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Biomedical subjects

G Steg

Publications and source records attributed to G Steg.

At least 19 recordsLinked to original sources

Load force during manual transport in Parkinson's disease.

OBJECTIVES: To search for a physiological method for the measurement of upper extremity dexterity during activities of daily life in Parkinson's disease (PD). MATERIALS AND METHODS: We examined load force output during manual transport in seven patients with PD and 10 healthy controls. PD patients were measured in both the non-medicated and medicated states. The test movement included two continuous sub-movements: an upward-forward transport of an object from the table to the stand, and a downward-backward transport of the object from the stand to the table. Hand movements were recorded using an optoelectronic camera, and load force was measured using a force sensor installed in the test object. RESULTS: Compared with the controls, PD patients had a different pattern of load force output characterized by slower force development and release, lower peak force, and less dynamic force generation during movement. After medication, the speed of force development and the level of peak force increased in the patients. CONCLUSIONS: These findings suggest that PD impairs the production of preprogrammed movements. The movements observed in the PD patients may result from compensatory strategies relying more on feedback mechanisms.

Arm↗

Reperfusion syndrome: relationship of coronary blood flow reserve to left ventricular function and infarct size.

OBJECTIVES: We tested the hypothesis that the reperfusion syndrome (RS), defined as an additional elevation of the ST segment upon reperfusion, may be a marker of microcirculatory reperfusion injury during acute myocardial infarction (AMI). BACKGROUND: The pathophysiology of the RS is unknown, and its prognostic implications are controversial. METHODS: Twenty-one patients with an anterior AMI treated < or =12 h after onset by primary coronary angioplasty (PTCA) were studied. Coronary velocity reserve (CVR), an index of microcirculatory function, was measured using a Doppler guidewire. Left ventricular (LV) ejection fraction, infarct size (percent defect) and LV end-systolic volume index (LVESVi) were evaluated by radionuclide ventriculography, 201T1 single-photon emission computed tomography and contrast ventriculography, respectively. RESULTS: Baseline ST elevation and pain-to-TIMI 3 time were similar in patients with and without RS. Patients with RS (10/21) had a lower post-PTCA CVR than patients without RS (median [95% confidence interval]: 1.2 [1-1.3] vs. 1.6 [1.5-1.7], p < 0.005). Even though predischarge CVR was similar in the two groups, infarct size at six weeks (26 [21 to 37] vs. 14 [10-17]% 201T1 defect, p = 0.001) and predischarge LVESVi (45% [40 to 52] vs. 30% [29 to 38] mL/m2, p = 0.001) were larger, and LV ejection fraction at six weeks (40% [37 to 46] vs. 55% [50 to 60], p = 0.004) was lower in patients with RS than in patients without RS. CONCLUSIONS: Patients with RS during primary PTCA for an anterior AMI have a transiently lower CVR than patients without RS, but sustained LV dysfunction and larger infarct size, suggesting that RS is a marker of microcirculatory reperfusion injury.

Aged↗

The ENACT study: a pan-European survey of acute coronary syndromes. European Network for Acute Coronary Treatment.

AIM: The European Network for Acute Coronary Treatment (ENACT) study was designed to collect prospective information across Europe on the relative frequency, diagnosis and management of the whole spectrum of acute coronary syndromes. METHODS: Cardiologists, who were respondents to mailings sent out to 17 European countries with the target of reaching one centre per million inhabitants, completed a prospective patient record, each physician providing information on 10 consecutive patients with a working diagnosis on admission of acute coronary syndrome, and a questionnaire. RESULTS: A total of 390 responses were received (0.91/10(6)population) with data on 3092 patients in 29 countries. The patient population comprised 1431 (46%) with an initial working diagnosis of unstable angina/non-ST-segment elevation myocardial infarction, 1205 (39%) with myocardial infarction and 445 (14%) with suspected acute coronary syndrome. The ratio of unstable angina to myocardial infarction was 1.2:1 and this was similar across Europe. An initial diagnosis of myocardial infarction was more likely to be confirmed than unstable angina or suspected acute coronary syndrome. There were wide variations in the rates of angiography and percutaneous coronary intervention across Europe. Most unstable angina patients received aspirin, nitrates and heparin (unfractionated heparin 44% intravenous, 16% subcutaneous; low-molecular-weight heparin 50%). Overall, 50% of unstable angina patients and 34% of myocardial infarction patients received low-molecular-weight heparin and 6% and 8% respectively received a glycoprotein IIb/IIIa inhibitor, but there were large inter-country differences. There were also national differences in the use of calcium antagonists, angiotensin-converting enzyme inhibitors and beta-blockers. CONCLUSION: The ENACT study provides robust data, for the first time, on the relative frequency of unstable angina and acute myocardial infarction across Europe. It provides insight into differences in management across Europe and a reference benchmark of current treatment.

