Maciej Dryjski - Academia.edu (original) (raw)

Papers by Maciej Dryjski

Journal of Vascular Surgery, Dec 1, 1996

We have recently shown that nicotine and its metabolite cotinine are mitogenic for smooth muscle ... more We have recently shown that nicotine and its metabolite cotinine are mitogenic for smooth muscle cells in vitro. In the present study, we examined the effect of nicotine and cotinine on the production of growth factors and the expression of matrix metalloproteinases in smooth muscle cells. Methods: Smooth muscle cells were harvested from human arteries and grown in culture. Subconfluent cultures were incubated for 24 hours in M199 containing 0.1% fetal bovine serum with or without nicotine or cotinine at concentrations ranging from 10-9 m o l / L to 10-6 mol/L. The supernatants and cell lysates were assayed by enzyme-linked immnnosorbent assay for basic fibroblast growth factor (bFGF), tumor necrosis factor alpha (TNF-~), platelet-derived growth factor AB (PDGF-AB), and transforming growth factor beta (TGF-~). Matrix metalloproteinase expression was determined in subcontinent cultures incubated in albumin with or without nicotine or cotinine at 10-8 m o l / L and 10-7 m o l / L for 6, 12, 18, 24 and 36 hours. Northern blot analyses were performed with human cDNA probes for collagenase-1, stromelysin-1, gelatinase A, gelatinase B, and triose phosphate isomerase. Blots were quantified by phosphor-imaging techniques. Results: Both nicotine and cotinine stimulated the production and secretion of bFGF in a dose-dependent manner. PDGF, TNF-eg and TGF-~ secretions were not significantly affected by nicotine or cotinine. Collagenase was up-regulated by nicotine at 18 and 24 hours (4.5-fold to 5.8-fold) and by cotinine at 18 hours (from 5.0-fold to 29-fold). Stromelysin-1 was up-regulated by nicotine and cotinine at 12 and I8 hours (1.5-fold to 7.0-fold). Gelatinase A generally peaked at 12 hours and was up-regulated by both agents (2.0-fold to 6.5-fold). Conclusion: Nicotine and cotinine enhanced the production of bFGF, a major mitogen for smooth muscle cells, and up-regulated the expression of several matrix metalloproteinases that are critical in cell migration. These data demonstrate mechanisms by which smoking may contribute to the development of intimal hyperplasia, atherosclerosis, and aneurysms.

Vascular, Jun 1, 2005

A Baker&a... more A Baker's or popliteal cyst is a synovial cyst in the popliteal fossa arising from the knee joint. The majority of patients develop a popliteal mass that is asymptomatic, but in a small percentage of patients, complications and symptoms occur; these may not only encompass the popliteal veins and arteries but may also include cyst leakage, infection, hemorrhage, and compartment syndrome. Severe lower limb ischemia caused by a Baker's cyst is extremely rare, having been reported only six times since 1960; all patients were treated with surgical intervention. We report the case of a 29-year-old male presenting with right calf claudication caused by a Baker's cyst. The patient was managed nonoperatively with nonsteroidal anti-inflammatory agents, proper exercises, and close observation. His claudication improved progressively and had completely disappeared at 12 months of follow-up. A repeat duplex arterial study showed that increased blood flow to the right foot and the right ankle/brachial index improved to 0.97 from 0.67. Repeat ultrasonography demonstrated that the size of the cyst decreased from 4.5 x 1.5 cm to 2.8 x 0.9 cm. The patient had been followed for 20 months and remained asymptomatic in the last 8 months. We will continue to follow the patient to evaluate the long-term outcome. In summary, our own data and literature review suggest that the limb ischemia caused by Baker's cyst may be a transient condition and can be managed nonoperatively in selected patients.

European Journal of Vascular and Endovascular Surgery, Dec 1, 1998

Objectives: thrombolytzc therapy is frequently used to manage vascular graft thrombos~s. However,... more Objectives: thrombolytzc therapy is frequently used to manage vascular graft thrombos~s. However, long-term patency after thrombolyszs remazns poor. The purpose of thzs study was to character~se the morphological and functional response of endothehal cells (EC) exposed to a thrombus and subsequently lytzc therapy. Methods: human EC were exposed to human whole blood thrombus for 2, 6, 12, and 24 h The thrombus was lysed with urokinase. Cell morphology was studied wzth electron m~croscopy. Northern blot analyses were performed with human c-DNA probes for endothehn-1, thrombomoduhn, tissue factor, tzssue plasmmogen activator, plasmmogen activator mhzbztor, and trlose phosphate isomerase. Results: EC retraction occurred for each period of mcubatzon. Thrombomoduhn expression was zncreased 2.2-fold at 6 h and 2 4-fold at 24 h. t-PA expresston was depressed proportzonally to the durahon of thrombus exposure. PAl and TF expresswn transzently ~ncreased 1.5-fold at 2 h of exposure and returned to basehne at 6 h. Endothehn expression remained unchanged Conclusions, except for a transzent zncrease m TF expression and reversal of the tPA/PAI ratio, EC exposed to thrombus do not appear to become actzvely procoagulant. The ~ncrease zn TM expression may reflect enhanced thromboresistance. However, EC retractzon may be responszble for an ~ncrease thrombogemc~ty of saphenous vezn graft after thromboszs and Urok~nase therapy.

