Turpentine- and fibrin-induced pleuritis in nude mice. Histopathological, cellular and biochemical changes.

Turpentine was injected into the right pleural cavity of nude immune-incompetent mice, causing a temporary irritative exudative pleuritis. A transient occurrence of so-called rheumatoid arthritis cells was observed in the pleural fluid together with parallel characteristic biochemical changes. In similar experiments in nude mice, however, immunization followed by intrapleural application of bovine fibrin showed irritative "dry" pleuritis without the presence of rheumatoid arthritis cells. This is in contrast with previous results from similar experiments done using normal mice. The conclusion from the present experiments is that in nude immune-incompetent mice only the non-immunological, turpentine-induced pleuritis will generate cellular and biochemical changes typical of the rheumatoid disease in patients, while the fibrin-induced pleuritis fails to show similar changes. This suggests that the rheumatoid-like pleural changes described in the present experiments in nude mice have a non-immunological basis.

Fine structure of neutrophils from turpentine-induced pleuritis in mice, simulating rheumatoid arthritis cells.

Pleural effusions were made by intrapleural turpentine installation in mice. The fine structure of inflammatory cells from the effusions was normal except for lipid inclusions. The same type of inclusion was previously found in neutrophils from pleural effusions in patients with tuberculous infection, rheumatoid disease, or carcinomatosis. The lipid inclusions observed in neutrophils from an irritative turpentine-induced pleurisy should be considered as "fatty change", and are structurally similar to the rheumatoid arthritis cells seen in patients with different diseases.

Rheumatoid arthritis cells and biochemical changes in turpentine-induced pleuritis in rabbits.

When turpentine was instilled into the right pleural cavity in rabbits a pleural effusion developed in half of the animals, with a low pH, low glucose concentration, high lactic dehydrogenase activity and the constant presence of rheumatoid arthritis cells in the affected pleural cavity. The biochemical values in the pleural fluid were significantly different from the values for normal pleural fluid obtained by a special microtechnique. These changes resulting from the experimentally induced, simple, irritative turpentine pleuritis are similar to the findings in the pleural effusion in human rheumatoid pleuritis; this implies that such changes are probably non-specific and without evidence of an immunological background.

A prospective evaluation of the clinical value of nation-wide DNA fingerprinting of tuberculosis isolates in Denmark.

SETTING: Denmark, a country with a low incidence of tuberculosis (TB). OBJECTIVE: To evaluate the value of the nation-wide DNA fingerprinting of Mycobacterium tuberculosis isolates performed in Denmark since 1992. DESIGN: Prospective study of consecutive patients with culture-verified TB from five large TB Departments in Denmark during a 7-month period in 1998. Results of IS6110 RFLP and spoligotyping were compared to those in the nation-wide Danish DNA-fingerprint database which covers approximately 95% of all culture-verified TB cases from 1992 onwards. Questionnaires asking about contact tracing and epidemiological links were sent to the patients' treating physicians. RESULTS: Of the 177 patients included in the study, 57 were Danes, one was from Iceland, 111 were immigrants, and eight were from Greenland. Responses to the questionnaires were obtained from 163 patients (92%). Four cases of unsuspected transmission were detected: one of nosocomial spread of TB, one of occupational acquisition of TB and two of transmission in an international school, leading to further contact tracing among 75 schoolchildren. These four cases were all the result of short-term contacts. In 22 cases, contact with one or more TB patient(s) was reported. In six of these, the DNA-fingerprint result revealed that the presumed contact could not be the source of infection, even though in two of the cases the known TB contact was from the household. CONCLUSION: Nation-wide DNA fingerprinting of TB isolates provides information that could not have been obtained otherwise, and contribute to the understanding of TB transmission in Danish society. In some cases the results lead to further contact tracing. Short-term contact can apparently result in transmission of TB.

Artificial pneumothorax by the Veress cannula: efficacy and safety.

