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Biomedical subjects

M Thunell

Publications and source records attributed to M Thunell.

At least 19 recordsLinked to original sources

Synergistic interaction between ORM1 and C3 types in disease associations.

In previous studies of orosomucoid (ORM) types and disease the ORM1 1 type has been found to be associated with sarcoidosis and other immunogenetic diseases, and the ORM 1 2 type with different types of carcinomas. We report significant associations between ORM1 and C3 types in sarcoidosis and breast cancer, but not in healthy individuals. The ORM1 1 and C3S variants in combination increased the risk of sarcoidosis, and the ORM1 2 and C3F variants together gave an increased risk of breast cancer. A probable mechanism may be that the ORM1 and C3 molecules modify the immune response by interacting with the lymphoid cell surface.

Alleles↗

Orosomucoid and haptoglobin types in patients with sarcoidosis.

Association with HLA and complement factors has been reported in sarcoidosis, and the results of previous studies suggest a multifactorial and immunogenetic etiology of the disease. We have studied two genetic acute-phase reactant systems, orosomucoid (ORM) and haptoglobin (HP), in 226 patients with sarcoidosis and population controls from northern Sweden. Significant allele and phenotype differences between patients and controls were found in both systems. The ORM1 phenotype showed a significant increase in sarcoidosis (RR = 1.34, p = 0.036), which was more pronounced among patients with low (< 1,500 nkat/l) angiotensin-converting enzyme levels (RR = 1.83, p = 0.00065) and hypercalcemia (RR = 3.69, p = 0.0023). The HP1 type was significantly increased among the sarcoidosis patients (RR = 1.57, p = 0.013). The results suggest that the ORM1 1 and HP1 types may be contributory determinants in the multifactorial etiology of sarcoidosis.

Female↗

Endobronchial biopsy positive sarcoidosis: relation to bronchoalveolar lavage and course of disease.

Sixty-two patients with newly diagnosed sarcoidosis were examined with fibreoptic bronchoscopy, endobronchial biopsies and bronchoalveolar lavage (BAL) were analysed. Epithelioid granulomatosis in endobronchial biopsies were found in 28 (45%) of the patients (BPOS). The patients in this BPOS group showed higher inflammatory activity in BAL fluid compared to those with negative biopsies (BNEG), with significant increases in lymphocyte and mast cell counts, and concentrations of procollagen III peptide and albumin. The patients were followed over a period of 2 years. The BPOS group tended to have a worse clinical course with more patients having a progressive disease and more patients requiring treatment with systemic steroids. We conclude that the findings of epithelioid granulomatosis in endobronchial biopsies may reflect a more intense and widespread inflammation in the lung.

Adult↗

Exercise test in patients with sarcoidosis. The importance of repolarization disturbances.

The study population comprises 28 patients with sarcoidosis who all had repolarization disturbances in their exercise ECGs. None of the patients had hypertension or known cardiovascular disease, and all but two were non-smokers. The mean age was 45 years. Exercise test with beta-adrenergic blockade was performed within one month of the first examination. Persisting abnormal ST-T changes in exercise ECGs after beta-blockade were seen in 12 (43%) patients. No significant relationship was found between persisting ST-T changes and age, sex, chest X-ray stage, lung function or working capacity. In an earlier study, we found ST-T abnormalities in exercise ECG in 56 of 127 individuals (44%) in a consecutive 5-year study of patients with newly detected sarcoidosis. From this and the present report we postulate that, in our region, as much as 20% of the patients with newly detected sarcoidosis might have organic myocardial disease, possibly of sarcoid origin, as shown by repolarization disturbances in exercise ECG. If ECG abnormalities in the ST-T region are present in patients with sarcoidosis, exercise ECG with beta-blockade is a simple way of establishing suspicion of organic myocardial lesions. If exercise ECG abnormalities in the ST-T region persist after beta-blockade, careful clinical follow-up is recommended, and, in some patients early steroid therapy should be considered.

Arrhythmias, Cardiac↗

Hyaluronic acid in bronchoalveolar lavage fluid in patients with sarcoidosis: relationship to lavage mast cells.

