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Biomedical subjects

A Jawien

Publications and source records attributed to A Jawien.

12 recordsLinked to original sources
PubMed2006

Sarpogrelate, a 5-hT2A receptor antagonist in intermittent claudication. A phase II European study.

This was a multinational, multicentre, double-blind Phase II study in Europe to evaluate the efficacy and safety of two dose regimens (200 mg bid and 200 mg tid) of sarpogrelate (MCI-9042, 5-HT2A receptor antagonist) compared to placebo in patients with stable, moderately severe intermittent claudication. Following a single-blind placebo run-in period of 6 weeks, 364 (309 male and 55 female) patients (59.2 +/- 8.4 years, mean +/- SD) were randomized to receive sarpogrelate 200 mg bid, 200 mg tid or placebo for 24 weeks with a follow-up of 8 weeks. The primary objective was the increase of absolute claudication distance (ACD) at the end of treatment (week 24) compared to placebo. Analysis of covariance (ANCOVA) was performed on the log-transformed percentage of baseline ACD: loge(ACD/baseline). A responder analysis (defined as a > or = 50% improvement in ACD) was also performed. There was a marked training/placebo effect on the ACD which persisted up to 16 weeks. At 24 weeks the primary objective did not reach statistical significance (200mg bid vs placebo, p = 0.225; 200mg tid vs placebo, p = 0.580). In the responder analysis, 200 mg bid showed a statistically significant difference vs placebo (p = 0.035). In the exploratory analysis with completers (patients completing all treadmill tests), there was a statistical difference in ACD/baseline change for 200 mg bid (p = 0.035) and in the responder analysis for 200 mg tid (p = 0.044) at 24 weeks compared to placebo. Both treatments showed a carry-over effect for ACD during the 8-week follow-up (weeks 28-32). The treatment was well tolerated and no clinically significant safety concerns were reported. In conclusion, the study results confirm that sarpogrelate is well tolerated and although the primary endpoint failed to reach statistical significance, the responder analysis showed an increased absolute walking distance, which makes a further trial warranted, including a larger population, and possibly also a longer treatment period.

Adult↗
PubMed2005

Sciatic nerve varices.

OBJECTIVE(S): To describe patients presenting with sciatic nerve varices (SNV), presenting pitfalls in diagnosis and management. DESIGN: Case series. METHODS: Patients were investigated using duplex ultrasonography pre-operatively in three cases. Treatment was undertaken both by surgery and by foam sclerotherapy. RESULTS: Clinically, SNV appeared just below the popliteal skin crease, lateral to the small saphenous vein (SSV). In two cases SNV occurred alone, in two further cases SNV occurred in conjunction with varices from other sources. Symptoms of 'sciatic' pain were present in all. Foam sclerotherapy (1% Polidocanol) was undertaken in one case with a varix. Complete obliteration of the vein and resolution of all symptoms was achieved at the 1-month follow-up examination. Surgical management was used in the other cases. CONCLUSION: The sciatic nerve vein follows the fibular saphenous nerve (lying superficial to the fascia in the leg). This nerve arises from the common peroneal nerve (in the popliteal fossa), and is a major branch of the sciatic nerve. Varices of the associated vein appear to be the result of a dysplasia. This condition may be more common than is currently recognised.

Humans↗
PubMed2005

Tissue factor, tissue factor pathway inhibitor and vascular endothelial growth factor-A in carotid atherosclerotic plaques.

OBJECTIVE: To determine the concentration of tissue factor (TF), tissue factor pathway inhibitor (TFPI) and vascular endothelial growth factor A (VEGF-A) in carotid plaques. MATERIALS AND METHODS: Thirty-eight consecutive patients (20 symptomatic, 18 asymptomatic) undergoing carotid endarterectomy were enrolled into the current study. The concentration of TF, TFPI and VEGF-A in carotid plaque homogenates and blood plasma was measured using enzyme immunoassay. RESULTS: The concentration of TF in carotid plaque homogenates was 60 fold higher than in blood plasma. There were no statistically significant differences between the concentration of TF, TFPI and VEGF-A in symptomatic and asymptomatic plaques. Carotid plaques of diabetic patients contained an increased level of TF and VEGF-A ( p = 0.002, p = 0.005). The plaque concentration of VEGF-A was elevated among older patients ( p = 0.02). Carotid plaques of non-smokers contained an increased level of TFPI ( p = 0.03). The concentration of TF, TFPI and VEGF-A in carotid plaques correlated positively with plasma level of these factors ( R = 0.86; p < 0.0001; R = 0.91; p < 0.0001; R = 0.80; p = 0.001, respectively). A highly positive correlation between concentration of VEGF-A and TF, TFPI in carotid plaques was also observed ( R = 0.75; p < 0.001; R = 0.62; p < 0.001, respectively). CONCLUSIONS: TF, TFPI and VEGF-A concentrations do not differ in atheroma removed from symptomatic and asymptomatic patients but are higher in diabetic patients. There is a highly positive correlation between the level of VEGF-A and TF, TFPI in carotid plaques.

