reports updated information regarding the mechanisms of chemoresistance (from MOC-1 to MOC-5) in gastric cancer, the advances made in the prediction of the failure of chemotherapeutic treatment, and novel strategies based on gene therapy currently being developed to treat these tumors.

Cotransfected human chondrocytes: over-expression of IGF-I and SOX9 enhances the synthesis of cartilage matrix components collagen-II and glycosaminoglycans

Damage to cartilage causes a loss of type II collagen (Col-II) and glycosaminoglycans (GAG). To restore the original cartilage architecture, cell factors that stimulate Col-II and GAG production are needed. Insulin-like growth factor I (IGF-I) and transcription factor SOX9are essential for the synthesis of cartilage matrix, chondrocyte proliferation, and phenotype maintenance. We evaluated the combined effect of IGF-I and SOX9 transgene expression on Col-II and GAG production by cultured human articular chondrocytes. Transient transfection and cotransfection were performed using two mammalian expression plasmids (pCMV-SPORT6), one for each transgene. At day 9 post-transfection, the chondrocytes that were over-expressing IGF-I/SOX9 showed 2-fold increased mRNA expression of the Col-II gene, as well as a 57% increase in Col-II protein, whereas type I collagen expression (Col-I) was decreased by 59.3% compared with controls. The production of GAG by these cells increased significantly compared with the controls at day 9 (3.3- vs 1.8-times, an increase of almost 83%). Thus, IGF-I/SOX9 cotransfected chondrocytes may be useful for cell-based articular cartilage therapies.

BK Virus Nephropathy in Kidney Transplantation: An Approach Proposal and Update on Risk Factors, Diagnosis, and Treatment.

BK virus belongs to Polyomaviridae family; it causes 95% of nephropathy cases related to polyomavirus, with the other 5% caused by JC virus. Nephropathy jeopardizes graft function, causing a premature failure of the graft in 1%-10% of patients with kidney transplants. Nowadays, antiviral effective treatment is unknown, which is why blood and urine screening of renal transplantation patients has become the most important recommendation to guide the decrease of immunosuppression, and the only proven method to decrease poor outcomes. Different interventions, such as cidofovir, leflunomide, fluoroquinolones, and intravenous immunoglobulin, have been attempted with no improvement at all. This review aims to summarize the most relevant features of BK virus, historical issues, transmission mechanisms, risk factors, and therapeutic interventions.

Impact of human leukocyte antigen molecules E, F, and G on the outcome of transplantation.

BACKGROUND: HLA class I molecules are divided into classic (Ia) and nonclassic (Ib). Nonclassic HLA molecules (E, F, and G) have acquired relevance owing to their immunomodulatory properties and possible repercussions for induction of tolerance in organ transplantation. The objective of this study was to identify the impact of these molecules on transplant success or failure. METHODS: A systematic review of literature was performed with the use of MeSH terms in Pubmed. Clinical trials, randomized clinical trials, case-control studies, and reviews from the past 15 years were included. RESULTS: HLA-E*0103/E*0103 genotype is associated with lower risk of graft-versus-host disease, decreased mortality, and greater disease-free survival after bone marrow transplantation. There were no significant associations between HLA-F and clinical outcomes in any of the studies. Elevated serum levels of HLA-G were associated with a lower incidence of rejection in hepatic and renal transplantation during the 1st year and lower T-cell response after bone marrow, liver, and kidney transplantation. Detection of mRNA of HLA-G1 was also associated with less graft rejection. CONCLUSIONS: Current literature suggests that nonclassic HLA Ib molecules play an important role in immunotolerance in organ transplantation; however, more studies are required to predict outcomes related to specific genotypes.

Resistance index measured by Doppler ultrasound as a predictor of graft function after kidney transplantation.

INTRODUCTION: Doppler ultrasound (US) has become the primary imaging technique for the evaluation of renal transplants. It provides information about the intrarenal resistance index (RI). A high RI is seen in every form of graft dysfunction. In this article, we review the utility of sonography, particularly the intrarenal RI measured early after renal transplant, as a predictor of acute and chronic clinical outcome in patients. RESULTS: RI is a valuable marker to determine graft function and related vascular complications. It reveals a strong correlation with serum creatinine levels measured days after transplant. Its elevation is typical for acute tubular necrosis and can be used to predict its duration. An RI >1 (absent end-diastolic flow) seen in the first weeks after transplant is associated with impaired renal graft recovery. In addition, it is an early predictor of chronic allograft nephropathy (even correlated with biopsy results), which will allow a change in therapy. CONCLUSIONS: RI measured serially in the early period after kidney transplantation is a valuable marker for determining renal graft function. It is also useful for demonstrating various types of graft dysfunction; however, it cannot differentiate between them. In recent studies, extrarenal factors in kidney transplantation (eg, recipient's age) may significantly influence RI in the recipient, demonstrating that RI depends on the vascular characteristics of the recipient and not on the graft itself.