Acute Disease↗

Relationship between resting 201Tl reverse redistribution, microvascular perfusion, and functional recovery in acute myocardial infarction.

UNLABELLED: 201TI reverse redistribution is a common finding early after reperfusion therapy for myocardial infarction. Its mechanism and clinical implications remain unclear. The aim of this study was to clarify the relationships between reverse redistribution, microvascular perfusion, and myocardial viability. METHODS: Resting, 10-min-postinjection, and redistribution 201TI data obtained for 33 patients 8 and 42 d after the onset of acute myocardial infarction were compared with echocardiographic wall motion measured acutely and on day 42. Microvascular perfusion was assessed by myocardial contrast echocardiography performed 10 min after restoration of complete patency of the infarct artery. RESULTS: Marked significant reverse redistribution was found on day 8 (absolute change, 7.5%+/-7.9% of the 10-min-postinjection defect size; P<5x0.000001) and significantly decreased on day 42 (2.7%+/-6.8%; P = 0.004 between days 8 and 42). The 10-min-postinjection defect size best predicted the final infarct size on day 42 and was closely related to microvascular perfusion. Patients with adequate reperfusion had a smaller postinjection defect on day 8 (21.1%+/-14.6%) and a larger reverse redistribution (10.2%+/-6.1%) than did patients with no reflow (35.3%+/-13% and 3.2%+/-9.2%, respectively; P<0.04 for both). CONCLUSION: Reverse redistribution was marked early after myocardial infarction in patients with complete patency of the infarct artery and decreased in subsequent weeks. Reverse redistribution was associated with restoration of adequate microvascular reperfusion and with myocardial salvage and viability. The early postinjection scans on day 8 were the relevant images for assessing myocardial salvage and predicting wall motion recovery.

Coronary Circulation↗

Involvement of the endothelin system in experimental critical hind limb ischemia.

BACKGROUND: Endothelin- (ET-1) is involved in the pathogenesis of several ischemic diseases. We investigated the hypotheses that ET-1 is involved in the pathogenesis of experimental critical hind limb ischemia and that ET-1 receptor antagonists have a protective effect. MATERIALS AND METHODS: Critical hind limb ischemia was achieved by exclusion of the femoral artery and embolization of collateral vessels in rats. The induction of endothelin system components by ischemia was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) (mRNAs) and immunoassay (peptides) in the plasma and ischemic muscles 5 hr (H5), 5 days (D5) and 14 days (D14) after ischemia. Two groups of rats received 100 mg/kg/day of either Bosentan, a mixed ET(A/B) receptor antagonist (n = 12), or LU 135252, a selective ET(A) receptor antagonist (n = 9), and a control group without treatment (n = 12) served as control. Muscle blood flow and ischemia were monitored in the ischemic limb by laser Doppler and phosphorylase activity, respectively. RESULTS: The procedure induced an 80% decrease in muscle blood flow and complete suppression of phosphorylase activity without necrosis. At day 14, the tissue blood flow remained reduced by 70% and phosphorylase activity was suppressed completely. There was up-regulation of preproendothelin-1, preproET-3, endothelin converting enzyme-1, and ET(A). ET(B) receptor mRNAs in ischemic muscle at day 5 and day 14 was accompanied by an increase in muscle concentration of ET-1 at day 5, without significant changes in plasma endothelin. Treatment with Bosentan and LU 135252 increased tissue blood flow and reduced muscle ischemia at day 14. CONCLUSIONS: Tissue production of ET- 1 is up-regulated in experimental critical hind limb ischemia. Inhibition of the endothelin system by a mixed ET(A/B) receptor antagonist may protect, at least in part, against muscle injury.

Animals↗

Catheter-based reperfusion of unprotected left main stenosis during an acute myocardial infarction (the ULTIMA experience). Unprotected Left Main Trunk Intervention Multi-center Assessment.

