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Biomedical subjects

A K Tassiopoulos

Publications and source records attributed to A K Tassiopoulos.

15 recordsLinked to original sources
PubMed2001

Construction and biological characterization of an HB-GAM/FGF-1 chimera for vascular tissue engineering.

OBJECTIVE: Cardiovascular tissue engineering approaches to vessel wall restoration have focused on the potent but relatively nonspecific and heparin-dependent mesenchymal cell mitogen fibroblast growth factor 1 (FGF-1). We hypothesized that linking FGF-1 to a sequence likely to bind to cell surface receptors relatively more abundant on endothelial cells (ECs) might induce a relative greater EC bioavailability of the FGF-1. We constructed a heparin-binding growth-associated molecule (HB-GAM)/FGF-1 chimera by linking full-length human HB-GAM to the amino-terminus of human FGF-1beta (21-154) and tested its activities on smooth muscle cells (SMCs) and ECs. METHODS: Primary canine carotid SMCs and jugular vein ECs were plated in 96-well plates in media containing 10% fetal bovine serum and grown to approximately 80% confluence. After being growth arrested in serum-free media for 24 hours, the cells were exposed to concentration ranges of cytokines and heparin, and proliferation was measured with tritiated-thymidine incorporation. Twenty percent fetal bovine serum was used as positive control, and phosphate-buffered saline was used as negative control. RESULTS: In the presence of heparin the HB-GAM/FGF-1 chimera stimulated less SMC proliferation than did the wild-type FGF-1 with a median effective dose of approximately 0.3 nmol versus approximately 0.1 nmol (P <.001). By contrast, the chimera retained full stimulating activity on EC proliferation with a median effective dose of 0.06 nmol for both cytokines. Unlike the wild-type protein, the chimera possessed heparin-independent activity. In the absence of heparin, the chimera induced dose-dependent EC and SMC proliferation at 0.06 nmol or more compared with the wild-type FGF-1, which stimulated minimal DNA synthesis at 6.0-nmol concentrations. CONCLUSIONS: The HB-GAM/FGF-1 chimera displays significantly greater and uniquely heparin-independent mitogenic activity for both cell types, and in the presence of heparin it displays a significantly greater EC specificity.

Animals↗
PubMed2001

Nonsaphenous superficial vein reflux.

BACKGROUND: Information on nonsaphenous superficial venous reflux is lacking. This study was designed to determine the prevalence of reflux in nonsaphenous veins, their association and correlation with risk factors, and signs and symptoms of chronic venous disease (CVD). METHODS: Information on 835 limbs in patients with signs and symptoms of CVD were prospectively entered into a customized database. These patients had been referred from the venous clinic to the vascular laboratory for color-flow duplex scanning evaluation of the lower-limb veins. All patients were examined for reflux in the standing and sitting positions. Nonsaphenous reflux was defined as that in superficial veins that are not part of the greater or lesser saphenous systems. Particular attention was paid to the patterns of reflux and anatomy of the nonsaphenous veins from the proximal to the distal ends, including their connections with the saphenous and deep veins. RESULTS: Nonsaphenous venous reflux was found in 84 limbs (10%) of 72 patients, 67 of whom were women. The mean number of pregnancies in these patients was higher than that of 100 randomly selected women with saphenous reflux (3.2 vs 2.2). According to CEAP classification, 90% of the limbs were in CVD classes 1 through 3 and only 10% had skin damage (classes 4-6). Symptoms were present in 67 limbs (80%). Forty-two limbs (50%) had reflux in tributaries of lateral, posterior, and medial thigh. These veins were connected with perforators uniting with the deep femoral, femoral, and muscular veins of the thigh in 36 limbs. Reflux in these perforators was detected in 19 limbs. Reflux arising from the pelvic veins was found in 29 limbs (34%), 18 of which were from vulvar veins medial to saphenofemoral junction and 11 of which were from veins in the gluteal area. Incompetent veins from the sciatic nerve were found in nine limbs (10%). Reflux in the vein of the popliteal fossa was found in seven limbs (8%). Reflux in knee tributaries was detected in three limbs (4%), two of which were connected with posterolateral knee perforators and one with the posterior tibial nerve veins. CONCLUSIONS: The prevalence of nonsaphenous reflux in our practice was 10%. The vast majority of these patients (93%) were women with a mean of 3.2 pregnancies. Ninety percent of these limbs have signs and symptoms assigned to CVD classes 1 to 3. These data may simply reflect the referral pattern, but also a possible association with female sex and number of pregnancies. The unusual anatomy of these veins stresses the importance of color-flow duplex scanning before surgery.