In 16 patients with pulmonary fibrosis, an artificial pneumothorax was introduced using the Veress cannula and the Saugman water manometer. Atmospheric air was introduced by fractionated insufflation to a total volume of 800 ml (median). The interpleural space was found on the first attempt, and in all cases, fractionated insufflation of atmospheric air was conducted while the intrapleural pressure was controlled with the water manometer. In one case, the procedure was stopped because of a rise in the pleural pressure after insufflation of only 50 ml air. This was undoubtedly caused by pleural adhesions not visible on chest X-ray. The main concern with air insufflation is air embolism but this was not observed clinically in any of the present cases. The patients in the present study all suffered from pulmonary fibrosis judged by clinical examination, chest X-ray and pulmonary function tests. Despite a diffusion capacity (DCO/VA) with a median value of 48% expected, the procedure was well tolerated. It has previously been shown that artificial pneumothorax preceding thoracoscopy is well tolerated due to hyperventilation, with an increase in respiratory frequency and a fall in arterial CO2 concentration (PaCO2), while pH and arterial O2 concentration (PO2) remain constant. This probably also explains the tolerance of the patients in this material. Insufflation of air as described here should be restricted to senior pulmonologists because it is an infrequent procedure. The present authors found the procedure to be uncomplicated and easy to perform with little discomfort to the patients.

Medical thoracoscopy, results and complications in 146 patients: a retrospective study.

In a retrospective study the results of medical thoracoscopy in 147 patients were reviewed; 136 of the patients had pleural effusion and 11 patients had diffuse pulmonary infiltration. All the pleural exudates were initially screened three times successively and found to be sterile and without tumour cells. All thoracoscopies were performed with local anaesthesia, with the 'open technique', and nine different doctors performed the thoracoscopies. The overall diagnostic sensitivity was 90.4%. The results demonstrated 62% with malignancy of the pleura, and 38% revealed benign pleural diseases, among them 2% with tuberculosis. The sensitivity for malignancy was found to be 88% and the specificity 96%. The most common primary lung cancer with involvement of the pleura was the adenocarcinoma (62%), and the most common metastatic tumour originated from the breast (28%). The sensitivity for tuberculosis was 100% and the specificity 100%. No mortality was found, and the morbidity was low at about 0.6% (empyema, pleuro-cutaneous fistula, transcutaneous growth of tumour (mesothelioma)). In 64% of the patients the thoracoscopy resulted in treatment (pleurodesis, antituberculous treatment, chemotherapy and peroral steroid therapy). The medical diagnostic thoracoscopy in local anaesthesia is a simple, low-cost investigation with a relatively high diagnostic accuracy, no mortality and a low morbidity.

The anti-inflammatory profile of inhaled corticosteroids combined with salmeterol in asthmatic patients.

Inhaled corticosteroid (ICS) therapy such as fluticasone propionate (FP) is effective in moderate-to-severe asthma, but for patients on ICS who still experience symptoms, treatment guidelines recommend either increasing the dose of ICS or adding a long-acting beta2-agonist such as salmeterol or formoterol. Several studies have now shown that adding salmeterol provides greater clinical benefit than increasing the dose of ICS, raising the question of whether salmeterol has an additive or complementary anti-inflammatory effect to that of ICS. Recent studies on bronchial biopsies and bronchoalveolar lavage from asthmatic patients treated with either salmeterol. FP or placebo in addition to low-dose ICS have demonstrated that addition of salmeterol produces independent or additional reductions in several pro-inflammatory cells, cytokines and cell adhesion molecules compared with FP. Such complementary anti-inflammatory effects may explain the improved control of asthma symptoms and exacerbations observed when salmeterol is added to low-dose ICS therapy, and may help to modify the long-term sequelae of asthma. These findings also indicate, contrary to earlier speculation, that salmeterol does not have a pro-inflammatory effect or mask persistent airway inflammation. This review presents the results of recent studies and suggests possible mechanisms for the additional antiinflammatory effects of salmeterol.

Transbronchial lung biopsy through the fibre optic bronchoscope. Results and complications in 452 examinations.

During 1986-1989, diagnostic fibre optic bronchoscopy (FOB) was performed in local anaesthesia in 1144 consecutive patients. Of these, 405 (35%) patients, median age 59 years, had transbronchial lung biopsy (TBB) performed under fluoroscopic guidance; 47 patients had a rebronchoscopy, i.e. in total 452 FOB were evaluated. The indication for TBB was localized pulmonary lesions in 279 (69%) patients, and diffuse pulmonary lesions in 126 (31%) patients. Localized lesions: TBB yielded a clinically relevant diagnosis in 55.2% of the patients. Of the 110 patients with malignancy, the overall diagnostic strength was 45.5%. Of the 159 patients with non-malignant lesions, 65.4% were diagnosed by TBB. The diagnostic yield increased with the number of biopsy specimens (< or = 4 biopsies, 52%; > 4 biopsies, 70%. P < 0.05). In 155 patients with well defined, circumscribed lesions, the diagnostic yield of TBB increased with the size of the lesion (< 31 mm, 47%; 31-60 mm, 54%; > 60 mm, 60%, P = 0.09), and decreased with the distance of the lesion from the main carina < 61 mm, 70%; 61-100 mm, 52%; > 100 mm, 40% P < 0.02). Diffuse lesions: TBB yielded a clinically relevant diagnosis in 66.7% of the patients. Of the 15 patients with malignancy, 73.3% were diagnosed by TBB. Of the 93 patients with non-malignant lesions, 78.5% were diagnosed by TBB. The diagnostic yield showed a trend to increase with the number of biopsy specimens (< or = 4 biopsies, 65%; > 4 biopsies, 71%, P = 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of malignant pleural effusion: pleurodesis using a small percutaneous catheter. A prospective randomized study.