The ULTIMA registry was a prospective, multicenter, international registry of 277 patients who underwent percutaneous coronary interventions of unprotected left main trunk stenosis. The 40 patients who underwent an emergency percutaneous left main intervention for acute myocardial infarction are the focus of this study. We compared the results of primary angioplasty with primary stenting, characterizing both the short-term (in-hospital) and long-term (12-month) outcomes. Of the 40 patients, 23 underwent primary angioplasty, whereas 17 underwent primary stenting. The angiographic success rate was an 88% for the cohort. The in-hospital death or coronary artery bypass grafting rate was 65% for the entire group, 74% for the percutaneous transluminal coronary angioplasty group (PTCA), and 53% for the stent group (p = 0.2). The in-hospital death rate was 55% for the entire cohort, 70% for the PTCA group, and 35% for the stent group (p = 0.1). The 12-month rate of death or bypass surgery was 83% and 58% for the PTCA and stent groups, respectively (p = 0.047). The 12-month survival rate was 35% and 53% for the PTCA and stent groups, respectively (p = 0.18). Bypass surgery was required in 6 patients in the PTCA group and 2 patients in the stent group (p = 0.07). Patients undergoing percutaneous interventions for unprotected left main myocardial stenosis during an acute myocardial infarction are critically ill; an initial percutaneous revascularization approach appears feasible and may be the preferred revascularization strategy. Primary stenting was associated with improved clinical outcomes.

Aged↗

NC100100, a new echo contrast agent for the assessment of myocardial perfusion--safety and comparison with technetium-99m sestamibi single-photon emission computed tomography in a randomized multicenter study.

BACKGROUND AND HYPOTHESIS: Myocardial contrast echocardiography using second-generation agents has been proposed to study myocardial perfusion. A placebo-controlled, multicenter trial was conducted to evaluate the safety, optimal dose, and imaging mode for NC100100, a novel intravenous second-generation echo contrast agent, and to compare this technique with technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT). METHODS: In a placebo-controlled, multicenter trial, 203 patients with myocardial infarction > 5 days and < 1 year previously underwent rest SPECT and MCE. Fundamental and harmonic imaging modes combined with continuous and electrocardiogram-- (ECG) triggered intermittent imaging were used. Six dose groups (0.030, 0.100, and 0.300 microliter particles/kg body weight for fundamental imaging; and 0.006, 0.030, and 0.150 microliter particles/kg body weight for harmonic imaging) were tested. A saline group was also included. Safety was followed for 72 h after contrast injection. Myocardial perfusion by MCE was compared with myocardial rest perfusion imaging using MIBI as a tracer. RESULTS: NC100100 was well tolerated. No serious adverse events or deaths occurred. No clinically relevant changes in vital signs, laboratory parameters, and ECG recordings were noted. There was no significant difference between adverse events in the NC100100 (25.7%) and in the placebo group (17.9%, p = 0.3). Intermittent harmonic imaging using the intermediate dose was superior to all other modalities, allowing the assessment of perfusion in 76% of all segments. Eighty segments (96%) with normal perfusion by SPECT imaging also showed myocardial perfusion with MCE. However, a substantial percentage of segments (61-80%) with perfusion defects by SPECT imaging also showed opacification by MCE. This resulted in an overall agreement of 66-81% and a high specificity (80-96%), but in low sensitivity (20-39%) of MCE for the detection of perfusion defects. CONCLUSION: NC100100 is safe in patients with myocardial infarction. Intermittent harmonic imaging with a dose of 0.03 microliter particles/kg body weight can be proposed as the best imaging protocol. Myocardial contrast echocardiography with NC 100100 provides perfusion information in approximately 76% of segments and results in myocardial opacification in the vast majority of segments with normal perfusion as assessed by SPECT. Although the discrepancies between MCE and SPECT with regard to the definition of perfusion defects requires further investigation, MCE with NC 100100 is a promising technique for the noninvasive assessment of myocardial perfusion.

Aged↗

Percutaneous delivery of the gax gene inhibits vessel stenosis in a rabbit model of balloon angioplasty.

OBJECTIVES: The expression of gax, an anti-proliferative homeobox gene, is rapidly downregulated in vascular smooth muscle cells (VSMCs) following arterial injury. Here we performed percutaneous adenovirus-mediated gene transfer into the iliac arteries of normal rabbits using a channel balloon catheter to assess the effects of gax overexpression on neointima formation, lumen diameter, reendothelialization and functional vasomotion. METHODS: A channel balloon catheter was used to perform both the arterial injury and local gene delivery. In each animal both iliac arteries were randomly assigned to receive either an adenovirus expressing the gax gene (Ad-Gax) or the beta-galactosidase gene (Ad-beta gal). In a second group of animals arteries were randomly assigned to receive either Ad-beta gal or saline. RESULTS: At one month, angiography revealed 36% less luminal narrowing in the Ad-Gax-treated arteries relative to the Ad-beta gal-treated control arteries. Histological analysis revealed that the intimal/medial ratio (I/M) was reduced by 56% in the Ad-Gax group. Endothelium-dependent vasomotion was not affected by the gax gene transfer. In the second group, no statistically significant differences were found between the saline and the Ad-beta gal-treated vessels for any of these parameters. CONCLUSIONS: Percutaneous adenovirus delivery of the gax gene to rabbit iliac arteries following endothelial denudation and vessel wall injury reduces neointimal hyperplasia and luminal stenosis, but does not affect endothelium-dependent vasomotion. This study demonstrates that a VSMC transcription factor can potentially be utilized for the development of a molecular therapy for vascular disorders.

