[Papillary adenoma of type-II pneumocytes as a rare differential diagnosis of a solitary pulmonary nodule]. / Papilläres Adenom der Typ-II-Pneumozyten als seltene Differenzialdiagnose eines pulmonalen Rundherdes.

The case of a 66-year-old, asymptomatic patient with a papillary adenoma of type-II pneumocytes is reported. Following the coincidental radiologic finding of a solitary pulmonary nodule, the diagnosis could be established in a bronchoscopically obtained endobronchial biopsy. A resection of the involved segments S8-10 on the left side was performed. Papillary adenoma of type-II pneumocytes is a rare tumor, whose origin is suspected in progenitor cells of the bronchioloalveolar epithelium with the potential to differentiate towards type-II pneumocytes and clara cells. The tumor is regarded as benign, however, a malignant potential is not excluded by some authors.

Enhancement of mitral regurgitation and normal left atrial color Doppler flow signals with peripheral venous injection of a saccharide-based contrast agent.

OBJECTIVES: The saccharide ultrasound contrast agent SHU 508 A was used to test the hypothesis that an intravenous, transpulmonary contrast method can enhance color Doppler flow signals in the left atrium in a clinically useful manner. BACKGROUND: Color Doppler display of mitral regurgitation may be unreliable because of variable signal to noise ratios that are at times poor. Traditional contrast agents enhance color Doppler flow signals in the right heart chambers. This study describes our observation of a recently developed contrast agent, SHU 508 A, capable of pulmonary transit after peripheral venous injection. METHODS: Control subjects (n = 10) and patients with suspected mitral regurgitation (n = 23) were studied by color Doppler flow imaging before and after 3-g intravenous doses of SHU 508 A. Reference grading of mitral regurgitation (0 to 3) was formulated from left ventricular angiography. In the four-chamber view of the left atrium, we selected for analysis the systolic frame with the maximal retrograde jet of mitral regurgitation (aliased/blue) and the diastolic frame with the maximal color coding from anterograde pulmonary venous flow (red) for planimetry and for grading the intensity of the color Doppler signal (0 to 5). RESULTS: The score of the color Doppler signal intensity increased by > or = 2.5 after 3 g of SHU 508 A (p < 0.001). Flow detection improved, as shown by the increased jet area of mitral regurgitation (> or = 170%), after 3 g of SHU 508 A (3 +/- 3 vs. 12 +/- 8 cm2, p < 0.001) and by a > or = 200% increase in normal anterograde flow area (p < 0.001) in both the mitral regurgitation group and the control group. After contrast enhancement, the correlation between angiographic grading and the relation of jet area to the left atrial area increased from r = 0.79 to r = 0.91. CONCLUSIONS: Contrast-mediated increased echogenicity of the left atrial blood pool improves the signal to noise ratio of Doppler images of mitral regurgitation and anterograde atrial flow. The technique is safe and simple and seems to minimize variability due to instrument design and anatomic signal attenuation.

Pharmacological actions of the selective and non-selective beta-adrenoceptor antagonists celiprolol, bisoprolol and propranolol on human bronchi.