International Wound Journal, Mar 11, 2008

This prospective, non comparative study evaluated the safety and effectiveness of an adhesive gel... more This prospective, non comparative study evaluated the safety and effectiveness of an adhesive gelling foam dressing in pressure ulcer management. Twenty‐three subjects with exuding pressure ulcers were recruited from seven centres in the USA and Canada. Study treatment included an adhesive gelling foam dressing, optional tape/roll bandaging and mandatory pressure‐reducing/relieving devices. Subjects were followed until ulcer healing, for up to 28 days, or on patient withdrawal from the study, whichever came first. Dressings were changed at least once every 7 days. Mean percentage change in ulcer area from baseline to final measurement was −13%. Investigators reported healing or subjective improvement of ulcer condition in 61% of patients. Mean dressing wear time was 4·2 days. Subjects found the dressing was comfortable, soothing and cushioning in situ at 80%, 64% and 70% of dressing changes, respectively. Subjects reported pain severity of none or mild for every dressing change. Fourteen subjects experienced adverse events, including seven subjects with study‐related maceration, erythema, wound enlargement, blister or infection. A regimen including an adhesive gelling foam dressing proved to be safe and effective for managing exudate, protecting the surrounding skin, minimising pain and supporting healing of pressure ulcers with exudate.

Vascular, 2005

Distal peripheral microembolism is caused by embolization of atherosclerotic debris into small ar... more Distal peripheral microembolism is caused by embolization of atherosclerotic debris into small arteries and arterioles. The recent advances in endovascular technique have been met with a gradual increase in the incidence of iatrogenic atheroembolism. This review seeks to explore the nature of distal peripheral microembolism, pathophysiology, and the management options, with a focus on iatrogenic distal peripheral microembolism.

Journal of Cardiovascular Surgery, Apr 23, 1983

Thrombosis Research, 1983

Uptake and inhibition of thrombin on the endothelium of porcine aorta was studied in vitro. The t... more Uptake and inhibition of thrombin on the endothelium of porcine aorta was studied in vitro. The thrombin was labelled with 125J and its enzyme activity was measured with an amidolytic assay. After exposure to the aorta both the enzyme activity and radioactivity disappeared from the solution and were recovered as surface bound activities. The rate of inhibition of the surface bound thrombin was determined in presence or absence of plasma. In presence of plasma the endothelially confined enzymatic activity was rapidly inhibited, no enzymatic activity was recovered in plasma. The surface bound radioactivity, however, decreased slowly and was recovered in plasma. In absence of plasma only slow inhibition took place. It is concluded that thrombin taken up on the endothelium is rapidly inhibited there by an interaction with plasma and then released in an inactivated state. An alternative conclusion, based on the anticoagulant and antithrombotic actions of the endothelial fibrin lining is briefly discussed.

American Journal of Surgery, Feb 1, 2005

Background: Hemorrhage from large retroperitoneal veins is usually controlled by suturing the ven... more Background: Hemorrhage from large retroperitoneal veins is usually controlled by suturing the venous tear. Infrequently, the extent and location of the tear and amount of hemorrhage preclude successful suturing. Methods: In seven patients with severe hemorrhage from large retroperitoneal veins encountered in association with resection of retroperitoneal sarcoma (6) or repair of a ruptured abdominal aortic aneurysm (1), packing of the area with sufficient amounts of Surgicel (Ethicon, Johnson & Johnson, Somerville, NJ) and pressure for one half hour was used. Results: All seven patients did not show any bleeding postoperatively and no clinical sequelae developed, with the exception of one patient who developed an abscess requiring drainage. Conclusion: Internal packing with Surgicel appears to be reliable in controlling venous hemorrhage not manageable by the standard methods and may be preferable to roll gauze packing.

Thrombosis and Haemostasis, 1985

The endothelium is an important compartment for uptake and inhibition of thrombin. The amount of ... more The endothelium is an important compartment for uptake and inhibition of thrombin. The amount of enzymatically active bound thrombin can be detected with both small synthetic substrates and with aid of fibrinogen as substrate. The present study was designed to investigate the relation between endothelially bound thrombin with amidolytic activity towards a synthetic substrate (S-2238) and thrombin capable of converting fibrinogen by measuring generation of fibrinopeptide A (FPA). The luminal surfaces of rabbit aortae (2 cm2) were exposed in vitro to thrombin (0.625-5.0 NIH units/ml). Thrombin disappeared from the solution and a certain fraction was recovered on the surface. There was a linear relationship between the amount of thrombin on the surface and the concentration of thrombin in the incubation mixture. Approximately one third of the thrombin measured with S-2238 was also able to cleave fibrinogen. After incubation with defibrinogenated plasma almost total inhibition of fibrinogen splitting activity occurred within 30 sec. The inhibition of the amidolytic activity was less complete. When endothelially bound thrombin was exposed to plasma much less FPA was generated than in a fibrinogen solution. A minor fraction of endothelially bound thrombin was inhibited also upon incubation with Tyrode without recovery of any enzymatic activity in the solution. The results indicate that a fraction of thrombin bound to the endothelium has retained enzymatic activity and that a fraction of the enzymatically active thrombin is capable of converting fibrinogen. Inhibition of thrombin enzymatic activity occurs rapidly upon exposure to plasma. The endothelium itself has a minor inhibitory effect also in the absence of plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombosis and Haemostasis, 1985

