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Biomedical subjects

J Megerman

Publications and source records attributed to J Megerman.

At least 19 recordsLinked to original sources

Development of a new approach to vascular access.

Three modes of access for hemodialysis (HD) have been available for over 20 years, the native arterial to venous (A-V) fistula, the polytetrafluorethylene (PTFE) graft fistula, and the central venous catheter. Overall, vascular access remains the single most costly source of morbidity and hospitalization in HD patients, indicating a severe need for improvement in this area. A significant contributor to access morbidity is the HD catheter, which protrudes through the skin and is subject to frequent infection. Subcutaneous ports have been developed to overcome this problem with catheters, but their application to HD has been elusive for 2 reasons, the use of a degradable septum that becomes vulnerable to infection with the use of large bore needles and the presence of a nonlinear flow path which produces damage to blood cells and stimulates thrombus formation at the required high flow rates. A new device, the Dialock, overcomes these objections by its use of a mechanical valve that maintains a linear flow path without directly contacting the blood. Results of a pilot study with 23 patients demonstrated a 78% cumulative survival rate after 1 year with a reduced rate of infection compared to catheters and sustained blood flow of 330 ml/min. The device represents a most promising advance in vascular access.

Arteriovenous Shunt, Surgical↗

Dialock: a new vascular access device for extracorporeal renal replacement therapy. Preliminary clinical results.

BACKGROUND: Vascular access, a vital tool for end-stage renal disease patients, remains a weak component of extracorporeal renal replacement therapy (RRT) and the first cause of morbidity. Permanent catheters proposed as an alternative to permanent AV fistulae are associated with a significant risk of infection. A subcutaneously implantable chamber connected to permanent catheter appears highly desirable to reduce such hazards. METHODS: Dialock, a metallic port-like valve device connected to permanent silicone twin catheters has been developed (Biolink Corp, Middleboro, MA, USA). After being implanted subcutaneously below the clavicle, Dialock provides a linear flow passage to two Silastic catheters placed in the right atrium via the right internal jugular vein. The valve is accessed percutaneously each dialysis session with needle cannulae that functionally convert the device into twin catheters. Interdialytic patency of the catheters is ensured by antithrombotic lock (heparin or low-molecular-weight heparin). RESULTS: Dialock was implanted in 10 ESRD patients (64+/-12 years) under general anaesthesia, with almost immediate use for HD. RRT consisted of three HD sessions per week lasting 4 h; 699 HD sessions were performed. Average duration of use was 5.7 patient-months (1.3-9.6 months). Patient satisfaction was evident in all cases. Three episodes of bacteraemia occurring in the early phase of the study were cured by appropriate antibiotics. No device was removed because of infection. Skin condition at the puncture sites has remained satisfactory in all patients. Nurse training for cannulating was brief (2-3 x). Effective blood flow was 307+/-3.3 ml/min, with a venous pressure of 195+/-39 mmHg and a recirculation rate of 6.7+/-0.8%. Effective Kt/V dp delivered was 1.36+/-0.03 with a nPCR of 1.20+/-0.005 g/kg/day. Haematoma and a small amount of bleeding of the skin puncture sites observed in the initial period of the study were effectively prevented by reducing heparin lock volume. CONCLUSIONS: The Dialock device offers a new and interesting vascular access alternative for haemodialysis bridging the 'gap' between permanent catheters and arteriovenous fistulae. Dialock's place in the vascular access strategy for haemodialysis patients deserves further long-term clinical studies.

Adult↗

Initial results of a new access device for hemodialysis technical note.

BACKGROUND: A new subcutaneous device (DIALOCKtrade mark) provides vascular access to patients who currently require hemodialysis (HD). The device consists of a port-like valve, implanted subcutaneously below the clavicle, which provides a linear flow passage to two catheters placed in the right atrium via the internal or external jugular vein. The valve is accessed percutaneously with needle-cannulas that functionally convert the device to twin catheters for connecting the patient to the HD lines. METHODS: The device was implanted in 10 outpatients under local anesthesia. Patients used the device during dialysis 3 times/week, and data were collected on blood flow, pressures, adverse events and patient and nurse satisfaction. RESULTS: The device was used for HD almost immediately (median 3 days after implantation) and functioned successfully for more than nine months (mean +/- SD 7.3 +/- 1.5) in all but one patient who died of unrelated causes after one month; there were >800 dialysis sessions total. Blood flows over 300 ml/min were consistently achieved (average 326 +/- 40) with venous and arterial pressures of 200 +/- 44 and -246 +/- 29 mm Hg, respectively. After 66 patient-months, condition of the needle puncture sites remained satisfactory. Five systemic infections occurred in four patients, producing 2.3 bacteremic episodes per 1000 patient-days. All resolved without the need for device removal. There were no infections at the puncture sites. Two patients required fibrin sheath stripping of their catheters, one whose heparin lock was not changed for 23 days (for reasons unrelated to the device). Patient and nurse acceptance was excellent. CONCLUSION: The device represents a positive improvement in the area of HD access.