Chronic Disease↗
PubMed2000

Current concepts in chronic venous ulceration.

OBJECTIVES: despite numerous reports on the distribution of reflux in patients with venous ulceration, there is no consensus on the contribution of each venous system. This study was performed to evaluate the distribution of reflux in this group of patients. METHODS: a literature search from 1980 to 1998 was performed. Because duplex scanning is the best method for detecting venous reflux, we only included reports that used this diagnostic modality. All studies with less than 30 ulcerated limbs were excluded. Since most reports did not give detailed data on perforator veins, reflux in these veins was combined with the superficial and deep veins. Documented episodes of superficial or deep vein thrombosis were noted. RESULTS: thirteen studies that included 1249 ulcerated limbs fulfilled the inclusion criteria. The mean age of patients was 59 years (95% CI: 54-63, range: 14-93). Reflux was detected in 1153 (92%) of limbs. Reflux confined to the superficial veins alone was seen in 45% of limbs, in the deep veins alone in 12% and in both the superficial and deep veins in 43% of limbs. The overall involvement of the superficial veins was 88% and of the deep veins 56% (p <0. 0001). A documented episode of deep vein thrombosis was reported in only six of the 13 studies and the incidence was found to be 32%. CONCLUSIONS: reflux in the superficial veins is seen in 88% of limbs with venous ulcers (CEAP classes 5 and 6). Isolated superficial vein incompetence is detected in 45%, while reflux in the deep venous system alone is seen in only 12%. These data have significant clinical implications, since reflux in the superficial system can be easily eliminated by excision of the affected veins.

Chronic Disease↗
PubMed2000

Prevalence of deep venous reflux in patients with primary superficial vein incompetence.

PURPOSE: This prospective study was designed to determine the prevalence of deep reflux and the conditions under which it may occur in patients with primary superficial venous reflux and absence of deep venous thrombosis (DVT). METHODS: We studied 152 limbs in 120 consecutive patients in the standing position who had superficial venous reflux with color flow duplex scanning. Limbs with documented evidence of DVT or post-thrombotic vein wall changes during the examination were studied but not included in the analysis. Limbs were divided into those that had at least reflux in the saphenofemoral, the saphenopopliteal, or the gastropopliteal junction and into those with nonjunctional reflux in the superficial and gastrocnemial veins. Peak velocity and duration of reflux were measured. To examine the recirculation theory, we tested the deep veins by occluding and refluxing saphenous veins 10 cm below the sampling site. RESULTS: Thirteen limbs in 11 patients (9%) were excluded because of previous DVT. Of the remaining 139 limbs, 106 (76%) had junctional reflux. Saphenofemoral junction was involved in 89 limbs (84%), saphenopopliteal junction in 18 (17%), and gastropopliteal junction in 7 (4%). In 33 limbs (24%), reflux was detected in the main trunk or tributaries of the saphenous veins alone with no junctional incompetence. Femoral or popliteal reflux was present in 31 limbs (22%). This reflux was segmental in 27 limbs, and it was limited in the junction in 24 limbs. The mean duration of deep venous reflux was 0.9 seconds, it ranged from 0.6 to 3.7 seconds, and it was significantly shorter than that in the superficial veins (2.6 seconds; P <.0001). In the absence of junctional reflux, the prevalence of deep venous insufficiency (DVI) was significantly lower compared with that in limbs with junctional involvement (2 of 33 vs 29 of 106; P =.038). The mean duration of deep venous reflux in these groups was comparable (0.85 seconds vs 0. 91 seconds; P =.44). Occlusion of the incompetent superficial veins reduced somewhat the duration of the deep venous reflux but did not abolish it (0.88 seconds vs 0.82 seconds; P =.072). The presence of DVI was associated with junctional reflux of high peak velocity and long duration. CONCLUSIONS: The prevalence of DVI in patients with primary superficial venous reflux and without history of DVT is 22%. However, this reflux is segmental, mainly in the common femoral vein, and is of short duration. It is associated with the presence of junctional incompetence that has a high peak velocity and long duration. These findings may explain why surgical correction of superficial reflux abolishes DVI.

