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M Griffin

Publications and source records attributed to M Griffin.

At least 19 recordsLinked to original sources

Role of the cross-linking enzyme tissue transglutaminase in the biological recognition of synthetic biodegradable polymers.

The calcium-dependent cross-linking enzyme tissue transglutaminase (tTgase, type II) is a potential novel player at the cell surface, where its contribution to cell adhesion and stabilization of the extracellular matrix is becoming increasingly recognized. We investigated whether tTgase enhances the biological recognition of poly (DL lactide co-glycolide) (PLG), poly (epsilon-caprolactone) (PCL), and poly (L lactide) (PLA), biomaterials widely used in medical implants. Three cell-model systems consisting of human osteoblasts, endothelial cells (ECV-304), and Swiss 3T3 fibroblasts were utilized, in which tTgase expression was modulated by gene transfer, and the ability of cells to spread on these polymers was quantified in relation to the altered level of expressed tTGase. Results show that over-expression of tTgase in human osteoblasts positively correlated with cell spreading on PLG, while no attachment and spreading was found on PCL and PLA. Antisense silencing of tTgase in the endothelial cells led to a marked reduction of cell spreading on all polymers. The hydrophobic nature of PLC also appeared to favor endothelial cell attachment. Spreading of Swiss 3T3 fibroblasts on these biomaterials was only slightly affected by increased expression of tTgase, although cell spreading on control glass was increased. We propose that the consideration of tTgase-mediated bioactivity in novel biomaterials may improve cell attachment and promote biocompatibility.

3T3 Cells↗

Predicting hospital mortality for patients in the intensive care unit: a comparison of artificial neural networks with logistic regression models.

OBJECTIVE: Logistic regression (LR), commonly used for hospital mortality prediction, has limitations. Artificial neural networks (ANNs) have been proposed as an alternative. We compared the performance of these approaches by using stepwise reductions in sample size. DESIGN: Prospective cohort study. SETTING: Seven intensive care units (ICU) at one tertiary care center. PATIENTS: Patients were 1,647 ICU admissions for whom first-day Acute Physiology and Chronic Health Evaluation III variables were collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We constructed LR and ANN models on a random set of 1,200 admissions (development set) and used the remaining 447 as the validation set. We repeated model construction on progressively smaller development sets (800, 400, and 200 admissions) and retested on the original validation set (n = 447). For each development set, we constructed models from two LR and two ANN architectures, organizing the independent variables differently. With the 1,200-admission development set, all models had good fit and discrimination on the validation set, where fit was assessed by the Hosmer-Lemeshow C statistic (range, 10.6-15.3; p > or = .05) and standardized mortality ratio (SMR) (range, 0.93 [95% confidence interval, 0.79-1.15] to 1.09 [95% confidence interval, 0.89-1.38]), and discrimination was assessed by the area under the receiver operating characteristic curve (range, 0.80-0.84). As development set sample size decreased, model performance on the validation set deteriorated rapidly, although the ANNs retained marginally better fit at 800 (best C statistic was 26.3 [p = .0009] and 13.1 [p = .11] for the LR and ANN models). Below 800, fit was poor with both approaches, with high C statistics (ranging from 22.8 [p <.004] to 633 [p <.0001]) and highly biased SMRs (seven of the eight models below 800 had SMRs of <0.85, with an upper confidence interval of <1). Discrimination ranged from 0.74 to 0.84 below 800. CONCLUSIONS: When sample size is adequate, LR and ANN models have similar performance. However, development sets of < or = 800 were generally inadequate. This is concerning, given typical sample sizes used for individual ICU mortality prediction.

APACHE↗

Decreased efficiency of trypsinization of cells following photodynamic therapy: evaluation of a role for tissue transglutaminase.