Thrombin activity was assayed on the aortic surface of rabbits after soft tissue trauma or endoth... more Thrombin activity was assayed on the aortic surface of rabbits after soft tissue trauma or endothelial injury caused by a balloon catheter. The animals were sacrificed by exsanguination 20 minutes or 3 hours after either type of trauma. Thrombin amidolytic activity on the luminal surface of the aorta was measured by exposing it to a synthetic chromogenic substrate. Thrombin activity appeared on the aortic endothelium 3 hours but not 20 minutes after soft tissue trauma. Heparin prevented the appearance of thrombin activity completely only if given just before the trauma. After endothelial injury, thrombin activity appeared on the vascular surface after 3 hours but not after 20 minutes. Thrombin activity appearing on the endothelium after soft tissue trauma may explain posttraumatic thrombotic events. The thrombin activity could, however, also be directed towards activation of protein C in which case an anticoagulant effect is obtained. Thrombin appearing after endothelial injury may enhance reactivity on the damaged vessel wall.

Annals of Emergency Medicine, Apr 1, 1989

A comparison of gastric lavage versus peritoneal lavage rewarming was studied in a hypothermic ra... more A comparison of gastric lavage versus peritoneal lavage rewarming was studied in a hypothermic rabbit model. The gastric lavage group (n = 5) had a mean rewarming time of 136 +/- 25.1 minutes versus the peritoneal lavage group (n = 6) mean rewarming time of 131.7 +/- 27.9 minutes (p = .795). Good correlation was found between tympanic membrane temperature readings and both rectal temperature readings (r = .69) in the gastric lavage group and esophageal temperature readings (r = .90) in the peritoneal lavage group. Gastric lavage and peritoneal lavage have the same rewarming rates in the present hypothermic model.

European Surgical Research, 1985

The aim of this study was to investigate the uptake and inactivation of thrombin on aortic endoth... more The aim of this study was to investigate the uptake and inactivation of thrombin on aortic endothelium and neo-intima developing on vascular grafts in pigs and dogs. Thrombin, measured with a synthetic chromogenic substrate, was found on the grafts, particularly on grafts with an incompletely developed neo-intima. After incubation of grafts and aortic segments with thrombin in vitro, significantly more thrombin was taken up on the grafts as compared to aortic endothelium. In the presence of plasma, surface-bound thrombin was inactivated much faster on aortic endothelium than on neo-intima. If surfaces loaded with thrombin in vitro were incubated with a balanced salt solution the enzyme was inhibited much more slowly. Thrombin activity on the neo-intima may contribute to graft thrombosis.

Journal of Cellular Physiology, Oct 1, 1988

The effects of the polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) on the secre... more The effects of the polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) on the secretion of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) were evaluated using cultured bovine aortic endothelial cells. All three polyamines enhanced PA secretion in a time‐ and dose‐dependent manner, with a potency rank order of SPM > SPD > PUT. The PA stimulation required both RNA and protein synthesis, as evidenced by inhibition of polyamine‐induced PA secretion by actinomycin D and cycloheximide. The inhibitors of polyamine biosynthesis methylglyoxal bis‐(guanylhydrazone) (MGBG) and dl‐(difluoromethyl) ornithine (DFMO) alone did not affect basal or polyamine‐induced PA secretion, with the exception that MGBG reduced the effect of PUT. Polyamine‐treated cells enhanced secretions of both tissue‐type and urokinase‐type PA. The results of the present study suggest that polyamines may play a role in the regulation of PA synthesis and secretion and that this function can be modified under pathophysiological conditions affecting cellular and tissue levels of polyamines.

Prostaglandins, 1991

This study evaluated the efficacy of a prostacyclin analog, iloprost, and a thromboxane A2 recept... more This study evaluated the efficacy of a prostacyclin analog, iloprost, and a thromboxane A2 receptor antagonist, daltroban, as inhibitors of experimental intimal hyperplasia. The vascular injury model used is based on an endothelial injury induced by a brief infusion of air into an isolated segment of the common carotid artery in the rat. Iloprost and daltroban were administered by continuous IV infusion for two weeks. The infusion rates were 0.1 micrograms/kg/min for iloprost and 0.1 mg/kg/hr for daltroban; these dosing rates are associated with significant alterations in eicosanoid-related pharmacologic effects. The animals were sacrificed at two weeks and the carotid arteries fixed in situ for light microscopy. The myointimal thickening was measured as the intima to media area (I/M) ratio. The control animals developed marked intimal thickening, with an I/M ratio of 0.76 +/- 0.12 (mean +/- SEM; N = 7). There was no inhibition of intimal hyperplasia (P greater than 0.05) after either iloprost (I/M ratio: 1.04 +/- 0.13; N = 8) or daltroban (I/M ratio: 0.70 +/- 0.04; N = 6). It is concluded that neither of these two modulators of eicosanoid activity, iloprost and daltroban, inhibit intimal hyperplasia following experimental endothelial injury.