Adenoviridae↗

Optimal techniques for arterial gene transfer.

Cardiovascular gene therapy is becoming a clinical reality due to improved vectors, delivery systems and careful experimental validation studies. Nearly all cardiovascular diseases are amenable to gene therapy, but the optimal combination of vector, delivery system and therapeutic gene is likely to be unique to each application. Currently, the most efficient vectors available are replication-defective adenoviral vectors, but transgene expression is limited in time due to a strong immune response. Conversely, non-viral vectors or plasmid DNA may be used safely but have very limited efficiency. Percutaneous, catheter-based delivery is feasible for most applications. The ultimate issues that will decide of the future of gene therapy are safety of the transfer and delivery techniques as well as cost/effectiveness comparisons with alternative therapies, including local delivery of drugs, proteins and/or mechanical devices.

Arteries↗

Permanent Electronic Storage of Angiographic Images in the Catheterization Laboratory: High-Resolution and Real-Time Acquisition on Optical Laserdiscs.

The use of electronic ÒfilmlessÓ media for long-term archiving of coronary angiograms has been impeded by the problems of image storage and data transfer among institutions. Although long-term analogue storage of the images is presently feasible, and much less costly than digital storage, processing has been limited to a 625 lines video format, not optimal for high quality images. We developed a bi-directional 1249/625 lines converter, able to store and to replay high resolution (1249 lines) video images, from Component Record Video (CRV) Optical Laser (Analogue) Videodisks. Image quality and medical relevance were evaluated five ways: 1) Outside experts compared 593 static images stored on CRV discs to the same images stored in a high-resolution digital format blinded to source of image. The four experts found no visual or medical difference in 98% of evaluated images and minor differences in the remainder. The differences in the remaining images were not consistent among experts. 2) Two of the experts also compared the enhanced CRV optically stored image to the image obtained on simultaneously recorded 35mm cine film, and found the enhanced CRV stored image to be superior or similar, but never inferior to the film image. 3) 90 representatives from 63 outside institutions compared images from both a digital hard drive and the enhanced CRV optical (analogue) storage displayed at a Windows based digital workstation. During the test they were blinded as to the source of the images. The representatives found no difference in image resolution, quality, diagnostic accuracy, and medical relevance. 4) We evaluated quantitative coronary angiography (QCA) on standard coronary test phantoms using enhanced CRV stored images digitally processed. The correlation of the enhanced CRV image to the actual size of the phantom vessels was similar to the results obtained in the literature from digitally stored images. 5) 78 arterial measurements ranging 0.65 to 4.85 mm were evaluated both from the digital hard disc (D) and the CRV optical disc (CRV), using the same QCA analytical package. The correlation coefficient and the Standard Error of the Estimate between D and CRV values were respectively 0.997 and 0.076, no systematic over or underestimation occurred, and the mean variability was inferior to 0.1 mm. CONCLUSION: High-Resolution CRV-optical storage represents a cost-effective solution for excellent image quality equivalent to digitally stored images, permitting permanent electronic archiving inside the cath-lab, and allowing digital image processing and digital image communication.

Journal Article↗

Perspectives of arterial gene therapy for the prevention of restenosis.

Restenosis remains the main limitation of interventional cardiology. Restenosis is an important target for gene therapy since it is frequent (30% of patients), costly (estimated $2 billion annually), refractory to all pharmacological therapies, and related, at least in part, to smooth muscle cell proliferation which is an inviting target for antiproliferative molecular strategies. Because cell division is ultimately controlled by intranuclear events, the protein product of genes selected for their antiproliferative effects usually remains inside the cells. Consequently, the transfer of growth-inhibitory genes needs to be efficient-i.e., involve a large proportion of smooth muscle cells populating the angioplasty site. To date, adenoviral vectors are, by far, the most efficient vectors to perform in vivo arterial gene delivery. These vectors, as well as others, have been recently used to demonstrate that therapeutic genes encoding cytolytic (thymidine kinase) or cytostatic (hypophosphorylatable retinoblastoma protein, endothelial nitric oxide synthase, gax, etc.) products successfully inhibit smooth muscle cell proliferation and related intimal hyperplasia. Despite substantial progress, major technical issues remain to be addressed before gene therapy is applied to clinical restenosis. First-generation recombinant adenoviruses evoke both cellular and humoral immune responses leading to local toxicity and transient gene expression. Moreover, the low efficiency of gene transfer to atherosclerotic arteries may further impair the biological effect of antiproliferative genes. Finally, restenosis is a multifactorial phenomenon in which intimal hyperplasia plays an important but not exclusive role. Prevention of constrictive remodeling should also be taken into account in an integrated genetic strategy to prevent restenosis.

