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Biomedical subjects

Claus D Claussen

Publications and source records attributed to Claus D Claussen.

At least 109 records · Page 6Linked to original sources

Benefit of anatomical-functional image fusion in the diagnostic work-up of neuroendocrine neoplasms.

The aim of this prospective study was to evaluate anatomical-functional image fusion using the new technology of combined transmission and emission tomography (SPET/CT) in patients with neuroendocrine tumours (NET). Fifty-four patients with known or suspected NET prospectively underwent both tumour scintigraphy with (111)In-octreotide (n=43) or (123)I-MIBG (n=11) and contrast-enhanced high-end spiral CT. Scintigraphy was performed using a gamma camera (Millennium VG & Hawkeye, GE) with an integrated X-ray tube for combined transmission and emission tomography. SPET and high-end CT were interpreted blinded with regard to localisation and classification of lesions. Analysis of fused images (SPET/CT) was done on a lesion-by-lesion basis, followed by re-evaluation of SPET and high-end CT by consensus. The standard of reference for confirming the presence or absence of malignancy was either histopathology or clinical and imaging follow-up data. A total of 120 lesions were identified by CT and/or scintigraphy. This group included four patients with negative SPET but eight liver lesions on CT that were proven to be metastases. We excluded from the analysis two patients with no evidence of tumour on either modality, two lesions that lacked comparison with the standard of reference and two patients, each with two lesions, who were lost to follow-up. In 56 of the 114 evaluated lesions (49%), the results of SPET and CT were concordant; all lesions were interpreted as malignant. In 58 of 114 lesions (51%), consensus reading of fused images changed the image interpretation of 39 CT scans and 19 SPET studies: 31 lesions previously interpreted as equivocal (n=10) or benign (n=21) were re-classified as malignant and 27 lesions previously interpreted as equivocal (n=19) or malignant (n=8) were re-evaluated as benign. The highest accuracy (99%) in classifying NET lesions was achieved by combined analysis of SPET/CT ("hawkeye") and high-end CT. The specificity of SPET/CT was significantly higher than that of CT alone (P=0.0026) and slightly higher than that of SPET alone, but the accuracy of SPET/CT was inferior to that of side-by-side analysis of SPET and high-end CT (P=0.013) or visual correlation of SPET/CT and high-end CT (P<0.0001). Therapy was changed in 14 of 50 patients (28%) owing to the results of image fusion: in five patients tumour could be excluded, three patients were spared unnecessary surgery because of additional lesions indicating systemic tumour spread, in four patients the surgical approach was changed owing to precise tumour localisation and minimising of the surgical field, and in two patients medical and radiopeptide therapy was changed. Anatomical-functional image fusion allows for improved localisation and characterisation of NET with resultant alteration of the treatment approach in a substantial proportion of patients.

Adult↗

Lipid content in the musculature of the lower leg assessed by fat selective MRI: intra- and interindividual differences and correlation with anthropometric and metabolic data.

PURPOSE: To assess the muscular lipid content (LC) in different muscle groups of the lower leg by a magnetic resonance imaging technique working with chemical shift selective excitation, and comparison with anthropometric and metabolic data. MATERIALS AND METHODS: Examinations were performed in 67 volunteers (54 male/13 female, age 29 +/- seven years) on a 1.5 T whole body imager, applying a highly selective spectral-spatial technique for fat selective MRI. LC was measured in six calf muscles and correlated with body mass index (BMI), percent body fat (PFAT), and insulin sensitivity (IS) of the subjects. RESULTS: Mean muscular LC of all subjects was between 2.0% (Tibialis posterior [TP]) and 3.8% (Peroneus muscles) with female subjects showing a significantly higher LC in all muscle groups (P < 0.05 each). LCs correlated moderately with BMI (R between 0.39 [TP] and 0.53 [GM]) and with PFAT (R between 0.38 [TP] and 0.62 [GM]). Insulin-resistant subjects showed slightly but not significantly increased LC compared to insulin-sensitive subjects in BMI-matched subgroups. CONCLUSION: The fat-selective MRI technique allows a reliable non-invasive measure of muscular lipids - even in muscle groups with inherent low LC - within a relatively short measurement time of about three minutes. The presented data reveal interesting interrelationships between LC and anthropometric and metabolic data, and therefore provide new insight into muscular fat metabolism.

Adult↗

Scimitar syndrome: morphological diagnosis and assessment of hemodynamic significance by magnetic resonance imaging.

