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Biomedical subjects

H Fabel

Publications and source records attributed to H Fabel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Enhanced expression of fas ligand (CD95L) on T cells after segmental allergen provocation in asthma.

BACKGROUND: Little is known about the termination of the T-cell driven inflammation found in patients with allergic asthma. OBJECTIVE: Because signals delivered through Fas/Fas ligand can lead to T-cell apoptosis, we investigated the expression of Fas and Fas ligand on peripheral blood- and bronchoalveolar lavage fluid (BALF)-derived T cells and the percentage of apoptotic BALF cells in asthma. METHODS: Nine atopic subjects with mild asthma and 9 control subjects underwent segmental sham and allergen challenge. Flow cytometry was used to determine the T-cell expression of Fas and Fas ligand, and the terminal dUTP nick end labeled technique was applied to detect apoptotic BALF cells. RESULTS: In asthmatic and control subjects almost all T cells in the BALF expressed Fas antigen without changes after saline or allergen challenge. A small percentage of T cells in BALF expressed the Fas ligand. In asthmatic subjects, but not in control subjects, there was a significant increase in Fas ligand after allergen challenge (CD3: 0.8% +/- 0.6% [baseline] vs 3.2% +/- 1.2% [allergen challenge]; CD4: 1.8% +/- 0.0% vs 4.3% +/- 1.8%; CD8: 2.8% +/- 2.4% vs 9.1% +/- 4.8%) but not after saline challenge, with a significant correlation to the percentage of BALF eosinophils. Apoptotic BALF cells were localized exclusively in macrophages at a very low frequency (0.03% to 0.15%) and without changes after saline or allergen challenge in both groups. CONCLUSION: In asthma there is an upregulation of Fas ligand on T cells in BALF after allergen challenge. Because there is no evidence for increased apoptosis, this phenomenon may reflect antigen-induced T-cell activation rather than apoptosis.

Adult↗
PubMed1999

Lung transplantation--10-year experience.

OBJECTIVE: The experience at our institution with various forms of lung transplantation (heart-lung, double lung and single lung) from December 1987 to September 1998 is reviewed and discussed. METHODS: During this decade, 282 procedures (46 heart-lungs (HLTx), 142 double lungs (DLTx) and 94 single lungs (SLTx)) have been performed in 258 patients (140 male, 118 female; age: 38 +/- 13 years). Major indications included pulmonary fibrosis (n = 73), obstructive lung disease (n = 55), cystic fibrosis (n = 48), primary pulmonary hypertension (n = 36), secondary pulmonary hypertension (majority Eisenmenger's syndrome) (n = 30), and retransplantation (n = 24). RESULTS: Early postoperative mortality (<90 days) was 13.9% (n = 36). The 1-, 3-, and 5-year survival rates in all recipients was 77, 70 and 63%, respectively. There was no significant difference in 1-year survival rates between the different procedures (HLTx: 78%, DLTx: 77%, SLTx: 77%). Significantly better 1-year survival was achieved in patients with cystic fibrosis (89%), pulmonary fibrosis (81%), obstructive lung disease (74%), and Eisenmenger's syndrome (83%) when compared to patients with primary pulmonary hypertension (55%). Survival rates remained unchanged during this period despite expanding indications during the last years. Causes of death in 90 recipients (HLTx: n = 19, DLTx: n = 37, SLTx: n = 34) included sepsis (n = 42), obliterative bronchiolitis (n = 28), cardiac failure (n = 5), and early allograft dysfunction (n = 2). Freedom from bronchiolitis obliterans syndrome (BOS) (>stage I ISHLT) was 80% at 1 year and 45% at 5 years. CONCLUSIONS: Lung transplantation offers a true therapeutic option with good early and midterm results. Yet, chronic graft dysfunction represents a major obstacle for long-term benefit of this procedure.

Adolescent↗
PubMed1999

Exogenous surfactant improves survival and surfactant function in ischaemia-reperfusion injury in minipigs.

