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Biomedical subjects

P Markart

Publications and source records attributed to P Markart.

12 recordsLinked to original sources
PubMed2007

Safety and tolerability of bosentan in idiopathic pulmonary fibrosis: an open label study.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease for which no effective treatment exists. In the present study, 12 IPF patients underwent analysis of gas exchange properties using the multiple inert gas elimination technique on day 1 before and after the administration of 125 mg bosentan, a dual endothelin antagonist. Following this, patients received chronic administration for 12 weeks (62.5 mg b.i.d. in week 1, 125 mg b.i.d. thereafter). The primary objective was to determine the effect of bosentan on gas exchange (day 1) and on oxygen saturation and minute ventilation (week 2). With one exception, where redistribution of total pulmonary blood flow from normal ventilation/perfusion (V'/Q') areas (93% before, 72% after bosentan) to low V'/Q' areas (0% before, 22.2% after) was encountered, no patient showed any change in gas exchange (mean+/-SD shunt flow (% of cardiac output) 8.5+/-3.4% before, 6.1+/-2.3% after bosentan; day 1) or oxygen saturation and minute ventilation (week 2). Similarly, none of the secondary parameters was significantly changed either at week 2 or at the end of the study period (week 12). Five patients developed respiratory infections and two died because of pneumonia; this was judged as being unrelated to bosentan intake. In conclusion, bosentan administration does not seem to induce clinically relevant gas exchange abnormalities in idiopathic pulmonary fibrosis patients.

Administration, Oral↗
PubMed2006

Minimal immunoreactive plasma beta-endorphin and decrease of cortisol at standard analgesia or different acupuncture techniques.

BACKGROUND AND OBJECTIVE: Acupuncture has been claimed to be associated with activation of the endogenous antinociceptive system. The analgesic effects of acupuncture have been ascribed to beta-endorphin interacting with opioid receptors. However, firstly, the release of beta-endorphin into the blood has been proven to be induced by stress, i.e. under dysphoric conditions, and, secondly, if released under stress, beta-endorphin has been shown not to be analgesic. Our aim was to test whether beta-endorphin immunoreactive material is released into the cardiovascular compartment during acupuncture comparing the most frequently used types of acupuncture with standard pain treatment under apparently low stress conditions. METHODS: This prospective study included 15 male patients suffering from chronic low back pain. beta-Endorphin immunoreactive material and cortisol were measured in the plasma of patients who underwent, in random order, therapy according to a standard pain treatment, traditional Chinese acupuncture, sham acupuncture, electro acupuncture and electro acupuncture at non-acupuncture points before, at and after the treatment. Statistical analysis was performed using two-way ANOVA with repeated measures. RESULTS: A decrease in plasma cortisol concentration measured over the five treatment protocols was highly significant (P < 0.001). The beta-endorphin immunoreactive material concentrations in plasma were minimal at all times and in all treatment conditions. The influence of treatments by various acupuncture procedures on cortisol and beta-endorphin immunoreactive material plasma concentrations over the three time points was not significantly different. CONCLUSIONS: beta-endorphin immunoreactive material in blood is not released by any type of acupuncture as tested under low stress conditions.

Acupuncture Analgesia↗
PubMed2006

Surfactant protein C mutations in sporadic forms of idiopathic interstitial pneumonias.

Interstitial pneumonias have recently been associated with mutations in the gene encoding surfactant protein C (SFTPC). In particular, SFTPC mutations have been reported in a number of familial forms of pulmonary fibrosis and in infants with interstitial lung diseases. The present study searched for SFTPC mutations in adult patients with sporadic idiopathic interstitial pneumonia. In total, 35 adult patients with sporadic idiopathic interstitial pneumonia and 50 healthy subjects were investigated for SFTPC mutations by direct DNA sequencing. Of the patients with sporadic idiopathic interstitial pneumonia, 25 suffered from idiopathic pulmonary fibrosis and 10 patients from nonspecific interstitial pneumonia. Only two frequent nonsynonymous variants, T138N and S186N, were detected. Allele frequencies of both variations as well as of other identified noncoding alterations did not differ significantly between the diverse patient groups and control subjects. In conclusion, mutations in the gene encoding surfactant protein C are not common in sporadic cases of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia, suggesting that the mutated gene does not play an important role in the pathogenesis of these forms of idiopathic interstitial pneumonia.