Identifying the cellular responses to photodynamic therapy (PDT) is important if the mechanisms of cellular damage are to be fully understood. The relationship between sensitizer, fluence rate and the removal of cells by trypsinization was studied using the RIF-1 cell line. Following treatment of RIF-1 cells with pyridinium zinc (II) phthalocyanine (PPC), or polyhaematoporphyrin at 10 mW cm-2 (3 J cm-2), there was a significant number of cells that were not removed by trypsin incubation compared to controls. Decreasing the fluence rate from 10 to 2.5 mW cm-2 resulted in a two-fold increase in the number of cells attached to the substratum when PPC used as sensitizer; however, with 5,10,15,20 meso-tetra(hydroxyphenyl) chlorine (m-THPC) there was no resistance to trypsinization following treatment at either fluence rate. The results indicate that resistance of cells to trypsinization following PDT is likely to be both sensitizer and fluence rate dependent. Increased activity of the enzyme tissue-transglutaminase (tTGase) was observed following PPC-PDT, but not following m-THPC-PDT. Similar results were obtained using HT29 human colonic carcinoma and ECV304 human umbilical vein endothelial cell lines. Hamster fibrosarcoma cell (Met B) clones transfected with human tTGase also exhibited resistance to trypsinization following PPC-mediated photosensitization; however, a similar degree of resistance was observed in PDT-treated control Met B cells suggesting that tTGase activity alone was not involved in this process.

Animals↗

Femoral atherosclerosis in an older British population: prevalence and risk factors.

Most estimates of the prevalence of peripheral atherosclerosis have been based on intermittent claudication or lower limb blood flow. The aim of this study was therefore to determine the prevalence of underlying femoral plaque, and to determine its association with other cardiovascular disease and risk factors. Presence of plaque was identified using ultrasound in a random sample of men (n=417) and women (n=367) aged 56-77 years. Coexistent cardiovascular disease, exercise and smoking were determined by questionnaire, blood pressure was recorded, and serum cholesterol and plasma fibrinogen were determined. Of the 784 subjects that were scanned, 502 (64%) demonstrated atherosclerotic plaque. Disease prevalence increased significantly with age (P<0.0001), and was more common in men (67.1 vs. 59.4%, P<0.05). Subjects with femoral plaque had a significantly greater odds of previous ischaemic heart disease (OR 2. 2, 95% CI 1.3, 3.7) and angina (OR 1.7, 95% CI 1.03, 2.7), but not of stroke or leg pain on exercise. Current and ex-smoking, raised serum total cholesterol and plasma fibrinogen levels, but not blood pressure, were associated with an increased risk of femoral plaque, independent of age and sex. Frequent exercise and a high HDL cholesterol were significantly associated with lower risk. In conclusion, therefore, atherosclerotic disease of the femoral artery affects almost two-thirds of the population in late middle age. It is associated with an increased prevalence of ischaemic heart disease and angina, but whether detecting at risk individuals using ultrasound offers advantages over simpler and less expensive risk factor scoring requires evaluation in trials.

Age Distribution↗

Hemispheric symptoms and carotid plaque echomorphology.

PURPOSE: In patients with carotid bifurcation disease, the risk of stroke mainly depends on the severity of the stenosis, the presenting hemispheric symptom, and, as recently suggested, on plaque echodensity. We tested the hypothesis that asymptomatic carotid plaques and plaques of patients who present with different hemispheric symptoms are related to different plaque structure in terms of echodensity and the degree of stenosis. METHODS: Two hundred sixty-four patients with 295 carotid bifurcation plaques (146 symptomatic, 149 asymptomatic) causing more than 50% stenosis were examined with duplex scanning. Thirty-six plaques were associated with amaurosis fugax (AF), 68 plaques were associated with transient ischemic attacks (TIAs), and 42 plaques were associated with stroke. B-mode images were digitized and normalized using linear scaling and two reference points, blood and adventitia. The gray scale median (GSM) of blood was set to 0, and the GSM of the adventitia was set to 190 (gray scale range, black = 0; white = 255). The GSM of the plaque in the normalized image was used as the objective measurement of echodensity. RESULTS: The mean GSM and the mean degree of stenosis, with 95% confidence intervals, for plaques associated with hemispheric symptoms were 13.3 (10.6 to 16) and 80.5 (78.3 to 82.7), respectively; and for asymptomatic plaques, the mean GSM and the mean degree of stenosis were 30.5 (26.2 to 34.7) and 72. 2 (69.8 to 74.5), respectively. Furthermore, in plaques related to AF, the mean GSM and the mean degree of stenosis were 7.4 (1.9 to 12. 9) and 85.6 (82 to 89.2), respectively; in those related to TIA, the mean GSM and the mean degree of stenosis were 14.9 (11.2 to 18.6) and 79.3 (76.1 to 82.4), respectively; and in those related to stroke, the mean GSM and the mean degree of stenosis were 15.8 (10.2 to 21.3) and 78.1 (73.4 to 82.8), respectively. CONCLUSION: Plaques associated with hemispheric symptoms are more hypoechoic and more stenotic than those associated with no symptoms. Plaques associated with AF are more hypoechoic and more stenotic than those associated with TIA or stroke or those without symptoms. Plaques causing TIA and stroke have the same echodensity and the same degree of stenosis. These findings confirm previous suggestions that hypoechoic plaques are more likely to be symptomatic than hyperechoic ones. They support the hypothesis that the pathophysiologic mechanism for AF is different from that for TIA and stroke.

