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Biomedical subjects

T O Wagner

Publications and source records attributed to T O Wagner.

At least 37 records · Page 2Linked to original sources
PubMed1997

Analysis of leukocyte activation during acute rejection of pulmonary allografts in noninfected and cytomegalovirus-infected rats.

After human lung transplantation acute rejection and cytomegalovirus (CMV) infections may occur, probably contributing to the development of chronic rejection. We established a model of subacute allograft rejection in rats to analyze leukocyte activation and effects of a CMV infection. Histoincompatible lung transplants (BN/LEW) without immunosuppression (group A) and lungs of initially immunosuppressed animals (group B) were analyzed. The production of inflammatory mediators (interleukin-6, tumor necrosis factor alpha, nitric oxides) and the expression of MHC class II antigens by alveolar and lung tissue macrophages were significantly enhanced during the alloresponse. In recipients without immunosuppression (group A) allograft necrosis was detected by day 6, whereas group B allografts were fully rejected by day 25. In allografts of immunosuppressed, CMV-infected animals (group C) the CMV infection was clearly aggravated and the number of activated lung tissue macrophages was increased when compared with noninfected allografts or isografts. The subacute model provides the advantage of allowing us to study mechanisms of acute rejection without the effects of reperfusion injury. Furthermore these findings underline the role of inflammatory mediators produced by macrophages during rejection.

Acute Disease↗
PubMed1997

Decreased expression of the cystic fibrosis transmembrane conductance regulator protein in remodeled airway epithelium from lung transplanted patients.

The absence or mislocalization of cystic fibrosis transmembrane conductance regulator (CFTR) is regarded as being specific for cystic fibrosis (CF). In principle, the supply of a non-CF lung transplant to a CF patient should bring up normal CFTR expression in the lower airways. Immunolocalization of CFTR and of epithelial differentiation markers (ie, cytokeratins 13, 14, and 18, and desmoplakins 1 and 2) was carried out on 21 mucosal biopsies from the upper lobe of grafts in non-CF (n = 12) and CF patients (n = 9) retrieved between days 23 and 1,608 after lung transplantation. Biopsy specimens from seven non-CF and four CF patients presented either a pseudostratified respiratory epithelium or slight basal cell hyperplasia. CFTR was distributed at the apical membrane of the ciliated cells. In remodeled epithelia with basal cell hyperplasia or squamous metaplasia, CFTR was either weakly expressed in the cytoplasm of the superficial epithelial cells or was undetectable. The extent of epithelium remodeling was significantly correlated with an impairment of lung function. The results suggest that posttransplant airway epithelium dedifferentiation of the graft leads to the loss of properly targeted CFTR irrespective of the underlying disease of the recipient.

Adult↗
PubMed1997

Rehabilitation results of patients with multiple injuries and multiple organ failure and long-term intensive care.

BACKGROUND: Multiple organ failure is regarded to be the major complication of trauma victims treated in the intensive care unit. Long-term rehabilitation results of this special group of patients have not been analyzed so far. METHODS: Fifty patients with multiple injuries and multiple organ failure (Injury Severity Score > or = 36.8) were followed-up 4.9 +/- 0.3 years after the trauma. To show any organotopic sequelae, laboratory tests for the function of lungs, liver, kidney, and the hematologic system were performed. Additionally their functional (locomotion and neurologic system) and occupational rehabilitation results were investigated. RESULTS: The laboratory tests showed entirely normal results. The only pathologic values could be found in the lung function tests. Nineteen percent of the patients showed nonphysiologic results in either spirometry, body plethysmography, or diffusion capacity of carbon monoxide. In more than 25% of the patients, permanently decreased range of motion (limitation of more than 30% of the entire range of motion) of the elbow, hip, knee, or ankle joint were found. In 40% of the patients, permanent motoric nerve lesions were identified; in 50% of the patients, permanent sensoric nerve lesions could be verified. The return to work rate was 60%. CONCLUSIONS: Patients with multiple injuries, who survived multiple organ failure during their long-term intensive care treatment, show an excellent functional and occupational rehabilitation result. They show no major sequelae in their organ function even years after the trauma. Although often these patients suffer from permanent central or peripheral paralysis and decreased range of motion, this finding does not correlate with the patients' ability to return to work.

