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Biomedical subjects

G Wozniak

Publications and source records attributed to G Wozniak.

At least 19 recordsLinked to original sources
PubMed2005

[Mechanisms influencing cellular physiology as a concept of treatment for wound healing disturbances].

AIM: Recent knowledge about repair mechanisms in different types of tissue is the basic of actual therapeutic efforts. Center of several experimental and clinical approaches is the influencing of angiogenesis with an also distinct meaning concerning wound healing. Therefore, application of growth factors, gene transfer, and employment of genetically manipulated cells often aim at angiogenesis. Nevertheless, manipulation of angiogenesis also leads to secondary problems such as hyperpermeability followed by impairment of local wound milieu. Our study was done to identify mechanisms to protect from disturbances of endothelial barrier function. METHOD: In a first experimental investigation on cultured endothelial cells, the influence of plasma-transglutaminase (Factor XIII) to endothelial barrier function was studied. In a second step, the influence of Factor XIII on wound healing properties was investigated in patients with a chronic venous ulceration. RESULTS: Activated Factor XIII (FXIIIA*) led to a dose-dependent reduction of endothelial cell permeability of 30 % compared to control with a maximum effect using 1 to 5 U/mL. Clinical investigation revealed a nearly complete reduction of wound secretion. CONCLUSION: Experimental studies revealed that activated Factor XIII stabilizes endothelial barrier under basic conditions as well as under conditions of induced hyperpermeability. Clinical study revealed that Factor XIII also distinctly reduces wound secretion. Therefore, plasma-transglutaminase may offer a new therapeutic option to treat the local or generalized leakage-syndrome.

Administration, Topical↗
PubMed2005

Use of LifeSite port systems for hemodialysis in Germany.

AIM: Studies haveshown lower infection rates of port systems compared to established, transcutaneous cuffed-tunneled dialysis catheters. This was shown in otherwise quite healthy patients starting hemodialysis treatment. It is unclear to what extent these results can be applied to countries such as Germany where, unlike the US, central venous access systems are used mainly for patients with a high comorbidity. We investigated complications in patients with exhausted access sites and a high comorbidity. METHOD: In a retrospective, representative multicenter study, 34 patients with a high rate of comorbidity were assessed. The age was 67.5 +/- 12.5 years, the median number of failed AV fistulas or AV grafts was 4 (0-18). RESULTS: The survival rate was 84.9%, 55.2% and 55.2% after 6, 12 and 24 months, respectively. The rate of local and systemic infections was 2.83 per 1,000 patient days. Thrombotic events occurred at a rate of 2.26 per 1,000 patient days. We did not see a statistically significant effect using 0.2% sodium oxychlorosene (n = 13) or 70% isopropyl alcohol solution (n = 21) as the antimicrobial solution used before opening the valve of the port with the dialysis needle. CONCLUSIONS: We showed that complications of hemodialysis treatment using LifeSite vascular access systems in patients with very high co-morbidity in Germany seem to occur less often than those reported for cuffed-tunneled catheters and were not more frequent than those reported for other patient groups using LifeSites in the US. Technical survival rates were encouraging for up to two years. LifeSite port systems might be a good or even better central venous access than cuffed-tunneled catheters for patients in which an AV fistula or -graft is not possible.

Aged↗
PubMed2005

Split-course accelerated hyperfractionation (CHA-CHA) for advanced head and neck cancers -- preliminary results.