1. The pharmacological actions of the beta-adrenoceptor antagonists, celiprolol, bisoprolol and propranolol were investigated in human lung tissue by radioligand binding experiments as well as in human isolated bronchi by functional experiments in organ baths. 2. Data from lung tissue were compared to those obtained from myocardial membranes. 3. Lung tissue was obtained from 10 patients having undergone lung resection for bronchial carcinoma and myocardial tissue from a patient who had received a heart transplantation. 4. In radioligand binding experiments, celiprolol exhibited a high affinity binding to beta 1-adrenoceptors in heart and a low affinity binding to beta 2-adrenoceptors in lung tissue. The selectivity obtained for the beta 1-adrenoceptor was calculated to a factor of eleven. 5. Compared to bisoprolol and propranolol, celiprolol elicited the lowest affinity for the beta-adrenoceptor, as judged from the K1-values. 6. In the absence and presence of the guanine nucleotide Gpp(NH)p celiprolol did not affect receptor binding. 7. In functional experiments on intact bronchi, celiprolol, bisoprolol and propranolol failed to produce relaxation (+/- forskolin) or a significant difference in efficacy in antagonizing the relaxant effects of isoprenaline. However, a rank order of potencies was revealed (propranolol:bisoprolol:celiprolol = 46:12:1). 8. Plasma concentrations for celiprolol and bisoprolol usually achieved in vivo were below the IC50 value obtained in vitro. In contrast, for propranolol, plasma concentrations were nearly identical with the IC50 value. 9. It is concluded that celiprolol is a selective beta 1-adrenoceptor antagonist on human heart and has no agonistic properties on intact human bronchi. Compounds such as celiprolol and bisoprolol may in comparison to propranolol, possess reasonable therapeutic advantages in the treatment of patients with obstructive lung disease due to their low affinity for beta 2-adrenoceptors.

Implantation of Accuflex and Strecker stents in malignant bronchial stenoses by flexible bronchoscopy.

Silicone and metal stents are available for the treatment of malignant bronchial stenoses. This project sought to compare the self-expanding nitinol Accuflex stent (Boston Scientific Corp; Watertown, Mass) with the passively expandable tantalum Strecker stent (Boston Scientific Corp; Watertown, Mass), both implanted by flexible bronchoscopy under local anesthesia and sedation. In 51 patients with malignant bronchial stenosis, 14 nitinol and 51 tantalum stents were used and stenoses of 75 to 100% were treated. The intervention was successful in all but one patient; a mean patency of 93% was achieved. In the follow-up period, the probability of survival was significantly lower in patients with total bronchus occlusion than in patients with stenotic alterations (44 vs 109 days; p<0.05). In 10 patients, lung function analysis after stent implantation revealed a significant increase in PaO2 (65 vs 71 mm Hg; p<0.01), inspiratory vital capacity (2.5 vs 2.7 L; p<0.05), and FEV1 (1.8 vs 2.0 L; p<0.05). Mucus retention was the main (39%) adverse factor in the early phase after stent implantation, whereas tumor penetration became the most frequent problem (67%) in the later phase. Recanalizing interventions were necessary in 18% of the cases in which tumor penetration occurred. Stent distortion occurred in 12 patients with Strecker and in none with Accuflex stents. In comparison to the Strecker stent, the self-expanding Accuflex stent is preferable owing to its excellent flexibility and faster delivery system. Both types of stents could be sufficiently deployed within the lesion and allowed for highly precise positioning. Furthermore, no general anesthesia was required. The fiberbronchoscopic mode of implantation under sedation is very efficient even for tumor patients with severe impairment of their physical and respiratory condition.

Control of pacemaker rate by impedance-based respiratory minute ventilation.

Several studies have shown that the capability for exercise can be increased in patients with pacemakers by means of adjusting the rate. Respiration is one of the parameters considered for rate control. The aim of our study was to determine how respiratory parameters such as ventilation, tidal volume, and respiratory rate are capable of controlling the pacemaker rate, especially when measured indirectly by means of impedance plethysmography. We examined four volunteers and eight patients with implanted cardiac pacemakers using bicycle ergometry at increasing work loads. We recorded heart rate, uptake of oxygen, and ventilation directly (by pneumotachygraphy) and indirectly (by chest wall impedance plethysmography). A good correlation of directly to indirectly measured ventilation (r = 0.8687) was found. Our study suggests that respiratory minute volume is more appropriate for rate control of physiologic pacemakers than tidal volume or respiratory rate alone. Measurement by means of impedance plethysmography is sufficiently precise to be used for this purpose. Further studies must be conducted as to the optimum realization within an implantable device.

Nocturnal asthma. Beta 2-adrenoceptors on peripheral mononuclear leukocytes, cAMP- and cortisol-plasma concentrations.