Journal of Vascular Surgery, Apr 1, 1997

Intimal hyperplasia caused by smooth muscle cell (SMC) proliferation is the major cause of infrai... more Intimal hyperplasia caused by smooth muscle cell (SMC) proliferation is the major cause of infrainguinal graft failure within the first 12 months. Tobacco smoking is associated with a twofold increase in graft failure within the first year of extremity bypass surgery, but the mechanism is not clearly understood. This study evaluated the effect of nicotine and its major stable metabolite cotinine on vascular SMC proliferation in vitro. SMC were harvested from human arteries and grown in culture with standard methods. Cells were seeded at a density of 1.8 x 10(4) cells/well in 24 multiwell dishes and cell cycle-synchronized. Subsequently the SMC were incubated with media containing 0.1% or 15% fetal bovine serum and nicotine or cotinine at concentrations ranging from 10(-9) mol/L to 10(-6) mol/L. Control samples were incubated with corresponding media but without the drugs. SMC proliferation was determined at 4 days with a cell counter. DNA synthesis was assessed at 24 hours with 3H-thymidine uptake. The results were expressed as a percentage change compared with the control samples (mean +/- SEM). Results were analyzed by analysis of variance and t tests. In the presence of serum both nicotine and cotinine at concentrations of 10(-7) and 10(-8) mol/L were mitogenic for SMC in vitro (p < 0.05). A weak mitogenic effect was observed at a low serum concentration for cotinine but not nicotine. Cotinine at a concentration of 10(-9) mol/L, a level seen among passive smokers, was a statistically significant stimulus for DNA synthesis in both minimum serum and serum-supplemented media. At high concentrations both substances were toxic for the cells. We have demonstrated a potential role for nicotine and cotinine in the development of intimal hyperplasia and ultimately failure of the vascular reconstruction.

Journal of Vascular Surgery, 2021

OBJECTIVE Short and mid-term outcomes of endovascular aortic repair (EVAR) have made it a standar... more OBJECTIVE Short and mid-term outcomes of endovascular aortic repair (EVAR) have made it a standard treatment for abdominal aortic aneurysms (AAA), but newer generation devices have yet to demonstrate improved long-term rates of complications, reinterventions and survival. The TREO stent-graft is a latest generation device and is being evaluated for approval in the US. METHODS A multicenter, non-randomized, investigational device exemption (IDE) clinical trial assessed safety and effectiveness of the TREO device, with Core Laboratory assessment of imaging, and independent adjudication of safety. The primary effectiveness endpoint was successful aneurysm treatment at one year. The primary safety endpoint was the incidence of major adverse events (MAEs) at 30 days. RESULTS 150 patients (132 men, 88.0%) with infrarenal abdominal aortic (87.3%) or aorto-iliac (12.7%) aneurysms were enrolled. Data were normally distributed: mean age was 71.7 (± 7.4) years. The MAE incidence at 30 days was .7%. One subject experienced two MAEs, myocardial infarction and procedural blood loss of 1,000 cc. The proportion of successful aneurysm treatment at one year was 93.1%. Longer-term follow-up continues; there has been no aneurysm-related mortality to date. At the three-year time point, cumulative all-cause mortality was 10.7% (n = 16), 2.7% type I endoleaks (n = 4); 0% type III endoleaks; 54.3% of patients had > 5 mm of sac shrinkage; 9.3% had secondary interventions (n = 14). CONCLUSIONS Safety and effectiveness of endovascular repair of abdominal aneurysms with TREO were demonstrated with 93.1% successful aneurysm treatment at one year and 54.3% of patients had aneurysm sac shrinkage > 5 mm at three years. Long-term follow-up continues and will show whether these favorable outcomes are sustained.

VIIIth International Congress on Thrombosis and Haemostasis, 1981

The present investigation was designed to investigate the capacity of normal vessels to inactive ... more The present investigation was designed to investigate the capacity of normal vessels to inactive activated coagulation enzymes.Fresh and frozen porcine and canine aortae were exposed in virto to thrombin, dissolved in an albumin solution. Thrombin activity appearing on the vascular wall was assayed with a chromogenic substrate (S-2238-Kabi). Aortic endothelium retained considerable amounts of thrombin. After exposure of the aorta with plasma, a rapid inactivation of thrombin was observed. Exposure of the thrombin-absorbed endothelium to a modified Ringer’s solution resulted in a much slower inactivation. A similar slow inactivation was seen after exposure with plasma devoid of anti thrombin III. No difference was observed between fresh aortae and those stored in a frozen state. No inactivation occured during the observation time when the thrombin-albumin solution was mixed with the modified Ringer’s solution without presence of aortic endothelium and when mixed with normal plasma on...

Thrombosis and Haemostasis, 1983

SummaryThe aim of the investigation was to clarify the uptake of thrombin on vascular endothelium... more SummaryThe aim of the investigation was to clarify the uptake of thrombin on vascular endothelium and the inhibition of thrombin on the endothelium in the presence or absence of plasma. Segments of porcine aorta were used. Thrombin was labelled with 125I and its enzymatic activity was assayed amidolytically using a specific chromogenic substrate. After exposure to the endothelium both enzymatic activity and radioactivity disappeared from the thrombin solution and were recovered as surface bound activities.The enzyme activity confined to the endothelium rapidly disappeared in the presence of plasma but no activity was recovered in the plasma. The surface confined radioactivity, however, decreased slowly and was quantitatively recovered in the plasma. In the absence of plasma, i. e. in the presence of a balanced Ringer’s solution, only slow disappearance of thrombin enzymatic activity occurred although the rate of disappearance was higher than that of release of radioactivity.It is co...

Polish Journal of Surgery, 2007

Individual scientists in cancer research are usually dedicated, honest, hard-working people who o... more Individual scientists in cancer research are usually dedicated, honest, hard-working people who often reach levels of excellence, at the personal level. The purpose of the following review is not to criticize as deficient the individual efforts, but rather to point out deficiencies in our collective approach in elucidating the problem of CANCER.