Amaurosis Fugax↗

Gender-related differences in proliferative response of cardiac fibroblasts to hypoxia: effects of estrogen.

Ischemic heart disease is more prevalent in men than in women. The remodeling of extracellular matrix, is a structural correlate of heart failure of ischemic origin and proliferation of cardiac fibroblasts is a key factor in this remodeling. We asked if proliferative response of male and female cardiac fibroblasts is differentially susceptible to hypoxia. DNA synthesis, using 3H-thymidine incorporation was compared under hypoxia (2% O2) in cardiac fibroblasts obtained from adult, age-matched male and female rat heart. In female cells DNA synthesis remained unchanged under hypoxia and this resistance was dependent on tyrosine kinase activation, as it was abolished in the presence of genistein, a tyrosine kinase inhibitor. Male cells, on the other hand, were susceptible to hypoxia and their DNA synthesis was reduced significantly (70%, (p < 0.0001). This effect was partially reversed by inhibition of tyrosine kinase. Western analysis showed a higher abundance of tyrosine phosphorylated proteins in male cells compared to female cells as well as differences in molecular weight of basal and hypoxia-induced tyrosine-phosphorylated proteins between male and female cells. The presence of estrogen (17-beta estradiol, 10 nM) altered the response of both cells to hypoxia. In female cells the combined effect of hypoxia and estrogen led to inhibition of DNA synthesis, whereas in male cells estrogen partially reversed the hypoxia-induced inhibition of DNA synthesis (37% (p < 0.01) inhibition in the presence of estrogen vs. 70% (p < 0.0001) inhibition in the absence of estrogen). The effects of estrogen in male and female cells were mediated via estrogen receptors as they were reversed by the pure anti-estrogen, ICI 182,780. Western analysis of cell lysate showed hypoxia-induced increase in the level of estrogen receptor beta in both male and female cells. Gel shift analysis showed hypoxia-induced increase in cytoplasmic ERE (estrogen response element)-binding activity and decrease in nuclear ERE-binding in male cells. In female cells cytoplasmic and nuclear ERE-binding activities remained unchanged under hypoxia. Together, these data demonstrate that while female cells are resistant to hypoxia-induced inhibition in DNA synthesis, male cells are susceptible; intracellular pathways involving tyrosine phosphorylation are involved in the response of both cells; and estrogen, via estrogen-receptor-dependent mechanisms, differentially alters the response of male and female cells to hypoxia.

Age Factors↗

Prevalence of lower respiratory tract infections in hospitalized patients in the United Kingdom and Eire--results from the Second National Prevalence Survey.