To evaluate pathophysiologic mechanisms of the predominantly nocturnal complaints in atopic bronchial asthma, the expression and function of beta 2-adrenoceptors on peripheral mononuclear leukocytes (pMNL), the cAMP--as well as the cortisol--plasma concentrations were studied in eight healthy men and ten so far untreated male asthmatic patients at 4-h intervals for 24 h. No difference was seen in the beta 2-adrenoceptor density (Bmax) on pMNL between healthy and asthmatic men (24-h means +/- SE: 908 +/- 59 sites per cell and 821 +/- 54 sites per cell, respectively). The equilibrium dissociation constant (Kd), however, was significantly higher in the asthmatic patients (24-h mean +/- SE: 8.8 +/- 1.2 pmol/L vs 3.0 +/- 0.2 pmol/L in healthy men, p less than 0.0001), which is equivalent to a lower affinity of the beta 2-adrenoceptors for the radioligand 125iodocyanopindolol. Bmax showed a statistically significant circadian variation, but Kd did not. The circadian variation in Bmax was reflected in the basal intracellular cyclic adenosine-monophosphate (cAMP) content of the cells investigated. High Kd values (equivalent to low receptor affinities) tended to be associated with small increases of the intracellular cAMP content after in vitro stimulation by 10(-7) mol/L isoprenaline (isoproterenol) (24-h mean +/- SE: 1.4 +/- 0.2 pmol/10(6) cells; r = -0.529, p = 0.05 at r = -0.549, n = 10). Plasma cAMP concentrations were found to be significantly lower in the asthmatic patients (24-h means +/- SE: 22.9 +/- 1.3 nmol/L vs 29.1 +/- 1.1 nmol/L, p less than 0.0001). Plasma cortisol concentrations were significantly higher in the asthmatic patients (24-h means +/- SE: 0.500 +/- 0.084 mumol/L vs 0.319 +/- 0.063 mumol/L). The results support the hypothesis that a lesion of the beta-adrenergic system contributes to the pathophysiology of atopic bronchial asthma. In the patients investigated in this study, such a lesion could be demonstrated in the affinity rather than in the number of beta 2-adrenoceptors expressed on peripheral cells of the immune system (pMNL). According to present-day knowledge of adrenergic effects on pMNL, such an affinity decrease of beta 2-adrenoceptors could account for overshooting immune responses. In association with other factors influencing respiratory function, it could be responsible for the predominantly nocturnal complaints in atopic bronchial asthma. Plasma cortisol concentrations did not appear to be related to the principal cause of "nocturnal asthma;" they rather reflected an endogenous defense mechanism to the disease.

[Risk assessment of patients before lung surgery]. / Risikoabschätzung von Patienten vor Lungenresektion.

Lung resection offers the best prospect of long-term survival in patients with nonmetastatic pulmonary neoplasia. In view of the dismal prognosis of unresected bronchial cancer, surgical resection should be encouraged even in patients with reduced cardiopulmonary function. Accurate estimation of the postoperative cardiopulmonary function is therefore desirable to avoid (a) refusal of potentially curative treatment and (b) severe postoperative disability. The origins of post-resection morbidity and mortality are multifactorial. Thus, no single pulmonary function test or hemodynamic measurement can accurately and reliably predict postoperative cardiorespiratory complications. Criteria of functional operability should be based on percent of predicted value, so that patient's age, sex, and height will be taken into consideration. Exercise testing offers the advantage that both pulmonary and cardiac risk can be evaluated simultaneously. The high predictive value of maximal oxygen uptake (VO2max) in assessing postoperative morbidity and mortality is established. The calculation of predicted postoperative lung function (ppo) is of importance. The postoperative values for the forced expiratory volume in one second (FEV1-ppo), the transfer factor (TL,CO-ppo), and VO2max-ppo can be predicted by using the same formula. Patients with nearly normal lung function (FEV1, TL,CO > 75% predicted) and no concomitant cardiac disease can undergo lung resection right up to pneumonectomy without further diagnostic procedures. In the others, FEV1-ppo and TL,CO-ppo should be estimated first by taking into account the number of segments to be resected. Patients with values < 30% predicted are usually regarded as being inoperable, whereas values > 40% predicted qualify for resection without the need for further diagnostics. VO2max < 10 ml/kg/min or < 40% predicted are prohibitive for surgery. If VO2max is > 20 ml/kg/min or > 75% predicted, functional operability without limitation is given. For those cases where diagnostic uncertainty still remains, FEV1-ppo, TL,CO-ppo, and VO2max-ppo can be calculated by means of quantitative lung scans. Patients with either FEV1-ppo and TL,CO-ppo < 30% predicted or VO2max-ppo < 8 ml/kg/min or < 35% predicted are deemed inoperable.

