Biomedical subjects

S Elsasser

Publications and source records attributed to S Elsasser.

At least 37 records · Page 2Linked to original sources

PubMed1994

Evaluation of high-risk lung resection candidates: pulmonary haemodynamics versus exercise testing. A series of five patients.

We compared the value of exercise testing and measurement of pulmonary haemodynamics (PH) in the pre-operative assessment of 5 patients (mean age: 64 years, 3 men) with clinical stage I or II bronchogenic carcinoma and severe chronic obstructive pulmonary disease. They were considered at high risk due to poor pulmonary function tests (PFT); (one or more of the following): (1) radionuclide calculated postlobectomy FEV1 < 30% predicted, (2) diffusion capacity or transfer factor < 60% predicted, combined with a fall in PaO2 on maximal exercise of > 5 mm Hg, (3) a PaCO2 at rest of > 45 mm Hg. Maximal oxygen uptake (VO2max) during symptom-limited cycle ergometry and PH were measured in these 5 patients. They were considered eligible for lobectomy if they fulfilled at least one of the two criteria: (1) mean pulmonary artery pressure (PAP) of < 35 mm Hg and pulmonary vascular resistance of < 190 dyn.s.cm-5 at moderate exercise (40 W), (2) a VO2max of > or = 15 ml/kg/min. Six months postoperatively PFT and VO2max were measured again. PAP40W was 21, 38, 38, 46 and 52 mm Hg, respectively, which would have excluded 4/5 patients from surgery. VO2max was 21.7, 14.9, 13.4, 19.2 and 18.6 ml/kg/min, respectively, which would have excluded 2/5 patients. Expressed in percent predicted, however, VO2max was > or = 69% in all 5 patients, indicating only mild impairment of exercise capacity in the 2 patients with < 15 ml/kg/min VO2max. Therefore all 5 patients were offered surgery and underwent lobectomy. Apart from 1 prolonged air leak no complications occurred, the mean hospital stay was 16 days (13-21).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Bronchoprotection by salmeterol: cell stabilization or functional antagonism? Comparative effects on histamine- and AMP-induced bronchoconstriction.

Salmeterol provides bronchoprotection against a number of constrictor stimuli for more than 12 h after a single dose. This effect could be due either to functional antagonism at the level of airway smooth muscle or to cell-stabilizing effects of the compound. In this study, we attempted to clarify this mechanism by comparing the effects of salmeterol (50 micrograms), salbutamol (200 micrograms) and placebo on the airway responsiveness to histamine (to assess functional antagonism), and to adenosine 5'-monophosphate (AMP) (to assess additional cell-stabilizing effects), 14 h after drug treatment. Thirteen patients with mild allergic asthma were studied in a double-blind, randomized protocol on 6 days, at least 48 h apart. Forced expiratory volume in one second (FEV1) was measured before and 15 min after inhalation of the study medication. Then, 14 h later (8 a.m. the following morning), a bronchoprovocation test with histamine or AMP was performed. We found that 14 h after inhalation, salmeterol still had a significant effect on FEV1 in comparison to placebo and salbutamol. The provocative dose producing a 20% fall in FEV1 (PD20histamine) was significantly increased after salmeterol, whilst the increase in PD20AMP did not reach significance. The shift in PD20 (in doubling dose steps) induced by salmeterol pretreatment was not different between histamine and AMP. We conclude that the prolonged protective effect of salmeterol occurs via an extended bronchodilating and functional antagonistic action and not via a cell-stabilizing effect.

Adenosine Monophosphate↗

PubMed1993

[Severe hemoptysis in pulmonary vasculitis].

A 27-year-old man, in good health but a moderate smoker, suddenly had two episodes of haemoptysis. Routine clinical examination was unremarkable. Erythrocyte sedimentation rate was increased to 34 mm/h. The chest radiography showed ill-defined, contrast-poor infiltrations bilaterally, as well as left hilar enlargement. Lung scintigraphy and pulmonary arteriogram suggested pulmonary embolism, possible from a "pelvic vein spur", i.e. an intimal proliferation due to crossing of the common iliac artery over the pelvic vein. He was placed on oral anticoagulants. Three months later he had another severe haemoptysis, providing the indication for an exploratory thoracotomy. This revealed the left pulmonary artery wall to have inflammatory changes with aneurysmal dilatation. The aneurysm was plicated. Histological examination demonstrated chronic vasculitis as seen in Behçet's syndrome, a diagnosis confirmed by the findings of ulcers of the oral mucosa and the presence of HLA B5 allo-antigens. Immunosuppressive treatment was given with prednisone (1 mg/kg), azathioprine (2.5 mg/kg) and ciclosporin (5 mg/kg). Over the next 12 months there has been only one further haemoptysis.