Adult↗
PubMed2000

Angiogenic mechanisms of endothelialization of cardiovascular implants: a review of recent investigative strategies.

Both cardiovascular implants and therapeutic interventions on native arteries fail due to biologic responses occurring at the blood/prosthesis/arterial wall and tissue/prosthesis/arterial wall interfaces, resulting in the failure modes of thrombosis and myointimal hyperplasia. Systemic pharmacologic approaches including use of anti-coagulant and anti-platelet agents have significant untoward side effects and have not resulted in a dramatic impact on failure modes in many applications, including small diameter vascular grafts. Local delivery of therapeutic agents via surface attachment with defined release kinetics may alter thrombogenicity and/or myointimal hyperplasia. Therapeutic agents may include a spectrum of biologic agents from peptides to endothelial cells. Efficient attachment and release of these agents in biologically active form is dependent upon improved methods of surface modification. The intended action of the biologic agent may similarly be impacted by the surface and bulk characteristics of the underlying biomaterial. It is often assumed, without concrete data. that surface re-endothelialization may have a beneficial impact on both thrombogenicity and myointimal hyperplasia. New clinical data on endothelial cell seeding has been supportive. Spontaneous re-endothelialization may be stimulated via an induced directed angiogenesis resulting in trans-interstitial capillarization and surface endothelialization. Recent advances in therapeutic angiogenesis have suggested the power of angiogenic factors to induce neovascularization of ischemic tissue beds. These concepts have been used to surface modify prosthetic devices with either VEGF or FGF and both in vitro and animal data suggest a potent stimulation of surface re-endothelialization. Neither of these growth factors is likely to be ideal. VEGF is relatively endothelial cell specific but is a relatively weak endothelial cell mitogen. FGF-1 and FGF-2 are more potent mitogens but are less cell specific. Recent work has led to the generation of mutant growth factors via site-induced mutagenesis and results of several such FGF mutants on endothelial cell and smooth muscle cell proliferative response have been studied. The use of 'designer growth factors' on cardiovascular implants and on manipulated native vessels may have a significant positive impact on re-endothelialization and thereby on the failure modes of thrombosis and myointimal hyperplasia.

Animals↗
PubMed1999

Segmental pulmonary vascular responses to changes in pH in rat lungs: role of nitric oxide.

BACKGROUND: Respiratory or renal failure is associated with changes in blood pH. Changes in pH may have profound effects on vascular tone and reactivity. Site of action of acidosis in the pulmonary vasculature and the role of nitric oxide production remain unclear. METHODS: We utilized isolated rat lung preparation perfused with autologous blood (Hct = 20%, flow rate = 33 ml/min), and investigated the effect of acidosis and alkalosis (induced by ventilation with high and low inspired CO2) on vascular resistance and the role of nitric oxide during resting and elevated tone conditions. Changes in resistance were described in terms of small and large arteries and veins, using the vascular occlusion technique. RESULTS: Acidosis (Pco2 = 66.7 +/- 0.7 mmHg, pH = 7.17 +/- 0.01, Po2 = 255 +/- 3 mmHg) caused vasoconstriction under resting and increased vascular tone conditions (U46619-induced). The changes in resistance occurred primarily in the small arteries. In contrast, alkalosis (Pco2 = 20.1 +/- 0.3 mmHg, pH = 7.61 +/- 0.01, Po2 = 244 +/- 3 mmHg) caused vasodilation only at elevated tone conditions. Nitro-L-arginine (LNA), an inhibitor of nitric oxide synthase, increased vascular resistance slightly but did not modulate the responses to pH, suggesting that such responses are not nitric oxide dependent. During KCl-induced contraction, the effects of pH were abolished. CONCLUSIONS: We conclude that in rat lung, acidosis causes an increase in pulmonary vascular resistance at normal and elevated tone conditions. Furthermore, the response is limited primarily to the small arteries, and is not mediated by nitric oxide. Alkalosis tends to cause the opposite effects. The effects of acidosis and alkalosis were abolished when vascular tone was elevated with a low dose of KCl, suggesting that vascular response to pH may involve changes in membrane potential.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Acidosis stimulates nitric oxide production and lung damage in rats.