The aim of this prospective, randomized study was to investigate the possibility of performing pleurodesis using a small percutaneous catheter (Cystofix catheter, CH10, 65 cm) inserted at bedside in patients with recurrent malignant pleural effusion and to compare this catheter with a conventional large bore chest tube (CH24) placed in connection with diagnostic thoracoscopy. After drainage pleurodesis was performed with tetracycline as sclerosing agent. Of 18 evaluable consecutive patients (mean age 67.8 years) nine were randomized for pleurodesis with the small and nine for the large catheter. In the former group, the majority (seven of nine) did not find insertion of the catheter more unpleasant than thoracentesis. In the latter group only a few (two of nine) found insertion comparable with thoracentesis (P < 0.05). All patients found the presence of the large catheter very or somewhat unpleasant (two and seven patients), whereas this was only the case for a few (no and two patients) treated with the small catheter (P < 0.05). In the former group three patients required new thoracentesis, whereas this was only the case for two patients in the latter group (P > 0.05). No complications were seen. We conclude that pleurodesis in patients with recurrent malignant pleural effusion can be performed with a small percutaneous catheter (Cystofix) with an effect similar to that obtained with a large-bore chest tube and with less discomfort for the patient.

Classification of pulmonary lesions into central and peripheral with a template applied on chest X-ray.

To facilitate the understanding of the anatomical localization of pulmonary lesions and to optimize diagnostic evaluation, a template was designed which, on conventional chest X-rays, could be employed to discriminate between central and peripheral pulmonary lesions. The term 'central' implies that the lesion should be visible in the tracheobronchial tree through a fibre-optic bronchoscope, and the term 'peripheral' suggests that the lesion is not visible through a bronchoscope. In 20 patients examined by fibre-optic bronchoscopy, the bronchoscope was wedged into four pre-selected segmental bronchi in each lung. Using fluoroscopy, the tip of the bronchoscope was marked out on the skin with leadshot. On subsequent chest X-rays, with posterior-anterior and right lateral views, the distances and angles of the markings of the bronchi were mapped out in relation to the main carina. These data were used to design the template.

Salmeterol reduces the need for inhaled corticosteroid in steroid-dependent asthmatics.

Previous results have demonstrated addition of long-acting beta2-adrenergic agonists to be beneficial in asthma patients already receiving inhaled corticosteroid. The purpose of this study was to determine, qualitatively as well as quantitatively, the steroid-sparing properties of salmeterol in stable asthma patients receiving maintenance inhaled corticosteroids (800-1600 microg day(-1)). In these patients, the daily dose of beclomethasone dipropionate was reduced by 200 microg each week until asthma deteriorated, with the minimal acceptable dose (MAD) being defined as the dose one step above deterioration (sensitivity period). Following this, patients received three times the MAD for 2 weeks. Patients were randomized to receive either salmeterol 50 microg twice daily or placebo and the MAD was again determined (treatment period). Forced expiratory volume in 1 sec (FEV1) was measured each week. Morning and evening peak expiratory flow (PEF), symptom score and use of bronchodilator were recorded each day. Fifteen patients received salmeterol and 19 placebo. The MAD was significantly lower in the salmeterol group compared with placebo during the treatment period (P<0.01). A 50% reduction of the MAD was achieved by more patients treated with salmeterol than placebo (P = 0.001). Salmeterol caused a significantly greater reduction in daytime symptom score and use of as-needed beta2-agoinist therapy between sensitivity and treatment periods compared with placebo (P<0.05 for both). The results demonstrate, that the addition of salmeterol to corticosteroid treatment offers a clinically relevant potential for reduction of inhaled corticosteroid dose in steroid sensitive asthmatics.