Hyaluronate (hyaluronic acid), a potential marker for activated pulmonary fibroblasts, appears in increased concentrations in bronchoalveolar lavage fluid from patients with sarcoidosis. The mechanisms underlying fibroblast proliferation are largely unknown but activated alveolar T lymphocytes and macrophages probably play a part; the mast cell is also important for fibroblast proliferation. This study was designed to determine whether there is any association between pulmonary mast cells in lavage fluid, which are known to be increased in patients with sarcoidosis, and signs of pulmonary fibroblast activation. A strong correlation was found between lavage fluid hyaluronate and recovered mast cells (r = 0.72, p less than 0.001). Moreover, mast cell and hyaluronate estimations correlated inversely with lung volume and transfer factor for carbon monoxide, and both indices increased with advancing radiological sarcoid stage. Macrophage and granulocyte counts were normal in lavage fluid from patients with sarcoidosis and were not related to lavage fluid hyaluronate or laboratory signs of the disease in the lungs. Lymphocytes were recovered in increased numbers (p less than 0.001) and were related to the lavage fluid mast cells and hyaluronate. It is concluded that in sarcoidosis release of hyaluronate into the airways is related to the degree of lung disease and to the local inflammatory reaction in the lung as defined by increased numbers of mast cells and lymphocytes in lavage fluid. The findings may reflect a link between the immune system, activation of mast cells, and a pulmonary fibroblast proliferation.

Adult↗

The mast cell and signs of pulmonary fibroblast activation in sarcoidosis.

Hyaluronate and type III procollagen propeptide were assayed in bronchoalveolar lavage (BAL) fluids from patients with sarcoidosis. Levels were significantly elevated suggesting increased rates of synthesis of these connective tissue components in the lung. They were strongly related to each other (p less than 0.001) favoring the idea of a common cellular origin, as a suggestion activated fibroblasts. There was a significant inverse correlation (p less than 0.001) between lavage hyaluronate or procollagen propeptide and the clinical severity of the disease process defined by lung volume, diffusion capacity and pulmonary radiological findings. Correlation of clinical findings with lavage cell profiles was poor except for recovered mast cells (p less than 0.001). Lavage mast cell counts were also closely associated with BAL fluid hyaluronate and procollagen peptide (p less than 0.001). These findings may reflect a link between the mast cell, the activation of fibroblasts, and the progress of connective tissue changes in sarcoid lung.

Adult↗

Pulmonary function in patients with sarcoidosis. A three year follow-up.

During a 3 year period, 101 patients were consecutively diagnosed as having sarcoidosis. During the 3 year follow-up 9 patients died, 6 of them directly or indirectly due to their sarcoidosis. In 78 patients bronchoscopy and spirometry were performed at the primary investigation, and after 3 years a new spirometry was performed. A positive bronchial mucosal biopsy, bronchial sarcoidosis, was found in 31 (40%) of the 78 patients. Mean values of vital capacity, total lung capacity and forced expiratory volume in one second were normal in both patients with bronchial sarcoidosis and those without. Abnormal spirometry was found in 16 (21%) patients at the initial examination and in 11 (14%) at the follow-up. There were 10 (32%) patients with and 6 (13%) without bronchial sarcoidosis who had an abnormal spirometry. At follow-up a normalized lung function was found in 8 (50%) of the 16 patients with abnormal spirometry. Only 3 (4.8%) patients with initially normal lung function had abnormal lung function at follow-up. Our findings indicate a very little risk of developing abnormal lung function if there are normal findings at the primary investigation. Corticosteroids seem to have some effect, especially in patients with endobronchial sarcoidosis.

Adult↗

Mast cells and lysozyme positive macrophages in bronchoalveolar lavage from patients with sarcoidosis. Valuable prognostic and activity marking parameters of disease?

In the deteriorating group of sarcoidosis patients, progress towards pulmonary fibrosis is a major problem. In order to benefit from corticosteroids, it is important for the treatment to start early. We studied a group of 45 patients with sarcoidosis. Most of them were newly detected patients and none were under or had currently received corticosteroid therapy. The patients were followed for at least six months. We found that increased amounts of polymorphonuclear neutrophils (PMN) or lysozyme-positive macrophages (Lys+MF) and mast cells (MC) in bronchoalveolar lavage (BAL) could implicate a bad prognosis.

Bronchi↗

Procollagen III peptide in bronchoalveolar lavage fluid. A potential marker of altered collagen synthesis reflecting pulmonary disease in sarcoidosis.

Type III procollagen N-terminal peptide was not detectable in bronchoalveolar lavage fluid from healthy volunteers but was present in fluid from the majority of patients with pulmonary sarcoidosis (N = 110); the mean concentration was 0.6 micrograms/liter returned fluid, range less than or equal to 0.2 to 19.5 or, expressed in relation to the amount of albumin recovered, 9.5 mg/gm albumin (range less than or equal to 1 to 45). The serum concentrations in the patients with sarcoidosis were normal. Significant inverse correlations were found between lavage fluid procollagen peptide and vital capacity (p less than 0.001), forced expiratory volume (p less than 0.01), and diffusion capacity (p less than 0.01). Lavage fluid procollagen peptide was also related to pulmonary radiological findings (p less than 0.001) and serum levels of angiotensin converting enzyme (p less than 0.001). These findings support the hypothesis that procollagen peptide in lavage fluid is a potential marker of activated pulmonary fibroblasts or an expanded fibroblast mass associated with interstitial lung fibrosis.

