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M F Fillinger

Publications and source records attributed to M F Fillinger.

33 records · Page 2Linked to original sources
PubMed1997

Cost-effective use of the noninvasive vascular laboratory: potential trends related to increased economic pressures.

Because noninvasive studies typically are used in the place of more costly and more invasive technologies, the vascular laboratory remains a key element in the care of vascular patients. We have examined an established model for vascular laboratory cost/efficiency analysis in light of trends toward decreased reimbursement. In this study, we review potential strategies for more cost-effective laboratory management, including the impact of part-time technologists, staggered work hours, and equipment allocation. As the need to decrease costs continues, the greatest pressure will be felt in the areas of personnel and equipment costs. Diligence and dedication will be required to prevent these pressures from creating a negative impact on the quality of studies, patient access to care, and technological innovation.

Cost-Benefit Analysis↗
PubMed1996

Endothelial cell modulation of smooth muscle cell morphology and organizational growth pattern.

Intimal hyperplasia is characterized by smooth muscle cell (SMC) dedifferentiation from a contractile to a synthetic phenotype prior to migration and proliferation. Regulatory mechanisms controlling SMC phenotype are not well known. This study examined the effect of endothelial cells (ECs) on SMC morphology in coculture. Subcultured bovine ECs and SMCs were plated on opposite sides of a 13 microns thick, semipermeable membrane (0.45 micron pores, Cyclopore) to allow potential humoral and cellular cross-membrane communication. SMCs were studied (5 wells/group) in coculture opposite confluent ECs (EC/SMC) and alone (SMC controls). After 4 days of culture in Dulbecco's modified Eagle medium/2.5% calf serum, SMCs were harvested. The ratio of protein/DNA was measured as an index of SMC hypertrophy (synthetic SMC phenotype). SMCs were examined with light and scanning electron microscopy to evaluate cell surface area, cellular morphology, and macroscopic growth characteristics. Flow cytometry was used to determine the cellular RNA/DNA ratio. SMC control cultures had a significantly greater protein-to-DNA content than SMCs cocultured with ECs (175 +/- 9 vs. 115 +/- 7 micrograms protein/micrograms DNA; p < 0.001). SMC control cultures also had 6.5 times greater cell surface area (5.8 +/- 0.3 x 10(3) microns2) than cocultured SMCs (0.9 +/- 0.1; p < 0.001). In SMC control cultures, SMC hypertrophy and rapid "hill and valley" formation were observed. In contrast, SMCs from the EC/SMC group exhibited a more spindle-shaped, contractile-appearing phenotype with more uniform, evenly distributed cells and no hill and valley formation. SMC control cultures also had a higher RNA/DNA ratio. Thus the presence of confluent ECs substantially altered the morphology and growth characteristic normally observed for SMCs in vitro. This coculture system provides a model to further study EC-SMC interaction, which could have important in vivo consequences.

Animals↗
PubMed1996

Endothelial cells modulate smooth muscle cell morphology by inhibition of transforming growth factor-beta 1 activation.

BACKGROUND: We have previously demonstrated in a coculture model that endothelial cells (ECs) exert regulatory control over smooth muscle cell (SMC) morphology. This study was performed to test the hypothesis that ECs inhibit transforming growth factor-beta 2 (TGF-beta 1) activation through the release of plasminogen activator inhibitor (PAI-1). METHODS: Bovine SMCs were cultured on a thin, semipermeable membrane, either alone or opposite ECs in coculture (SMC/EC). Conditioned media and cell lysates at 1, 5, and 21 days were assayed for TGF-beta 1 and PAI-1 by enzyme-linked immunoabsorbent assay. Cell proliferation rates, protein, and DNA content were measured and compared with SMC morphology. RESULTS: Activation of TGF-beta 1 was significantly decreased (1.2% versus 18.9% active TGF-beta 1 p < 0.05) and PAI-1 was increased (659 pg/ml versus 343 pg/ml p < 0.05) in SMC/EC medium on day 1, compared with the medium of SMC alone. Significantly higher levels of PAI-1 were measured in cell lysates of cocultured ECs (128 pg/micrograms DNA) than in cocultured SMCs (5.8 pg/micrograms DNA, p < 0.05). SMC/EC coculture prevented the SMC hill-and-valley growth morphology seen in SMCs cultured alone. CONCLUSIONS: In a model designed to study SMC/EC interactions, it was seen that ECs can alter growth characteristics of SMCs by producing PAI-1, which interferes with the plasminogen pathway of TGF-beta 1 activation. This suggests that reduced EC PAI-1 production could play a role in alteration of SMC phenotype in vivo.