During 1993 and 1994, the Hospital Infection Society conducted its Second National Prevalence Survey of infections in patients in British hospitals. The prevalence rates for hospital-acquired (HA) and community-acquired (CA), lower respiratory tract infections (LRTIs) were 2.4% and 6.1%, respectively; this shows an increase over that reported in the First National Prevalence Study. The prevalence rate of HA infections for ventilated patients was 18.6%. The prevalence was greater in males, odds ratio (OR, 95% CI) for HA-LRTIs (1.4, 1.1-1.6) and CA-LRTIs (1.2, 1.1-1.3) than in females. In the case of both HA-LRTIs and CA-LRTIs, there was an increase in prevalence in patients with age >75 years, (HA-LRTIs 1.7, 1.3-2.2; CA-LRTIs 1.7, 1.0-2.7). Results of multivariable logistic regression analysis showed an increased risk of HA-LRTIs in patients who had a nasogastric tube (3.6, 2.3-3.6), were ventilated (2.3, 1.6-3.2), trauma patients (2.2, 1.5-3.0), chronic obstructive airway disease (COAD), (1.9, 1.5-2.3), a tracheostomy (1.9, 1.3-2.7), prior blood transfusion (1.5, 1.2-1.8), smokers (1.4, 1.1-1.6) or on systemic corticosteroid therapy (OR 1.3, 1.1-1.6). Community-acquired LRTIs were positively associated with cystic fibrosis (33.7, 19.1-59.3), HIV (9.8, 6.5-14.8), COAD (4.8, 3.8-4.8), systemic corticosteroid therapy (2.5, 2.2-2.8), tracheostomy (1.8, 1.1-2.9), males (1.2, 1.1-1.3) and smoking (1.2, 1.1-1.4).

Adolescent↗

The efficacy of the new SCD response compression system in the prevention of venous stasis.

OBJECTIVE: The current commercially available sequential intermittent pneumatic compression device used for the prevention of deep venous thrombosis has a constant cycle of 11 seconds' compression and 60 seconds' deflation. This deflation period ensures that the veins are filled before the subsequent cycle begins. It has been suggested that in some positions (eg, semirecumbent or sitting) and with different patients (eg, those with venous reflux), refilling of the veins may occur much earlier than 60 seconds, and thus a more frequent cycle may be more effective in expelling blood proximally. The aim of the study was to test the effectiveness of a new sequential compression system (the SCD Response Compression System), which has the ability to detect the change in the venous volume and to respond by initiating the subsequent cycle when the veins are substantially full. METHODS: In an open controlled trial at an academic vascular laboratory, the SCD Response Compression System was tested against the existing SCD Sequel Compression System in 12 healthy volunteers who were in supine, semirecumbent, and sitting positions. The refilling time sensed by the device was compared with that determined from recordings of femoral vein flow velocity by the use of duplex ultrasound scan. The total volume of blood expelled per hour during compression was compared with that produced by the existing SCD system in the same volunteers and positions. RESULTS: The refilling time determined automatically by the SCD Response Compression System varied from 24 to 60 seconds in the subjects tested, demonstrating individual patient variation. The refilling time (mean +/- SD) in the sitting position was 40.6 +/- 10. 0 seconds, which was significantly longer (P <.001) than that measured in the supine and semirecumbent positions, 33.8 +/- 4.1 and 35.6 +/- 4.9 seconds, respectively. There was a linear relationship between the duplex scan-derived refill time (mean of 6 readings per leg) and the SCD Response device-derived refill time (r = 0.85, P <. 001). The total volume of blood (mean +/- SD) expelled per hour by the existing SCD Sequel device in the supine, semirecumbent, and sitting positions was 2.23 +/- 0.90 L/h, 2.47 +/- 0.86 L/h, and 3.28 +/- 1.24 L/h, respectively. The SCD Response device increased the volume expelled to 3.92 +/- 1.60 L/h or a 76% increase (P =.001) in the supine position, to 3.93 +/- 1.55 L/h or a 59% increase (P =. 001) in the semirecumbent position, and to 3.97 +/- 1.42 L/h or a 21% increase (P =.026) in the sitting position. CONCLUSIONS: By achieving more appropriately timed compression cycles over time, the new SCD Response System is effective in preventing venous stasis by means of a new method that improves on the clinically documented effectiveness of the existing SCD system. Further studies testing its potential for improved efficacy in preventing deep venous thrombosis are justified.

Adult↗

Field-by-field evaluation of intraoperative transoesophageal echocardiography interpretative skills.