Activities of Daily Living↗
PubMed1997

[Cell biology of bronchial asthma: interesting new methods. Intracellular determination of cytokines in T-cells and basic proteins in eosinophilic granulocytes using flow cytometry].

Clinical studies on pathophysiological mechanisms of asthma bronchiale require methods of investigation that are simple, reproducible and rapid in respect of analysing relevant inflammatory cells and mechanisms. The article presents two new flow cytometric methods enabling on single-cell level the determination of expression of intracellular cytokines in T-cells and of basic proteins in eosinophilic granulocytes. Both techniques of examination can be performed either with whole blood or with cells from bronchoalveolar lavage without preceding cell separation techniques. First results reveal interesting new aspects with regard to the expression of IFN-gamma, IL-2, IL-4 and IL-5 in T-cells, and of ECP and EPO in eosinophils in bronchial asthma.

Asthma↗
PubMed1997

[Why do adults with mucoviscidosis refuse a medically recommended course of intravenous antibiotic therapy?].

BACKGROUND: Regular courses of intravenous antibiotics are recommended for the treatment of chronic Pseudomonas aeruglnosa (PA) infection in patients with cystic fibrosis. We report the results of interviews performed to evaluate why a subgroup of patients vote against regular intravenous (i.v.) antibiotic treatment. METHODS: Structured interviews covering a) the individual's perception of chronic PA infection, b) the patient's expectations regarding the effectiveness of i.v. treatment, c) the patient's personal reasons for refusal of i.v. treatment. STUDY COHORT: 16 out of 18 adult patients treated in the adult CF outpatient clinic at Hannover Medical School who had voted against the physician's recommendation to receive regular i.v. therapy twice a year. RESULTS: More than one half of the patients did not regard chronic PA infection as important due to the lack of specific symptoms. A subgroup of patients had no idea of what their clinical status should be if i.v. antibiotics would be necessary; these patients reported prior experience of treatment courses which had been ineffective and had been instituted after talking into the patients. The most frequent reasons against IV treatment were not being sick enough and fear of adverse drug effects. ASSESSMENT: The results are being discussed considering the physician-patient relationship. The reasons why patients refuse help should be extensively explored rather than simply addressing this attitude as "non-compliance". Patients, too, come to reasonable decisions, and it is important to know their thoughts and reasoning if one intends to influence them.

Adult↗
PubMed1997

Changes in cardiovascular risk factors and hormones during a comprehensive residential three month kriya yoga training and vegetarian nutrition.

In participants of a comprehensive residential three month yoga and mediation training programme living on a low fat lacto-vegetarian diet changes in cardiovascular risk factors and hormones were studied. Substantial risk factor reduction was found. Body mass index, total serum and LDL cholesterol, fibrinogen, and blood pressure were significantly reduced especially in those with elevated levels. Urinary excretion of adrenaline, noradrenaline, dopamine, aldosterone, as well as serum testosterone and luteinizing hormone levels were reduced, while cortisol excretion increased significantly.

Adolescent↗
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↗
PubMed1996

Metabolic, endocrine, haemodynamic and pulmonary responses to different types of exercise in individuals with normal or reduced liver function.