Adult↗

Scalene lymph node biopsy. A diagnostic method in sarcoidosis.

Right-sided scalene lymph node biopsy was performed on 167 patients with sarcoidosis. The surgical technique is described in detail. There were no complications, apart from two cases of minor postoperative haemorrhage. The diagnostic yield in sarcoidosis was 84% (140/167 patients). Scalene lymph node biopsy, performed by trained surgeons, is concluded to be a good alternative to other biopsy methods in sarcoidosis.

Adult↗

Pulmonary function in patients with endobronchial sarcoidosis.

Sixty-four patients with clinically, radiologically and histopathologically established sarcoidosis were studied by bronchoscopy and static and dynamic spirometry. Sarcoid bronchostenosis was established by bronchoscopy in nine patients. Twenty-one had bronchial sarcoidosis without stenosis and 34 had no evidence of bronchial sarcoidosis. Patients with sarcoid bronchostenosis showed a marked impairment of lung function, mostly with an obstructive pattern. There was no improvement in lung function after bronchodilatation in these patients. Obstructive spirometry pattern was also found in three patients with bronchial sarcoidosis stage II without stenosis. None of the patients without bronchial sarcoidosis had an obstructive pattern. All six patients with restrictive spirometry pattern in the two groups without bronchostenosis had stage II sarcoidosis. At follow-up, lung function had improved in five patients, four with sarcoid bronchostenosis and one patient with stage II without bronchial sarcoidosis. Four of these patients were treated with oral corticosteroids. When clinical signs of airway obstruction are present in patients with sarcoidosis, bronchial sarcoidosis with or without bronchostenosis should be suspected. When bronchial sarcoidosis is present, oral corticosteroid treatment should be tried.

Adult↗

Cardiopulmonary function in sarcoidosis.

Hemodynamics, angiocardiographic findings and lung function were evaluated in 10 patients with clinically, radiologically and histopathologically established sarcoidosis. All 10 patients had cardiac symptoms and/or abnormal ECG. Right and left heart catheterization, angiocardiography, spirometry and diffusion capacity were performed in all patients. Pulmonary hypertension was present in the two patients with stage III sarcoidosis and in 7 of 8 patients with stages I and II. Right ventricular end-diastolic pressure was elevated in 6 patients. Seven patients had findings compatible with a failing left ventricle with elevated end-diastolic pressure and/or elevated pulmonary capillary wedge pressure. None of the patients had entirely normal hemodynamic findings. Angiocardiography showed a low ejection fraction in 6 patients but no wall asynergy. Right ventricular angiography and coronary angiography were normal in all patients. Findings compatible with failure of the left and right ventricle of the heart was common in our sarcoid patients with cardiac symptoms and/or abnormal ECG. Impairment of the pulmonary function does not seem to be the only reason for the hemodynamic findings, thus indicating the possibility of myocardial sarcoidosis.

Angiocardiography↗

Comparison of flexible fiberoptic bronchoscopy and scalene lymph node biopsy in the diagnosis of sarcoidosis.

The diagnostic accuracy achieved by taking bronchial mucosal and lung biopsies through flexible fiberoptic bronchoscopes was compared with scalene lymph node biopsy in 55 patients with sarcoidosis. The diagnostic yield with flexible fiberoptic bronchoscopy was 62 per cent in the whole material and increased to 76 per cent in patients with stage II sarcoidosis. Scalene lymph node biopsy was positive in 80 per cent. Flexible fiberoptic bronchoscopy is a useful method for obtaining biopsy material in sarcoidosis, especially in stage II sarcoidosis. We consider flexible fiberoptic bronchoscopy and scalene lymph node biopsy the methods of choice in the diagnosis of sarcoidosis.

Adult↗

Musculo-skeletal symptoms in early sarcoidosis. Twenty-four newly diagnosed patients and a two-year follow-up.

Musculo-skeletal symptoms were screened in 24 consecutive patients with newly diagnosed sarcoidosis and followed up two years later. Ten patients had joint involvement. Symptoms were most frequently found in ankle joints, followed by hand and knee joints. Arthritis was found in seven (29%) patients, two of whom suffered from monoarthritis of foot and wrist joint, respectively. Three patients had tenosynovitis. Muscle symptoms such as myalgia were present in six patients. Open biopsy of the gastrocnemius muscle showed epithelioid cell granulomatosis in nine of 20 patients. Only three of these nine patients had symptoms of myalgia, although not in the biopsied muscle. At follow-up, musculo-skeletal symptoms were found in only three patients, all of whom initially had Löfgren's syndrome.

Adult↗