Systemic hypotension during sepsis is thought to be due to nitric oxide (NO) overproduction, but it may also be due to acidosis. We evaluated in healthy rats the consequences of acid infusion on NO and blood pressure. Sprague-Dawley rats were anesthetized, and ventilated with room air. The animals were randomized into four groups. Group 1 (C, n = 10) received only normal saline at rates comparable to the other groups. Group 2 (A1, n = 10) received hydrochloric acid at 0.162 mmol in the first 15 to 30 min, followed by a continuous infusion of 0.058 mmol/h for 5 h. Group 3 (AG+A1, n = 6) was pretreated with aminoguanidine (AG, 50 mg/kg), and HCl was infused as above. Group 4 (A2, n = 7) received HCl at twice the rate used in A1. Nitric oxide concentration in the exhaled gas (ENO), blood gases, and mean arterial pressure were measured every 30 min. Acid infusion in A1 caused the pH to fall gradually from 7.43 +/- 0. 01 to 7.13 +/- 0.05. This moderate decrease in pH was associated with a marked increase in ENO (1.6 +/- 0.3 to 114.2 +/- 22.3 ppb), an increase in plasma nitrite/nitrate (17.3 +/- 3.7 to 35.2 +/- 4.3 microM), and a significant decrease in blood pressure (110.5 +/- 6.3 to 63.3 +/- 15.0 mm Hg). Furthermore, acidosis caused lung inflammation, as suggested by the increase in lung myeloperoxidase activity (282.2 +/- 24.7 to 679.3 +/- 57.3 U/min/g) and lung injury score (1.7 +/- 0.2 to 3.5 +/- 0.6). Acidosis after AG pretreatment was associated with a similar change in pH, but the increase in ENO, nitrite/nitrate, and systemic hypotension were prevented. Furthermore, lung injury was attenuated by AG, as suggested by a lower myeloperoxidase activity, though lung injury score was not altered. In this model, moderate acidosis causes increases in NO, hypotension, and lung inflammation. Lung inflammation and injury are due in part to acidosis and NO production. This is the first report to show a direct effect of chronic acidosis on NO production and lung injury. These results have profound implications on the role of acidosis on NO production and lung injury during sepsis.

Acidosis↗
PubMed1998

Neutrophil sequestration in the lung following acute aortic occlusion starts during ischaemia and can be attenuated by tumour necrosis factor and nitric oxide blockade.

OBJECTIVES: To investigate the role of lower extremity ischaemia in acute lung injury with special emphasis on the role of tumour necrosis factor (TNF) and nitric oxide (NO) as mediators of neutrophil (PMN) chemotaxis in the lung. DESIGN: Prospective randomised study. MATERIALS AND METHODS: Sprague-Dawley rats were randomized into four groups: group 1 (x-clmap): aorta clamped just above the bifurcation for 3 h; group 2 (AG): 50 mg/kg aminoguanidine, a specific inducible NO synthase (iNOS) inhibitor, was administered prior to aortic occlusion; group 3 (Steroids): 1 mg/kg dexamethasone was administered prior to aortic occlusion; and group 4 (TNFbp): 2 mg/kg TNFbp, a PEGylated dimeric form of the high affinity TNF receptor I (R1) was administered prior to aortic occlusion to block TNF action. Groups 2, 3 and 4 were subjected to the same ischaemia time as group 1. NO concentration in the exhaled gas (ENO) was measured in 30 min intervals. At the end of the 3 h ischaemia, one lung was excised and fixed for routine histological evaluation, and the other underwent bronchoalveolar lavage (BAL). PMN chemotaxis towards the BAL fluid was then measured using the blindwell technique. RESULTS: ENO in group 1 increased from 0.9 +/- 0.3 ppb at baseline, to 41.3 +/- 9.2 ppb at the end of ischaemia. Animals in this group exhibited significant lung inflammation. Aminoguanidine, dexamethasone and TNFbp blocked NO production (peak ENO values of 7.2 +/- 1.9, 12.6 +/- 1.3 and 8.9 +/- 1.7 ppb for groups 2, 3 and 4 respectively), decreased PMN chemotaxis and sequestration in the lung, and attenuated lung inflammation. CONCLUSIONS: Acute lung injury resulting from distal aortic occlusion starts during ischaemia. TNF and NO blockade decrease PMN chemotaxis and sequestration and attenuate the lung injury process.