Reperfusion injury is the major cause of early morbidity and mortality after lung transplantation. This complication has been experimentally linked to dysfunction of pulmonary surfactant. Therefore, the hypothesis that reperfusion injury might be preventable by exogenous surfactant treatment was tested. Left lungs of minipigs were exposed to 120 min of ischaemia, and the lungs were then reperfused for up to 7 h. Animals were divided into a control group and a surfactant group (n=5 each). The surfactant group received 50 mg x kg(-1) Alveofact intrabronchially via a bronchoscope at the beginning of the ischaemic period. Bronchoalveolar lavage was performed at baseline before ischaemia and 90 min after reperfusion. Surfactant treatment significantly improved short-term survival. Pulmonary vascular resistance increased markedly in control animals leading to right heart failure and death within 3 h after reperfusion whereas the surfactant-treated animals survived the 7 h observation period. After reperfusion, alveolar accumulation of neutrophils and exuded proteins was present in both groups to the same extent. Surfactant activity after reperfusion deteriorated markedly in the control group but was preserved in the surfactant group. In conclusion, early surfactant treatment alleviates the deterioration of surfactant function and improves survival in this minipig model of ischaemia-reperfusion injury.

Animals↗
PubMed1999

Dysfunction of pulmonary surfactant in asthmatics after segmental allergen challenge.

Increased airway resistance in asthma may be partly due to poor function of pulmonary surfactant. This study investigated the inflammatory changes of bronchoalveolar lavage fluid (BALF) and the performance of BALF surfactant in healthy control subjects (n = 9) and patients with mild allergic asthma (n = 15) before and after segmental challenge. BALF was obtained for baseline values, and 24 h after challenge with saline solution in one lung segment and with allergen in another. Cell counts, phospholipid and protein concentrations, and ratios of small to large surfactant aggregates (SA/LA) were analyzed. Surface tension was determined with a pulsating bubble surfactometer, and the ability of the BALF surfactant to maintain airway patency was assessed with a capillary surfactometer. Baseline values of control subjects and asthmatics were not different. Challenge with saline and antigen raised total inflammatory cells in both control subjects and asthmatics. Allergen challenge of asthmatics, but not of healthy volunteers, significantly increased eosinophils, proteins, SA/ LA, and surface tension at minimum bubble size, and diminished the time the capillary tube is open. In conclusion, allergen challenge in asthmatics induced surfactant dysfunction, probably mainly because of inhibiting proteins. During an asthma attack, narrow conducting airways may become blocked, which might contribute to an increased airway resistance.

Adult↗
PubMed1999

Determination of cardiac output by the Fick method, thermodilution, and acetylene rebreathing in pulmonary hypertension.

Assessment of cardiac output is an important part of the management of patients with pulmonary hypertension. The accuracy of the thermodilution technique in patients with low cardiac output or severe tricuspid regurgitation has been questioned. To address this issue, we simultaneously compared 105 cardiac output measurements by the Fick method and thermodilution in 35 patients with pulmonary hypertension. Moreover, we evaluated the acetylene rebreathing technique, a noninvasive method of determining cardiac output. The mean difference +/- 95% limit of agreement between thermodilution and the Fick method was +0.01 +/- 1.1 L/min. The mean difference +/- 95% limit of agreement between acetylene rebreathing and the Fick method was -0.23 +/- 1.14 L/min. Neither the mean agreement nor the 95% limits of agreement of both thermodilution and acetylene rebreathing with the Fick method were affected by the presence of low cardiac output or severe tricuspid regurgitation. We conclude that thermodilution and acetylene rebreathing are useful tools for assessing cardiac output in patients with pulmonary hypertension, even in the presence of low cardiac output or severe tricuspid regurgitation.

Acetylene↗
PubMed1999

Hyperuricaemia in patients with right or left heart failure.