The purpose of the study was to evaluate toxicity and effectiveness of the split course, accelerated hyperfractionation with a planned gap (CHA-CHA) on a base of the pilot group treatment results. The material consisted of 27 patients with advanced (T2N2c-3, T3-4N2), oral cavity, oro- hypopharynx and larynx cancers, irradiated with a df 1.6 Gy twice a day, with 6-hour gap, up to TD 64 Gy in 28 days, with 8-day gap in a middle. Mean tumor dimensions were 4.2 and 3.9 cm in X and Y axes, respectively and mean nodes dimensions 3.9 cm in both axes. The course and intensity of the mucositis were evaluated in the Dische scale together with the degree of a tumor and nodes regression. Survival analysis and dependencies evaluation between physical/biological factors and treatment results were performed. The mucositis intensity was high from 2nd to 5th week (the highest mean - 15 Dische points in 4th week), but on acceptable level. 54.5% of CR of the tumor and 57.1% of nodes were noted. Survival analysis showed 44% of a 2-year and 35% of a 4-year OS and 44% of a 2-year and 38% of a 4-year survival excluding deaths from distant metastases. Correlation between the hemoglobin level and the nodal regression two months after the radiotherapy (p=0.01), showed the tumor diameter and TCP (p=0.047), the OS and the nodes diameter (p=0.004), the PS (p=0.02) and the hemoglobin level (p=0.04). CHA-CHA could be a valid method in advanced head and neck cancer treatment but its efficacy should be confirmed in randomized phase of trial.

Adult↗
PubMed2003

Intracellular adhesion molecule-1 in patients developing pulmonary insufficiency after cardiopulmonary bypass.

OBJECTIVES: Cardiopulmonary bypass activates adhesion molecules, which are associated with systemic inflammation and organ dysfunction. The intracellular adhesion molecule-1 (ICAM-1) has been evaluated in patients presenting pulmonary dysfunction after cardiac surgery. MATERIALS AND METHODS: Postoperative serum levels of the ICAM-1 were measured in 40 patients who underwent isolated coronary artery bypass grafting, in 28 with uneventful postoperative recovery (70 %) (Group 1), and in 12 (30 %) with postoperative respiratory insufficiency (Group 2), defined by the need for prolonged (> 24 hours) mechanical ventilation using a fractional oxygen concentration of > 40 %. RESULTS: Patients in group 1 were ventilated for 12.21 +/- 4.86 hours and those in group 2 for 92.91 +/- 48.14 hours (p < 0.001). ICAM-1 decreased from 145.98 +/- 73.40 ng/ml to 81.15 +/- 114.82 ng/ml in group 1, while in group 2 ICAM-1 showed a significant higher level and increased to 435.01 +/- 130.02 ng/ml (p < 0.001). The leukocyte count increased in both groups as well as the C-reactive protein (CRP) during the postoperative course. The CRP behaves similar in both groups (p = 0.636) in contrast to the leukocyte count which was significantly higher in group 2 (p < 0.01). While none of the patients in group 1 died the mortality in group 2 was 50 % (p < 0.001). CONCLUSION: Respiratory insufficiency after cardiopulmonary bypass is associated with a distinct increase in the ICAM-1. The reason for the increase of the ICAM-1 in this small subset of patients has not been clarified.

Aged↗
PubMed2002

[Factor XIII and endothelial barrier function].

Activated factor XIII (FXIIIa) crosslinks fibrin monomers to a stable clot. Due to this function, FXIIIa plays a major role in hemostasis and fibrinolysis. Additionally, it is well known that FXIIIa has a special meaning in cell adhesion and migration, in generation of extracellular matrix, in tissue repair and wound healing. New experimental studies revealed a FXIIIa stabilizing endothelial barrier function. In this function, FXIIIa reduces endothelial permeability for macromolecules in cultured endothelial monolayers and prevents impending barrier failure in coronary arteries of isolated hearts. This effect is due to the cross-linking of several proteins within the extracellular matrix, especially in the interendothelial clefts.

Cell Adhesion↗
PubMed2002

[Factor XIII and wound healing].

In addition to those wounds with increasing fragility of capillaries during impaired healing, there are especially long lasting diabetic wounds or calf ulcerations due to chronic venous insufficiency or postthrombotic syndrome that show a failure of endothelial barrier function with an increased permeability as an important part of its pathophysiological situation. The possibility of controlling this increased permeability is of great therapeutical interest and may give distinct benefit for wound healing. In the close past, clinical as well as experimental studies revealed the plasma transglutaminase (factor XIIIa) as potential new strategy in treatment of increased vascular permeability.