Analysis of Variance↗
PubMed1998

Treatment of septic shock in rats with nitric oxide synthase inhibitors and inhaled nitric oxide.

OBJECTIVE: To evaluate the effect of treatment with a combination of nitric oxide synthase inhibitors and inhaled nitric oxide on systemic hypotension during sepsis. DESIGN: Prospective, randomized, controlled study on anesthetized animals. SETTING: A cardiopulmonary research laboratory. SUBJECTS: Forty-seven male adult Sprague-Dawley rats. INTERVENTIONS: Animals were anesthetized, mechanically ventilated with room air, and randomized into six groups: a) the control group (C, n=6) received normal saline infusion; b) the endotoxin-treated group received 100 mg/kg i.v. of Escherichia coli lipopolysaccharide (LPS, n=9); c) the third group received LPS, and 1 hr later the animals were treated with 100 mg/kg i.v. Nw-nitro-L-arginine (LNA, n=9); d) the fourth group received LPS, and after 1 hr, the animals were treated with 100 mg/kg i.v. aminoguanidine (AG, n=9); e) the fifth group received LPS and 1 hr later was treated with LNA plus 1 ppm inhaled nitric oxide (LNA+NO, n=7); f) the sixth group received LPS and 1 hr later was treated with aminoguanidine plus inhaled NO (AG+NO, n=7). Inhaled NO was administered continuously until the end of the experiment. MEASUREMENTS AND MAIN RESULTS: Systemic mean blood pressure (MAP) was monitored through a catheter in the carotid artery. Mean exhaled NO (ENO) was measured before LPS (T0) and every 30 mins thereafter for 5 hrs. Arterial blood gases and pH were measured every 30 mins for the first 2 hrs and then every hour. No attempt was made to regulate the animal body temperature. All the rats became equally hypothermic (28.9+/-1.2 degrees C [SEM]) at the end of the experiment. In the control group, blood pressure and pH remained stable for the duration of the experiment, however, ENO increased gradually from 1.3+/-0.7 to 17.6+/-3.1 ppb after 5 hrs (p< .05). In the LPS treated rats, MAP decreased in the first 30 mins and then remained stable for 5 hrs. The decrease in MAP was associated with a gradual increase in ENO, which was significant after 180 mins (58.9+/-16.6 ppb) and reached 95.3+/-27.5 ppb after 5 hrs (p< .05). LNA and AG prevented the increase in ENO after LPS to the level in the control group. AG caused a partial reversal of systemic hypotension, which lasted for the duration of the experiment. LNA reversed systemic hypotension almost completely but only transiently for 1 hr, and caused severe metabolic acidosis in all animals. The co-administration of NO with AG had no added benefits on MAP and pH. In contrast, NO inhalation increased the duration of the reversal in MAP after LNA, alleviated the degree of acidosis, and decreased the mortality rate (from 55% to 29%). CONCLUSIONS: In this animal model, LPS-induced hypotension was alleviated slightly and durably after AG, but only transiently after LNA. Furthermore, co-administration of NO with AG had no added benefits but alleviated the severity of metabolic acidosis and mortality after LNA. We conclude that nitric oxide synthase (NOS) inhibitors, given as a single large bolus in the early phase of sepsis, can exhibit some beneficial effects. Administration of inhaled NO with NOS inhibitors provided more benefits in some conditions and therefore may be a useful therapeutic combination in sepsis. NO production in sepsis does not seem to be a primary cause of systemic hypotension. Other factors are likely to have a major role.