Bronchoscopy of lung cancer.

Lung cancer is a leading cancer site in men and women with a high incidence and mortality rate. Most patients are diagnosed when the disease has already spread. An early, detection and immediate and accurate histological or cytological diagnosis are essential for a hopeful outcome. In most patients, bronchoscopy is the method of choice in establishing a suspected lung neoplasm. With the rigid and flexible method, two complementary techniques are available. The methods bear a very low mortality rate if sufficient monitoring and resuscitative instrumentation is available. Rigid bronchoscopy offers the possibility of obtaining large biopsy specimens from the tumorous tissue and provides an effective tool in the control of major haemorrhage. However, it cannot be used for the inspection of further peripherally located parts of the bronchial system and needs general anaesthesia. In contrast, the flexible method can be quickly and readily performed at practically any location using portable equipment. Bronchi can be inspected up to the 8th order and with bronchial washing, forceps biopsy, brush biopsy and fluorescence bronchoscopy techniques with a high diagnostic yield are available. This holds true, especially if these sampling techniques are used as complementary methods.

Influence of OM-85 BV on different humoral and cellular immune defense mechanisms of the respiratory tract.

To clarify the mode of action of an oral bacterial extract (OM-85 BV) on local airway immunity pre- and posttherapeutic washings from bronchoalveolar lavage (BAL) fluid of 28 adult patients with nonobstructive chronic bronchitis were analysed. In comparison to healthy controls, an elevation of total cell count due to an increased number of PMN leukocytes, and an impaired activity of the alveolar macrophages measured by the chemiluminescence response to opsonized zymosan was observed in patients with chronic bronchitis. After treatment with OM-85 BV, the BAL CD4+/CD8+ lymphocyte ratio and BAL interferon-gamma levels were increased. The alveolar macrophage activity was normalized and the BAL IgA was regulated from a reduced or hyperelevated to a moderately increased level.

[Immediate suppression of endogenous cortisol secretion after single oral administration of 6-alpha-methylprednisolone]. / Unmittelbare Unterdrückung der endogenen Kortisolsekretion nach oraler Einzeldosis von 6-alpha-Methylprednisolon.

Plasma samples from 5 asthma patients were taken in 4-h intervals before and 1, 2, 4 and 6 h after the oral application of 100 mg methylprednisolone. Reversed-phase HPLC allowed simultaneous measurement of both endogenous hydrocortisone and exogeneous methylprednisolone. Suppression of endogeneous hydrocortisone secretion occurs immediately after administration of a single oral dose of an exogeneous glucocorticoid and cannot be avoided by morning application.

Atrial natriuretic peptide in acute hypoxia-exposed healthy subjects and in hypoxaemic patients.