Animals↗
PubMed1996

Carotid duplex criteria for a 60% or greater angiographic stenosis: variation according to equipment.

PURPOSE: The purpose of this study was to evaluate the carotid duplex criteria for a > or = 60% angiographic internal carotid artery (ICA) stenosis and the degree of variation among duplex scanners. METHODS: Carotid duplex criteria for a > or = 60% angiographic stenosis were evaluated in two ICAVL-accredited vascular laboratories with different brands of duplex scanners (Siemens-Quantum and Diasonics in Laboratory A, ATL and Diasonics in Laboratory B). Analysis was performed for 360 carotid bifurcations in 180 consecutive patients who had concurrent angiographic and duplex evaluation. Blinded angiogram evaluation was performed with precision electronic calipers on magnified views, with stenosis calculated by criteria of the Asymptomatic Carotid Atherosclerosis Study and the North American Symptomatic Carotid Endarterectomy Trial. Duplex data included internal carotid artery peak systolic velocity (ICA PSV), ICA end-diastolic velocity, and the ratio of ICA PSV to common carotid artery (CCA) PSV (ICA/CCA ratio). RESULTS: The most accurate determination of a > or = 60% ICA stenosis was obtained with ICA/CCA ratio and ICA PSV, but the optimal threshold differed for all four scanners. The optimal ICA/CCA ratio varied from 2.6 to 3.3, and the optimal ICA PSV varied from 190 to 240 cm/sec. All four scanners produced criteria that give a positive predictive value > 90% while maintaining accuracy at > or = 90%. Logarithmic transformation of duplex variables created a linear relationship between duplex values and angiographic stenosis, allowing statistical evaluation of scanner operating characteristics by linear regression analysis and analysis of covariance. This analysis revealed that the mathematic equation relating duplex values with angiographic percent stenosis was statistically different for one of the four scanners (p < 0.05). Scanner differences did not appear to be due to technologists, because the regression lines were nearly identical for the two Diasonics scanners despite use by different technologists. Ignoring the significant difference in operating characteristics for one of the four scanners would result in a mean error for predicting a 60% stenosis of 14% to 18% (equating a 46% or 78% stenosis with a 60% stenosis). CONCLUSIONS: We conclude that the correlation of duplex data with angiographic percent stenosis and the duplex criteria for a > or = 60% stenosis are machine-specific. Regression analysis can determine whether apparent differences are due to chance or significant differences in scanner characteristics. Future studies should include regression analysis according to equipment type.

Aged↗
PubMed1994

Effect of endothelial cells and transforming growth factor-beta 1 on cultured vascular smooth muscle cell growth patterns.

Smooth muscle cells (SMCs) cultured alone exhibit characteristic "hill and valley" macroscopic growth features. We studied smooth muscle cells cocultured with endothelial cells and the effect of transforming growth factor beta 1 on smooth muscle cells: Bovine smooth muscle cells were plated on 13 microns-thick semipermeable membranes. Smooth muscle cells were cultured either alone (in Dulbecco's Modified Eagles Media/2.5% calf serum, four wells/group); with neutralizing anti-transforming growth factor-beta 1 antibody (10 micrograms/ml); with the protease inhibitor aprotinin (prevents plasmin-mediated activation of transforming growth factor-beta 1, 200 mg/ml); or in the presence of confluent bovine endothelial cells cocultured on the opposite side of the membrane before plating smooth muscle cells. After 72 hours in culture smooth muscle cell organizational growth characteristics were examined by light microscopy. Hill and valley formation by smooth muscle cells resulted in areas of the membrane becoming devoid of smooth muscle cells, whereas other areas developed multilayered densely populated smooth muscle cells. Computed planimetry was used to measure this bare surface area to quantitate the extent of hill and valley growth, which was compared between groups by analysis of variance. Smooth muscle cells cultured alone demonstrated prominent hill and valley formation with a bare surface area of 2.64 +/- 0.51 mm2. Smooth muscle cells exposed to transforming growth factor-beta 1 antibody had much less hill and valley formation (bare surface area 0.92 +/- 0.29, p < 0.01), whereas aprotinin virtually prevented hill and valley formation (bare surface area 0.0, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Vein adaptation to the hemodynamic environment of infrainguinal grafts.