Urinary tract infection and kidney transplantation: a review of diagnosis, causes, and current clinical approach.

Urinary tract infection (UTI), including bacteriuria, cystitis, and pyelonephritis, is the most common infectious complication after kidney transplantation (KTx). Over the past few years, many medical groups assumed this pathological process to be a "benign" disease in kidney transplant recipients (KTxR). However, increased medical and scientific advances in knowledge and management of KTx complications have raised questions about UTI as a pathological process that decreases and worsens kidney allograft function and survival. This review sought to clarify diagnostic criteria, as well as to describe factors associated with UTI in KTxR that expose its effects on the allograft. We sought to show the uncertainty of important topics within the field of UTI among kidney allograft recipients and to propose a practical clinical approach to KTxRs with UTI.

No correlation between the expression of FXR and genes involved in multidrug resistance phenotype of primary liver tumors.

Farnesoid X receptor (FXR) has been recently reported to enhance chemoresistance through bile acid-independent mechanisms. Thus, FXR transfection plus activation with GW4064 resulted in reduced sensitivity to cisplatin-induced toxicity. This is interesting because primary tumors of the liver, an organ where FXR is expressed, exhibit marked refractoriness to pharmacological treatment. Here we have determined whether FXR is upregulated in hepatocellular carcinoma (HCC), cholangiocarcinoma (CGC) and hepatoblastoma (HPB) and whether this is related with the expression of genes involved in mechanisms of chemoresistance. Using RT-QPCR and Taqman low density arrays we have analyzed biopsies from healthy livers or surgically removed tumors from naive patients and cell lines derived from HCC (SK-HEP-1, Alexander and Huh7), CGC (TFK1) and HPB (HepG2), before and after exposure to cisplatin at IC50 for 72 h. In liver tumors FXR expression was not enhanced but significantly decreased (healthy liver > HCC > HPB ≈ CGC). Except for CGC, this was not accompanied by changes in the proportions of FXR isoforms. Changes in 36 genes involved in drug uptake/efflux and metabolism, expression/function of molecular targets, and survival/apoptosis balance were found. Changes affecting SLC22A1, CYP2A1 and BIRC5 were shared by HCC, CGC and HPB. Similarity in gene expression profiles between cell lines and parent tumors was found. Pharmacological challenge with cisplatin induced changes that increased this resemblance. This was not dependent upon FXR expression. Thus, although FXR may play a role in inducing chemoresistance under certain circumstances, its upregulation does not seem to be involved in the multidrug resistance phenotype characteristic of HCC, CGC and HPB.

Minor histocompatibility antigens as risk factor for poor prognosis in kidney transplantation.

Progress in transplantation has relied on similar human leukocyte antigen (HLA) matching between the donor and the patient, while the role of other immunologic factors like non-HLA markers including minor histocompatibility antigens (miHA) are currently in the forefront. miHA are polymorphic proteins that vary even in monozygotic twins. The best known is the H-Y antigen, but there are also other autosomal miHA and MICA (MHC class I chain-related gene A). miHA have been well studied in transplantation of hematopoietic precursors, but not in solid organ transplantation. The most important studies in this field relate to incompatibility of H-Y antigen as a risk factor in kidney transplantation, although the findings are still inconclusive. This review presents the role of minor histocompatibility antigens in solid organ transplantation, especially of the kidney.

Significance of cytomegalovirus prophylaxis strategies and development of cancer in kidney transplant recipients.

Cytomegalovirus (CMV) infection is one of the most common complications among kidney transplant recipients; two approaches preventing this complication are currently available: universal prophylaxis (UP) and pre-emptive therapy (PT). Despite some differences, similar effectiveness and safety have been proven in several studies for both strategies. However, Spinner et al compared both treatments in 115 renal transplant recipients showing deaths were more likely to occur in patients who received UP. Most of these deaths (2/4 cases) occurred because malignancies developed. This finding is paradoxical because CMV is considered a potentially oncogenic virus and, therefore, UP (a longer therapy compared with the PT) should not be linked with the emergence of a greater number of tumors. New evidence suggests that changes in host immune response triggered by CMV infection may have a mitigating effect on the development of tumors. It is now known CMV infection produces a clonal expansion of gamma delta T lymphocytes which can elicit an aggressive response against neoplastic cells. Currently, UP is the therapy most frequently used in Colombian transplant centers; however, doses administered vary depending on several clinical and laboratory factors. There are no clinical cohorts treated with PT. Reviewing the impact of different length dosing schemes is important for creating an immune response affecting malignancy development in kidney transplant recipients.