Adult↗

The relationship between plasma insulin level, prostaglandin production by adipose tissue, and blood pressure in normal rats and rats with diabetes mellitus and diabetic ketoacidosis.

There is a correlation between circulating insulin levels and blood pressure over a wide range of insulin levels and in a variety of clinical conditions. Production of prostaglandin (PG)E(2) (PGE(2)) and prostacyclin (PGI(2)), two potent vasodilators, by adipose tissue is increased in severe insulin deficiency, eg, diabetic ketoacidosis (DKA), explaining the decreased peripheral vascular resistance in DKA. Conversely, decreased production of PGE(2) and PGI(2) may mediate the relationship between hyperinsulinemia and hypertension. Although insulin inhibits PG production in normal rat adipose tissue, PG production in adipose tissue from patients or experimental animals with nonketotic diabetes mellitus (DM) and DKA has not been studied. We examined the effect of plasma insulin levels on blood pressure and on adipose tissue PG production in rats with DM and DKA and normal rats. There was a significant relationship between plasma insulin level and blood pressure in rats with DM and normal controls (P < .021) and in rats with DKA and normal controls (P < .0001). There was an inverse linear correlation between plasma insulin levels and basal 6-keto-PGF(1 alpha) production by a mixture of adipocytes and endothelial cells from epididymal adipose tissue in rats with DKA and normal rats (P < .0252, R2 = .67). Rates of basal glycerol, PGE(2), and 6-keto-PGF(1alpha) production by a mixture of adipocytes and endothelial cells from epididymal adipose tissue were significantly higher in rats with DKA than in normal rats. These rates were also higher in rats with DM than in normal rats, but only glycerol values were statistically significant. In rats with DM, PGE(2) production induced by epinephrine 2 x 10(-5) mol/L (but not lower concentrations) was significantly greater than basal production (P < .05); production of 6-keto-PGF(1alpha) was not stimulated. In rats with DKA, 6-keto-PGF(1alpha) production induced by epinephrine 2 x 10(-5) mol/L (but not lower concentrations) was significantly greater than basal production (P < .05); production of PGE(2) was not stimulated. We conclude the following: (1) there is a close correlation between circulating insulin level and systemic blood pressure when rats with DM and DKA are compared with controls; (2) in insulin deficiency, PGI(2) and PGE(2) production are increased in adipose tissue versus normal tissue; and (3) the correlation between insulin level and blood pressure may be mediated by the inhibitory effect of insulin on vasodilative PG production by adipose tissue.

Adipose Tissue↗

Device for the application of a dynamic biaxially uniform and isotropic strain to a flexible cell culture membrane.

A large number of studies have demonstrated that mechanical perturbation modulates cellular metabolism; however, the systematic characterization of the molecular and cellular transduction mechanisms underlying mechanically induced metabolic modulation has been impeded, in part, by the limitations of the mechanical device. The objective of this investigation was to develop an in vitro experimental system that would provide independent control of the spatial and temporal biaxial strain distribution imposed on a flexible transparent tissue culture membrane that permits attachment, proliferation, and maintenance of the phenotypic expression of cultured embryonic osteoblasts. Such a device would permit a systematic investigation of the cellular response to specific, independently controlled parameters of mechanical deformation. Using a prototype device designed to impose a dynamic sinusoidal spatially isotropic biaxial strain profile, we confirmed experimentally that the strain was biaxially uniform and isotropic (radial = circumferential strain over the entire culture membrane) to within 14% (SD/mean) for the range of the peak strains tested (2.3-9.4%). Additionally, the uniformity was maintained at 1 Hz for at least 5 days of continuous operation. This experimental verification of the theoretically predicted isotropic strain profile suggests that the design principle is sound. Embryonic osteoblasts cultured on the flexible substrate proliferated and exhibited a temporal pattern of phenotypic expression (extracellular matrix accumulation and mineralization) comparable with that observed on polystyrene of tissue culture grade.

Animals↗

Prevention of venous thromboembolism in trauma patients.