Scimitar syndrome has a variable presentation depending on the age at which the diagnosis is made. We report a case of a young woman (age 18 years) with suspected right pulmonary hypoplasia in whom a scimitar syndrome was diagnosed. Using MRI morphological findings and hemodynamic significance of the syndrome were assessed. Left-to-right shunt was calculated from blood flow measurements performed in the ascending aorta, the main pulmonary artery, and the aberrant scimitar vein.

Adolescent↗

Impact of glafenine hydrochloride on human endothelial cells and human vascular smooth muscle cells: a substance reducing proliferation, migration and extracellular matrix synthesis.

The aim of this study was to examine the effects of glafenine hydrochloride (a nonsteroidal anti-inflammatory drug) on proliferation, clonogenic activity, cell-cycle, migration, and the extracellular matrix protein tenascin of human aortic smooth muscle cells (haSMCs) and human endothelial cells (ECs) in vitro.HaSMCs and ECs were seeded in tissue culture flasks. The cells were treated for 4 days with glafenine hydrochloride (10 microM, 50 microM, 100 microM). Half of the treated groups were incubated again with glafenine hydrochloride, the other half received medium free of glafenine hydrochloride every 4 days until day 20. The growth kinetics and clonogenic activity were assessed. Cell cycle distribution was investigated by FACS, migratory ability was evaluated, and effects on extracellular matrix synthesis were assessed by immunofluorescence. Glafenine hydrochloride inhibited the proliferation and clonogenic activity of haSMCs and ECs in a dose-dependent manner. A block in the G2/M phase and a reduction in the G1 phase occurred. The migratory ability of haSMCs was impaired in a dose-dependent manner and the extracellular matrix protein tenascin was reduced. As glafenine hydrochloride has the ability to fully inhibit proliferation and to partially inhibit migration in haSMCs, it could be an interesting substance for further research in the field of restenosis therapy.

Actins↗

Non-invasive evaluation of coronary artery bypass grafts using multi-slice computed tomography: initial clinical experience.

Recurrence of angina pectoris in patients with previous coronary artery bypass graft (CABG) surgery due to severe coronary artery disease (CAD) is a common problem. Non-invasive imaging of coronary artery bypass grafts by computed tomography was first described in the early 1980s. Meanwhile, multi-slice computed tomography (MSCT) is now available. This new technique allows detection of coronary lesions with good sensitivity and specificity due to continuous improvement and modification of this method. The aim of this study was to investigate whether stenosis or occlusion of CABG can be detected by MSCT. Ten consecutive male patients (mean age 61+/-9.1 years) with previous CABG surgery and 21 bypass grafts (14 venous grafts, seven arterial grafts) were included in this study. Conventional coronary angiography and MSCT angiography (MSCTA) were performed in all patients. MSCTA results were compared with coronary angiography in regard of visualization and lesion detection in CABG. The analysis of MSCTA was performed blinded to the angiographic results. It was found that 18 of 21 bypass grafts (86%) were analyzable by MSCTA: seven of 21 (33%) grafts showed a significant stenosis (>75%), while six of them were detected by MSCTA (sensitivity: 86%, positive predictive value: 0.75). Dissection of one arterial graft could not be evaluated by MSCTA. Twelve of 13 grafts without severe lesion showed no significant stenosis in MSCTA (negative predictive value: 0.86). All grafts without severe lesions by MSCT showed no significant lesion in X-ray angiography (specificity: 100%). MSCTA is a promising new method for the detection of lesions in coronary artery bypass grafts. However, these data based on a small number has to be reevaluated by larger studies.

Aged↗

Noninvasive evaluation of the prevalence of noncalcified atherosclerotic plaques by multi-slice detector computed tomography: results of a pilot study.

BACKGROUND: Multi-slice detector computed tomography (MDCT) not only allows for the determination of coronary calcifications, but also for the noninvasive visualization of noncalcified plaques. Thus, coronary artery disease (CAD) can be detected at a fairly early stage. Since data on the prevalence of potentially rupture prone noncalcified coronary lesions are still missing, it was aim of the present investigation to study this in patients with a distinct cardiovascular risk profile, but without known CAD. METHODS: 68 patients with clinical suspicion of CAD and multiple cardiovascular risk factors were included in this prospective study. Calcium scoring, as well as the detection of noncalcified plaques were performed using a Somatom VZ scanner (Siemens, Forchheim, Germany). RESULTS: Calcium scoring could be performed in all patients on native scans; 63/68 (96%) of contrast enhanced scans showed sufficient image quality to perform a screening for noncalcified plaques. The three scans without diagnostic image quality had been performed at heart rates of 95 +/- 18/min. Coronary calcifications were found in 36/65 (55%) patients (Agatston score: 247 +/- 358). Additional noncalcified plaques were detected in 16/36 (45%) of these patients; 29/65 (45%) patients had no coronary calcifications (Agatston score: 0), but noncalcified plaques could be detected in 3/29 (10%) of these patients. CONCLUSIONS: The prevalence of noncalcified plaques was 29% in the whole study group, and even in 10% of patients without coronary calcifications. Further prospective large scale studies are required to confirm these data, and to evaluate the clinical implication of this finding.