Factor XIII↗
PubMed2001

Expression of sodium pump isoforms and other sodium or calcium ion transporters in the heart of hypertensive patients.

The sodium pump (Na(+),K(+)-ATPase; EC 3.6.1.37) of animal cell membranes is the enzyme responsible for the maintenance of membrane potential, for the function of secondary active transporters, and for osmoregulation of the cell. Since inhibition of the enzyme by cardiac glycosides results in increased contractility of the heart muscle and increased blood pressure, we were interested in whether there is a correlation between hypertension and expression of the various isoforms of the sodium pump. In addition, we also examined the expression of the isoforms of the sarcoplasmic and plasma membrane Ca(2+)-ATPase, the Na(+)/Ca(2+)- and Na(+)/H(+)-exchangers, and Na(+) channel and Ca(2+) channel isoforms. Total mRNA was isolated from 50 mg tissue from the right atrium of hypertensive and normotensive patients who were undergoing cardiac surgery. After reverse transcription and subsequent amplification of ion transporter-specific cDNA fragments by polymerase chain reaction (PCR) in the presence of [alpha-(32)P]dCTP, quantification of the amplified fragments was carried out by the Phosphorimager technique. The data obtained show that the alphal subunit mRNA is expressed similarly in normotensive and hypertensive patients. The amount of alpha2 subunit mRNA, however, is increased 5-fold in hypertensive patients. In the same group, the amount of alpha3 isoform is also significantly increased, although not as dramatically as the alpha2 isoform. Besides the Na(+),K(+)-ATPase isoforms, a significant increase in the expression of mRNA for the Na(+)/Ca(2+)-exchanger and the plasma membrane Ca(2+)-ATPase isoforms was detected. It is possible that the observed changes in mRNA expression for these ion transporters reflect compensatory mechanisms to overcome a defective Na(+) and Ca(2+) metabolism in the tissues of hypertensive patients or reflect defects directly involved in the cause of hypertension. The expression of mRNA for all other transporters investigated was unaltered.

Adult↗
PubMed2001

Protein synthesis of human articular chondrocytes cultured in vitro for autologous transplantation.

Chondrocytes in hyaline cartilage produce typical matrix proteins, the most abundant of them being collagen type II and aggrecan. Chondrocytes in monolayer cell culture dedifferentiate and gain fibroblastic phenotype. The cells gradually start to produce collagen type I while the production of collagen type II and aggrecan decreases. Transplantation of autologous chondrocytes cultured in vitro is used for treatment of aseptic articular cartilage lesions. For this purpose, cartilage biopsy is taken and isolated cells are subsequently proliferated in a monolayer cell culture. When implanted, the cells start to produce specific cartilaginous matrix that fills the defect. Prior to surgical procedure the cells can also be cryopreserved for longer periods of time after reaching appropriate numbers. We tested the influence of cultivation time and number of continuous culture passages as well as the influence of cryopreservation on the matrix protein synthesis of human articular chondrocytes. The ability of dedifferentiated chondrocytes to redifferentiate has been monitored by measuring matrix protein synthesis of the cells, re-seeded in agarose suspension culture. The results obtained show progressive dedifferentiation during monolayer cell culture procedures, facilitated by cryopreservation. Successful redifferentiation of cells re-seeded in suspension cultures was observed regardless of the previous level of chondrocyte dediferentiation.

Cartilage, Articular↗
PubMed2001

Determination of optimal transport conditions for biopsies of human articular cartilage as well as for suspensions of cultured chondrocytes used in autologous transplantation.