Angioplasty, Balloon, Coronary↗

Nonlimited exercise test combined with high-dose dipyridamole for thallium-201 myocardial single-photon emission computed tomography in coronary artery disease.

Clinical, electrocardiographic, and thallium-201 single-photon emission computed tomography data were evaluated in 397 consecutive patients divided into 3 groups according to coronary hyperemic stimulation: 186 patients (group I; Ex) had maximal symptom-limited exercise ergometric stress testing, 93 patients (group II; Dip) had intravenous dipyridamole (0.7 to 0.8 mg/kg) stress testing, and 118 patients (group III; Dip+Ex) had dipyridamole (0.7 to 0.8 mg/kg) plus nonlimited (i.e., symptom-limited) exercise stress testing, achieving a maximal workload (mean +/- SD) of 102 +/- 37 W. Clinical tolerance was higher in Ex than in Dip groups (p < 0.01), and tended to be higher in Dip+Ex than in Dip groups (p = NS). Image quality--as judged by signal-to-noise ratios--was superior in Ex and Dip+Ex groups when compared with the Dip group (p < 0.01). Chest pain and electrocardiographic positivity were more frequent in the Dip+Ex group than in the Dip group (p < 0.05), despite more extensive coronary artery disease (CAD) in the Dip group; and reversible scintigraphic defects were more frequent in Dip+Ex versus Dip (p < 0.01) and in Ex versus Dip groups (p < 0.05) in patients with established CAD, as well as for the whole group. We conclude that, in patients unable to achieve 85% of their maximal predicted heart rate, the combination of high-dose dipyridamole plus nonlimited exercise stress testing is superior to dipyridamole stress testing alone, and comparable to maximal exercise testing.

Aged↗

Motor performance in normal pressure hydrocephalus assessed with an optoelectronic measurement technique.

The motor performance of 10 patients with normal pressure hydrocephalus (NPH) was clinically assessed with the aid of a computer assisted optoelectronic movement analysis system (Mac Reflex). We used the Posturo Locomotion Manual (PLM) method that gives a quantitative estimation of the postural, locomotor and manual performance in freely moving humans. Measurements were done before intervention, after CSF tap test and 3 months post installation of a CSF ventriculo peritoneal shunt. Comparison was made to data from 10 matched normal subjects and 10 patients with Parkinson's disease (PD). Shunt operation of the NPH patients and l-dopa treatment of the Parkinson patients improved the motor performance to a comparable degree. However, while the NPH patients improved the speed in the PLM test after the operation, the PD patients also improved the co-ordination after l-dopa treatment. This could indicate a different mechanism behind the improvement of motor performance in NPH and PD after intervention.

Aged↗

Motor function in 90-year olds measured by optoelectronic kinesiology and activities of daily living.

Computer-assisted optoelectronic movement analysis using a Posturo-Locomotor-Manual (PLM) test, and assessment with an ADL (Activities of Daily Living) scale were performed in 36 (18 women and 18 men) 90-year-old subjects as part of a larger study. In the PLM test, the subjects were asked to pick up an object placed on the floor, and carry it to a shelf at the height of their chin and at a distance of 150 cm from the starting position. In the ADL assessment, the subjects were classified as ADL-dependent or independent in each of 4 instrumental (cleaning, shopping, transport and cooking) and 5 personal activities (bathing, dressing, going to the toilet, transfer and feeding). ADL independence was defined as being able to perform ADL activities without assistance from another person. In this study, ADL-dependent subjects performed the PLM test considerably more slowly than the ADL-independent group. A correlation was found in females between poorer ADL performance and slower and less co-ordinated PLM test results. Particularly, the Postural and Locomotor phases representing lower limb mobility correlated to the ADL steps. In males, no such correlation was found, indicating that factors other than mobility were important for ADL performance in this group, e.g., cooking skills. The relationships between the PLM test and the ADL assessment estimating practical motor function could be an indication that the PLM test is not only a strict laboratory method, but also measures components of everyday motor activities. Combined use of optoelectronic measurements and ADL scales will improve measurements of motor performance in elderly persons.

Activities of Daily Living↗