Plasma atrial natriuretic peptide (ANP) is an endogenous vasodilator, which might counteract pulmonary hypertension due to hypoxaemia. The aim of this study was to investigate the influence of acute and chronic hypoxia on plasma (ANP) concentrations in humans. Venous plasma ANP concentrations in six healthy subjects were measured before and after inhalation of hypoxic air (11% O2) at rest for 30 min, and following 5 min of mild hypoxic exercise (25 W). Pulmonary arterial plasma ANP levels were determined in 31 right heart catheterized patients with lung disease. In healthy subjects, mean arterial oxygen tension (Pao2) was 6.8 +/- 1.9 kPa after 30 min hypoxia at rest, and 4.7 +/- 0.9 kPa after hypoxic exercise testing. Hypoxia at rest did not induce significant changes in ANP concentrations, whereas hypoxic exercise led to significantly increased ANP levels. Among hypoxaemic patients, significantly elevated plasma ANP levels were found only in the subgroup with increased mean pulmonary artery pressure, but not in the subgroup with normal pulmonary artery pressure. In summary, severe acute hypoxia induced by hypoxic exercise, but not moderate acute hypoxia at rest, leads to increased ANP levels in healthy subjects. Chronic hypoxia alone does not lead to elevated plasma ANP levels; whereas, hypoxia combined with pulmonary hypertension causes increased plasma ANP concentrations in diseased subjects.

[Palliative intrabronchial laser treatment of malignant bronchial stenosis using the fiberbronchoscope]. / Palliative intrabronchiale Laser-Behandlung maligner Bronchusstenosen mit dem Fiberbronchoskop.

During a period of 15 months we performed a laser therapy of bronchi stenosis due to malignant tumors in 28 patients. We used a Neodym-YAG-Laser (MBB-AT, Munich), guided through a fiberbronchoscope (Olympus BF-1 TR). 59% of total-stenoses and 83% of the partly occluded bronchi could be opened sufficiently. During a follow-up period of 12 months (mean 4.7 m) 83% of the bronchi remained open. According to our experience, fractional tissue removal is the method of choice rather than all-at-once coagulation since tissue edema may cause bronchial occlusion 1 to 3 days after treatment. We think, if surgical treatment is ruled out, intrabronchial laser coagulation is an alternative with little impairment of the patient to prevent hypoventilation and repair functional conditions.

[Continuous transcutaneous blood gas monitoring during fiberbronchoscopy]. / Kontinuierliche transkutane Blutgasüberwachung während der Fiberbronchoskopie.

In 28 patients PO2 and PCO2 were measured continuously during diagnostic fiberbronchoscopy by means of transcutaneous electrodes (PtcO2 and Ptc CO2 System TCM Radiometer Copenhagen). A mean decrease in PtcO2 of 31% (s +/- 16.5%) was found. This effect can be prohibited by using oxygen insufflation at a rate of 0.5 liters per minute by nasal tube. The positive effect of fiberbronchoscopic lavage in cases of severe dyscrinism is documented. A mean increase in PtcO2 of 42% was found after the procedure, but there is a time lag of 20-30 minutes until the maximal increase is reached. In patients with known but not acute bronchial asthma the irritation of the bronchial system by fiberbronchoscopy induces a histamine release. There is no relation between the release of histamine and the decrease in arterial oxygen tension.

Local immunity in patients with chronic bronchitis and the effects of a bacterial extract, Broncho-Vaxom, on T lymphocytes, macrophages, gamma-interferon and secretory immunoglobulin A in bronchoalveolar lavage fluid and other variables.

In 28 adult patients with nonobstructive chronic bronchitis we investigated components of the immune system of the lower airways and the effects of treatment with Broncho-Vaxom (BV). An analysis of the washing from bronchoalveolar lavage (BAL) showed, in comparison with healthy controls, an elevation of total cell count (p = 0.003) as well as the IgA/albumin values (p = 0.02) and a reduction of the macrophage activity (p less than 0.001) in patients with chronic bronchitis. After BV a reduction in the total cell count (p = 0.05), an increase in the helper/suppressor T lymphocyte ratio (due mainly to the reduction in the suppressor cells; p = 0.04), a modulation of the IgA/albumin ratio, a stimulation of the impaired alveolar macrophage activity (p = 0.03) and increased concentrations of gamma-interferon (p = 0.03) were found in the BAL fluid of patients with chronic bronchitis. The salivary IgA/albumin ratio remained unchanged, the serum IgE concentration fell (p = 0.02) and the urinary IgA concentration rose (p = 0.002). Bronchial mucosa lesions, evaluated endoscopically in terms of structural damage, hyperemia and mucus production, were improved (p less than 0.01). These findings indicate that orally administered BV modulates disordered local and systemic immune functions in patients with chronic bronchitis.