Calcinosis↗

All-trans and 9-cis retinoid acids inhibit proliferation, migration, and synthesis of extracellular matrix of human vascular smooth muscle cells by inducing differentiation in vitro.

The aim of this study was to evaluate the effects of 9-cis retinoid acid (9-cis RA) and all-trans RA (ATRA) on proliferation, migratory ability, synthesis of extracellular matrix, intracellular signal transduction, and differentiation of human aortic smooth muscle cells (haSMCs) in vitro. Changes of cell proliferation following incubation with RAs in different doses (10-6 M, 10-7 M, and 10-8 M) were determined directly by proliferation kinetics and indirectly by bromodeoxyuridine enzyme-linked immuno sorbant assays and colony-formation assays. The migratory ability of haSMCs was examined with the help of migration assays. The production of the extracellular matrix protein tenascin was explored by immunostaining. The amounts of total p44/p42 mitogen-activated protein kinases (MAPKs) and their phosphorylated forms were detected with the help of Western blots. To judge the state of differentiation of haSMCs, cell cycle distribution and the pattern of alpha-actin were analyzed. Both RAs clearly inhibited the proliferation of haSMCs in a dose-dependent manner. 9-cis RA had a tendency to be more effective than ATRA. After treatment with RAs, the migratory ability was especially reduced during stimulation with platelet-derived growth factor (PDGF) and the synthesis of tenascin decreased. Although the total p44/p42 MAPKs were downregulated, the amounts of activated forms increased markedly in the cells incubated with RAs and particularly stimulated with PDGF. The cell-cycle analysis demonstrated an increased G1-phase, complemented by a stronger expression of alpha-actin after treatment. 9-cis RA especially has the potential to inhibit the proliferation, migration, and synthesis of extracellular matrix of haSMCs by inducing differentiation in vitro.

Alitretinoin↗

In vivo efficiency of four commercial monopolar radiofrequency ablation systems: a comparative experimental study in pig liver.

RATIONALE AND OBJECTIVES: To evaluate the efficiency of 4 radiofrequency (RF) systems by assessing the amount of delivered energy for each thermal induced lesion after perfusion mediated RF ablation and to compare the influence of perfusion mediation types on the energy efficiency. METHODS: A total of 43 ablations in 16 male landrace pigs with 4 RF devices were performed strictly according to the manufacturers' instructions. Total absorbed energy was computed and then related to 3D volumetry obtained after histopathological evaluation. Sixteen ablations were performed under physiological liver perfusion and 27 ablations with occlusion of portal vein, hepatic artery, or both vessels. Energy efficiency values of the RF systems for different vascular occlusion techniques were compared and analyzed by a nonparametrical rank sum test. RESULTS: Under physiological perfusion, the average energy delivered to produce 1-cm3 lesion size was calculated to 1650 +/- 929, 3097 +/- 389, 8312 +/- 2068, and 5493 +/- 2306 Watt x s/cm3 for the Berchtold, Radionics, Radiotherapeutics, and RITA system, respectively. After perfusion-mediated RF ablation, artery occlusion was not as effective as portal vein occlusion, which reduced the energy to 587 +/- 148, 869 +/- 276, and 903 +/- 394 Watt. s/cm3 for the Berchtold, Radionics, and Radiotherapeutics system, respectively. The occlusion of vessels, portal vein, and artery or portal vein alone increased the energy efficiency compared with physiological liver perfusion or occlusion of the artery (P = 0,003). CONCLUSIONS: Under physiological liver perfusion the open perfused system and the internally cooled system provided the best efficiency values with lowest standard deviations. The energy efficiency was increased markedly for all systems after occlusion of the portal vein either alone or in combination with arterial occlusion. Occlusion of the hepatic artery did not improve the efficiency.

Animals↗

Comparison of volume-rendered and surface-rendered MR colonography.

