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Biomedical subjects

M Griffin

Publications and source records attributed to M Griffin.

At least 91 records · Page 5Linked to original sources

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↗

Vascular screening in andropause: non-invasive investigations in vascular disease screening.

Erectile dysfunction (ED) can be associated with atherosclerotic disease. It is therefore important to be able to evaluate the extent of arterial disease. This includes subclinical arterial disease. We have developed a score based on high-resolution-B-mode ultrasound scanning of the carotid-femoral bifurcations. This is a cost-effective screening procedure that correlates well with the risk of cardiovascular events. The penile circulation can also be investigated to assess local circulation and the level of fibrosis. During this investigation it is worthwhile evaluating the carotid-femoral arteries because the risk factors that predict ED are the same as those for atherosclerosis. Penile fibrosis contributes to the pathogenesis of ED. Whether this change is associated with hypertension needs to be established by further studies.

Arterial Occlusive Diseases↗

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↗

Tissue transglutaminase is an important player at the surface of human endothelial cells: evidence for its externalization and its colocalization with the beta(1) integrin.

We recently reported [J. Cell Sci. 110, 2461-2472 (1997)] that reduced expression of tissue transglutaminase (tTgase, type II) in human endothelial cell line ECV304 led to impaired cell spreading and adhesion; however, there is no immunocytochemical evidence for its presence and specific location at the surface of these cells. In this report we have stably transfected the same cell line with the cDNA for human tTgase which has been tagged at the C-terminus of the encoded protein with a 12-amino-acid peptide from protein kinase C epsilon. Using antibodies directed against this epitope tag peptide we show for the first time using immunogold electron microscopy and fluorescent immunocytochemistry the presence of cell surface-related tTgase. In cells undergoing attachment and cell spreading the enzyme appears to be concentrated at cell adhesion points which are rich in beta(1) integrin, suggesting that these areas may be the initial focal points for enzyme externalization. In more spread and confluent cells the enzyme appears more diffusely distributed along the basal membrane, with increased concentrations found at areas of cell-cell and cell-substratum contact. These findings strengthen the argument for the enzyme's role in cell-matrix interactions.

Base Sequence↗

The role of duplex scanning in the diagnosis of lower limb arterial disease.

Color flow duplex imaging of the iliac and femoropopliteal arteries was performed in patients undergoing angiography. The aim of the study was to determine: (1) in what percentage of patients could the iliac arteries be adequately visualized to enable a diagnosis, (2) the overall accuracy of duplex scanning in the diagnosis of arterial disease, and (3) whether there is a useful duplex criterion for the selection of patients for angioplasty. One hundred and twenty patients (79 males, 41 females; mean age 64.4 years) had duplex scans prior to angiography (2-7 days) and the results were compared. The duplex criteria of an increase in the peak systolic velocity ratio (PSVR) >2 and lesions <5 cm were used to signify hemodynamically significant stenosis (>50% narrowing), the presence of plaque and calcification in the arterial wall with alteration of PSVR and lesions >5 cm, diffuse disease, and the absence of flow on color/Doppler interrogation, occlusion. The results show that duplex scanning is a useful screening tool and may be effectively used to diagnose iliac and femoropopliteal disease in nearly 80% of patients. Angiography will be needed in those in whom duplex scanning is inconclusive, or, prior to intervention in those with disease suitable for surgical reconstruction or angioplasty, diagnosed on the basis of duplex scans.

Angiography↗

Ultrasonic plaque character and outcome after lower limb angioplasty.

PURPOSE: The value of ultrasonic plaque characteristics in identifying patients at "high-risk" of restenosis after percutaneous transluminal angioplasty (PTA) was studied. METHODS: Thirty-one arterial stenoses (6 common iliac, 2 external iliac, 1 profunda femoris, 21 superficial femoral, and 1 popliteal) in 17 patients who underwent angioplasty were studied by means of duplex scanning. With a computer-based program, B-mode images were digitized and normalized using 2 reference points, blood and adventitia. A grey level of 0 to 5 was allocated for the lumen (blood) and 180 to 190 for the adventitia on a linear gray scale of 0 to 255 (0 = absolutely black; 255 = absolutely white), and the overall plaque gray-scale median (GSM) of the pixels of the plaque was used as a measure of plaque echodensity. After PTA, follow-up of stenoses was done on day 1, weekly for 8 weeks, at 3 months, 6 months, and 1 year. The total plaque thickness (sum of anterior and posterior components), minimal luminal diameter (MLD), and peak systolic velocity ratio (PSVR) were measured for all stenoses. An increase of more than 2 in the PSVR was the duplex criterion used to signify restenosis. RESULTS: The GSM of the stenoses before angioplasty ranged from 6 to 71 (mean, 31.3 +/- 17.9); 17 stenoses had a GSM less than 25 (mean, 18.7 +/- 5.3), and 14 had a GSM more than 25 (mean, 46.4 +/- 15.8). When the GSM was less than 25, the absolute reduction in plaque thickness on day 1 post-PTA was 3.3 +/- 1.8 mm, in contrast to 1.8 +/- 1.6 mm when GSM was more than 25 (P <.03). The restenosis rate (PSVR more than 2) was 41% at 6 months and remained unchanged at 1 year. When the GSM was less than 25, restenosis occurred in 11% of lesions, in comparison with 78% when the GSM was more than 25 (P <.001). CONCLUSION: Plaque echodensity can be used to evaluate stenoses before PTA, to predict initial success and identify a subgroup that has a high prevalence of restenosis. The identification of a group at "high-risk" of restenosis can improve the selection of patients for the procedure and also be used in prospective studies on the prevention of restenosis.