Adult↗
PubMed2006

[Differential therapy of pulmonary fibrosis].

Pulmonary fibrosis is the final outcome of a numerous and heterogeneous group of pulmonary disorders grouped together under the family of diffuse parenchymal lung diseases. Safe identification of the underlying condition is difficult but is the prerequisite for any therapeutic attempt. In principle, diffuse parenchymal lung diseases may be divided into those forms being triggered by an initial inflammatory process (e. g. sarcoidosis, hypersensitivity pneumonitis), and those being most likely triggered by epithelial injury (idiopathic pulmonary fibrosis). Steroids and immunosuppressants do have their role in treatment of the former group, although the efficacy on long-term outcome is not entirely clear. In contrast, steroids and immunosuppressants are only rarely helpful in the latter condition. Novel therapeutic strategies for the treatment of idiopathic pulmonary fibrosis are currently under preclinical or clinical assessment and include antioxidative agents and agents that block alveolar coagulation or different growth factors.

Antioxidants↗
PubMed2004

Alveolar antioxidant status in patients with acute respiratory distress syndrome.

In the acutely inflamed lung, oxidant stress occurs within the alveolar compartment. Under these conditions, the regulation of low molecular weight antioxidants in the epithelial lining fluid is poorly understood. Therefore, antioxidant levels were measured in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome (ARDS; n=40) and in healthy volunteers (n=20). Reduced glutathione (GSH), oxidised glutathione (GSSG; enzymatic assay), retinol (vitamin A), alpha-tocopherol (vitamin E), ascorbic acid (vitamin C), uric acid (all by HPLC), plasmalogens (1-alkenyl-2-acyl phospholipids), polyunsaturated fatty acids (PUFA; both by gas-liquid chromatography), and F2-isoprostanes (ELISA) were quantified. All values are expressed as concentrations in cell-depleted BALF. GSSG (ARDS: 0.13+/-0.02 microM; control: 0.03+/-0.01 microM; mean+/-sem) and F2-isoprostanes (ARDS: 78+/-10 pM; control: 26+/-5 pM) were increased in ARDS, thus indicating oxidant stress. GSH levels in patients did not change significantly, whereas concentrations of vitamins A and C, vitamin E (ARDS: 77+/-15 nM; control: 26+/-3 nM) and uric acid (ARDS: 11.8+/-2.2 microM; control: 0.7+/-0.0 microM) were significantly elevated in ARDS. PUFA of total lipids, which may act as sacrificial antioxidants, increased by a factor of approximately 3 in patients, but plasmalogens showed a significant decrease. In conclusion, low molecular weight antioxidants are elevated in the alveolar compartment of patients with acute respiratory distress syndrome. Further research is warranted to elucidate the molecular mechanisms underlying this finding.

Adult↗
PubMed2002

Aprotinin reduces blood loss in off-pump coronary artery bypass (OPCAB) surgery.