Administration, Inhalation↗
PubMed1997

Role of nitric oxide and tumor necrosis factor on lung injury caused by ischemia/reperfusion of the lower extremities.

PURPOSE: Acute aortic occlusion with subsequent ischemia/reperfusion (I/R) of the lower extremities is known to predispose to lung injury. The pathophysiologic mechanisms of this injury are not clear. In the present study, we studied the role of tumor necrosis factor (TNF) and nitric oxide (NO) in lung injury caused by lower extremity I/R. METHODS: A rat model in which the infrarenal aorta was cross-clamped for 3 hours followed by 1 hour of reperfusion was used. The rats were randomized into five groups: group 1, aorta exposed but not clamped; group 2, aorta clamped for 3 hours, followed by 1 hour of reperfusion; group 3, 1 mg/kg dexamethasone administered before the aorta was clamped; group 4, 25 mg aminoguanidine, a specific inducible NO synthase (iNOS) inhibitor, administered before the aorta was clamped; and group 5, 2 mg/kg TNFbp, a PEG-ylated dimeric form of the high-affinity p55 TNF receptor I (RI), administered before the aorta was clamped. NO concentration in the exhaled gas (ENO) was measured, as an index of NO production by the lung, in 30 minute intervals during I/R. Serial arterial blood samples for TNF assay were obtained during the course of the experiment. At the end of the experiment, the lungs were removed and histologically examined for evidence of injury. RESULTS: ENO in group 2 increased from 0.7 +/- 0.3 ppb at baseline to 54.3 +/- 7.5 ppb at the end of ischemia and remained stable during reperfusion (54.6 +/- 8.5 ppb at the end of reperfusion). ENO production was blocked by aminoguanidine, by dexamethasone, and by TNFbp given before aortic occlusion. Serum TNF in groups 2, 3 and 4 increased rapidly during early ischemia, reaching its peak value 60 minutes after occlusion of the aorta, then gradually declined to baseline levels at the end of ischemia, and remained low during reperfusion. TNFbp decreased serum TNF concentration significantly when it was given before aortic occlusion. Histologic examination of the lungs at the end of the experiment revealed that aminoguanidine, dexamethasone, and TNFbp had a protective effect on the lungs. CONCLUSIONS: Serum TNF increases rapidly during lower extremity ischemia and causes increased production of NO from the lung by upregulating iNOS. Increased NO is associated with more severe lung injury, and iNOS blockade has beneficial effects on the lung. TNF blockade before ischemia decreases NO production by the lung and attenuates lung injury. ENO can be used as an early marker of lung injury caused by lower extremity I/R.

Animals↗
PubMed1997

Cardiac rupture due to blunt trauma.

Cardiac rupture due to blunt trauma has been recognized with increasing frequency over the past two decades. The mortality rate is high and the majority of patients die before they arrive at the emergency department. A high index of suspicion and prompt surgical intervention are crucial for survival. We report the management of two patients, one with a double right atrial tear and one with a single right atrial tear, after each was involved in a motor vehicle accident.

Accidents, Traffic↗
PubMed1996

Small bowel fistulas.

The treatment of small bowel fistulas remains a difficult problem. Spontaneous closure rates of 30% are currently being achieved after 4 to 6 weeks of conservative therapy with bowel rest, TPN, octreotide, and control of sepsis. Resection of the fistulous bowel is warranted if fistula closure has not occurred by 4 to 6 weeks.

Enteral Nutrition↗
PubMedDate not supplied

Nutritional support in the patient with HIV infection.

Weight loss and malnutrition are the most common symptoms associated with active infection with human immunodeficiency virus. The origin of the malnutrition is considered multifactorial and broadly includes decreased nutrient intake, nutrient malabsorption, and metabolic alterations. Steady advances have been made in understanding the mechanisms underlying weight loss in these patients. The utility and optimal modes of nutrition support have not yet been fully established.

Acquired Immunodeficiency Syndrome↗