A quality assurance system is essential for the credibility and structured growth of anaesthesiology-based transoesophageal echocardiography (TEE) programmes. We have developed software (Q/A Kappa), involving a 400-line source code, capable of directly reporting kappa correlation coefficient values, using external reviewer interpretations as the 'gold standard', and thereby allowing systematic assessment of the validity of intraoperative echocardiographic interpretation. This paper presents assessment of the validity of 240 intraoperative anaesthesiologists' echocardiographic interpretations, and, in addition, the results of field testing of this prototypical software. Data, derived from consecutive cardiac surgery patients, consisted of standardized two-dimensional transoesophageal echocardiographic, colour flow and Doppler imaging sequences. Intraoperative and off-line 'gold standard' TEE interpretations were compared for 19 fields or variables using the Q/A Kappa program. The kappa correlation coefficients were highly variable and dependent on the examination field, ranging from 0.08 for apical regional wall motion scores to 1.00 for tricuspid regurgitation grade, left atrial measurement, aortic valve anatomy and left ventricular long axis and short axis global function. The correlation coefficients were also operator dependent. These data (480 interpretations) were also manually integrated into the equation required for calculation of values of the variable kappa correlation coefficient. The relationship between Q/A Kappa-derived values and manually calculated values was highly significant (p < 0.001; r = 1.0). The implications and possible explanations of the results for particular examination fields are discussed. This study also demonstrates successful seamless functioning of this software program from data entry, segmentation into tables and valid statistical analysis. These findings suggest that it is practical to provide sophisticated continuous quality improvement TEE data on a routine basis.

Adult↗

A prospective study of faecal bile acids and colorectal cancer.

A prospective study of 7079 people aged 45-74 recruited through general practices in South Wales, Herefordshire and Edinburgh, Scotland was undertaken to test the hypothesis that faecal bile acids are implicated in the causation of large bowel cancer. The population was recruited between 1974 and 1980 and the response rate for stool collection was 67%. Bile acid analyses were performed on those cases that presented by 1990. It was decided in advance to examine the hypothesis separately for left- and right-sided bowel cancer because of known epidemiological differences between the two sites and to exclude the cases presenting within 2 years of the stool sample from the analyses because the cancer could have been present at recruitment and might have possibly affected faecal bile acid concentrations. Each case (n = 51 left-sided and 8 right-sided) was matched with three controls by age (within 5 years), sex, place of residence and time of providing the stool sample (within 3 months). Statistical analyses using conditional logistic regression showed no significant differences between the left-sided cases and controls for any of the concentrations of individual bile acids, total bile acid concentrations, faecal neutral steroids, percentage bacterial conversion and the ratio of lithocholic acid to deoxycholic acid concentrations. There was a statistically significant (P = 0.021) association of the presence of chenodeoxycholic acid (5/8 samples) in the right-sided cases compared with the controls (3/23), odds ratio 6.26 (95% confidence interval 1.19, 32.84). A high proportion of primary bile acids has also been found in other studies of patients with a genetic predisposition to proximal bowel cancer, however this pattern may also occur in low risk groups, such as Indian vegetarians, suggesting that they may predispose to right-sided bowel cancer only in the presence of other, as yet unknown factors. If bile acids are involved in the causation of large bowel cancer, they may be part of a complex set of interacting factors.

Aged↗

Superficial vein valve repair with a new external valve support (EVS). The IMES (International Multicenter EVS Study).