[Formoterol as inhalation powder in the treatment of patients with reversible obstructive lung diseases. A 3-month placebo-controlled comparison of the effects of formoterol and salbutamol, followed by a 12-month period with formoterol alone]. / Formoterolinhalationspulver til behandling af patienter med reversibel obstruktiv lungesygdom. En tremåneders placebokontrolleret sammenligning af effekten af formoterol og salbutamol, efterfulgt af en 12-måneders opfølgningsperiode med formoterol alene.

This article is based on a study first published in Allergy. The bronchodilating effect of the long acting beta 2-agonist formoterol dey powder (dp) 12 micrograms twice daily was compared to salbutamol 400 micrograms four times daily and placebo in patients with reversible obstructive airway disease. The study design consisted of a closed 12-week double-blind, placebo-controlled, multicentre trial followed by an open noncomparative, multicentre 12-month follow-up trial, in which tolerability of formoterol dp was assessed. A total of 304 patients aged 18-79 years were randomized. The bronchodilating effect of formoterol, assessed by morning premedication peak flow rate, was significantly superior to placebo (p < 0.0001) and salbutamol (p < 0.001). Efficacy was maintained during the open follow-up study. Formoterol 12 micrograms twice daily significantly reduced morning and evening asthma symptoms and sleep disturbances, and significantly reduced the need for rescue medication. In conclusion, formoterol 12 micrograms dp twice daily was significantly superior to both salbutamol 400 micrograms dp four times daily and placebo, and reduced asthma symptoms significantly. Overall, formoterol showed a tolerability profile comparable to that of salbutamol, and no tachyphylaxis was observed during one year of treatment.

[Diagnostic invasive procedures in the diagnosis of primary lung cancer. Diagnostic value and complications]. / Diagnostiske invasive undersøgelser ved primaer lungecancer. Diagnostisk voerdi og komplikationer.

The invasive procedures used in the diagnosis of primary lung cancer are reviewed based on the literature. The choice of method should be related to its diagnostic accuracy, complications and cost. The chest x-ray provides the background for the further choice of diagnostic method. In central tumors, bronchoscopy meets the requirements and in peripheral lesions percutaneous transthoracic needle biopsy fulfils the conditions. In some centres, mediastinoscopy is preferred in all cases preoperatively, while others only perform this examination if a CT-scan shows mediastinal lymph nodes larger than 1 cm in diameter. If the latter procedure is followed, 10-30% of the patients will have lymph node metastases. Thoracoscopy is used when a pleural effusion remains undiagnosed after pleuracentesis. A considerable amount of patients will be shown to have pleural neoplastic spread even though cytological examination of the pleural fluid did not demonstrate malignant cells. The complication rates in all methods are low.

[Broncholithiasis and lithoptysis]. / Broncholithiasis og lithoptysis.

Broncholithiasis and lithoptysis are rare phenomenons. A case of broncholithiasis in a woman, 58 years of age, with previous tuberculosis is presented, and the literature on broncholithiasis and lithoptysis is reviewed.

[Primary tuberculous pleurisy. The course of 3 untreated cases]. / Primaer tuberkuløs pleuritis. Tre ubehandlede kliniske forløb.

Three patients with pleurisy, all exposed to tuberculosis (TB) in their environment, are presented. The etiology of the pleurisy was not initially uncovered and as the pleurisy resolved spontaneously, the patients were discharged from follow up after four to 21 months. Within two to 12 months hereafter, the patients showed up with post-primary tuberculosis: (case I) with miliary tuberculosis incl. meningeal tuberculosis, case II with apical lung tuberculosis and case III with extrapulmonary tuberculosis of the bones. After six months of combined anti-tuberculosis chemotherapy all patients recovered completely. Primary tuberculous pleurisy is known usually to be self-limited but the reactivation rate is high; up to 65% of the adult patients develop post-primary tuberculosis within five years, if not treated. Therefore, prompt diagnosis and treatment are important. Pleurisy in patients with TB in their environment should be intensively examined with cultures of all potentially diagnostic specimens; cultures from pleura fluid alone have a low diagnostic yield and diagnostic blind closed or thoracoscopic open biopsy from the pleura for cultures and histologic examination should be performed whenever possible. If the etiology is not found, the patient should be followed for at least five years.

[Autofluorescence bronchoscopy: Laser imaging fluorescence endoscope]. / Autofluorescensbronkoskopi: "Laser imaging fluorescense endoscope".

The LIFE (laser imaging fluorescence endoscope) system has been shown to increase the diagnosis of dysplasia and carcinoma in situ when used in combination with conventional bronchoscopy. A doubling to tripling of the rate of early centrally located lung cancer diagnosis is a step forward in the detection of early lung cancer. A wide spectrum of interventional procedures for endoluminal treatment of lung cancer in functionally inoperable patients makes it possible to treat this group of patients. The LIFE system works without exogenous sensitisers, with no increase in complications as compared to conventional bronchoscopy, and takes only a little longer in examination time.