UNLABELLED: The liver is central to the metabolic response to exercise but measurements of effects of reduced liver function on the physiological adaptation to exercise are scarce. We investigated metabolic, endocrine, pulmonary and haemodynamic responses to exercise in 15 healthy untrained controls (Co) and in 30 subjects with reduced liver function (i.e. liver cirrhosis, Ci). The following protocols were used: protocol 1 maximal oxygen uptake (VO2max) and anaerobic threshold (AT), protocol 2 stepwise increases in exercise intensity from 0 to 40% VO2max giving steady-stage conditions, protocol 3 1 h exercise at 20% VO2max. Muscle glycogen content was determined in 15 Ci. Spirometry was essentially normal in Ci. RESULT: protocol 1 Ci had impaired VO2max and reduced AT (P < 0.05). Basal plasma concentrations of insulin, glucagon, growth hormone and adrenaline were increased in Ci (P < 0.05); cortisol was normal. During exercise, only glucagon remained different between groups. In protocol 2 Ci had decreased resting respiratory exchange ratio (RQ: p < 0.05) associated with increased plasma concentrations of free fatty acids and glycerol. They had disproportionately enhanced lipolysis and RQ. heart rate (+24%), ventilation (+28%), thermal effects of exercise (+31%) and intrapulmonary shunt volume (+76%), which accounted for 11.7 (SD 3.0) or 7.4 (SD 0.9%) of cardiac output during exercise in Ci and Co, respectively (P < 0.05 for all the differences reported). The metabolic effects of Ci were independent of the clinical and nutritional state of the patients. In protocol 3 muscle glycogen content was highly variable in Ci, but mean values were normal [16.9 (SD 8.9) mumol.g-1 wet mass]. Glycogen content positively correlated with resting and exercise-induced RQ, but negatively correlated with the exercise-induced alterations in plasma glucose concentration. From these results we concluded that with reduced liver function VO2max and AT are reduced, but metabolic, pulmonary and haemodynamic responses per unit power output are enhanced. Muscle glycogen content would seem to contribute to the metabolic response, but its mobilization to be limited in individuals with reduced liver function.

Adult↗
PubMed1996

Circulating complement proteins in patients with sepsis or systemic inflammatory response syndrome.

The systemic inflammatory response of the body to invading microorganisms, termed sepsis, leads to profound activation of the complement system. Pathophysiological concepts suggest that complement activation occurs very early in this syndrome. Thus, we discuss whether the determination of concentrations of the complement components C3a, C5a, and C3 in plasma as well as of the C3a/C3 ratio might be helpful to diagnose sepsis early. For this purpose, 33 patients from an intensive care unit were monitored for 10 days. In comparison with healthy donors, C3a levels and the C3a/C3 ratio of intensive-care-unit patients were significantly elevated (P < 0.0001) on admission. In contrast, C3 levels were significantly reduced (P < 0.0001) but increased during the study. C5a levels in the plasma of healthy donors and patients were identical. Twenty-two of 33 patients fulfilled microbiological and clinical criteria of sepsis. Eleven patients had signs of systemic inflammatory response syndrome but no microbiological evidence of sepsis. The groups could be differentiated from each other by their C3a levels or their C3a/C3 ratios during the first 24 h after the clinical onset of sepsis (P < 0.05). Septic patients in shock had higher C3a levels than normotensive septic patients, although the differences were not significant. Nonsurvivors had significantly higher C3a levels on admission than survivors (P = 0.0185). No differences were found between septic patients who developed adult respiratory distress syndrome and those who did not. Thus, determination of C3a concentrations in plasma may prove useful (i) to diagnose sepsis early, (ii) to differentiate between patients with sepsis and those with systemic inflammatory response syndrome, and (iii) to assess prognosis.

Adolescent↗
PubMed1996

Time kinetics of the endocrine response to acute psychological stress.

A first-time parachute jump was chosen as a model to evaluate the endocrine response to acute psychological stress. In 43 inexperienced tandem parachutists, blood was drawn continuously from 2 h before to 1 h after the jump and analyzed at 10-min intervals for plasma concentrations of epinephrine (E), norepinephrine (NE), cortisol, GH, PRL, and TSH. In addition, heart rate was recorded throughout the experiment. There was a significant increase in heart rate and E concentrations during the jump itself. NE, cortisol, GH, PRL, and TSH peaked with a latency of 10-20 min. Apart from cortisol and TSH concentrations, which were still elevated 1 h after the stress event, plasma levels of the other endocrine variables normalized within 1 h following the jump. Statistically significant cross-correlations could be observed between E and NE (r = 0.60, no time lag) and between E and PRL (r = 0.58, 10-min time lag) only. Even in a very homogenous group of subjects and under well-controlled conditions, endocrine responses to acute psychological stress show considerable variations.

Adult↗
PubMed1996

Seasonal onset of bronchiolitis obliterans syndrome in lung transplant recipients.