OBJECTIVE: Effects of aprotinin in off-pump coronary artery bypass (OPCAB) surgery have not yet been described. This study analyses hemostasiologic changes and potential benefit in OPCAB patients treated with aprotinin. METHODS: In a prospective, double-blind, randomized study 47 patients undergoing OPCAB surgery were investigated. Patients received either aprotinin (2 x 10(6) KIU loading dose and 0.5 x 10(6) KIU/h during surgery, n=22) or saline solution (control, n=25). Activated clotting time was adjusted to a target of 250 s intraoperatively. Blood samples were taken up to 18h postoperatively: complete hematologic and hemostasiologic parameters including fibrinopeptide A (FPA) and D-dimer in a subgroup of 31 patients were analyzed. Blood loss, blood transfusion and other clinical data were collected. RESULTS: Both groups showed comparable demographic and intraoperative variables. Forty-one (87%) patients of the whole study group received aspirin within 7 days prior to surgery. Number of grafts per patient were comparable (2.9+/-1.0 [mean+/-SD] in the aprotinin group and 2.8+/-1.2 in control, P=0.83). Blood loss during the first 18 h in intensive care unit was significantly reduced in patients treated with aprotinin (median [25th-75th percentiles]: 500 [395-755] ml vs. 930 [800-1170] ml, P<0.001). Postoperatively only two patients (10%) in the aprotinin group received packed red blood cells, whereas eight (35%) in the control group (P=0.07). Perioperatively FPA levels reflecting thrombin generation were elevated in both groups. The increase in D-dimer levels after surgery was significantly inhibited in the aprotinin group (P<0.001). Early clinical outcome was similar in both groups. CONCLUSIONS: Aprotinin significantly reduces blood loss in patients undergoing OPCAB surgery. Inhibition of enhanced fibrinolysis can be observed. FPA generation during and after OPCAB surgery seems not to be influenced by aprotinin.

Aged↗
PubMed2002

Altered fatty acid composition of lung surfactant phospholipids in interstitial lung disease.

Deterioration of pulmonary surfactant function has been reported in interstitial lung disease; however, the molecular basis is presently unclear. We analyzed fatty acid (FA) profiles of several surfactant phospholipid classes isolated from large-surfactant aggregates of patients with idiopathic pulmonary fibrosis (IPF; n = 12), hypersensitivity pneumonitis (n = 5), and sarcoidosis (n = 12). Eight healthy individuals served as controls. The relative content of palmitic acid in phosphatidylcholine was significantly reduced in IPF (66.8 +/- 2.5%; means +/- SE; P < 0.01) but not in hypersensitivity pneumonitis (78.5 +/- 1.8%) and sarcoidosis (78.2 +/- 3.1%; control 80.1 +/- 0.7%). In addition, the phosphatidylglycerol FA profile was significantly altered in the IPF patients, with a lower relative content of its major FA, oleic acid, at the expense of saturated FA. In the phosphatidylcholine class, a significant correlation between the impairment of biophysical surfactant function and decreased percentages of palmitic acid was noted. We conclude that significant alterations in the FA profile of pulmonary surfactant phospholipids occur predominantly in IPF and may contribute to the disturbances of alveolar surface activity in this disease.

Adult↗
PubMed2001

Surfactant alteration and replacement in acute respiratory distress syndrome.

The acute respiratory distress syndrome (ARDS) is a frequent, life-threatening disease in which a marked increase in alveolar surface tension has been repeatedly observed. It is caused by factors including a lack of surface-active compounds, changes in the phospholipid, fatty acid, neutral lipid, and surfactant apoprotein composition, imbalance of the extracellular surfactant subtype distribution, inhibition of surfactant function by plasma protein leakage, incorporation of surfactant phospholipids and apoproteins into polymerizing fibrin, and damage/inhibition of surfactant compounds by inflammatory mediators. There is now good evidence that these surfactant abnormalities promote alveolar instability and collapse and, consequently, loss of compliance and the profound gas exchange abnormalities seen in ARDS. An acute improvement of gas exchange properties together with a far-reaching restoration of surfactant properties was encountered in recently performed pilot studies. Here we summarize what is known about the kind and severity of surfactant changes occurring in ARDS, the contribution of these changes to lung failure, and the role of surfactant administration for therapy of ARDS.

Animals↗
PubMed2000

Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome.