The aim of this international multicenter trial was to evaluate the effects of a new surgical device (Gore External Valve Support-EVS) and technique for external valvuloplasty of the long saphenous vein (LSV). Patients with superficial venous disease and venous hypertension due to pure superficial venous incompetence were randomized into two treatment groups, the first treated with "conventional treatment" (ligation or stripping) and the second with external valvuloplasty with the EVS. Patients with uncomplicated varicose veins within the age range of 35-65 years were included. Incompetence with presence of functional cusps at the saphenofemoral junction (SFJ), with vein dilatation were the main inclusion criteria. The EVS comprised of a GORE-TEX patch material (including a nitinol frame) that is placed around the vein, producing a reduction in the caliber of the vein. Also the vein section becomes elliptical. These combined actions are aimed to reduce incompetence, allowing a better closure of the cusps. The EVS was placed at the SFJ after limited dissection of the vein and ligation of collaterals. The procedure was randomized as an alternative to simple ligation or stripping (according with the procedure commonly used in the center). The associated ligation of distal incompetent veins was allowed. The main outcome measures of the study were evaluated by color-duplex (morphologic findings and evaluation of reflux) and with ambulatory venous pressure (AVP) or air-plethysmography (APG). Main endpoints of the first year of the study and main subject of this report (mainly concerning safety within the first year of follow-up) were considered presence/absence of reflux; patency of the veins; mobility/function of vein cusps; occurrence of thrombosis; tolerability of the device; and increased complexity and operating time needed for the EVS. At 1 year 30 patients had been randomized (14 EVS implanted, 16 controls). Reflux was absent in all EVS patients, all treated veins were patent, and all cusps were mobile. No thrombosis had been observed and the tolerability of the device was very good. The increased complexity required by placing the EVS was limited (5-12 minutes more). In conclusion results of the first year show efficacy and tolerability of the EVS. In selected patients (superficial LSV incompetence, reflux-dilatation, functional SFJ cusps, incompetence mainly due to enlargement of the vein), the EVS could be an effective alternative to "destructive" ligation and/or stripping of the vein. Prolonged follow-up will indicate the clinical potentials of the EVS.

Adult↗

Effects of shock waves on the microcirculation in critical limb ischemia (CLI) (8-week study).

Shock waves (SWs) are used to control and decrease pain in several clinical conditions (e.g., painful elbow and shoulder, etc). This clinical effect may be due to cellular stunning of the tissues (particularly nervous components) in the area treated with SW. It may also be the consequence of unknown metabolic actions on tissues, which may include changes in cellular permeability and the liberation of proteins and mediators locally acting on pain and nerve endings. The aim of this study was to evaluate the reduction in pain and the microcirculation improvement induced by SWs treatment in an 8-week study in patients with chronic limb ischemia (CLI). Patients with CLI (15 with rest pain only and 15 with rest pain and limited distal necrosis) were included. The treatment was based on a 30-minute SWs session, three times weekly for 2 weeks. Clinical and microcirculatory evaluation were performed with laser Doppler Po2 and Pco2 measurements. Pain was measured with an analogue scale line. A Minilith SL1 (Storz Medical, Switzerland) litotriptor was used. The parabolic reflector is coupled to the skin with a silicon water cushion. Focal pressure was adjusted between 6 and 70 Mpa in eight steps. The energy flux density was variable from 0.03 to 0.5 mJ/mm2. Focal diameter and distance were defined (depth of target within the patient's foot of about 70 mm). The coded intensity used in this study was between 6 and 8 and the application time was 20 min (at four impulses per second). Twenty-eight of the 30 patients with CLI (15 with rest pain only and 13 with necrosis) completed the study. The treatment was well tolerated. Blood pressure was unchanged after 8 weeks while the increase in laser Doppler flux was significant (p<0.05) (at all measurements after treatment). The ORACLE score at 1 and 8 weeks was decreased (p<0.05). The same trend was observed with the analogue scale line for pain (p<0.05). PO2 increased (p<0.05) and Pco2 decreased (p<0.05). Tibial pressure did not change. All patients observed an increase in their subjective pain-free walking distance. The improvement was still present after 8 weeks. In a separate subset of 37 patients (mean age 60+/-9 years; males) with CLI, a SWs dose-finding evaluation was performed. Flux changes were measured at the dorsum of the foot. Three treatment plans were used: (a) 20-minute SW treatment only once; (b) 20-minute SWs treatment every 2 days for 1 week; (c) 20 minutes every day for 1 week. Treatments were well tolerated. A different increase in flux was observed on the basis of different treatments. Flux variations generally indicated that increased SWs dosage was associated with proportional flux increase. Flux improvement was still present after 4 weeks. SWs treatment in CLI produced changes both in the microcirculation and on pain. These preliminary results are comforting and open new research options to be explored in the near future.

Aged↗

Predicting discharge destination for patients with severe motor stroke: important functional tasks.