Angioplasty, Balloon↗

Completing the molecular investigation into the HIV outbreak at Glenochil prison.

In a molecular investigation into the outbreak of HIV in Glenochil during the first 6 months of 1993, we previously demonstrated that 13 out of the 14 HIV positive inmates were infected with a virtually identical strain, and discounted 2 others as potential sources. Here we investigate a further 8 potential contacts and 4 potential sources which were identified in the companion paper. We were able to examine viral sequence from all but one of these 12 and results have revealed them to be distinct both from each other and the original 14. Thus, despite an intensive follow-up investigation, we have been unable to identify any further HIV infections that might have been part of the 1993 outbreak. It is possible that persons who were infected at that time remain undetected; however this and the companion report strongly suggest that if this were the case the likely numbers would be few.

Adult↗

Grading internal carotid artery stenosis using B-mode ultrasound (in vivo study)

OBJECTIVE: to determine the value of percentage area and diameter reduction in grading ICA stenosis using colour-coded B-mode transverse ultrasonic images. MATERIALS AND METHODS: measurement of the percentage area and diameter reduction of the common carotid, external carotid and internal carotid (at the point of maximum stenosis) were performed, using duplex scanning with colour-flow imaging preoperatively, in 33 patients (six patients were excluded). The duplex measurements were compared to the percentage area and diameter reduction from transverse section of the specimens. Peak systolic (PSV) and end-diastolic velocities (EDV) were measured at the proximal CCA and ICA within the jet of turbulence. A mm scale was placed next to the specimen block, which was captured by video. The area reduction was measured by playing the video and using the same duplex software. RESULTS: linear-regression analysis of the percentage area reduction of the in vivo against the specimen measurements showed a good linear relationship (r=0.9047). The in vivo duplex measurements had 95% confidence interval (CI) of 8% (95% CI of diameter reduction 5%). CONCLUSION: using the gold standard of fixed histological endarterectomy specimen, the results indicate that transverse image obtained with colour B-mode imaging is more appropriate in determining the degree of stenosis.

Blood Flow Velocity↗

Adult ontogeny of rat working memory of social interactions.

BACKGROUND: Social memory has features that may make it uniquely appropriate for studying normal aging. We used a cross-section experimental design with an animal model to survey the lifetime adult ontogeny of memory of a brief social interaction. METHODS: Groups of healthy adult male rats representing young adulthood (5 months), middle age (10 months), or old age (19-27 months) were tested weekly over a month in two paradigms. Basic social memory and social interference memory were quantified by differences between investigation times of a juvenile rat during a 5-min interaction (acquisition trial) and a second exposure (recall testing), with interexposure intervals (IEI) ranging from 15 min to 24 h. RESULTS: Although basic social memory of all age groups was similar at the brief or longer IEI, there were memory declines at intermediate IEI delays in older males, especially the oldest groups. Decrements to working memory appeared as early as middle-age when an unfamiliar juvenile was inserted between acquisition and recall testing. Nonetheless, our healthy old animals retained a robust ability to recall identity of a conspecific that a minute by minute comparison suggested involves similar behavioral means of gathering social information. CONCLUSIONS: Normative aging of working social memory in male rats can be characterized as being more fragile, beginning at middle age but without significant further decline until near the end of the life span. Functional impact of these age-dependent changes in social memory, on the other hand, may be minimal for all but the very oldest animals in the social group.

Aging↗

Systemic sclerosis (scleroderma) in two iron ore mines.

Six males with systemic sclerosis were observed in the work forces of two iron ore mines. The usual spectrum of clinical features encountered in systemic sclerosis patients were present. Histologic examination of pulmonary tissue was performed on three of the cases and showed features of both silicosis and scleroderma but to different degrees and stages of development. Exposure to high levels of silica-containing dusts had occurred in all six cases.

Adult↗

Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study.