Trauma patients are at risk for thromboembolic complications, but effective methods of prophylaxis have not been established for this heterogenous population. In this prospective trial, 400 trauma patients were assigned to one of three groups, depending upon their injuries, and randomized within each group to a treatment mode: Group I: sequential gradient pneumatic leg compression (SCD), low-dose subcutaneous heparin (H), or control (C); Group II: H or C; Group III: SCD or C. Venous duplex ultrasound examinations were performed on admission and weekly thereafter. Of the 251 patients who completed the study, 15 (6%) developed lower extremity venous thrombosis and two additional patients developed pulmonary embolism (one fatal). Significant risk factors associated with the development of thromboembolism included immobilization > 3 days, age 30 years or older, and the presence of pelvic or lower extremity fractures. In patients with neurotrauma who cannot receive heparin (Group III), the SCD was more effective than control in preventing DVT (p = 0.057). Neither H nor SCD appeared to offer protection for the other groups of trauma patients, but surveillance with ultrasound examinations allowed for prompt recognition and treatment of occult deep vein thrombosis.

Adolescent↗

Abnormal wall strain at distal end-to-side anastomoses.

Cyclic stretch has been demonstrated to induce proliferative and secretory activities by cultured arterial endothelial and smooth muscle cells, cellular processes that contribute to the development of intimal hyperplasia. A model of an end-to-side anastomosis was developed to examine the hypothesis that regions of the artery at such anastomoses are subjected to focally increased cyclic stretch, which may stimulate the development of intimal hyperplasia. Polytetrafluoroethylene grafts were anastomosed end to side to latex rubber tubes that have elastic properties similar to those of the human femoral artery. Pulse waves with physiologic pressure, rate, and contour were applied, and systolic and diastolic diameters were measured in two planes at longitudinal intervals. Circumferential strain imposed on the latex "artery" was calculated at each interval. Strain imposed perpendicular to the suture line was also measured. Circumferential strain was consistently maximal at a distinct region of the "artery" along the proximal third of the anastomosis (6.0 +/- 1.1% vs. 3.3 +/- 0.5% at other regions of the "artery"). The maximal strain across the suture line was found at precisely the same region (3.9 +/- 0.3% vs. 2.0 +/- 0.4%). The anastomotic region of the recipient artery in a distal end-to-side anastomosis is subjected to cyclic circumferential strains two times greater than those experienced by the remainder of the artery. This corresponds to a common location of intimal hyperplasia. Such strains may be a stimulus for intimal hyperplasia.

Anastomosis, Surgical↗

Compliance of vascular anastomoses with polybutester and polypropylene sutures.

PURPOSE: Polybutester suture is more easily stretched than other vascular sutures and may produce more compliant anastomoses. The effects of using polybutester and polypropylene sutures were compared acutely in arterial autografts and in chronic implants of cephalic vein grafts into the femoral arteries of dogs. METHODS: Paraanastomotic profiles of diameter and compliance were measured with echo-tracked ultrasonography, and profiles of intimal thickening were generated from histologic sections of the vessels harvested after 3 months. RESULTS: Polybutester produced more compliant anastomoses, compared with polypropylene, in arterial autografts (in vitro: 5.9% +/- 2.0% vs 3.3% +/- 0.6% diameter change/100 mm Hg, p < 0.01; in vivo: 3.1% +/- 1.1% vs 1.6% +/- 0.5%, p < 0.05), but this difference was not observed with vein as the graft material, either initially (1.1% +/- 1.2% vs 1.7% +/- 0.5%) or after 3 months (2.1% +/- 1.2% vs 2.4% +/- 0.8%). This dichotomy may reflect a governing influence of the stiffer veingrafts, compared with host artery (2.6% +/- 1.0% vs 5.4% +/- 1.2%), or the use of suboptimal tension on the polybutester suture when creating the anastomosis. CONCLUSIONS: Both sutures produced similar compliance and thickness profiles. Polybutester initially produces a more compliant anastomosis when both artery and graft are compliant, reducing anastomotic compliance mismatch. However, this benefit may not apply when the anastomosis includes a vessel of low compliance.

Anastomosis, Surgical↗

Magnetic resonance imaging of small arteries.

Magnetic resonance imaging (MRI) with receive-only surface coil technology was used to visualize and quantitative luminal diameters of small arteries in the rat. MRI measurements of normal and aneurysmal aortas, over a diameter range of 1-3 mm, were closely correlated with direct measurements made visually at laparotomy: measured differences averaged 0.16 mm, and the least-squares regression line (R2 = 0.97, P < 0.001) compared favorably to the line of equivalence, X = Y. This noninvasive but precise imaging modality demonstrates the potential value of using MRI to evaluate the diameter of small vessels, including the postoperative monitoring of arterial bypass graft patency in peripheral regions.