Journal of Vascular Surgery, Dec 1, 1996

We have recently shown that nicotine and its metabolite cotinine are mitogenic for smooth muscle ... more We have recently shown that nicotine and its metabolite cotinine are mitogenic for smooth muscle cells in vitro. In the present study, we examined the effect of nicotine and cotinine on the production of growth factors and the expression of matrix metalloproteinases in smooth muscle cells. Methods: Smooth muscle cells were harvested from human arteries and grown in culture. Subconfluent cultures were incubated for 24 hours in M199 containing 0.1% fetal bovine serum with or without nicotine or cotinine at concentrations ranging from 10-9 m o l / L to 10-6 mol/L. The supernatants and cell lysates were assayed by enzyme-linked immnnosorbent assay for basic fibroblast growth factor (bFGF), tumor necrosis factor alpha (TNF-~), platelet-derived growth factor AB (PDGF-AB), and transforming growth factor beta (TGF-~). Matrix metalloproteinase expression was determined in subcontinent cultures incubated in albumin with or without nicotine or cotinine at 10-8 m o l / L and 10-7 m o l / L for 6, 12, 18, 24 and 36 hours. Northern blot analyses were performed with human cDNA probes for collagenase-1, stromelysin-1, gelatinase A, gelatinase B, and triose phosphate isomerase. Blots were quantified by phosphor-imaging techniques. Results: Both nicotine and cotinine stimulated the production and secretion of bFGF in a dose-dependent manner. PDGF, TNF-eg and TGF-~ secretions were not significantly affected by nicotine or cotinine. Collagenase was up-regulated by nicotine at 18 and 24 hours (4.5-fold to 5.8-fold) and by cotinine at 18 hours (from 5.0-fold to 29-fold). Stromelysin-1 was up-regulated by nicotine and cotinine at 12 and I8 hours (1.5-fold to 7.0-fold). Gelatinase A generally peaked at 12 hours and was up-regulated by both agents (2.0-fold to 6.5-fold). Conclusion: Nicotine and cotinine enhanced the production of bFGF, a major mitogen for smooth muscle cells, and up-regulated the expression of several matrix metalloproteinases that are critical in cell migration. These data demonstrate mechanisms by which smoking may contribute to the development of intimal hyperplasia, atherosclerosis, and aneurysms.

Vascular, Jun 1, 2005

A Baker&a... more A Baker's or popliteal cyst is a synovial cyst in the popliteal fossa arising from the knee joint. The majority of patients develop a popliteal mass that is asymptomatic, but in a small percentage of patients, complications and symptoms occur; these may not only encompass the popliteal veins and arteries but may also include cyst leakage, infection, hemorrhage, and compartment syndrome. Severe lower limb ischemia caused by a Baker's cyst is extremely rare, having been reported only six times since 1960; all patients were treated with surgical intervention. We report the case of a 29-year-old male presenting with right calf claudication caused by a Baker's cyst. The patient was managed nonoperatively with nonsteroidal anti-inflammatory agents, proper exercises, and close observation. His claudication improved progressively and had completely disappeared at 12 months of follow-up. A repeat duplex arterial study showed that increased blood flow to the right foot and the right ankle/brachial index improved to 0.97 from 0.67. Repeat ultrasonography demonstrated that the size of the cyst decreased from 4.5 x 1.5 cm to 2.8 x 0.9 cm. The patient had been followed for 20 months and remained asymptomatic in the last 8 months. We will continue to follow the patient to evaluate the long-term outcome. In summary, our own data and literature review suggest that the limb ischemia caused by Baker's cyst may be a transient condition and can be managed nonoperatively in selected patients.

European Journal of Vascular and Endovascular Surgery, Dec 1, 1998

Objectives: thrombolytzc therapy is frequently used to manage vascular graft thrombos~s. However,... more Objectives: thrombolytzc therapy is frequently used to manage vascular graft thrombos~s. However, long-term patency after thrombolyszs remazns poor. The purpose of thzs study was to character~se the morphological and functional response of endothehal cells (EC) exposed to a thrombus and subsequently lytzc therapy. Methods: human EC were exposed to human whole blood thrombus for 2, 6, 12, and 24 h The thrombus was lysed with urokinase. Cell morphology was studied wzth electron m~croscopy. Northern blot analyses were performed with human c-DNA probes for endothehn-1, thrombomoduhn, tissue factor, tzssue plasmmogen activator, plasmmogen activator mhzbztor, and trlose phosphate isomerase. Results: EC retraction occurred for each period of mcubatzon. Thrombomoduhn expression was zncreased 2.2-fold at 6 h and 2 4-fold at 24 h. t-PA expresston was depressed proportzonally to the durahon of thrombus exposure. PAl and TF expresswn transzently ~ncreased 1.5-fold at 2 h of exposure and returned to basehne at 6 h. Endothehn expression remained unchanged Conclusions, except for a transzent zncrease m TF expression and reversal of the tPA/PAI ratio, EC exposed to thrombus do not appear to become actzvely procoagulant. The ~ncrease zn TM expression may reflect enhanced thromboresistance. However, EC retractzon may be responszble for an ~ncrease thrombogemc~ty of saphenous vezn graft after thromboszs and Urok~nase therapy.