In the United States and Europe, colorectal cancer is the second leading cause of cancer-related deaths. It is well known that colorectal carcinomas may originate from preexisting adenomas. For the visualization of colorectal cancer and other pathologic changes such as polyps, two 3D methods (volume-rendering (VR) and surface-rendering (SR)) in MR colonography were compared in our study. MR colonography was carried out in 17 patients on a 1.5 T MR scanner using a 10 mmolar gadolinium water solution enema. Coronal as well as rotated VR and SR views were compared in order to examine the technical quality (TQ) of the visualization model and grade of confidence (GC) in the pathological findings. Colonoscopic findings revealed 8 colorectal carcinoma, 10 patients with polyps, 4 diverticular disease, and 2 with redundant bowel loops. Based on a total of 248 colonic segments for both visualization methods, volume rendering were significantly superior to surface rendering for both, TQ (p<0.0001) and GC (p<0.0001). Volume rendering and surface rendering were not dependent on individual colon segments (p=0.13 for TQ and p=0.18 for GC) or on image rotation (p=0.06 for TQ and p=0.062 for GC). It is also independent of the type of pathology (p=0.31 for TQ and p=0.42 for GC) and the reviewers (p=0.62 for TQ and p=0.88 for GC). This indicates, that for the purpose of interpreting the technical quality and pathological findings, volume rendering is superior to surface rendering in MR colonography. Volume rendering could be used as an 3D visualization tool, enabling MR colonography examinations to be completed sooner in cases where colon distension is sufficient, and it would also provide an overview of potential mass lesions.

Aged↗

Virtual bronchoscopy: comparison of different surface rendering models.

The aim of this study was to compare different representation models of surface-rendered virtual bronchoscopy. 10 consecutive patients with inoperable primary lung tumors underwent thin-section spiral computed tomography. The structures of interest, the tracheobronchial system and anatomical and pathological thoracic structures were segmented using an interactive threshold interval volume-growing segmentation algorithm and visualized with the aid of a color-coded surface rendering method. For virtual bronchoscopy, the tracheobronchial system was visualized using a triangle-surface rendering model, a shaded-surface rendering model and a transparent shaded-surface rendering model. The triangle-surface rendering model allowed optimum detailed spatial representation of the dimensions of extraluminal anatomical and pathological mediastinal structures. As the lumen of the tracheobronchial system was less well defined, the rendering model was of limited use for depiction of the airway surface. The shaded-surface rendering model facilitated an optimum assessment of the airway surface, but the mediastinal structures could not be depicted. The transparent shaded-surface rendering model provides simultaneous adequate to optimum visualization and assessment of the intraluminal airway surface and the extraluminal mediastinal structures as well as a quantitative assessment of the spatial relationship between these structures. Fast data acquisition with a multi-slice detector spiral computed tomography scanner and the use of virtual bronchoscopy with the transparent shaded-surface rendering model obviate the need for time consuming detailed analysis and presentation of axial source images by providing improved the diagnostic imaging of endotracheal and endobronchial diseases and offering a useful alternative to fiberoptic bronchoscopy.

Bronchoscopy↗

MR imaging-guided adrenal biopsy using an open low-field-strength scanner and MR fluoroscopy.

OBJECTIVE: The aim of our study was to test the feasibility and specific properties of MR imaging-guided adrenal biopsy using an open 0.2-T scanner and MR fluoroscopic fast imaging with steady-state free precession sequences. CONCLUSION: MR imaging-guided biopsy of the adrenal gland is feasible and safe. In all patients, appropriate specimens were obtained with full diagnostic yield and accuracy. MR fluoroscopy is particularly useful to establish an oblique paravertebral access without pleural transgression. For final needle placement, supplementary breath-hold multislice sequences are required in most cases.

Adrenal Gland Neoplasms↗

Transjugular intrahepatic portosystemic shunts in children with biliary atresia.

PURPOSE: We retrospectively evaluated the technical and long-term clinical results of transjugular intrahepatic portosystemic shunts (TIPS) in children with portal hypertension and biliary atresia (BA). METHODS: Nine children with BA and recurrent bleeding from esophagogastric and/or intestinal varices were treated by TIPS at the age of 34-156 months and followed-up in two centers. Different types of stents were used. RESULTS: Shunt insertion succeeded in all patients, but in two a second procedure was necessary. Seven procedures lasted more than 3 hr, mainly due to difficult portal vein puncture. Variceal bleeding ceased in all patients; however, 16 reinterventions were performed in eight patients for clinical reasons (n = 11) and sonographically suspected restenosis (n = 5). Four patients underwent successful liver transplantation 4-51 months after TIPS and five are in good clinical conditions 64-75 months after TIPS. CONCLUSION: TIPS in children with BA is technically difficult, mainly due to periportal fibrosis and small portal veins. Frequency of reinterventions seems to be higher compared with adults.