Aged↗
PubMed2004

Selected haemostatic factors in carotid bifurcation plaques of patients undergoing carotid endarterectomy.

OBJECTIVE: To determine the concentration of selected haemostatic factors (HFs): thrombin-antithrombin complexes (TAT), antithrombin (AT), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1) and D-dimers in carotid bifurcation plaques and to compare plaque composition in different subgroups of patients (mainly those with symptomatic and asymptomatic carotid stenosis). MATERIALS AND METHODS: Thirty-eight consecutive patients (20 symptomatic, 18 asymptomatic) undergoing carotid endarterectomy were enrolled in the study. The concentration of selected HFs in carotid plaques was measured using mainly enzyme immunoassay (ELISA). Simultaneously, the concentration of HFs in plasma was also obtained. RESULTS: Symptomatic plaques contained significantly more TAT complexes (p=0.03). AT was found only in nine out of 38 carotid plaques and was present mainly in symptomatic carotid plaques (n=8/9)(p<0.006). No significant differences were found between symptomatic and asymptomatic carotid plaques with respect to t-PA, PAI-1 and D-dimers concentration. There was an increased concentration of TAT (p<0.001), t-PA (p<0.02) and D-dimers (p<0.02) in carotid plaques of diabetic patients. Patients with coexisting intermittent claudication had elevated levels of D-dimers in carotid plaques (p<0.02). The only positive correlation was demonstrated between the concentration of AT in plasma and carotid plaques (R=0.76; p=0.02). CONCLUSIONS: All the evaluated HFs are the components of a carotid plaque. Symptomatic patients have increased concentration of TAT complexes in a carotid plaque. The symptomatic carotid plaque contains AT more frequently, which correlates positively with AT plasma levels. The most marked changes in the carotid plaque haemostatic composition (expressed by elevated levels of TAT, t-PA and D-dimers) have diabetic patients.

Aged↗
PubMed2001

Further evidence that oxidative stress may be a risk factor responsible for the development of atherosclerosis.

There are numerous data suggesting that oxidative stress may be involved in the development of atherosclerosis. Therefore, in the present study we measured the amount of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), one of the typical biomarkers of oxidative stress, in DNA isolated from lymphocytes of the patients and in the control group. Levels of antioxidant vitamins (A, C, and E) and intracellular labile iron pool (LIP), which can influence oxidative stress, were also determined. Blood samples were obtained from a control group of 55 healthy persons and from 43 atherosclerotic patients. 8-OH-dG and the vitamin levels were measured by high-performance liquid chromatography. Labile iron pool in lymphocytes was analyzed by fluorescent assay. The levels of 8-OH-dG and LIP were significantly higher and vitamin C concentration was significantly lower in the patient group than in the control group. The rest of the analyzed parameters do not significantly differ between the groups. A lower concentration of vitamin C and higher levels of labile iron pool in a group of atherosclerotic patients when compared with the control group may lead to oxidative stress, which is manifested by a higher level of 8-OH-dG in blood lymphocytes. All these factors may create an environment that promotes the development of atherosclerosis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

8-Oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine levels in human urine do not depend on diet.

In the present study, we used the method involving HPLC pre-purification followed by gas chromatography with isotope dilution mass spectrometric detection for the determination of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 8-oxo-7,8-dihydroguanine (8-oxoGua) in human urine. The mean levels of 8-oxoGua and 8-oxodGuo in the urine samples of the subjects on unrestricted diet were respectively 1.87 nmol/kg 24 h (+/-0.90) and 0.83 nmol/kg 24 h (+/-0.49), and in the case of the groups studied, they did not depend on the applied diet. The sum of the amounts of both compounds in urine can give information about the formation rate of 8-oxoGua in cellular DNA. It is also likely that the levels of modified nucleo-base/side in urine sample are reflective of the involvement of different repair pathways responsible for the removal of 8-oxodGuo from DNA, namely base excision repair (BER) and nucleotide excision repair (NER).