Autologous transplantation of chondrocytes is currently being promoted as a novel approach for the treatment of deep cartilage lesions. Briefly, the method involves enzyme-mediated release of chondrocytes from cartilage biopsies, the expansion of cells by in vitro cultivation and their re-implantation into the defect. The success of this technique depends on many factors including transport conditions for both, cartilage biopsies from the operating hall to the laboratory and the return transport of final suspension of cultured chondrocytes. To determine the extent of cellular damage in biopsies, chondrocytes were enzymatically isolated following a few days of tissue preservation in different tissue culture media. The proportion of dead cells was assessed by Trypan blue staining and counting. The viability was not dependant of the type of the medium used and remained approximately 50% in all samples, even after 72 h. To develop optimal conditions for transport of final chondrocyte suspension, isolated cells were firstly grown in monolayer cultures. Cell suspensions in media with different additives were injected into special glass containers used for the transport and left at 4 degrees C or 25 degrees C for up to 3 days. During this period every 24 h the samples were taken and viability as well as apoptosis levels were assessed. Viability of cells in suspensions at 25 degrees C decreased significantly and became inadequate already after 48 h. In contrast to that, the proportion of viable cells at 4 degrees C remained above 80% even after 48 h. In the majority of the samples, culture medium containing serum and vitamin C provided the best conditions for long-term preservation of chondrocytes.

Apoptosis↗
PubMed2001

Factor XIII prevents development of myocardial edema in children undergoing surgery for congenital heart disease.

In a prospective investigation of perioperative cardiac edema formation requiring a delayed sternal closure, we identified thrombin increase combined with a simultaneous decrease of factor XIII as a probable cause. After experimental studies additionally revealed that factor XIII could protect endothelial barrier function, we did another prospective randomized trial in which factor XIII or placebo was preoperatively substituted. The substitution finally showed distinct effects minimizing the incidence of myocardial swelling. Therefore, the clinical application of factor XIII may have a valuable therapeutic benefit in cases of leakage syndrome during extracorporeal circulation in congenital heart surgery.

Cardiomyopathies↗
PubMed1999

Effect of factor XIII on endothelial barrier function.

The effect of factor XIII on endothelial barrier function was studied in a model of cultured monolayers of porcine aortic endothelial cells and saline-perfused rat hearts. The thrombin-activated plasma factor XIII (1 U/ml) reduced albumin permeability of endothelial monolayers within 20 min by 30 +/- 7% (basal value of 5.9 +/- 0.4 x 10(-6) cm/s), whereas the nonactivated plasma factor XIII had no effect. Reduction of permeability to the same extent, i.e., by 34 +/- 9% could be obtained with the thrombin-activated A subunit of factor XIII (1 U/ml), whereas the iodoacetamide-inactivated A subunit as well as the B subunit had no effect on permeability. Endothelial monolayers exposed to the activated factor XIII A exhibited immunoreactive deposition of itself at interfaces of adjacent cells; however, these were not found on exposure to nonactivated factor XIII A or factor XIII B. Hyperpermeability induced by metabolic inhibition (1 mM potassium cyanide plus 1 mM 2-deoxy-D-glucose) was prevented in the presence of the activated factor XIII A. Likewise, the increase in myocardial water content in ischemic-reperfused rat hearts was prevented in its presence. This study shows that activated factor XIII reduces endothelial permeability. It can prevent the loss of endothelial barrier function under conditions of energy depletion. Its effect seems related to a modification of the paracellular passageways in endothelial monolayers.

Animals↗
PubMed1999

Selective Cerebral Perfusion Via Innominate Artery in Aortic Arch Replacement Without Deep Hypothermic Circulatory Arrest.