Based on the clinical observation that patients with right or left heart failure often present with hyperuricaemia, the relation between serum urate values and haemodynamic variables was studied in patients with primary pulmonary hypertension (PPH) as well as in patients with advanced ischaemic heart disease or dilated cardiomyopathy. The study was a retrospective analysis of 39 patients with PPH and 36 patients with left heart disease, examining serum urate levels in association with haemodynamic variables. Elevated urate concentrations were found in 79% of the PPH patients. There was no association between serum urate levels and mean pulmonary artery pressures, but a significant correlation was found between urate levels and the cardiac index (r=0.48; p=0.0021) and an even stronger correlation between serum urate levels and mean right atrial pressures (r=0.83; p<0.0001). A similar association was found in a subgroup of 21 PPH patients not receiving diuretics. In 36 patients with ischaemic heart disease or dilated cardiomyopathy, hyperuricaemia was present in 78% and was significantly associated with elevated right atrial pressures (r=0.40; p=0.031) and even more so with elevated left atrial pressures (r=0.55; p=0.0005) but not with the cardiac index (r=0.034; p=0.86). The data show that hyperuricaemia in patients with cardiac dysfunction is closely related to elevated right or left atrial filling pressures.

Adult↗
PubMed1998

Lung transplantation for cystic fibrosis--a single center experience over 8 years.

OBJECTIVE: Colonization of the lung and mediastinal lymph nodes with multi-resistant bacteria, diabetes and malnutrition represent potential risk factors for lung transplantation in cystic fibrosis. We therefore reviewed our experience in this patient population. METHODS: Between December 1988 and March 1997, 219 lung and heart-lung transplantations were performed at our institution. Of these, 39 procedures were done in 35 patients with cystic fibrosis. All candidates (mean age 26 years) were oxygen dependent (preoperative mean PO2: 44.8 +/- 9.1 Torr, preoperative mean PCO2: 53.4 +/- 10.5 Torr, one patient on respirator). Of the primary operations, 34 were performed as bilateral sequential lung transplants, one as a heart-lung transplantation. RESULTS: Mean duration on respirator for survivors was 3.1 (1-12) days, mean ICU and hospital stay were 4.7 (1-13) and 28 (12-79) days, respectively. The 3-month mortality rate was 5.7% (two patients died due to acute graft failure on days 36 and 73). Other causes of death in the follow-up were cerebral bleeding (one patient) and chronic graft failure (three patients). The survival rates were 91% at 1 year, 83% at 3 years and 76% at 5 years. In eight patients, a bronchiolitis obliterans syndrome (BOS) developed (in four cases grade 3). The freedom of BOS (grade 1 or more) at 1, 3 and 5 years was 87, 79 and 55%, respectively. Four retransplantations were performed. Of the 29 patients alive, only seven are physically limited. CONCLUSION: Bilateral lung transplantation for cystic fibrosis allows for acceptable early- and long-term results. Postoperative survival is not impaired by infection, diabetes and malnutrition. Long-term functional outcome seems to be comparable to lung transplantation in patients without infectious pulmonary disease.

Adult↗
PubMed1998

Frequencies of T cells expressing interleukin-4 and interleukin-5 in atopic asthmatic children. Comparison with atopic asthmatic adults.

T-cell-derived cytokines have been implicated in the pathogenesis of asthma and it has been suggested that Th2-type cytokines (interleukin-4 [IL-4], interleukin-5 [IL-5]) are pivotal in the allergic inflammation. However, there are little data on human cytokine production by individual T cells at the protein level, in particular in asthmatic children. In this study we analyzed the cytokine production at the single cell level in peripheral blood from mild atopic asthmatic (AA) children and adults and age-matched atopic nonasthmatic (AN) and nonatopic nonasthmatic (NN) control subjects (n = 9 in each group) using the technique of intracellular cytokine detection by flow cytometry. Comparing asthmatic children with atopic and nonatopic control subjects, an increased percentage of IL-5-producing T cells (AA: median 4.9% [range 1.1 to 8.9%]; AN: 0.3% [0.2 to 0.9%], p = 0.003; NN: 0.4% [0.1 to 3.8%], p = 0.001) was detectable, with a positive correlation to the number of peripheral eosinophils and to bronchial hyperresponsiveness. The frequency of IL-4-producing T cells was increased in both atopic groups compared with nonatopic controls (AA: 1.2% [0.2 to 2.6%], p = 0.011; AN: 0.8% [0.4 to 3.7%], p = 0.007; NN: 0.4% [0.2 to 0.9%]) with a positive correlation to total IgE concentration. In adults there were no differences in IL-5- or IL-4-producing T cells between all three groups. A substantial proportion of T cells coproducing IL-4 and IL-5 was not detectable in children and adults. These findings indicate that in asthmatic children the frequencies of Th2-type-producing T cells are increased and that expression of IL-4 and IL-5 is regulated independently.