International Wound Journal, Mar 11, 2008

This prospective, non comparative study evaluated the safety and effectiveness of an adhesive gel... more This prospective, non comparative study evaluated the safety and effectiveness of an adhesive gelling foam dressing in pressure ulcer management. Twenty‐three subjects with exuding pressure ulcers were recruited from seven centres in the USA and Canada. Study treatment included an adhesive gelling foam dressing, optional tape/roll bandaging and mandatory pressure‐reducing/relieving devices. Subjects were followed until ulcer healing, for up to 28 days, or on patient withdrawal from the study, whichever came first. Dressings were changed at least once every 7 days. Mean percentage change in ulcer area from baseline to final measurement was −13%. Investigators reported healing or subjective improvement of ulcer condition in 61% of patients. Mean dressing wear time was 4·2 days. Subjects found the dressing was comfortable, soothing and cushioning in situ at 80%, 64% and 70% of dressing changes, respectively. Subjects reported pain severity of none or mild for every dressing change. Fourteen subjects experienced adverse events, including seven subjects with study‐related maceration, erythema, wound enlargement, blister or infection. A regimen including an adhesive gelling foam dressing proved to be safe and effective for managing exudate, protecting the surrounding skin, minimising pain and supporting healing of pressure ulcers with exudate.

Vascular, 2005

Distal peripheral microembolism is caused by embolization of atherosclerotic debris into small ar... more Distal peripheral microembolism is caused by embolization of atherosclerotic debris into small arteries and arterioles. The recent advances in endovascular technique have been met with a gradual increase in the incidence of iatrogenic atheroembolism. This review seeks to explore the nature of distal peripheral microembolism, pathophysiology, and the management options, with a focus on iatrogenic distal peripheral microembolism.

Journal of Cardiovascular Surgery, Apr 23, 1983

Thrombosis Research, 1983

Uptake and inhibition of thrombin on the endothelium of porcine aorta was studied in vitro. The t... more Uptake and inhibition of thrombin on the endothelium of porcine aorta was studied in vitro. The thrombin was labelled with 125J and its enzyme activity was measured with an amidolytic assay. After exposure to the aorta both the enzyme activity and radioactivity disappeared from the solution and were recovered as surface bound activities. The rate of inhibition of the surface bound thrombin was determined in presence or absence of plasma. In presence of plasma the endothelially confined enzymatic activity was rapidly inhibited, no enzymatic activity was recovered in plasma. The surface bound radioactivity, however, decreased slowly and was recovered in plasma. In absence of plasma only slow inhibition took place. It is concluded that thrombin taken up on the endothelium is rapidly inhibited there by an interaction with plasma and then released in an inactivated state. An alternative conclusion, based on the anticoagulant and antithrombotic actions of the endothelial fibrin lining is briefly discussed.

American Journal of Surgery, Feb 1, 2005

Background: Hemorrhage from large retroperitoneal veins is usually controlled by suturing the ven... more Background: Hemorrhage from large retroperitoneal veins is usually controlled by suturing the venous tear. Infrequently, the extent and location of the tear and amount of hemorrhage preclude successful suturing. Methods: In seven patients with severe hemorrhage from large retroperitoneal veins encountered in association with resection of retroperitoneal sarcoma (6) or repair of a ruptured abdominal aortic aneurysm (1), packing of the area with sufficient amounts of Surgicel (Ethicon, Johnson & Johnson, Somerville, NJ) and pressure for one half hour was used. Results: All seven patients did not show any bleeding postoperatively and no clinical sequelae developed, with the exception of one patient who developed an abscess requiring drainage. Conclusion: Internal packing with Surgicel appears to be reliable in controlling venous hemorrhage not manageable by the standard methods and may be preferable to roll gauze packing.

Thrombosis and Haemostasis, 1985

The endothelium is an important compartment for uptake and inhibition of thrombin. The amount of ... more The endothelium is an important compartment for uptake and inhibition of thrombin. The amount of enzymatically active bound thrombin can be detected with both small synthetic substrates and with aid of fibrinogen as substrate. The present study was designed to investigate the relation between endothelially bound thrombin with amidolytic activity towards a synthetic substrate (S-2238) and thrombin capable of converting fibrinogen by measuring generation of fibrinopeptide A (FPA). The luminal surfaces of rabbit aortae (2 cm2) were exposed in vitro to thrombin (0.625-5.0 NIH units/ml). Thrombin disappeared from the solution and a certain fraction was recovered on the surface. There was a linear relationship between the amount of thrombin on the surface and the concentration of thrombin in the incubation mixture. Approximately one third of the thrombin measured with S-2238 was also able to cleave fibrinogen. After incubation with defibrinogenated plasma almost total inhibition of fibrinogen splitting activity occurred within 30 sec. The inhibition of the amidolytic activity was less complete. When endothelially bound thrombin was exposed to plasma much less FPA was generated than in a fibrinogen solution. A minor fraction of endothelially bound thrombin was inhibited also upon incubation with Tyrode without recovery of any enzymatic activity in the solution. The results indicate that a fraction of thrombin bound to the endothelium has retained enzymatic activity and that a fraction of the enzymatically active thrombin is capable of converting fibrinogen. Inhibition of thrombin enzymatic activity occurs rapidly upon exposure to plasma. The endothelium itself has a minor inhibitory effect also in the absence of plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombosis and Haemostasis, 1985