To attain satisfactory results in aortic arch surgery a reliable method of cerebral protection, avoidance of emboli, and control of hemorrhage is mandatory. Deep hypothermic circulatory arrest is the most common technique at present but gives only a limited period of protection, whereas a complicated aortic arch operation may require more time than anticipated. Therefore the selective cannulation and perfusion of the innominate artery has not been widely used until now because it is uncertain whether the left hemisphere of the brain is adequately perfused. Between 1990 and 1995, 21 of 69 patients within the last 36 months, consisting of 15 men and 6 women averaging 45 +/- 13.4 years, underwent operative treatment for aneurysm (n = 9) or type A dissection (n = 12) involving the aortic valve and aortic arch; selective innominate perfusion (SCP [i]) in moderate hypothermia (28 degreesC) for brain protection was used. Extended perioperative monitoring included bilateral somatosensory-evoked potentials (SEP), transcranial Doppler sonography (TCD), a computer-aided topographical electro-encephalometry (CATEEM), and analysis of the arterial and venous oxygen saturation and desaturation. Mean time periods were 229.7 +/- 56.5 minutes for extracorporeal circulation, 151.7 +/- 34.1 minutes for aortic cross-clamping, and 67.05 +/- 34.03 for selective cerebral perfusion via the innominate artery. Not once did the intraoperative monitoring reveal hints of cerebral damage due to inadequate perfusion. All patients survived surgery but two could not be weaned from the respirator; one died 2 days and the other 6 days after the operation due to multiple organ failure (MOF). Another two patients died after 13 days due to untreatable septic syndrome with pulmonary insufficiency. All four patients died within 30 days, during which time they had aortic dissection involving the complete aortic arch and severe aortic valvular incompetence (grade IV). There was no late death and follow-up time of 19.76 +/- 8.04 months revealed an overall mortality rate of 19%. Only temporary neurological affections (left-sided hemiparesis) were found in two patients (9.5%). Additionally, we observed neuropsychological disturbances in one of these. Our first experience with selective cerebral perfusion via innominate artery and the attendant CATEEM monitoring for assessment of adequate bilateral cerebral perfusion suggests that this method is a useful addition to the armamentarium in complicated aortic arch surgery.

Journal Article↗
PubMed1999

Topical treatment of venous ulcer with fibrin stabilizing factor: experimental investigation of effects on vascular permeability.

BACKGROUND: The clinical observation of distinct reduction of wound secretion tendency during treatment of venous leg ulcer with topically applied factor XIII let us speculate that this enzyme may be involved in modulation of vascular permeability. METHODS: For experimental study porcine aortic endothelial cells were cultured on filter membrane to confluent monolayer. Endothelial covered filters then were used in a two-compartment modell creating an artificial luminal and abluminal compartment. To investigate the influence of factor XIII on endothelial barrier function, we measured the flux of trypan blue-labeled albumin through endothelial monolayers by spectrophotometer. RESULTS: Monolayers that were exposed to factor XIII showed a distinct (n = 10, p < 0.05) decrease of albumin flux in contrast to control. This effect was not dependent on serum substrates. Partially, the permeability reducing effect was due to a certain amount of albumin that is a stabilizing component of Fibrogammin HS. CONCLUSION: Although the mechanism is unclear at the moment, we conclude that reduction of endothelial permeability can be achieved by factor XIII which may play an important role in wound healing of venous leg ulcer.

Administration, Topical↗
PubMed1999

[Factor XIII: experimental and clinical results in diabetic foot ulcer].

Several diseases show an impairment of vascular barrier function. In the past, we found out that topically applied plasmatic factor XIII distinctly reduced secretion tendency and improved granulation in venous ulcer. Increased vascular permeability is also discussed in patients with a long lasting diabetic status being a relevant cause of impaired local wound healing. Therefore, we introduced the topical application of factor XIII into the therapy of diabetic foot ulcer. After basic experimental investigations revealed that factor XIII significantly reduces endothelial permeability of cultured endothelial cells, the first clinically treated diabetic patients showed encouraging results, too.

Administration, Topical↗
PubMed1998

An assessment of selective cerebral perfusion via the innominate artery in aortic arch replacement.