PURPOSE: Although arteries appear to remodel in response to changes in hemodynamic parameters such as shear stress, little is known about functioning human vein grafts. This study was designed to explore diameter changes in human saphenous vein grafts after infrainguinal bypass. METHODS: We used duplex ultrasonography to measure hemodynamic variables that might affect the diameter of 48 in situ saphenous vein grafts during the first year after infrainguinal arterial bypass. Volumetric flow rate, average velocity, peak systolic velocity, and vein diameter in the proximal and distal thirds of these grafts were each measured at 1 week and at 3, 6, and 12 months after operation. Veins were divided into three groups based on initial size (1 week after bypass) in the below-knee segment: small, < 3.5 mm diameter; medium, 3.5 to 4 mm diameter; and large, > 4 mm diameter. RESULTS: Distal vein diameters at 1 week for small, medium, and large grafts were 2.9 +/- 0.1, 3.7 +/- 0.1, and 4.3 +/- 0.1 mm, respectively (p < 0.001), but by 12 months these diameters were 3.6 +/- 0.2, 3.8 +/- 0.2, and 3.9 +/- 0.2 mm, respectively (p = 0.54). Large veins decreased in diameter, whereas small veins increased in diameter, as confirmed by linear regression of percent change in diameter versus initial vein graft diameter (r = -0.62, p < 0.001). Volumetric flow rate, peak systolic velocity, and shear stress also tended to approach uniform values over time. Of the hemodynamic variables studied, the best predictor of diameter change was shear stress (linear regression of percent change in diameter vs shear stress, r = 0.67, p < 0.001). Veins with a diameter increase greater than 10% over time had significantly higher initial shear stress than veins with a diameter decrease greater than 10% over time (28.6 +/- 3.8 vs 13.1 +/- 1.8 dynes/cm2, p < 0.01), whereas initial volumetric flow rates in these two groups were similar (135 +/- 23 vs 130 +/- 15 ml/min). CONCLUSIONS: Infrainguinal in situ vein graft diameter, volume flow rate, peak systolic velocity, and shear stress all tend to stabilize at uniform values regardless of the initial vein graft diameter. Of the hemodynamic variables studied, shear stress is most strongly associated with the change in diameter over time. Thus human saphenous vein appears to be capable of adapting to its hemodynamic environment after arterial grafting by modulating diameter to normalize shear stress.

Adaptation, Physiological↗
PubMed1993

Vascular laboratory cost analysis and the impact of the Resource-Based Relative Value Scale payment system.

PURPOSE: This study compares the actual cost of performing noninvasive laboratory studies with reimbursement under the previous Medicare Part B system and under current resource-based relative value scale (RBRVS) guidelines. METHODS: We calculated the cost to operate our own laboratory and estimated national costs for small- and large-model laboratories. Reimbursement under Medicare Part B was calculated for each Current Procedural Terminology code from average Medicare reimbursement allowances and national case volumes in 1990, which were obtained from the Health Care Financing Administration. All data were expressed as dollars per hour of study time to allow universal comparison of costs and reimbursement among tests that require differing lengths of time for completion. RESULTS: Technical costs for laboratory time ranged from $143 to $173 per study hour. The largest components of laboratory expenses were fixed costs, including personnel (37% to 46%), equipment (30% to 42%), and facilities (6% to 8%). Variable costs such as billing (9% to 10%) accounted for most of the remainder. More efficient allocation of equipment resulted in lower costs in large laboratories, whereas continued use of depreciated equipment resulted in lower costs in our own laboratory ($127/hr). CONCLUSIONS: We project that technical reimbursement under RBRVS will be $82/hr nationally and $80/hr locally, whereas global reimbursement (technical plus professional) will be $116/hr and $110/hr, respectively. On the basis of 1990 case volumes, the RBRVS system will decrease national global reimbursement by at least 35% compared with the previous Medicare Part B system. Under the new system, technical reimbursement will decrease by an estimated 27% nationally, whereas professional reimbursement will decrease by 52%. Revenue under RBRVS will not meet the cost to perform studies either nationally or locally. Technical reimbursement is 37% to 54% below actual technical costs, and even global reimbursement is 13% to 34% less than technical costs. Our analysis revealed that costs will exceed reimbursement despite maximization of operating efficiency. This analysis applies to outpatients only. A case mix including inpatients will further reduce reimbursement, because only the professional component is allowed. By setting reimbursement of vascular laboratories below actual costs, the new RBRVS system may ultimately reduce the availability of noninvasive vascular testing for elderly patients.

Computer Simulation↗
PubMed1993

Volumetric blood flow measurement with color Doppler ultrasonography: the importance of visual clues.