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1992

Flow affects development of intimal hyperplasia after arterial injury in rats.

This study examined the effects of blood flow on intimal hyperplasia after balloon catheter injury of the rat common carotid artery. Flow was altered by ligation of the opposite common carotid artery (increased flow) or of the ipsilateral internal carotid artery (decreased flow). Blood flow decreased by 35% in the low-flow group and increased by 29% in the high-flow group. Similar changes in mean velocity were observed. Cross-sectional intimal area was significantly greater in the low- than the high-flow group at 2 weeks (0.11 +/- 0.01 versus 0.06 +/- 0.01 mm2, p less than 0.01) and 4 weeks (0.17 +/- 0.02 versus 0.12 +/- 0.01 mm2, p = 0.01) but not at 1 or 8 weeks. Smooth muscle cell proliferation rates (thymidine labeling indexes) were not different in high- and low-flow groups at 2 days and at 1 and 4 weeks. Matrix accumulation at 2 and 4 weeks was the same in both groups. Mature neointima did not respond to changes in flow; when vessel ligation was delayed until 2 months after injury, there was no effect on neointimal area. These data indicate that early neointimal hyperplasia is increased when flow is reduced, possibly because of alteration of smooth muscle cell migration.

Animals↗
PubMed1992

Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty.

Platelet-derived growth factor (PDGF) is a mitogen and chemoattractant for vascular smooth muscle cells (SMC) in vitro, but its activities in vivo remain largely undefined. We infused recombinant PDGF-BB (0.01-0.30 mg/kg per d i.v.) into rats subjected to carotid injury. PDGF-BB produced a small increase (two- to threefold) in medial SMC proliferation. More importantly, PDGF-BB greatly increased (20-fold) the intimal thickening and the migration of SMC from the media to the intima during the first 7 d after injury. These data provide support for the hypothesis that PDGF, and perhaps other platelet factors, might play an important role in the movement of mesenchymal cells into zones of injury undergoing repair.

Angioplasty, Balloon↗
PubMed1992

Thrombogenicity of gelatine impregnated vascular grafts--an experimental study.

Acute platelet deposition on a knitted Dacron graft impregnated with gelatine to confer zero porosity was compared to a standard knitted Dacron graft. The accumulation of platelets was assessed by reinfusion of 111In labelled platelets and imaging with a scintillation camera. The accumulation of platelets was significantly higher on the sealed grafts at the beginning of the experiments but a steady-state was rapidly achieved and no differences was observed regarding the patency.

Animals↗
PubMed1990

Experimental evaluation of polymerized Dacron grafts in the iliac position of pigs.

Three differently polymerized Dacron grafts were compared to ordinary Dacron grafts and polytetrafluoroethylene grafts in the iliac artery of pigs. The grafts were inserted end-to-side and left for 40 days. Explantation was performed after glutaraldehyde pressure fixation. Gross morphology, light microscopy, and scanning electron microscopy were used to examine the specimens. We concluded that the polymerized grafts behaved similarly to polytetrafluoroethylene grafts and had a very limited foreign body reaction. Endothelial-like cells covered most of the graft surface.

Animals↗
PubMedDate not supplied

Experience with Doppler investigations in vibration syndrome.

The aim of this study was to examine the possibility of applying Doppler flowmetry in diagnosing vascular changes in workers exposed to vibration. Polish, directional, continuous-wave Doppler apparatus UDP-10, has been used for evaluation of multisegmental blood pressure, velocity flow tracing and for making an ultrasonic "map" of the upper limbs. The thermal test used in this investigation allowed us to distinguish functional and organic alterations in the hand arteries. The present study has been performed in 113 workers, employed in an iron casting company and exposed to vibration. The control group comprised 62 healthy men. Raynaud's phenomenon has been found in 34 workers. It has been confirmed that Doppler equipment is a safe, noninvasive technique, with a high percentage of diagnostic accuracy and is a great aid in establishing the severity of symptoms in patients with vasospastic disease. As a result of our study the diagram for diagnosing patients with vasospastic disease has been elaborated and presented in this work.

Adult↗