Adult↗

PubMed1993

[Pathophysiology of cor pulmonale].

Chronic cor pulmonale is defined as right-heart hypertrophy or right-ventricular dilatation and/or chronic right-heart failure, secondary to disorders of the respiratory system. Most cases of cor pulmonale are secondary to chronic obstructive pulmonary disease. Other etiologies include restrictive lung diseases (e.g. idiopathic pulmonary fibrosis) and multiple pulmonary emboli, with the important, although small group of patients with chronic major vessel thromboembolism. In some instances abnormal ventilatory drive, disorders of the thoracic cage or neuromuscular diseases will eventually lead to cor pulmonale. Pathogenetic mechanisms involve hypoxic pulmonary vasoconstriction, mechanical narrowing of vessels and obstruction of the pulmonary vascular bed, which are discussed in further detail.

Humans↗

PubMed1993

Comparison of bronchodilator effects of fenoterol/ipratropium bromide and salbutamol in patients with chronic obstructive lung disease.

A double-blind, randomized cross-over trial was carried out in 24 patients with chronic airflow obstruction. The patients were required to demonstrate a minimum 15% absolute increase in forced expiratory volume (FEV1) after a standard dose (0.4 mg) of fenoterol (F). On a separate occasion the effect of ipratropium bromide (IB; 0.04 mg) on FEV1 was tested also; according to the increase in FEV1 the patients were grouped into IB responders (delta FEV1 > 15%) and IB nonresponders (delta FEV1 < 15%). Two puffs of F/IB (0.1 mg/0.04 mg), salbutamol (S; 0.2 mg) and placebo (P) were given by metered-dose inhaler at the same time of the day on three different occasions. FEV1 and specific airway resistance (sRaw) were assessed before and at specific intervals following inhalation. The results showed that F/IB and S produced similar maximal increases in FEV1 (delta FEV1 32% for F/IB and 31% for S) and decreases in sRaw (delta sRaw 24% for F/IB and 21% for S). These effects were significantly different both from baseline values and from P. FEV1 was still significantly different 8 h after inhalation from P in the F/IB group, but not in the group that received S. The effect of IB on FEV1 in the pretest was compared with the subsequent response to F/IB. In IB responders F/IB seemed to produce slightly more effective bronchodilation. Side effects were minimal and clinically insignificant. In conclusion, F/IB, with its ability to effect sustained bronchodilation without adverse side effects, is a viable alternative to a monotherapy in chronic obstructive pulmonary disease.

Aerosols↗

PubMed1992

[Pathophysiology of bronchial asthma].

Until recently asthma was considered to be caused mainly by bronchospasm of the smooth airway musculature. Accordingly beta-adrenergic agonists were the drugs of choice. During the last decade, however it has become increasingly clear that ongoing chronic inflammation of the bronchial wall plays a prominent role in the disease process. During the early bronchoconstriction after allergen challenge, histamine is probably the most important mediator. The late reaction is characterized by an inflammatory infiltration of the bronchial wall, notably by eosinophils and lymphocytes. A complex interplay of mediators as leukotrienes, prostaglandins and PAF may lead to a chronic inflammation. Inflammatory changes are seen in bronchial biopsies and broncho-alveolar lavage fluid even of mild and asymptomatic asthmatic patients. Based on this new disease concept, antiinflammatory drugs have become the mainstay of therapy even in mild to moderate asthmatics. Beta-adrenergic agonists remain the most important drug for the relief of acute bronchospasm.

Asthma↗

PubMed1992

[The treatment of terminal dyspnea].

Dyspnea can be defined as an unusual perception of respiration and/or urge to breath more than usual. Up to 70% of all tumour patients suffer at one time from this complaint, and often only an incomplete palliation is achieved. Dyspnea in the tumour patient is often associated with anxiety, which leads itself to a further exacerbation of dyspnea (through increased respiratory work and dead-space ventilation). A thorough evaluation should exclude treatable causes of dyspnea such as atelectasis, pleural effusions, pneumonias, congestive heart failure, pulmonary emboli, reversible exacerbations of coexisting obstructive lung disease, central tumour obstruction and pericardial effusion. Therapeutic measures include bronchoscopic suction of retained secretions and physical measures to reduce secretions. Supplemental oxygen is indicated in hypoxemic patients and in those who derive benefit of it. The nonspecific drug therapy with benzodiazepines and/or opiates remains clinically useful, although its efficacy is questioned by some controlled studies.