Angiography↗

MR imaging at rest early after myocardial infarction: detection of preserved function in regions with evidence for ischemic injury and non-transmural myocardial infarction.

Patients with subacute myocardial infarction were studied to detect regions of ischemic injury but with preserved myocardial function combining different MRI techniques. On a 1.5-T imaging system 27 patients were examined 7-14 days after acute myocardial infarction. The imaging protocol included T2-weighted fast spin-echo imaging, a cine fast low-angle shot (FLASH) 2D technique to determine regional function at rest, and a first pass as well as late contrast enhancement perfusion study injecting 0.1 mmol/kg Gd-DTPA. Preserved function was compared with the transmural extent of first-pass perfusion phenomena, increased T2 signal intensity (SI), and late contrast enhancement. Semi-quantitative first-pass perfusion parameters were correlated with quantitative myocardial wall thickening (MWT) and degree of coronary artery stenosis. Indicating ischemic injury increased T2 SI and late enhancement was present in 29 and 26% of segments. Preserved function was found predominantly in segments with non-transmural late enhancement (112 of 338 segments with late enhancement) and transmural increase of T2 SI (129 of 386 segments with increased T2 SI). A high-grade perfusion deficit was detected in 4% of all segments and regularly associated with markedly decreased systolic function. Correlation of first-pass perfusion parameters was observed with MWT (r=0.50-0.90, p<0.001) but not with the degree of coronary artery stenosis. Our data suggest that preserved function was detected in non-transmural myocardial infarction demonstrated by non-transmural late enhancement and increase of T2 SI.

Aged↗

Computer-aided diagnosis in contrast-enhanced CT colonography: an approach based on contrast.

Automation in colorectal mass detection is achieved as soon as the voxels representing colorectal masses can be automatically segmented. We tested the Hounsfield (HU) value in intensely contrast enhanced high-resolution CT colonography for automated segmentation of colorectal masses in 18 patients with 35 polyps (28 < 10 mm, 7 > or = 10 mm) and 7 carcinomas. Mean HU values of the colonic wall and masses were determined to deduce a gradient threshold for a segmentation process, which encodes the voxels bordering the colonic lumen with a colour ranging in intensity from 0 to 100% according to the selected gradient threshold range in the volume rendering. The results of the automated segmentation process were superimposed on a virtual double contrast and endoscopic display and validated through correlation with morphology. Mean HU values and their standard deviations for the colonic wall, polyps < 10 mm, polyps > or = 10 mm and carcinomas were 63 +/- 24, 154 +/- 38, 116 +/- 41 and 108+/-29 HU, respectively. A gradient threshold ranging from 90 to 160 HU resulted in colour pools in 6 of 7 of polyps > or = 10 mm, and 6 of 7 carcinomas that were significant enough to prospectively guide the reader's attention to these masses. Due to the superposition of "false-positive" voxels in the projection view, the virtual endoscopic perspective was superior to the virtual double contrast display for controlling the segmentation results. The HU value is promising for automated segmentation of colorectal masses but needs to be combined with morphological parameters to render automated colorectal mass detection more accurate. Further refinements of the method with subsequent analysis of its accuracy, as well as analogue studies with contrast-enhanced MRI, appear warranted. More information at http://www.multiorganscreening.org

Aged↗

CT-guided percutaneous drainage of intra-abdominal abscesses: APACHE III score stratification of 1-year results. Acute Physiology, Age, Chronic Health Evaluation.

Our objective was to evaluate the clinical success rates of percutaneously drained intra-abdominal abscesses using a risk stratification score for severely ill patients (APACHE III; Acute Physiology, Age, Chronic Health Evaluation). In 75 patients CT-guided percutaneous abscess drainage was performed to treat intra-abdominal abscesses. The clinical success rate based on a 1-year follow-up was correlated with abscess etiology, size, and structure, as well as with the initial APACHE III score. Clinical success, i.e., the complete removal of the abscess without surgical treatment, was observed in 62 of 75 patients (83%). Abscess size (<200 cm(3)) and abscesses with a simple structure correlated with higher clinical success rates. Patients presenting with APACHE III scores below 30 were treated by percutaneous abscess drainages (PAD) alone significantly more often than patients presenting with higher APACHE scores. The percutaneous drainage of intra-abdominal abscesses shows good long-term results as long as abscesses are singular, small (<200 cm(3)), and located in well accessible regions in combination with low APACHE scores (<30).