Thrombin activity was assayed on the aortic surface of rabbits after soft tissue trauma or endoth... more Thrombin activity was assayed on the aortic surface of rabbits after soft tissue trauma or endothelial injury caused by a balloon catheter. The animals were sacrificed by exsanguination 20 minutes or 3 hours after either type of trauma. Thrombin amidolytic activity on the luminal surface of the aorta was measured by exposing it to a synthetic chromogenic substrate. Thrombin activity appeared on the aortic endothelium 3 hours but not 20 minutes after soft tissue trauma. Heparin prevented the appearance of thrombin activity completely only if given just before the trauma. After endothelial injury, thrombin activity appeared on the vascular surface after 3 hours but not after 20 minutes. Thrombin activity appearing on the endothelium after soft tissue trauma may explain posttraumatic thrombotic events. The thrombin activity could, however, also be directed towards activation of protein C in which case an anticoagulant effect is obtained. Thrombin appearing after endothelial injury may enhance reactivity on the damaged vessel wall.

Annals of Emergency Medicine, Apr 1, 1989

A comparison of gastric lavage versus peritoneal lavage rewarming was studied in a hypothermic ra... more A comparison of gastric lavage versus peritoneal lavage rewarming was studied in a hypothermic rabbit model. The gastric lavage group (n = 5) had a mean rewarming time of 136 +/- 25.1 minutes versus the peritoneal lavage group (n = 6) mean rewarming time of 131.7 +/- 27.9 minutes (p = .795). Good correlation was found between tympanic membrane temperature readings and both rectal temperature readings (r = .69) in the gastric lavage group and esophageal temperature readings (r = .90) in the peritoneal lavage group. Gastric lavage and peritoneal lavage have the same rewarming rates in the present hypothermic model.

European Surgical Research, 1985

The aim of this study was to investigate the uptake and inactivation of thrombin on aortic endoth... more The aim of this study was to investigate the uptake and inactivation of thrombin on aortic endothelium and neo-intima developing on vascular grafts in pigs and dogs. Thrombin, measured with a synthetic chromogenic substrate, was found on the grafts, particularly on grafts with an incompletely developed neo-intima. After incubation of grafts and aortic segments with thrombin in vitro, significantly more thrombin was taken up on the grafts as compared to aortic endothelium. In the presence of plasma, surface-bound thrombin was inactivated much faster on aortic endothelium than on neo-intima. If surfaces loaded with thrombin in vitro were incubated with a balanced salt solution the enzyme was inhibited much more slowly. Thrombin activity on the neo-intima may contribute to graft thrombosis.

Journal of Cellular Physiology, Oct 1, 1988

The effects of the polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) on the secre... more The effects of the polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) on the secretion of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) were evaluated using cultured bovine aortic endothelial cells. All three polyamines enhanced PA secretion in a time‐ and dose‐dependent manner, with a potency rank order of SPM > SPD > PUT. The PA stimulation required both RNA and protein synthesis, as evidenced by inhibition of polyamine‐induced PA secretion by actinomycin D and cycloheximide. The inhibitors of polyamine biosynthesis methylglyoxal bis‐(guanylhydrazone) (MGBG) and dl‐(difluoromethyl) ornithine (DFMO) alone did not affect basal or polyamine‐induced PA secretion, with the exception that MGBG reduced the effect of PUT. Polyamine‐treated cells enhanced secretions of both tissue‐type and urokinase‐type PA. The results of the present study suggest that polyamines may play a role in the regulation of PA synthesis and secretion and that this function can be modified under pathophysiological conditions affecting cellular and tissue levels of polyamines.

Prostaglandins, 1991

This study evaluated the efficacy of a prostacyclin analog, iloprost, and a thromboxane A2 recept... more This study evaluated the efficacy of a prostacyclin analog, iloprost, and a thromboxane A2 receptor antagonist, daltroban, as inhibitors of experimental intimal hyperplasia. The vascular injury model used is based on an endothelial injury induced by a brief infusion of air into an isolated segment of the common carotid artery in the rat. Iloprost and daltroban were administered by continuous IV infusion for two weeks. The infusion rates were 0.1 micrograms/kg/min for iloprost and 0.1 mg/kg/hr for daltroban; these dosing rates are associated with significant alterations in eicosanoid-related pharmacologic effects. The animals were sacrificed at two weeks and the carotid arteries fixed in situ for light microscopy. The myointimal thickening was measured as the intima to media area (I/M) ratio. The control animals developed marked intimal thickening, with an I/M ratio of 0.76 +/- 0.12 (mean +/- SEM; N = 7). There was no inhibition of intimal hyperplasia (P greater than 0.05) after either iloprost (I/M ratio: 1.04 +/- 0.13; N = 8) or daltroban (I/M ratio: 0.70 +/- 0.04; N = 6). It is concluded that neither of these two modulators of eicosanoid activity, iloprost and daltroban, inhibit intimal hyperplasia following experimental endothelial injury.