Changes in the alveolar hemostatic balance in severe pneumonia were compared with those in the acute respiratory distress syndrome (ARDS). Analysis was performed in bronchoalveolar lavage fluids (BALF) of patients with ARDS triggered by nonpulmonary underlying events in the absence of lung infection (ARDS; n = 25), pneumonia demanding mechanical ventilation (PNEU-vent; n = 114), spontaneously breathing patients with pneumonia (PNEU-spon; n = 40), and ARDS in combination with lung infection (ARDS+PNEU; n = 43); comparison with healthy control subjects (n = 35) was performed. In all groups of patients, BALF total procoagulant activity was increased by nearly two orders of magnitude, being largely attributable to the tissue factor pathway of coagulation. Concomitantly, markedly reduced overall fibrinolytic capacity (fibrin plate assay) was noted in the lavage fluids of all patients. BALF levels of urokinase-type plasminogen activator were significantly reduced throughout, whereas the lavage concentrations of tissue-type plasminogen activator did not differ from those in control subjects. In addition, markedly enhanced levels of plasminogen activator- inhibitor I and alpha(2)-antiplasmin were noted in ARDS, ARDS+PNEU, and PNEU-vent, but not in PNEU-spon. In all groups of patients, the changes in the lavage enzymatic activities were paralleled by manifold increased BALF concentrations of fibrinopeptide A and D-dimer, reflecting in vivo coagulation processes. Within the overall number of patients with pneumonia, changes in the alveolar hemostatic balance were more prominent in alveolar and interstitial pneumonia than in bronchopneumonia. Acute inflammatory lung injury, whether triggered by nonpulmonary systemic events or primary lung infection, is thus consistently characterized by both enhanced procoagulant and depressed fibrinolytic activities in the alveolar lining layer, with the appearance of fibrin formation in this compartment. Profile and extent of changes in severe pneumonia demanding respirator therapy are virtually identical to those in ARDS, whereas somewhat less prominent alterations of the alveolar hemostatic balance are noted in spontaneously breathing patients with pneumonia.

Adolescent↗
PubMed1999

Cleavage of surfactant-incorporating fibrin by different fibrinolytic agents. Kinetics of lysis and rescue of surface activity.

Incorporation of surfactant into polymerizing fibrin causes loss of surface activity and marked retardation of clot lysis by plasmin (Günther and colleagues, Am. J. Physiol. 1994;267:L618-L624). We compared the efficacy of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), activated anisoylated streptokinase-plasminogen activator complex (APSAC), and plasmin to dissolve surfactant-incorporating fibrin. Alveofact was employed as a natural surfactant source, and plasminogen was coincorporated into the fibrin matrix at a physiologic ratio to fibrin. Fibrinolysis was quantified by the release of tracer from (125)I-labeled fibrin, and the pattern of split products was characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In addition, we investigated the fibrinolysis-related restoration of surface activity by measurement in the pulsating bubble surfactometer. Concentrations of all fibrinolytic agents were chosen to effect approximately 40% lysis of clot material in the absence of surfactant (control). When incorporated into the fibrin matrix, but not when admixed after clot formation, surfactant inhibited the cleavage of fibrin by all fibrinolytic agents in a dose-dependent manner. Interestingly, t-PA and u-PA were significantly less inhibited than was plasmin or APSAC. The pattern of arising fibrin scission products was identical for all fibrinolytic approaches and was independent of surfactant incorporation. Adsorption and minimum surface tension-lowering properties of Alveofact were almost completely lost upon incorporation into fibrin, but surface activity was fully restored upon sustained clot lysis with all fibrinolytic agents. We conclude that the fibrinolytic capacity of all agents investigated is markedly inhibited by surfactant incorporation in fibrin, but this inhibition is significantly less pronounced in the agents employing preincorporated plasminogen (t-PA and u-PA), as compared with plasmin and APSAC. The plasminogen activators may thus proffer to "rescue" pulmonary surfactant function by induction of fibrinolysis in the alveolar compartment.

Animals↗