BACKGROUND AND PURPOSE: B-mode ultrasound is a noninvasive method of examining the walls of peripheral arteries and provides measures of the intima-media thickness (IMT) at various sites (common carotid artery, bifurcation, internal carotid artery) and of plaques that may indicate early presymptomatic disease. The reported associations between cardiovascular risk factors, clinical disease, IMT, and plaques are inconsistent. We sought to clarify these relationships in a large, representative sample of men and women living in 2 British towns. METHODS: The study was performed during 1996 in 2 towns (Dewsbury and Maidstone) of the British Regional Heart Study that have an approximately 2-fold difference in coronary heart disease risk. The male participants were drawn from the British Regional Heart Study and were recruited in 1978-1980 and form part of a national cohort study of 7735 men. A random sample of women of similar age to the men (55 to 77 years) was also selected from the age-sex register of the general practices used in the original survey. A wide range of data on social, lifestyle, and physiological factors, cardiovascular disease symptoms, and diagnoses was collected. Measures of right and left common carotid IMT (IMTcca) and bifurcation IMT (IMTbif) were made, and the arteries were examined for plaques 1.5 cm above and below the flow divider. RESULTS: Totals of 425 men and 375 women were surveyed (mean age, 66 years; range, 56 to 77 years). The mean (SD) IMTcca observed were 0. 84 (0.21) and 0.75 (0.16) mm for men and women, respectively. The mean (SD) IMTbif were 1.69 (0.61) and 1.50 (0.77) mm for men and women, respectively. The correlation between IMTcca and IMTbif was similar in men (r=0.36) and women (r=0.38). There were no differences in mean IMTcca or IMTbif between the 2 towns. Carotid plaques were very common, affecting 57% (n=239) of men and 58% (n=211) of women. Severe carotid plaques with flow disturbance were rare, affecting 9 men (2%) and 6 women (1.6%). Plaques increased in prevalence with age, affecting 49% men and 39% of women aged <60 years and 65% and 75% of men and women, respectively, aged >70 years. Plaques were most common among men in Dewsbury (79% affected) and least common among men in Maidstone (34% affected). IMTcca showed a different pattern of association with cardiovascular risk factors from IMTbif and was associated with age, SBP, and FEV1 but not with social, lifestyle, or other physiological risk factors. IMTbif and carotid plaques were associated with smoking, manual social class, and plasma fibrinogen. IMTbif and carotid plaques were associated with symptoms and diagnoses of cardiovascular diseases. IMTbif associations with cardiovascular risk factors and prevalent cardiovascular disease appeared to be explained by the presence of plaques in regression models and in analyses stratified by plaque status. CONCLUSIONS: IMTcca, IMTbif, and plaque are correlated with each other but show differing patterns of association with risk factors and prevalent disease. IMTcca is strongly associated with risk factors for stroke and with prevalent stroke, whereas IMTbif and plaque are more directly associated with ischemic heart disease risk factors and prevalent ischemic heart disease. Our analyses suggest that presence of plaque, rather than the thickness of IMTbif, appears to be the major criterion of high risk of disease, but confirmation of these findings in other populations and in prospective studies is required. The association of fibrinogen with plaque appears to be similar to its association with incident cardiovascular disease. Further work elucidating the composition of plaques using ultrasound imaging would be helpful, and more data, analyzed to distinguish plaque from IMTbif and IMTcca, are required to understand the significance of thicker IMT in the absence of plaque.

Age Distribution↗

Regulation of cell surface tissue transglutaminase: effects on matrix storage of latent transforming growth factor-beta binding protein-1.

Using a cytochemical approach, we examined the role of tissue transglutaminase (tTgase, Type II) in the incorporation of latent TGF-beta binding protein-1 (LTBP-1) in the extracellular matrix of Swiss 3T3 fibroblasts in which tTgase expression can be modulated through a tetracycline-controlled promoter. Increased tTgase expression led to an increased rate of LTBP-1 deposition in the matrix, which was accompanied by an increased pool of deoxycholate-insoluble fibronectin. Matrix deposition of LTBP-1 could also be reduced by the competitive amine substrate putrescine. Immunolocalization at the fluorescence and electron microscopic level showed that extracellular tTgase is located at the basal and apical surfaces of cells and at cell-cell contacts, and that LTBP-1 is co-distributed with cell surface tTgase, suggesting an early contribution of tTgase to the binding of LTBP-1 to matrix proteins. LTPB-1 was also found to co-localize with both intracellular and extracellular fibronectin, and increased immunoreactivity for LTBP-1 and fibronectin was found in large molecular weight polymers in the deoxycholate-insoluble matrix of fibroblasts overexpressing tTgase. We conclude that regulation of tTgase expression is important for controlling matrix storage of latent TGF-beta1 complexes and that fibronectin may be one extracellular component to which LTBP-1 is crosslinked when LTBP-1 and tTgase interact at the cell surface. (J Histochem Cytochem 47:1417-1432, 1999)

3T3 Cells↗