Abdomen↗

Arterial laser welding with a 1.9 micrometer Raman-shifted laser.

A new 1.9 micron Raman-shifted neodymium:yttrium aluminum garnet (Nd:YAG) laser was used for small vessel welding. Bursting pressures and stresses of sutured and laser-welded arteriotomies created in the rat femoral artery and aorta were measured. Sutured arteriotomies had a significantly higher burst stress than laser-welded arteriotomies. Although there were no significant differences in burst stress at the various laser powers tested, an optimal power was identified. The laser was also used to weld transected rat aortas. The average power delivered was 200 mW for 30 seconds per anastomosis. The average time for completing an anastomosis was 6 minutes compared with 18 minutes when sutures were used. In relation to proximal aortic diameter, there was a 7.9% decrease at the anastomosis immediately (n = 4), and a 6.6% and 4.9% increase occurred at 24 hours (n = 4) and 10 weeks (n = 5), respectively. Acute anastomotic compliance, and compliance at 24 hours and 10 weeks were decreased by 47.2%, 39.5%, and 47.8%, respectively, and were similar to sutured anastomoses. Histology showed little thermal denaturation of the aorta within 0.6 mm of the anastomosis, approximately 1 mm of medial cell death, and nearly normal elastic fiber alignment. One focal false aneurysm was noted at 10 weeks. Although the sutured and laser-welded anastomoses share similar compliance changes, the laser-welded anastomoses are more isodiametric. This preliminary experience with the 1.9 micron laser shows the distinct advantages of a handheld fiber, no requirement for cooling irrigation, speed, and no difference in compliance from sutured anastomoses.

Analysis of Variance↗

A laboratory model to quantitate the resistance of collagen vascular grafts to biodegradation.

Recent reports have shown that despite extensive preclinical testing, vascular grafts of biological origin undergo severe biodegradation and aneurysm formation after two or more years of implantation in man. The purpose of this study was to develop a laboratory model to quantitate and correlate the stability of crosslinked collagen grafts in vitro and in vivo. This resistance to biodegradation was assessed by measuring changes in suture pullout force and sample weight in response to controlled digestion with bacterial collagenase, in 0.5-cm-long cylindrical graft segments (chemically processed bovine carotid artery and human umbilical cord vein) that were implanted in the rat subcutis for 2 to 12 weeks. Scar tissue was removed from the explants by brief enzymatic digestion, a process that was inhibited when graft segments had become infected. Changes in dry weight were more consistent than were changes in wet weight; drying the graft segments had no effect on their degradation in vivo or in vitro. Intact cylindrical rings suffered somewhat less damage than did opened, flattened cylinders. Graft degradation increased markedly with implantation time, and was detected after only 3 weeks. We conclude that the rat subcutis model, when combined with controlled enzymatic digestion, first to remove scar tissue and then to challenge structural integrity, provides an accelerated assay by which to predict the stability of collagen vascular grafts.

Animals↗

Longterm study of a compliant biological vascular graft.

Clinically implanted prostheses of biological origin have recently been shown to develop aneurysms within several years. To study this process, recently developed bovine heterografts that were implanted in canine ilio-femoral arteries for 27 to 45 months, were studied in vivo and in vitro. Seven out of seven grafts were patent with only one showing evidence of focal aneurysm. Measurements of mechanical properties, including water permeability, compliance, and burst pressure, and of heat shrink temperature and dry weight were obtained before and after a period of controlled exposure to bacterial collagenase; all data suggested that much of the original graft had been replaced with host tissue. However, enzyme susceptibility was less than that of fresh bovine arteries, indicating that at least some of the grafts' crosslinked collagen was preserved. The compliance of these explants was similar to that reported for autogenous vein. Histological examination of the graft wall revealed cellular "intimal" and adventitial zones containing host-generated collagen surrounding a central zone devoid of cellular infiltration, which appears to be unmodified graft "media" highly resistant to degradation. We conclude that, when properly processed, biological prostheses can act as a bioresorbable scaffold for the orderly replacement of structural elements during healing, promoting continued mechanical integrity of the graft. These promising results encourage the further development of prostheses of biological origin.

Animals↗

Transperitoneal versus retroperitoneal approach for aortic reconstruction: a randomized prospective study.