BACKGROUND: Bronchiolitis obliterans syndrome is the major complication in long-term survival of patients with lung transplants. Bronchiolitis obliterans syndrome is thought to represent a form of chronic allograft rejection and is associated with obstructive airways disease. Viral infections or other exogenous factors may trigger this condition. METHODS: Because respiratory viral infections show seasonal clustering we studied seasonal onset of bronchiolitis obliterans syndrome in 157 lung and heart-lung transplant recipients. Individual baseline values of forced expiratory volume in 1 second were evaluated according to the International Society for Heart and Lung Transplantation criteria. For bronchiolitis obliterans syndrome classification, values of forced expiratory volume in 1 second were determined by the average of two measurements made at least 1 month apart. Onset of bronchiolitis obliterans syndrome was defined as the date of the initial pulmonary function test showing a persistent decline of forced expiratory volume in 1 second. Other factors causing obstructive airways disease were excluded. RESULTS: Forty-nine patients (31%) showed development of bronchiolitis obliterans syndrome (n = 10 stage I, n = 13 stage II, n = 26 stage III) with onset of bronchiolitis obliterans syndrome 507 +/- 372 days (mean +/- standard deviation) after transplantation. Baseline value of forced expiratory volume in 1 second was reached at 270 +/- 231 days. Between January and March of each year onset of bronchiolitis obliterans syndrome developed in 23 patients (47%). In the second (April to June) and third (July to September) quarters a persistent decline of pulmonary function test results developed in 13 (27%) and 12 (24%) patients, respectively, whereas only 1 patient (2%) showed deterioration between October and December (p < 0.001). CONCLUSIONS: Seasonal clustering of onset of bronchiolitis obliterans syndrome might thus indicate underlying unknown infectious triggers.

Adult↗
PubMed1996

Enhancement of cytomegalovirus infection and acute rejection after allogeneic lung transplantation in the rat: virus-induced expression of major histocompatibility complex class II antigens.

BACKGROUND: Cytomegalovirus infection is considered a major complication after lung and heart-lung transplantation because it can trigger acute and chronic rejection. The potential mechanisms of lung transplant rejection induced by viral infection include the upregulation of expression of major histocompatibility complex antigens. To address this question, a model of rat cytomegalovirus infection and acute lung transplant rejection was established. METHODS: Lewis inbred strain rats received syngeneic (n = 25) or allogeneic (Brown-Norway inbred rat strain, n = 38) orthotopic left-side lung transplants. Triple-drug immunosuppression with cyclosporin A, methylprednisolone, and azathioprine was given from postoperative days 1 through 10. Rat cytomegalovirus was inoculated intraperitoneally on postoperative day 3. Two control groups, those infected with cytomegalovirus (n = 15) and those without rat cytomegalovirus infection (n = 6) were treated with identical immunosuppressive regimens. Animals were sacrificed on postoperative days 11, 15, 18, 20, and 25. The salivary glands and both lungs were removed for pathologic and immunohistochemical investigations. RESULTS: All animals inoculated with rat cytomegalovirus developed systemic viral infection on or after postoperative day 11, as confirmed by an assay of plaque-forming units and immunohistologic examination. Cytomegalovirus-induced expression of major histocompatibility complex class II antigens on vascular endothelial cells was seen in the nontransplanted lungs of rats, but no major histocompatibility complex class II antigens were detected on noninfected, nontransplanted lungs. Cytomegalovirus infection also was found to enhance major histocompatibility complex class II antigen expression on pneumocytes and leukocytes in rats. Acute rejection occurred in allogeneic transplants from postoperative days 15 through 25. The expression of class II antigens on endothelial cells, pneumocytes, and leukocytes was further enhanced during the course of allograft rejection in the cytomegalovirus-infected rats compared with the noninfected controls. In cytomegalovirus-positive rats, the rejection grade was higher than that in cytomegalovirus-negative rats on postoperative days 15 through 18. CONCLUSIONS: Our results indicate that cytomegalovirus induces and enhances the expression of major histocompatibility complex class II antigens on endothelial cells, pneumocytes and leukocytes. Upregulation by cytomegalovirus infection may trigger or promote acute rejection by alloantigenic T-lymphocyte stimulation after lung transplantation. By this mechanism it may strongly influence the long-term course of lung transplant rejection.