Airway Obstruction↗

PubMed1992

Role of multifunctional autonomously replicating sequence binding factor 1 in the initiation of DNA replication and transcriptional control in Saccharomyces cerevisiae.

Autonomously replicating sequence (ARS) binding factor 1 (ABF1) is an abundant DNA-binding protein that specifically recognizes the motif RTCRYN5ACG at many sites in the yeast genome, including promoter elements, mating-type silencers, and ARSs. Mutational analysis of these sites suggests that ABF1 is involved in constitutive and carbon source-regulated transcriptional activation, transcriptional silencing, and ARS activity. To better assess the role of ABF1 in DNA replication and transcriptional control, temperature-sensitive lethal mutations in the ABF1 gene were isolated. Several of the abf1(Ts) strains show rapid growth arrest at the nonpermissive temperature. At the semipermissive temperature, these strains show an ARS-specific defect in the mitotic stability of ARS-CEN plasmids, such that the abf1 mutants show defects in ARS function identical to those of mutants bearing the mutations in the cis-acting ABF1 binding sites analyzed previously by numerous investigators. Flow cytometric analysis and in vivo DNA labeling experiments on an alpha-factor synchronized abf1(Ts) strain showed that at the nonpermissive temperature, these cells fail to progress efficiently from G1 through S phase and synthesize DNA at 25% of the level seen in the isogenic ABF1 strain. RNA synthesis is also reduced in the abf1(Ts) strains. In addition, transcriptional activation by an ABF1 binding site upstream activation sequence is completely defective in an abf1(Ts) strain at the semipermissive temperature. These phenotypes provide evidence that the same protein, ABF1, functions in the initiation of DNA replication and transcriptional activation.

Alleles↗

PubMed1991

[Mediators and ARDS].

The symptoms of adult respiratory distress syndrome (ARDS) include dyspnea, tachypnea, hypoxemia refractory to supplemental oxygen and bilateral infiltrations in the chest X-ray. Neutrophils are implicated in the pathogenesis as important effector cells acting by release of mediators. Activation of the complement system has been shown in several studies and can induce lung damage directly in animal models. Proteases and collagenase have been found in elevated concentration in bronchoalveolar lavage fluid, while the amount of protease-inhibitors has been found to be reduced. Arachidonic acid metabolites of the cyclooxygenase and lipoxygenase pathway, such as prostaglandins and leukotrienes, may play a role in the pathogenesis or perpetuation of the disease process. The same holds true for cytokines such as interleukin-1 or tumor necrosis factor. All of them have been found to be elevated either in plasma or bronchoalveolar lavage fluid of ARDS patients. Several lines of evidence implicate oxygen radicals as important mediators of lung damage in ARDS. The therapeutic implications of these new insights into the pathogenesis of ARDS are briefly discussed.

Arachidonic Acid↗

PubMed1991

[Silicone endoprosthesis in the treatment of tracheobronchial stenosis. Report of the first 12 patients treated with this method].

Inoperable tracheobronchial stenoses are most often due to malignant disease. Apart from systemic therapy, various local treatment modalities such as laser resection, cryotherapy and endobronchial radiation therapy have been designed to maintain airway patency. Recently, various models of tracheobronchial stents (or endoprostheses) have been designed to maintain airway patency. They prevent recurring endobronchial tumor growth or progressive extrinsic compression of dilated airways. Silicone stents are highly suitable for this purpose. We treated 12 patients (11 males, 1 female, median age 68,5 years) suffering from bronchial carcinoma (6), esophageal carcinoma (4), metastatic colon carcinoma (1) and metastatic osteosarcoma (1). One stent per patient was inserted at the following sites: 6 in the right main bronchus, 4 in the trachea, 1 in the left main bronchus and 1 tracheobronchial left. We observed 2 complications: one obstruction of a bronchial stent by secretions which could be managed by fiberbronchoscopy and one short fire to a bronchial stent on repeat laser therapy. Rapid and lasting relief of dyspnea was observed in all patients. Our initial experience with a median follow-up of 2 months confirmed the easy insertion technique, the excellent effect and tolerance as well as the simple postoperative care of these silicone stents. Their use immediately after relief of a tracheobronchial obstruction by local means can be recommended.

Aged↗

PubMed1991

Verapamil in the prophylaxis of bronchial asthma. Is the bronchoprotective effect related to the plasma level?