Abdominal Abscess↗

Prospective comparison of [18F]fluorodeoxyglucose positron emission tomography with conventional assessment by computed tomography scans and serum tumor markers for the evaluation of residual masses in patients with nonseminomatous germ cell carcinoma.

BACKGROUND: To assess the ability of [(18)F]fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) to predict the viability of residual masses after chemotherapy in patients with metastatic nonseminomatous germ cell tumors (GCT), PET results were compared in a blinded analysis with computed tomography (CT) scans and serum tumor marker changes (TUM) as established methods of assessment. METHODS: Independent reviewers who were blinded to each other's results evaluated the PET results and corresponding CT scan and TUM results in 85 residual lesions from 45 patients. All patients were treated within prospective clinical trials and received primary/salvage, high-dose chemotherapy with autologous blood stem cell support for primary poor prognosis disease or recurrent disease. PET results were assessed both visually and by quantifying glucose uptake (standardized uptake values). Results were validated either by histologic examination of a resected mass and/or biopsy (n = 28 lesions) or by a 6-month clinical follow-up after evaluation (n = 57 lesions). RESULTS: F-18 FDG PET showed increased tracer uptake in 32 of 85 residual lesions, with 29 true positive (TP) lesions and three false positive (FP) lesions. Fifty-three lesions were classified by PET as negative (no viable GCT), 33 lesions were classified by PET as true negative (TN), and 20 lesions were classified by PET as false negative (FN). In the blinded reading of the corresponding CT scan and TUM results, 38 residual lesions were assessed correctly as containing viable carcinoma and/or teratoma. Forty-six lesions were classified as non-suspicious by CT scan/TUM (33 TN lesions and 14 falsely classified lesions). PET correctly predicted the presence of viable carcinoma in 5 of these 14 and the absence of viable carcinoma in 3 of these 14 lesions. Resulting sensitivities and specificities for the prediction of residual mass viability were as follows: PET, 59% sensitivity and 92% specificity; radiologic monitoring, 55% sensitivity and 86% specificity; and TUM, 42% sensitivity and 100% specificity. The positive and negative predictive values for PET were 91% and 62%, respectively. The diagnostic efficacy of PET did not improve when patients with teratomatous elements in the primary tumor were excluded from the analysis. In patients with multiple residual masses, a uniformly increased residual F-18 FDG uptake in all lesions was a strong predictor for the presence of viable carcinoma. CONCLUSIONS: F-18 FDG PET imaging performed in conjunction with conventional staging methods offers additional information for the prediction of residual mass histology in patients with nonseminomatous GCT. A positive PET is highly predictive for the presence of viable carcinoma. Other useful indications for a PET examination include patients with multiple residual masses and patients with marker negative disease.

Adult↗

Meclofenamic acid for inhibition of human vascular smooth muscle cell proliferation and migration: an in vitro study.

PURPOSE: The aim of the study was to examine the effects of meclofenamic acid on proliferation, clonogenic activity, migratory ability, cell cycle distribution and p44/42 MAPK (mitogen activated protein kinase) expression in serum-stimulated human aortic smooth muscle cells (haSMCs). METHODS: haSMCs were treated with meclofenamic acid in three different concentrations (10 mM, 100 mM, 200 mM) for 4 days. Then meclofenamic acid-free culture medium was supplemented until day 20. Growth kinetics were assessed. Cell cycle analysis was performed by flow cytometry. Clonogenic activity was evaluated with colony formation assays. Migratory ability was investigated by stimulation with platelet-derived growth factor (PDGF-BB) in 24-well plates with 8 mm pores membrane inserts. p44/42 MAPK was detected by Western blot technique. RESULTS: Meclofenamic acid inhibited the proliferation, clonogenic activity and migratory ability of haSMCs in a dose-dependent manner. Cell cycle analysis revealed a G2/M-phase block. The p44/42 MAPK was significantly reduced. CONCLUSION: Meclofenamic acid inhibits the proliferation and migration of haSMCs. If a sufficient dose of meclofenamic acid can be applied systemically or by local drug delivery it could be a valuable substance to prevent restenosis after angioplasty.

Cell Cycle↗