A prospective, randomized study was conducted to compare the retroperitoneal versus transperitoneal approach for elective aortic reconstruction. One hundred thirteen patients (transperitoneal = 59, retroperitoneal = 54) were randomized between March 1987 and October 1988. In addition, to assess the changing course of patients undergoing aortic reconstruction similar data were gathered retrospectively on a group of 56 patients undergoing aortic reconstruction by the same surgeons performed via a transperitoneal approach in 1984 to 1985. Randomized patients were identical in age, male to female ratio, smoking history, incidence and severity of cardiopulmonary disease, indication for operation, and use of epidural anesthetics. Details of operation including operative and aortic cross-clamp times, crystalloid and transfusion requirements, degree of hypothermia on arrival at the intensive care unit, and perioperative fluid and blood requirements did not differ significantly for patients undergoing transperitoneal versus retroperitoneal reconstruction. Respiratory morbidity, as assessed by percent of patients requiring postoperative ventilation, deterioration in pulmonary function tests, and the incidence of respiratory complications, was identical in randomized patients. Other aspects of postoperative recovery including recovery of gastrointestinal function, the requirement for narcotics, metabolic parameters of operative stress, the incidence of major and minor complications, and the duration of hospital stay were similar for randomized patients undergoing transperitoneal and retroperitoneal reconstruction. When compared to retrospectively reviewed patients having aortic reconstruction, randomized patients undergoing transperitoneal and retroperitoneal operations had highly significant (p less than 0.001) reductions in postoperative ventilation, transfusion requirements, and length of hospital stay. Such trends were all independent of transperitoneal versus retroperitoneal approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta, Abdominal↗

Fibronectin enhances early shear stress resistance of seeded adult human venous endothelial cells.

An in vitro parallel plate perfusion chamber was used to study the shear stress resistance of seeded adult human saphenous vein endothelial cells (AHSVECs) on glass surfaces coated with different substrates. Endothelial cells were seeded onto glass slides precoated with these substrates and then exposed to pulsatile flow with an average shear stress of 8 dyn/cm2 for 1 hr. After AHSVEC attachment periods of 15 min, 1 hr, and 2 hr, flow dislodged all but 1.4, 30.4, and 72.2%, respectively, of cells that had been seeded onto 1% gelatin. Control slides that were not exposed to flow retained 12.9% (P less than 0.03), 49.8% (NS), and 95.2% (NS) of seeded cells. Precoating the slides with 10 micrograms/ml fibronectin resulted in 69.4, 89.5, and 97.7% of cells remaining after flow, compared with 6.4% (P less than 0.03), 53.7% (NS), and 93.3% (NS), respectively, when using matched slides coated with 1% gelatin. Results with 20% fetal bovine serum as the substrate were not statistically different from those obtained with 1% gelatin. We conclude that fibronectin enhances the early attachment of AHSVECs to artificial surfaces and is, therefore, potentially useful for increasing attached cell yields on arterial prostheses prepared with immediate cell seeding techniques.

Cell Adhesion↗

Response of skin photoplethysmography, laser Doppler flowmetry and transcutaneous oxygen tensiometry to stenosis-induced reductions in limb blood flow.

Photoplethysmography (PPG), transcutaneous oxygen tensiometry (TCpO2) and laser Doppler flowmetry (LDF) were used to measure changes in perfusion of the distal lower limb of the pig, in response to a stenosis created in the external iliac artery. The severity of stenosis was quantitated by the ratio of peak systolic distal pressure to peak systolic proximal pressure (distal systolic pressure index, DSPI). PPG and LDF were immediately responsive to changes in perfusion pressure while TCpO2 responded much more slowly. PPG dropped precipitously in response to even a small reduction in perfusion pressure, reaching zero at a DSPI of approximately 0.3. TCpO2 was insensitive to the presence of a mild stenosis (DSPI greater than 0.6), but was highly sensitive in the range 0.6 greater than DSPI greater than 0.3. At lower DSPI values, TCpO2 also became zero, due in part to electrode consumption of oxygen. LDF readings were sensitive to changes in blood flow throughout the entire range of stenosis, down to the point of total occlusion, although changes were not significant at DSPI values greater than 0.6. Because LDF measures not only nutritional blood flow, but flow in AV shunts and subdermal plexuses as well, high LDF readings could erroneously suggest tissue viability and good healing potential. Resting levels of TCpO2 and LDF can be used to follow the progress of peripheral vascular disease, and used complementarily, in many cases, to evaluate the severity of flow impairment.

Animals↗