Effects of a bacterial extract on local immunity of the lung in patients with chronic bronchitis.

Our findings demonstrate that Broncho-Vaxom (BV) displays possibly via the gut-associated immune system different effects on the lymphatic system of the lung: a positive influence on the helper/suppressor T-lymphocyte balance, an increase of gamma interferon, a stimulation of the reduced alveolar macrophage activity, and a regulation of BAL IgA to a distinct level whereby the serum IgE is reduced. By these effects BV is able to modulate impaired local and systemic immune function. The observed relationship between the inflammation score and the BAL fluid composition supports the view that the improvement of the mucosa lesion found in nearly all of our patients with chronic bronchitis occurs as the result of the pleiotropic immunomodulating effects of Broncho-Vaxom.

[Disseminated histoplasmosis after a tropical visit in a patient with known sarcoidosis]. / Disseminierte Histoplasmose nach Tropenaufenthalt bei bekannter Sarkoidose.

A 40-year-old man with grade II sarcoidosis went on a two-week visit to Ecuador. Afterwards he was treated with low-dose corticosteroids because of slight deterioration on the X-ray film. Unilateral hilar enlargement followed by bouts of high fever and a greatly increased erythrocyte sedimentation rate, suggested an acute exacerbation of the sarcoidosis and was, therefore, treated with an increase in steroid dosage plus azathioprine. Bronchoalveolar lavage fluid and tissue samples from lung, bone-marrow and spleen were suggestive of an infection with Histoplasma capsulatum. There was now bilateral hilar enlargement with right upper lobe infiltration, marked hepatosplenomegaly and thrombocytopenia (17,000/microliters), but serological tests remained negative. The fulminant course with dissemination could not be arrested despite administration of fluconazole (400 mg/d) and amphotericin B (total dosage 1.14 g). Histoplasma capsulatum was cultured from lung and spleen tissue post-mortem.

[Flexible bronchoscopic implantation of Accuflex and Strecker stents in malignant bronchial stenoses]. / Flexible bronchoskopische Implantation von Accuflex und Strecker Stents bei malignen Bronchialstenosen.

Silicone and metal stents are available for the treatment of malignant bronchial stenoses. This project sought to compare the self-expanding nitinol Accuflex stent (Boston Scientific Corp; Watertown, Mass) with the passively expandable tantalum Strecker stent (Boston Scientific Corp; Watertown, Mass), both implanted by flexible bronchoscopy under local anesthesia and sedation. In 51 patients with malignant bronchial stenosis, 14 nitinol and 51 tantalum stents were used and stenoses of 75 to 100% were treated. The intervention was successful in all but one patient, a mean patency of 93% was achieved. In the follow-up period, the probability of survival was significantly lower in patients with total bronchus occlusion than in patients with stenotic alteration (44 vs 109 days; p < 0.05). In 10 patients, lung function analysis after stent implantation revealed a significant increase in PaO2 (65 vs 71 mm Hg; p < 0.01), inspiratory vital capacity (2.5 vs 2.7 L; p < 0.05), and FEV1 (1.8 vs 2.0 L; p < 0.05). Mucus retention was the main (39%) adverse factor in the early phase after stent implantation, whereas tumor penetration became the most frequent problem (67%) in the later phase. Recanalizing interventions were necessary in 18% of the cases in which tumor penetration occurred. Stent distortion occurred in 12 patients with Strecker and in none with Accuflex stents. In comparison to the Strecker stent, the self-expanding Accuflex stent is preferable owing to its excellent flexibility and faster delivery system. Both types of stents could be sufficiently deployed within the lesions and allowed for highly precise positioning. Furthermore, no general anesthesia was required. The fiber-bronchoscopy mode of implantation under sedation is very efficient even for tumor patients with severe impairment of their physical and respiratory condition.