Journal of Vascular Surgery, Apr 1, 1997

Intimal hyperplasia caused by smooth muscle cell (SMC) proliferation is the major cause of infrai... more Intimal hyperplasia caused by smooth muscle cell (SMC) proliferation is the major cause of infrainguinal graft failure within the first 12 months. Tobacco smoking is associated with a twofold increase in graft failure within the first year of extremity bypass surgery, but the mechanism is not clearly understood. This study evaluated the effect of nicotine and its major stable metabolite cotinine on vascular SMC proliferation in vitro. SMC were harvested from human arteries and grown in culture with standard methods. Cells were seeded at a density of 1.8 x 10(4) cells/well in 24 multiwell dishes and cell cycle-synchronized. Subsequently the SMC were incubated with media containing 0.1% or 15% fetal bovine serum and nicotine or cotinine at concentrations ranging from 10(-9) mol/L to 10(-6) mol/L. Control samples were incubated with corresponding media but without the drugs. SMC proliferation was determined at 4 days with a cell counter. DNA synthesis was assessed at 24 hours with 3H-thymidine uptake. The results were expressed as a percentage change compared with the control samples (mean +/- SEM). Results were analyzed by analysis of variance and t tests. In the presence of serum both nicotine and cotinine at concentrations of 10(-7) and 10(-8) mol/L were mitogenic for SMC in vitro (p < 0.05). A weak mitogenic effect was observed at a low serum concentration for cotinine but not nicotine. Cotinine at a concentration of 10(-9) mol/L, a level seen among passive smokers, was a statistically significant stimulus for DNA synthesis in both minimum serum and serum-supplemented media. At high concentrations both substances were toxic for the cells. We have demonstrated a potential role for nicotine and cotinine in the development of intimal hyperplasia and ultimately failure of the vascular reconstruction.

Journal of Vascular Surgery, 2021

OBJECTIVE Short and mid-term outcomes of endovascular aortic repair (EVAR) have made it a standar... more OBJECTIVE Short and mid-term outcomes of endovascular aortic repair (EVAR) have made it a standard treatment for abdominal aortic aneurysms (AAA), but newer generation devices have yet to demonstrate improved long-term rates of complications, reinterventions and survival. The TREO stent-graft is a latest generation device and is being evaluated for approval in the US. METHODS A multicenter, non-randomized, investigational device exemption (IDE) clinical trial assessed safety and effectiveness of the TREO device, with Core Laboratory assessment of imaging, and independent adjudication of safety. The primary effectiveness endpoint was successful aneurysm treatment at one year. The primary safety endpoint was the incidence of major adverse events (MAEs) at 30 days. RESULTS 150 patients (132 men, 88.0%) with infrarenal abdominal aortic (87.3%) or aorto-iliac (12.7%) aneurysms were enrolled. Data were normally distributed: mean age was 71.7 (± 7.4) years. The MAE incidence at 30 days was .7%. One subject experienced two MAEs, myocardial infarction and procedural blood loss of 1,000 cc. The proportion of successful aneurysm treatment at one year was 93.1%. Longer-term follow-up continues; there has been no aneurysm-related mortality to date. At the three-year time point, cumulative all-cause mortality was 10.7% (n = 16), 2.7% type I endoleaks (n = 4); 0% type III endoleaks; 54.3% of patients had > 5 mm of sac shrinkage; 9.3% had secondary interventions (n = 14). CONCLUSIONS Safety and effectiveness of endovascular repair of abdominal aneurysms with TREO were demonstrated with 93.1% successful aneurysm treatment at one year and 54.3% of patients had aneurysm sac shrinkage > 5 mm at three years. Long-term follow-up continues and will show whether these favorable outcomes are sustained.

VIIIth International Congress on Thrombosis and Haemostasis, 1981

The present investigation was designed to investigate the capacity of normal vessels to inactive ... more The present investigation was designed to investigate the capacity of normal vessels to inactive activated coagulation enzymes.Fresh and frozen porcine and canine aortae were exposed in virto to thrombin, dissolved in an albumin solution. Thrombin activity appearing on the vascular wall was assayed with a chromogenic substrate (S-2238-Kabi). Aortic endothelium retained considerable amounts of thrombin. After exposure of the aorta with plasma, a rapid inactivation of thrombin was observed. Exposure of the thrombin-absorbed endothelium to a modified Ringer’s solution resulted in a much slower inactivation. A similar slow inactivation was seen after exposure with plasma devoid of anti thrombin III. No difference was observed between fresh aortae and those stored in a frozen state. No inactivation occured during the observation time when the thrombin-albumin solution was mixed with the modified Ringer’s solution without presence of aortic endothelium and when mixed with normal plasma on...

Thrombosis and Haemostasis, 1983

SummaryThe aim of the investigation was to clarify the uptake of thrombin on vascular endothelium... more SummaryThe aim of the investigation was to clarify the uptake of thrombin on vascular endothelium and the inhibition of thrombin on the endothelium in the presence or absence of plasma. Segments of porcine aorta were used. Thrombin was labelled with 125I and its enzymatic activity was assayed amidolytically using a specific chromogenic substrate. After exposure to the endothelium both enzymatic activity and radioactivity disappeared from the thrombin solution and were recovered as surface bound activities.The enzyme activity confined to the endothelium rapidly disappeared in the presence of plasma but no activity was recovered in the plasma. The surface confined radioactivity, however, decreased slowly and was quantitatively recovered in the plasma. In the absence of plasma, i. e. in the presence of a balanced Ringer’s solution, only slow disappearance of thrombin enzymatic activity occurred although the rate of disappearance was higher than that of release of radioactivity.It is co...

Polish Journal of Surgery, 2007

Individual scientists in cancer research are usually dedicated, honest, hard-working people who o... more Individual scientists in cancer research are usually dedicated, honest, hard-working people who often reach levels of excellence, at the personal level. The purpose of the following review is not to criticize as deficient the individual efforts, but rather to point out deficiencies in our collective approach in elucidating the problem of CANCER.