[Percutaneous transthoracic needle aspiration biopsy. Diagnostic yield after negative fiberoptic bronchoscopy in patients with peripheral pulmonary infiltrations]. / Perkutan transtorakal nåleaspirationsbiopsi. Diagnostisk udbytte efter negativ fiberbronkoskopi hos patienter med perifert beliggende lungeinfiltrater.

The diagnostic potential of secondary transthoracic needle biopsy (TNB) following negative fiberoptic bronchoscopy in patients with peripheral circumscribed pulmonary lesions was evaluated in a retrospective study. The records from 224 patients who had TNB performed over a five-year period were reviewed. Of these, 103 patients met the criteria for inclusion in this series. The overall diagnostic yield of TNB in malignancy was 73.8% (54 of 73 patients). TNB allowed cytological classification of the tumour type in 72.2% (39 of 54 patients). Five of the 54 patients (9.3%) presented with small cell anaplastic bronchogenic carcinoma, diagnosed by TNB, and were treated with chemotherapy. Of the 49 patients with a negative TNB, 27 went on to diagnostic surgical procedures; 19 had malignancy, three benign tumour, two infection, and three sequelae after pulmonary infarction. The remaining 22 patients with undiagnosed lesions were followed long term, five showed progression of the pulmonary lesion suggesting malignancy. TNB appeared unsuitable in the diagnosis of benign lesions. Unspecific inflammation was not considered evidence of benignity, and therefore a definitive benign diagnosis was not made by TNB in this series. There were no serious complications to TNB. In 18.1% of the procedures a pneumothorax developed, indicating a chest tube in 8.6% of the procedures. TNB is a suitable diagnostic procedure with a high diagnostic yield in patients with peripheral, malignant pulmonary lesions.

[Lung cancer in 1993]. / Lungecancer 1993.

The incidence of lung cancer is increasing in Denmark, especially among women. Today, smoking is the most important risk factor for developing this disease. A review of the literature shows that the prognosis is still very poor regardless of histologic findings. Chemotherapy prolongs life moderately among patients with small cell carcinoma (SCLC). Furthermore, total resection of non small cell cancer (NSCLC) may improve survival over several years. In patients investigated for surgery, cancer dissemination should be determined, using radiologic and invasive investigations. A detailed spirometric investigation should also be performed, as lung function is a predictor of postoperative survival. Other kinds of treatment are available, and good coordination regarding information, supportive arrangements and symptomatic treatment is important.

[Oxygen therapy of chronic lung disease. Testing of a chemical oxygen generator--Vitaria]. / Iltbehandling til kronisk lungesyge. Afprøvning af en kemisk iltgenerator--Vitaria.

Twenty patients (11 females, nine males, mean age: 70.6 years) with chronic obstructive pulmonary disease and hypoxaemia took part in a randomized single blinded placebo-controlled clinical trial, testing the efficacy of a new transportable oxygen delivery system (VITARIA). The system consists of a container and a sodium carbonate containing powder (75 mg). When the powder is stirred in water in the container pure oxygen with a max flow of 1 l/min is delivered over a period of approximately 15 minutes. All patients had been receiving home oxygen treatment of at least 0.5 l/min for at least one month. Their baseline oxygen levels in arterial blood were mean 7.66 kPa, with a mean oxygen response to 0.5 l/min of oxygen of 2.54 kPa. In the placebo group no oxygen responses were seen, while in the Vitaria group a small but insignificant rise in arterial PaO2 was seen. No side effects were seen. In conclusion we find the system handy and easy to use but the recommended dose of powder is insufficient.

[Lymphangioleiomyomatosis]. / Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare disease, which only affects women of childbearing age. A case of LAM in a 36-year-old woman is presented. Patho-anatomical findings are smooth muscle hyperplasia leading to obstruction of lymphatics (possibly resulting in chylothorax), blood vessels (possibly resulting in haemoptysis) and bronchi (possibly resulting in emphysema and pneumothorax). High resolution computed tomography (HRCT) of the chest can show the typical multiple small cysts and bullous emphysema distributed diffusely throughout both lungs together with interstitial fibrosis. Treatment of the disease aims at an inhibition of the presumed growth-promoting effect of oestrogen on the smooth muscle cells. However, progression is often seen in spite of treatment.