Volumetric flow rates were obtained in an in vivo canine pulsatile flow model using color Doppler ultrasonography (CDUS) and timed collection (TC) over a range which included laminar and turbulent flow. CDUS demonstrated increasing flow disturbance as flow rates increased, with effects on velocity profile, diameter measurements, and flow symmetry. Data comparing CDUS and TC showed marked differences in laminar flow (regression: slope = 1.02; r2 = 0.93; mean error, 11%) and nonlaminar flow (slope = 0.53; r2 = 0.78; mean error, 26%). Assigning the angle of insonation precisely was crucial to measurement accuracy. CDUS quantitates volumetric blood flow with a reasonable degree of accuracy under laminar flow conditions. Visual clues provided by CDUS can help avoid errors associated with deviations from laminar flow.

Animals↗
PubMed1993

Combined carotid endarterectomy and coronary artery bypass in a community hospital.

A study examining combined carotid endarterectomy and coronary artery bypass (CAB) outside the metropolitan or university hospital setting was performed. Over a 5-year period, 52 patients underwent carotid endarterectomy and CAB under a single anesthetic. Twenty-two patients (42%) had unstable angina and 23 (44%) had previous neurologic symptoms. There were two postoperative strokes (4%), one ipsilateral and one contralateral to the endarterectomy site. No ipsilateral neurologic events occurred after discharge (mean follow-up 25 months). There were four deaths (8%), all of which were cardiac related. Three of the four deaths were in patients with a recent history of congestive heart failure, a subgroup with a high mortality rate (three of seven; 43%). Over the same period, 2421 patients underwent CAB alone with stroke and mortality rates of 1.4 and 2.0% respectively, while 344 patients had carotid endarterectomy alone with stroke and mortality rates of 0.6 and 0.6% respectively. It is concluded that the combined procedure can be performed in a community setting with morbidity and mortality rates similar to those for major centers. Although stroke and mortality rates for the combined procedure were higher than those for the isolated operations, this group has a high incidence of cardiac symptoms, including unstable angina and congestive heart failure. Patients with recent congestive heart failure had the highest mortality rate of any subgroup and these patients should be carefully examined with regard to selection for the combined procedure.

Adult↗
PubMed1993

The effect of endothelial cell coculture on smooth muscle cell proliferation.

PURPOSE: Smooth muscle cell (SMC) growth kinetics are often studied in culture without consideration of endothelial cell (EC) influences that occur in vivo. This study examined the time-dependent effect of EC on SMC in a new type of coculture system. METHODS: Bovine aortic EC and SMC were harvested from fresh specimens, grown to four passages from primary cultures, and plated on either side of a porous 13 microns thick polyethylene terephthalate membrane. SMC were studied in coculture opposite from confluent EC (EC/SMC). Controls included SMC cultured opposite SMC (SMC/SMC) or SMC alone (with no cells on the opposite side of the membrane, phi/SMC). After cocultures were established, SMC were harvested from 1 to 4 days after release from growth arrest (n = 5 cultures/day/group). SMC DNA and protein content and 3H-thymidine incorporation were measured in each group. SMC proliferation was indexed by 3H-thymidine incorporation per cellular DNA content. RESULTS: EC stimulated SMC proliferation 56% more than SMC/SMC cultures and 244% more than SMC alone on day 1 after growth arrest (p < 0.05). This effect decreased with time so that by day 4, EC seemed to inhibit SMC proliferation (49% less proliferation than SMC/SMC and 76% less than SMC alone, p < 0.05). SMC opposite EC had significantly less protein/DNA than control SMC, and they retained a thin, spindle shape compared with the hypertrophic appearance of SMC in the absence of EC. Electron microscopy revealed EC gap junctions and cytoplasmic projections from SMC of sufficient length to transverse the pores in the coculture membrane. CONCLUSIONS: This coculture method has several useful features, including an appropriate luminal/abluminal EC/SMC orientation, a short distance between the cell layers, the potential for cell-to-cell contact, and the ability to separate the cell types for assays. It is clear that EC markedly affect SMC proliferation, protein/DNA ratio, and structure in coculture with dynamic interactions occurring for at least 4 days. These effects must be considered when attempting to model in vivo phenomena in tissue culture.

Animals↗
PubMed1990

Does the end-to-end venous anastomosis offer a functional advantage over the end-to-side venous anastomosis in high-output arteriovenous grafts?