Acute Disease↗
PubMed1995

Bronchodilating effects of natriuretic and vasorelaxant peptides compared to salbutamol in asthmatics.

In animal studies, the bronchial effects of urodilatin (URO, CDD/ANP-95-126, INN: ularitide) were superior to those of cardiodilatin/atrial natriuretic peptide (CDD, CDD/ANP-99-126). We compared the bronchodilating properties of intravenous URO and CDD in 36 clinically stable asthmatics showing a beta 2-agonist-induced increase of the FEV1 by > or = 15%. Any aerosol medication was discontinued for at least 8 h prior to the study. After baseline measurements of lung function parameters (FEV1, VC, PEF, MEF75, MEF50, MEF25) an intravenous infusion of 5.7, 11.4 or 17.1 pmol/kg/min URO or CDD was administered for 40 min in the morning. All measurements were repeated every 10 min during the infusion, for 30 min thereafter, and after the inhalation of 1.25 mg salbutamol (SALB). Both peptides had significant effects. While 11.4 pmol/kg/min URO dilated the central airways (FEV1, PEF, MEF75) slightly more potently than the peripheral bronchioles (MEF50, MEF25), 17.1 pmol/kg/min URO was as effective as SALB at all levels of the tracheobronchial tree. CDD reached only 50% of the SALB effect without a predominant localization of its action. The cardiovascular parameters revealed a significantly stronger vasorelaxant activity of CDD. In conclusion, the dose-dependent bronchodilating properties of intravenous URO were significantly superior to those of CDD.

Adult↗
PubMed1995

Beta-endorphin, but not substance-P, is increased by acute stress in humans.

The role of neuropeptides in the psychoneuroendocrinological stress response is largely unknown. In this study the effect of acute psychological stress on beta-endorphin and substance-P plasma concentrations was investigated and further the effect of different anxiety levels or control attributions on beta-endorphin or substance-P levels were determined. Blood samples were obtained from 47 inexperienced tandem-parachutists 2 h before, immediately after, and 1 h after a parachute jump and plasma concentrations of beta-endorphin and substance-P were analysed. Anxiety levels and control attributions were assessed by psychometric scales. Whereas substance-P concentrations seemed to be unaffected by the jump stress, there was a transient but significant increase in beta-endorphin levels immediately after jumping. However, subjects higher in state-anxiety at the point of jumping (exit) displayed higher substance-P values at all three time points compared to the "low-anxiety" jumpers. In addition, stress-induced beta-endorphin secretion was dependent on subjective control attributions.

Adult↗
PubMed1995

Urodilatin (ularitide, INN): a potent bronchodilator in asthmatic subjects.

Atrial natriuretic peptide (CDD/ANP-99-126) has been identified as a bronchodilator in various species including humans. We investigated the effect of urodilatin (CDD/ANP-95-126) in 18 clinically stable asthmatics showing an increase of the FEV1 by > or = 15% after salbutamol inhalation. Prior to the study inhaled beta 2-agonists were withheld for 8 h. After baseline measurements of lung function parameters (FEV1, VC, PEF, MEF75, MEF50, MEF25), blood pressure, and heart rate in intravenous infusion of 20, 40 or 60 ng kg-1 min-1 urodilatin was administered for 40 min in the morning. All measurements were repeated every 10 min during the infusion, for 30 min thereafter, and after the inhalation of 1.25 mg salbutamol. Forty and 60 ng kg-1 min-1 urodilatin showed a significant effect on the central (FEV1, PEF, MEF75) and peripheral airways (MEF50, MEF25) after 10 min infusion (P < 0.05). A bronchodilation not significantly different from 1.25 mg salbutamol was induced by 40 ng kg-1 min-1 in the central airways only, while 60 ng kg-1 min-1 led to a similar effect at all levels of the bronchial tree. Lung function parameters returned to baseline within 30 min after cessation of the urodilatin infusion. Heart rate showed a tendency to increase after 40 min infusion (P < 0.05), but blood pressure did not change significantly. In conclusion, the maximal bronchodilating effect of intravenous urodilatin in clinically stable asthmatics was comparable to 1.25 mg salbutamol.

Adult↗