Imágenes de fluorescencia de rayos X en huesos humanos y su potencial aplicación in vivo / Images of X-ray fluorescence in human bones and their potential application in vivo

El conocimiento de la concentración y la distribución espacial de los elementos químicos presentes en diferentes órganos y tejidos resulta un parámetro útil para el diagnóstico de determinadas patologías o niveles por sobre los límites tolerables, por lo tanto el conocimiento de los elementos presentes en un tejido vivo, su concentración y distribución espacial podría proporcionar información relevante respecto del estado de salud de un individuo. Se presenta una aplicación de una nueva técnica de fluorescencia rayos X dispersiva en energía mediante barrido, la cual se puede aplicar a muestras de diferente composición y forma, a diferencia de, la mayoría de las técnicas existentes, que son aplicables sólo a muestras planas. Esta técnica permite la obtención de imágenes bidimensionales de los elementos químicos presentes en las muestras de un modo tanto mono como multielemental. En este trabajo es aplicada a un conjunto muestras óseas humanas y tarso y dedos de Gallus gallus (pollo) faenado, obteniéndose una distribución espacial 2D con diferentes niveles de intensidad fluorescente dependiendo del elemento detectado y de su concentración. Las imágenes logradas consideran áreas de hasta104 mm2, con una resolución espacial de hasta 0,25 mm2 y en un tiempo de adquisición de alrededor de 20 min. También se lleva a cabo un cálculo de la dosis de la radiación asociada a este tipo de análisis XRF, encontrándose que los niveles aplicados para la obtención de una imagen XRF son tolerables. Lo anterior permite concluir que sería posible el uso de esta técnica para una aplicación in vivo.

The knowledge of the concentration and spatial distribution that chemical elements present in different organs and tissues is a useful parameter for diagnosis of certain diseases or element levels above limits accepted as healthy. Therefore, development of techniques to identify the chemical elements present in a living tissue and obtaining information about their concentration and spatial distribution might be relevant to determine an individual's health status. This work presents an application of a new X-ray fluorescence technique, energy dispersive by scanning, which can be applied to samples of different composition and shape, unlike most of the existing techniques, only applicable to flat samples. This technique allows the acquisition of two-dimensional images of the chemical elements present in a sample in both mono and multi-elemental mode. In this work the technique is applied to a set of human bone samples and tarsus and fingers of a dead Gallus gallus (chicken), obtaining a 2D spatial distribution with different levels of fluorescence intensity, depending on the detected element and its concentration. The acquired images consider areas up to 104 mm2, with a spatial resolution of 400 mm2 and an acquisition time of about 20 min. Calculations of the radiation dose associated with this type of XRF analysis were also carried out, and the findings show that the levels applied to obtain an XRF image are tolerable. The latter leads to the conclusion that it would be possible to use this technique for an in vivo application.

Increased expression of the endothelin system in arterial lesions from patients with giant-cell arteritis: association between elevated plasma endothelin levels and the development of ischaemic events.

OBJECTIVE: Approximately 15-20% of patients with giant-cell arteritis (GCA) develop ischaemic complications often preceded by transient ischaemia. The expression of the endothelin (ET) system in GCA lesions was investigated to assess its relationship with the development of ischaemic complications. METHODS: Plasma ET-1 was quantified by immunoassay in 61 patients with biopsy-confirmed GCA and 16 healthy donors. ET-1, endothelin-converting enzyme (ECE-1) and endothelin receptor (ET(A)R and ET(B)R) messenger RNA were measured by real-time quantitative reverse transcriptase-PCR in temporal arteries from 35 of these patients and 19 control arteries. Proteins were measured by immunoassay and Western blot. RESULTS: ET-1 concentration was increased at the protein level in temporal artery samples from GCA patients compared with controls (0.98 (SEM 0.32) vs 0.28 (SEM 0.098) fmol/mg, p = 0.028). ECE-1, ET(A)R and ET(B)R/actin ratios (Western blot) were also significantly higher in GCA patients. Intriguingly, mRNA expression of ET-1, ECE-1 and both receptors was significantly reduced in GCA lesions compared with control arteries. When investigating mechanisms underlying these results, platelet-derived growth factor and IL-1beta, present in GCA lesions, were found to downregulate ET-1 mRNA in cultured human temporal artery-derived smooth muscle cells. Glucocorticoid treatment for 8 days did not result in significantly decreased endothelin tissue concentration (0.87 (SEM 0.2) vs 0.52 (SEM 0.08); p = 0.6). Plasma endothelin concentrations were higher in patients with ischaemic complications (1.049 (SEM 0.48) vs 1.205 (SEM 0.63) pg/ml, p = 0.032). CONCLUSIONS: The endothelin system is increased at the protein level in GCA lesions creating a microenvironment prone to the development of ischaemic complications. Recovery induced by glucocorticoids is delayed, indicating persistent exposure to endothelin during initial treatment.