Adult↗
PubMed1998

Pulmonary surfactant activity is impaired in lung transplant recipients.

Impaired graft function in the postoperative course after lung transplantation (LTx) may in part be due to alterations in pulmonary surfactant. Animal data provide increasing evidence for surfactant abnormalities in the early course after graft reperfusion. However, little is known about the integrity of the surfactant system in human lung transplant recipients. We therefore investigated surfactant properties in bronchoalveolar lavage fluid (BALF) of patients with lung transplants (n = 60) in comparison to that of healthy subjects (n = 10). The phospholipid concentrations of BALF and of surfactant subfractions were measured, and total protein was analyzed. Surface activity was measured with a pulsating bubble surfactometer (PBS). Minimum surface tension was 15.8 +/- 1.1 mN/m in lung transplant recipients, whereas healthy subjects had minimum surface tensions of 3.4 +/- 1.9 mN/m (p = 0.0004). As a marker for potential surfactant inhibition, protein-to-phospholipid (PL) ratios showed no significant differences in the two major study groups. The ratio of small surfactant aggregates to large surfactant aggregates was increased in patients with lung transplants (p = 0.043). Episodes of infection or rejection did not change surface activities, nor did they induce altered ratios of protein to PL or of small to large surfactant aggregates. Surfactant activity did not correlate with pulmonary-function data. Moreover, surface tension showed no correlation with the time after transplantation. Our results suggest a persistent impairment of biophysical surfactant properties after LTx, possibly due to type-II-cell malfunction.

Adult↗
PubMed1998

Plasma coagulation profiles in patients with severe primary pulmonary hypertension.

Patients with primary pulmonary hypertension (PPH) benefit from treatment with anticoagulants, and histological findings suggest that in situ thrombosis of pulmonary vessels contributes to the pathogenesis of this disease. The mechanisms that cause a hypercoagulable state in the pulmonary vascular bed have not been fully investigated. This study compared plasminogen plasma activity, protein C and protein S plasma activities, fibrinogen and fibrin degradation products (FGDP and FBDP, respectively), von Willebrand factor antigen (vWF-Ag), prothrombin fragment F1.2, thrombin-antithrombin complexes (TAT), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI) in 16 patients with PPH and in 16 healthy volunteers. In a subset of the PPH patients, these variables were also compared in simultaneously-obtained mixed-venous and arterial blood samples. Proteins C and S, FGDP, FBDP, and plasminogen levels as well as plasma concentrations of prothrombin fragment F1.2 and TAT were normal in the 16 patients with PPH. In contrast, the plasma activity of PAI was significantly elevated (p<0.0001). Arterial PAI levels were considerably higher than mixed venous PAI levels (p=0.0018), which may reflect intrapulmonary production. Furthermore, vWF-Ag levels were significantly elevated (p<0.0001), but there was no significant difference between mixed-venous and arterial blood. These data, on the whole, do not suggest increased thrombin activity in patients with primary pulmonary hypertension. However, the markedly elevated levels of plasminogen activator inhibitor as well as its transpulmonary gradient may provide a clue to locally impaired fibrinolysis in the pulmonary vascular bed.

Antithrombin III↗
PubMed1997

The role of pulmonary surfactant in obstructive airways disease.