A single oral dose of verapamil 80 mg was shown significantly to inhibit histamine-induced broncho-constriction in 8 out of 16 asthmatic subjects (maximum increase in PD20FEVHi 416%). There was still significant protection (delta PD20FEV1Hi greater than 100%) in the responders 5 h after the oral dose. The relationship of the bronchoprotective effect to the plasma level of verapamil was also examined. Responders and non-responders did not differ significantly in the peak plasma level or the time course of the plasma verapamil concentration. The protective effect was not correlated with the peak plasma level of verapamil or with the baseline bronchial hyperreactivity.

Administration, Inhalation↗

PubMed1991

Coronary vasodilatation and improved myocardial lactate metabolism after angiotensin converting enzyme inhibition with cilazapril in patients with congestive heart failure.

The effects of angiotensin converting enzyme inhibition on systemic and coronary hemodynamics and on myocardial lactate metabolism were investigated before and 2 and 6 hours after cilazapril at rest and during supine submaximal exercise in 10 patients with New York Heart Association class II or III chronic congestive heart failure. Angiotensin converting enzyme inhibition, indicated by a significant increase in plasma renin activity, resulted in significant reductions in blood pressure and systemic vascular resistance. Myocardial oxygen demand decreased (resting double product 10.9 +/- 3.7 vs 12.2 +/- 3.8 mm Hg beats/min 10(-3); p less than 0.05), but coronary sinus blood flow remained unchanged and calculated coronary resistance decreased (0.45 vs 0.5 units, rest 6 hours; p less than 0.05) suggesting coronary vasodilatation. Changes in coronary vascular resistance were directly related to changes in systemic vascular resistance (r = 0.75, p less than 0.5). Myocardial lactate extraction increased at rest (47 +/- 60 vs 134 +/- 132 mumol/min; p less than 0.5) and during exercise (27 +/- 54 vs 491 +/- 317 mumol/min; p less than 0.05) both in patients with coronary artery disease (n = 5) and idiopathic dilated cardiomyopathy (n = 5). Resting lactate production was converted to lactate extraction in two patients with coronary artery disease. Neither plasma catecholamine nor atrial natriuretic peptide concentrations changed significantly. The results suggest coronary vasodilation and improved aerobic myocardial metabolism by angiotensin converting enzyme inhibition in patients with congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1991

Effect of histamine on tracheal mucosal perfusion, water content and airway smooth muscle in sheep.

We examined the response of tracheal mucosal blood flow normalized for systemic arterial pressure (Qtrn), water content (VH20) and luminal dead space (Vtr) to nebulized histamine in intact, lightly anesthetized sheep. Nebulized histamine produced rapid increases in mean Qtrn (+84%) and VH2O (+85%), and a decrease in mean Vtr (-17%) (P less than 0.05) within 5 min post completion of challenge. Mean Vtr rapidly returned to baseline, while mean Qtrn and VH2O remained elevated for 60 and 90 min after challenge, respectively. Pretreatment with chlorpheniramine (H1-antagonist) blocked the changes in Vtr and VH2O, and attenuated the increase in Qtrn. Metiamide (H2-antagonist) pretreatment abolished the increase in Qtrn and blunted the increase in VH2O, but had no effect on the decrease in VTR. 2-methylhistamine (H1-agonist) decreased mean Qtrn and Vtr (P less than 0.05) and dimaprit (H2-agonist) increased mean Qtrn (P less than 0.05) without changing Vtr. Neither 2-methylhistamine nor dimaprit significantly altered VH2O. Atropine blocked histamine induced decreases in Vtr and slightly attenuated the increases in Qtrn and VH2O. Thus, histamine increased airway smooth muscle tone and mucosal water content principally via H1 receptors, and mucosal perfusion via H2 receptors. The airway smooth muscle contraction involved muscarinic pathways.

Animals↗

PubMed1991

Independent control of mucosal and total airway blood flow during hypoxemia.