Maintaining an adequate cerebral oxygen supply is a serious problem in aortic arch surgery. Deep hypothermic circulatory arrest is the most common method used for cerebral protection, but guarantees only a time-limited safety period. Based on experimental investigations, we applied selective cerebral perfusion via the innominate artery alone with only moderate hypothermia (28 degrees C) and without circulatory arrest in 25 consecutive patients undergoing surgical treatment of an aneurysm (n = 10) or acute type-A dissection (n = 15) involving the aortic valve and arch. In every case a test perfusion was carried out to assess whether the cerebral perfusion achieved would be adequate for the whole operation. In no case was the perfusion inadequate. As a new perioperative monitoring system, we used computer-aided topographical electroencephalometry (CATEEM). There were 18 male and 7 female patients, their age was 47.0 +/- 15.1 years (mean +/- SD). Mean time periods were 155.1 +/- 37.3 min for aortic cross-clamping, and 69.3 +/- 35 min for selective cerebral perfusion. Postoperatively, two patients (8%) revealed a temporary left-sided hemiparesis, and 4 patients (16%) died within 30 days. The overall mortality rate was 16% in a follow-up period of 24.2 +/- 9.5 months. In this small group the CATEEM monitoring enabled an intraoperative selection of patients with sufficient bihemispheric collateral circulation and therefore suitable for simple innominate artery perfusion.

Acute Disease↗
PubMed1998

Modulation of somatosensory evoked potentials under various concentrations of desflurane with and without nitrous oxide.

Continuous measurement of somatosensory evoked potentials (SEP) by means of characteristic changes in the signal pattern makes it possible to identify cerebral or spinal cord ischemia during critical phases of the operative procedure. A correct interpretation of the measurements is only possible, however, if the influence of drugs acting on the central nervous system is known. The authors were able to show that inhaled anesthetics have an impact on latencies and response amplitudes. This study examined the influence of various concentrations of desflurane on the conduction of SEP of the Median nerve. In addition, the authors determined how the supplementation of nitrous oxide (N2O) influences the stimulus response of the medianus nerve's SEP. Desflurane has been shown to produce dose-dependent increases in SEP latency (data in part for latency N2O: 0.5 minimum alveolar concentration [MAC] = 20.8 +/- 0.9; 1.5 MAC = 22.2 +/- 1.5; 1.5 MAC/N2O= 23.8 +/- 1.5) and decreases in amplitude, whereas cervically recorded subcortical SEP components are minimally influenced by desflurane. When nitrous oxide is added, there were marked reductions in amplitude (p<0.01) of the cortical stimulus response (1.5 MAC = 2.4 +/- 0.9; 1.5 MAC/N2O = 1.1 +/- 1). It can therefore be recommended that supplementation with N2O should be avoided in the presence of low initial amplitudes. Based on the study's results, the use of desflurane (up to 1.0 MAC) seems to be compatible with intraoperative monitoring of median somatosensory evoked potentials.

Anesthesia, Inhalation↗
PubMed1998

Superficial femoral vein in arterial reconstruction for limb salvage: outcome and fate of venous circulation.

BACKGROUND: In some particular cases in vascular surgery it is mandatory to perform arterial reconstruction using autologous graft. Since 1985, we have been using the superficial femoral vein for arterial substitute in the case of limb salvage, when another autologous vein has not been available. We made a prospective investigation on 32 patients over a mean period of 24.5+/-12.1 months (1 to 48 months) to evaluate the usefulness of superficial femoral vein (SFV) for distal arterial reconstructive surgery and to objectify the fate of venous circulation of the limb after removal of this vein. METHODS: There were 20 male and 12 female patients averaging 64.3+/-10.3 years, who underwent crural arterial reconstructive surgery using the composite technique (PTFE and SFV). All grafts had been placed subcutaneously in lateral to knee position. Mean length of removed superficial femoral vein was 13.2+/-9.4 cm. RESULTS: In 6 patients (18.7%), we found an early occlusion of bypass followed by major amputation in 5 cases (15.6%). Minor amputation had to be done in 12 patients (37.5%). Cumulative patency was 56.3% after 48 months. Following the removal of superficial femoral vein, we had no complications due to venous stasis. We found a significant increase of plethysmographically measured venous capacity (1.7+/-0.49 to 2.51+/-0.71 [p<0.01]) and venous outflow (14.9+/-5.34 to 23.9+/-10.4 [p<0.05]) after 7.7 months. We did not observe more significant changes of venous circulation during further follow-up. CONCLUSIONS: Despite overall good results, we only recommend the use of superficial femoral vein in hazardous situations, when other autologous material is not available.

Amputation, Surgical↗