This study explores the hemodynamics, mechanics, and biologic response of end-to-end versus end-to-side venous anastomoses in a canine arteriovenous graft model. Femoral polytetrafluoroethylene grafts were implanted bilaterally in a paired fashion (n = 22). Detailed local hemodynamic measurements were made by use of color Doppler ultrasound imaging at 1, 4, 8, and 12 weeks after implant. Measurements included volumetric flow rate and Doppler-derived spectral window (percent window) as a measure of turbulence. Amplitude and velocity of vessel wall movement were also measured. Volume of perivascular tissue vibration quantitated kinetic energy transfer through the vessel wall. Volumetric flow rate (end to end, 1013 +/- 70 ml/min; end to side, 1015 +/- 72 ml/min), percent window (end to end, 6.6% +/- 0.6%, end to side, 5.6% +/- 0.4%) and volume of perivascular tissue vibration (end to end, 19.6 +/- 1.2 ml, end to side, 16.3 +/- 1.8 ml) were statistically equivalent in the two graft types (end to end vs end to side p greater than 0.05). Both graft types developed venous intimal-medial thickening of a similar magnitude: end to end, 0.35 +/- 0.05 mm, end to side, 0.43 +/- 0.09 mm, normal vein 0.070 +/- 0.004 mm (analysis of variance [ANOVA] p less than 0.001, p less than 0.01 for end to end or end to side vs control, end to end vs end to side p greater than 0.05 by Student-Newman-Keuls test). The best correlations with venous intimal-medial thickening were obtained from inverse percent window (r = 0.84, p less than 0.001) and volume of perivascular tissue vibration (r = 0.68, p less than 0.001). In the end to end configuration the relative amplitude of venous wall movement decreased, and the relative velocity of wall motion increased over time. We conclude that in the circumstances of this high flow arteriovenous graft model the end-to-end venous anastomosis does not significantly differ from the end-to-side venous anastomosis in terms of flow stability, turbulence, or kinetic energy transfer. The magnitude of the hyperplastic response is statistically equivalent for the two anastomotic types, but the pattern is somewhat different, possibly providing evidence for differences in stress distribution. Differences in the relative amplitude and velocity of vessel wall movement suggest that anastomotic geometry may affect the way in which kinetic energy is dissipated at the graft/vessel interface.

Animals↗
PubMed1990

Graft geometry and venous intimal-medial hyperplasia in arteriovenous loop grafts.

This study explores graft geometry and hemodynamics in a reproducible canine arteriovenous loop graft model of intimal-medial hyperplasia. Untapered 6 mm diameter polytetrafluoroethylene grafts (n = 10) were paired with 4 to 7 mm taper (n = 5) or 7 to 4 mm taper (n = 5) grafts for a 12-week period. Several hemodynamic variables were assessed at multiple locations, and venous intimal-medial thickness was measured at locations corresponding to the hemodynamic measurements. Color Doppler imaging demonstrated energy transfer out of the vessel in the form of perivascular tissue vibration. This was quantitated by the distance required for Doppler signal attenuation or volume of the detected vibration signal. Differences among graft types were noted for pressure, flow velocity, tissue vibration, and venous intimal-medial thickness. Hyperplasia was significantly decreased in 4 to 7 mm taper grafts. Stepwise deletion regression indicated volume of the vibration signal had a better correlation with venous intimal-medial thickness than any other variable (r 0.9, p less than 0.001). We conclude that graft geometry can have a significant impact on hemodynamic factors and venous intimal-medial hyperplasia in arteriovenous loop grafts. Flow disturbances appear to cause energy transfer through the vessel wall and into perivascular tissue. Kinetic energy transfer in the form of perivascular tissue vibration was quantitated in vivo and correlates strongly with venous intimal-medial thickness.

Animals↗
PubMed1989

Beneficial effects of banding on venous intimal-medial hyperplasia in arteriovenous loop grafts.

Local hemodynamics were modified in a canine arteriovenous loop graft model by placing a flow-limiting band on femoral polytetrafluoroethylene (PTFE) grafts. Banded and unbanded grafts were implanted in a paired fashion. Hemodynamic studies included Reynolds number and phonoangiography as measures of turbulence. Intimal-medial thickness was measured 8 weeks after implantation. Reduction of the volumetric flow rate by 50 percent resulted in significant changes in flow velocity, flow pulsatility, pressure, and turbulence at the venous anastomosis. Hyperplastic lesions developed in a reproducible manner at the venous anastomosis of the unbanded but not the banded grafts, as evidenced by combined intimal-medial thickness measurements: unbanded grafts 0.68 +/- 0.13 mm (p less than 0.01 versus control), banded grafts 0.25 +/- 0.03 mm (p greater than 0.05 versus control). Stepwise regression analysis indicated Reynolds number had the best correlation with the development of hyperplasia (r = 0.915, p less than 0.005), this being the first time this correlation has been quantitatively determined. We conclude that flow disturbance or turbulence is a major factor in the development of venous intimal-medial hyperplasia in arteriovenous loop grafts.

Animals↗