In the larger airways, the blood circulation forms a subepithelial (mucosal) and outer (peribronchial) microvascular network. This raises the possibility that blood flow in these two networks is regulated independently. We used hypoxemia as a stimulus to induce changes in tracheal mucosal blood flow normalized for systemic arterial pressure (Qtr n) measured with an inert soluble gas technique and total bronchial blood flow (Qbr) and normalized Qbr (Qbrn) measured with an electromagnetic flow probe in anesthetized sheep. Fifteen minutes of hypoxemia [PO2 40 +/- 7 (SD) Torr] decreased mean Qtr n from 1.1 +/- 0.4 to 0.8 +/- 0.4 ml.min-1.mmHg-1.10(2) (-27%; P less than 0.05; n = 7) and increased mean Qbr n from 12.1 +/- 3.2 to 17.1 +/- 5.4 ml.min-1.mmHg-1.10(2) (+41%; P less than 0.05; n = 6). The rise in Qbr correlated with cardiac output (r = 0.68; P less than 0.05). Phentolamine pretreatment (0.1 mg/kg iv) blunted the hypoxemia-related decrease of mean Qtr n (-8%; P = NS). Tyramine (2.5 mg) applied locally to the trachea decreased mean Qtr n significantly after 30 and 45 min by 31 and 19%, respectively (P less than 0.05). 6-Hydroxydopamine (0.2 mg 4 times for 1 h locally applied) prevented the hypoxemia-induced as well as local tyramine-induced decrease in mean Qtr n (0 and 0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Use of flumazenil in intoxicated patients with coma. A double-blind placebo-controlled study in ICU.

In a double-blind placebo-controlled prospective clinical trial we studied the efficacy and safety of the benzodiazepine antagonist, flumazenil. In 23 patients admitted to the Intensive Care Unit with coma due to overdose with benzodiazepines or other sedatives, flumazenil i.v. (up to 2 mg or placebo) was given. In 13 patients given flumazenil the Glasgow Coma Scale (GCS) increased significantly from 4.9 to 7.8 (p less than 0.05). Six of these 13 patients, including mainly benzodiazepine mono-intoxications, needed only one series of injections (up to 1.0 mg flumazenil); the GCS increased thereby from 4.5 to 10.7 within a maximum of 5 min (p less than 0.01). In the remaining 7 patients, needing two series of injections of flumazenil (up to 2.0 mg), GCS did not rise significantly and coma was related to intoxications with nonbenzodiazepine sedatives, flunitrazepam and in one patient, encephalitis. In the 10 patients receiving placebo, the GCS did not change. A significant increase in the GCS from 5.5 to 10.8 (p less than 0.001) was, however, observed when flumazenil (up to 1.0 mg) was given after placebo. In patients with EEG monitoring the changes in waveform pattern paralleled the clinical response. Effects could be detected within 1-2 min after flumazenil injection and lasted up to 45 min. There were no adverse reactions or benzodiazepine withdrawal symptoms. We conclude that flumazenil is an effective and safe drug in the treatment of benzodiazepine overdose. The use of flumazenil is of diagnostic value in mixed-drug intoxications or coma of unknown origin and is of therapeutic importance for reversal of benzodiazepine intoxications.

Adolescent↗

PubMed1989

Methotrexate-induced pneumonitis: appearance four weeks after discontinuation of treatment.

A 71-year-old man with a long-standing history of rheumatoid arthritis required methotrexate treatment since 1986, with a total dose of 210 mg. In April 1987, before arthroplastic surgery, methotrexate was discontinued. Four weeks later a syndrome of fever, dry cough, shortness of breath, and diffuse air-space consolidations on the chest radiograph evolved. An antibiotic therapy had no beneficial effect, and a bronchoscopy yielded no pathogens. An open lung biopsy led to the diagnosis of methotrexate-induced pneumonitis. This is the first report of a case where methotrexate-induced pneumonitis developed several weeks after cessation of the treatment. Methotrexate can cause four types of pulmonary adverse reactions: pneumonitis, pulmonary edema, pulmonary fibrosis, and pleuritis. Possible pathogenetic mechanisms, symptoms, treatment, and prognosis are discussed.

Aged↗

PubMed1988

[Imaging procedures in parenchymatous lung processes].

Modern radiologic methods for assessment of parenchymal lung diseases are reviewed, with special reference to computed tomography (CT). In bronchogenic carcinoma and lung metastases CT is part of the initial workup, while in parenchymal lung diseases, emphysema and pulmonary infections CT should be used only for special indications. At present magnetic resonance imaging is inferior to CT in evaluating parenchymal lung diseases.

Bronchial Diseases↗

PubMed1988

[AIDS and the lungs].

About half of patients with acquired immune deficiency syndrome (AIDS) have an associated pulmonary disease which is more often due to infections than to tumors. Rapid diagnosis is important, especially in Pneumocystis carinii pneumonia, since the prognosis depends on early treatment. A patient in good condition may be managed on an ambulatory basis. The manifestations of tuberculosis are often atypical, i.e. noncavitating with a diffuse infiltrate, hilar adenopathy and extrapulmonary foci. Treatment of atypical mycobacteria is not clearly effective and empirical treatment has little point since the resistance pattern is unpredictable.

Acquired Immunodeficiency Syndrome↗