Many patients with severe stroke are capable of returning to the community after receiving rehabilitation services. The purpose of this study was to describe outcomes of patients with stroke in FIM-FRG STR1, a classification based on the Functional Independence Measure, and identify important functional tasks associated with discharge to home. FIM-FRG STR1 is one of nine subpopulations of stroke that have been identified based on motor/cognitive FIM subscale score and age. We reviewed the program evaluation data of 259 cases of stroke from 1993 to 1996. We performed a descriptive analysis of the data and a logistic regression analysis to determine which tasks measured by the FIM were associated with discharge destination, a key indicator of rehabilitation success. We found that three admission FIM variables (bladder management, toilet transfers, memory) and three discharge FIM variables (upper body dressing, bed/chair transfers, comprehension) were associated with discharge destination with up to 75% accuracy. The implications of these findings are discussed.

Aged↗

Comparability of the ultrasonic tissue characteristics of carotid plaques.

Hypoechoic carotid atherosclerotic plaques on ultrasonographic examination were found to be associated with cerebrovascular events. This underlines the need for an accurate evaluation of their echotexture characteristics. The objective of this study was to further validate a proposed method of normalization aiming to facilitate the comparability of these characteristics. The sonographic examination involved imaging of carotid plaques using duplex technique and capturing, digitization, and normalization in a computer in a standard way. In the first part, the interobserver and interscanner variability and the gain-level variability within the ultrasound unit were examined, before and after normalization, in terms of plaque echotexture. The second part investigated the effect of normalization on the echotexture of 419 symptomatic and asymptomatic plaques. Our results indicated that the normalization reduced the interscanner variability and the gain-level variability. The interobserver variability was excellent. In addition, this process further distinguished the echotexture characteristics of symptomatic and asymptomatic carotid plaques, which encourages the use of this method in natural history studies in persons with asymptomatic carotid atherosclerotic disease, aiming to identify those at higher risk for stroke. These patients might benefit from a carotid endarterectomy.

Adult↗

[Femoral artery pseudo-aneurysms--changes in treatment, report of 7 years].

The femoral artery remains the most used peripheral site for radiological catheter access. With a greater number of both diagnostic and therapeutic procedures being performed by interventional radiologists and cardiologists, and with larger catheters being used for stenting and endovascular grafting, the incidence of iatrogenic pseudo-aneurysms reported has reached as high as 0.5-2%. Ideally, they should thrombus spontaneously. However, when this does not occur, management options include: observation, ultrasound-guided obliterative compression, direct thrombin injection, embolization, stent graft insertion, and very rarely-surgery. During a 7-year period (1992-1999) we treated 131 cases of femoral artery false aneurysms. Until 1998 ultrasound-guided compression-obliteration, with a 95% success rate, was our method of choice. Since 1998, direct thrombin injection, with 100% success in 24 cases, has become our preferred method. It is pain-free, fully successful even in anticoagulated patients, and is currently our treatment of choice.

Aneurysm, False↗

Cell surface localization of tissue transglutaminase is dependent on a fibronectin-binding site in its N-terminal beta-sandwich domain.

Increasing evidence indicates that tissue transglutaminase (tTG) plays a role in the assembly and remodeling of extracellular matrices and promotes cell adhesion. Using an inducible system we have previously shown that tTG associates with the extracellular matrix deposited by stably transfected 3T3 fibroblasts overexpressing the enzyme. We now show by confocal microscopy that tTG colocalizes with pericellular fibronectin in these cells, and by immunogold electron microscopy that the two proteins are found in clusters at the cell surface. Expression vectors encoding the full-length tTG or a N-terminal truncated tTG lacking the proposed fibronectin-binding site (fused to the bacterial reporter enzyme beta-galactosidase) were generated to characterize the role of fibronectin in sequestration of tTG in the pericellular matrix. Enzyme-linked immunosorbent assay style procedures using extracts of transiently transfected COS-7 cells and immobilized fibronectin showed that the truncation abolished fibronectin binding. Similarly, the association of tTG with the pericellular matrix of cells in suspension or with the extracellular matrix deposited by cell monolayers was prevented by the truncation. These results demonstrate that tTG binds to the pericellular fibronectin coat of cells via its N-terminal beta-sandwich domain and that this interaction is crucial for cell surface association of tTG.

3T3 Cells↗