Pulmonary surfactant research has an increasing impact on treatment considerations in adult respiratory disorders, above all acute respiratory distress syndrome (ARDS). Obstructive airways diseases have only been sporadically addressed in this respect. In the last decade, direct and circumstantial evidence for surfactant as a contributing factor in the regulation of airway calibre has emerged. Morphologically, a bronchiolar surfactant layer has been demonstrated, whereby the airways are mostly supplied by alveolar surfactant components via the mucociliary escalator. Functionally, prevention of airway film collapse and collapse of the airway walls are important surfactant properties in maintaining airway stability. In addition to its surface activity, airway surfactant improves bronchial clearance and regulates airway liquid balance, thus indirectly modulating airway wall thickness and airway diameter. Surfactant has furthermore been shown to modulate the function of respiratory inflammatory cells. Its immunomodulatory activity includes suppression of cytokine secretion and transcription factor activation. This may be of importance in the inflammatory network of asthma. Thus, dysfunction of surfactant in obstructive lung disease might be one of the mechanisms leading to increased airway resistance, which is commonly thought to be due to narrowing of airways under humoral and nervous control. In animal models of asthma, surfactant dysfunction was demonstrated, which was possibly due to protein inhibition. Furthermore, surfactant therapy seems to be capable of preventing allergen-induced bronchoconstriction. Human studies on surfactant impairment in obstructive airways diseases are still scarce but the data available are consistent with animal studies. Antiobstructive pharmacotherapy, mainly with corticosteroids, might influence and improve airway surfactant balance, but the exact mechanisms and the overall effect of pharmacotherapy on surfactant function in obstructive airways disease has to be further elucidated. Our knowledge about the role of pulmonary surfactant in obstructive airways disease is still limited, but there is convincing evidence that pulmonary surfactant plays a role in keeping the airways open.

Airway Resistance↗
PubMed1997

Aerosolized surfactant inhibits acetylcholine-induced airway obstruction in rats.

Exogenous surfactant treatment inhibits antigen-induced airway obstruction in sensitized guinea-pigs. Aerosolized surfactant also improves respiratory function in asthmatic patients. The aim of the present study was to determine whether aerosolized surfactant inhibits nonallergic airway obstruction induced by acetylcholine. Anaesthetized Wistar rats were treated by aerosol with the beta2-adrenoceptor agonist terbutaline, surfactant (Alveofact), a surfactant-terbutaline combination, or vehicle (control). Animals were then challenged by aerosolized acetylcholine to elicit receptor-mediated airway obstruction. A second group of animals was challenged with intravenous acetylcholine. Respiratory function variables were measured by body plethysmography before and after treatment, and after the acetylcholine challenge. Baseline lung function values before and after treatment were similar in all groups. Acetylcholine challenge by aerosol increased lung resistance by 64% in control animals. Pretreatment with terbutaline and surfactant significantly limited the increase of lung resistance to +36 and +34%, respectively. Simultaneous aerosolization of surfactant and terbutaline also inhibited airway obstruction but their effects were not additive. By contrast, terbutaline treatment inhibited the effects of intravenous acetylcholine, but surfactant did not. In conclusion, we suggest that surfactant aerosol may prevent acetylcholine and other pharmacological agents from reaching the airway smooth muscle from the airway lumen but not via the bloodstream.

Acetylcholine↗
PubMed1996

[Bilateral surgical lung volume reduction in severe emphysema].

OBJECTIVE: To report preliminary results with a new surgical method of treating terminal emphysema by bilateral reduction of lung volume. PATIENTS AND METHODS: In a prospective study, the results obtained with the first 20 consecutive patients (mean FEV1: 590 +/- 180 ml) who underwent operative reduction of lung volume were recorded. 19 of the 20 patients had required continuous oxygen supply. RESULTS: The patients were extubated 8.5 +/- 6 h postoperatively; thoracic drainage was removed after 9 +/- 6 days. The degree of dyspnoea was decreased in all patients (3.5 +/- 0.5 vs 0.5 +/- 0.1). Significant reduction of overinflation occurred soon after the operation (residual volume 273 +/- 125 to 201 +/- 107% of normal; total capacity from 142 +/- 18 to 109 +/- 22% of normal), as well as reduction in the degree of obstruction (FEV1 from 18 +/- 6 to 24 +/- 7% of normal; for each, P < 0.05). One patient died 3 weeks post-operatively of Candida infection. CONCLUSION: The method looks promising for the treatment of selected patients and may thus provide an alternative to lung transplantation.

Adult↗