To determine the frequency of splenic involvement in sarcoidosis fine-needle aspiration biopsies ... more To determine the frequency of splenic involvement in sarcoidosis fine-needle aspiration biopsies of the spleen were performed in 77 patients with verified sarcoidosis. Splenic sarcoidosis was documented in 53% of the patients; in 67% of those with and in 47% of those without known extrathoracic manifestations. The majority of the patients had a normal spleen size. The results indicate that splenic involvement is common in sarcoidosis and even in the early stage of the disease. The splenic aspiration biopsy is a simple, safe, rapid and reliable diagnostic procedure.
The mean values of serum angiotensin-converting enzyme (ACE) activities and lysozyme (LZM) concen... more The mean values of serum angiotensin-converting enzyme (ACE) activities and lysozyme (LZM) concentrations measured during different phases of sarcoidosis coincided well with the clinical evaluation of the state of the disease. However, both enzymes, especially LZM, decreased before improvement was detected. Changes in these enzymes were in accord with the simultaneous clinical development in three fourths of cases. Incompatibility between clinical observations apnd LZM fluctuations was most frequently seen during active stable or inactive disease. LZM often decreased during the active stable phase and fluctuated irregularly during inactive disease. During the former phase LZM decrements possibly reflect decreasing activity of granulomatous macrophages and, in fact, precede detectable improvement. During inactive disease, on the other hand, cells were not connected with the disease process dominate LZM production. ACE changes paralleled the clinical development more often than corresponding LZM changes during stable sarcoidosis. This may have been misleading and due to a delayed reaction of serum ACE, compared with LZM, inreflecting the activity of granylomatous cells. This delayed reaction was also observed in connection with erythema nodosum. Stable ACE activity during inactive sarcoidosis indicated the usefulness of measurements when trying to predict a relapse. We conclude that ACE may be a secondary feature of sarcoidosis rather than a primary funtion of macrophage activity.
Serum angiotensin-converting enzyme (ACE) was studied in 51 patients with early or newly diagnose... more Serum angiotensin-converting enzyme (ACE) was studied in 51 patients with early or newly diagnosed sarcoidosis. Only 45% of these patients had increased ACE activity when their diagnosis was established, which diminishes the diagnostic value of this enzyme measurement. On the other hand, ACE accurately reflected disease activity, and it proved a useful tool for assessing of need for corticosteroid treatment. Patients with acute sarcoidosis associated with erythema nodosum (EN) had low ACE activity compared with the other patients with active, but less acute disease. Serum ACE was not significantly correlated with blood lymphocytes or the immunoglobulins, but there was a positive correlation between the enzyme and serum lysozyme, which strengthens the hypothesis of both enzymes being produced by the epithelioid cells of sarcoid granulomas.
The activity of serum angiotensin converting enzyme (ACE) was repeatedly measured together with s... more The activity of serum angiotensin converting enzyme (ACE) was repeatedly measured together with serum lysozyme (LZM) in patients with untreated sarcoidosis. Changes in the clinical picture were registered using chest X-ray, forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and appearance of extrapulmonary lesions. During a clinically unchanged period the highest ACE activity and the corresponding LZM value (not the highest value) were used for the calculation. A statistically significant change in ACE was noted when a normal chest X-ray changed to a stage II lesion or vice versa, and when a signficant change in FVC occurred. All other changes were insignificant. On the other hand, statistically significant changes in ACE were found during stable periods according to chest X-ray, FVC or DLCO. ACE is frequently elevated in serum of patients with active sarcoidosis. The fluctuations in activity mostly parallel the clinical course of the disease. The behaviour and metabolism of the enzyme need further investigation. An increased concentration of serum LZM is frequent in patients with active sarcoidosis. The highest LZM values are not always seen simultaneously with the highest ACE values, indicating that they probably express different dimensions of the disturbances in the sarcoid granuloma.
Serum angiotensin-converting enzyme (ACE) activity and lysozyme (LZM) concentration in 22 silicos... more Serum angiotensin-converting enzyme (ACE) activity and lysozyme (LZM) concentration in 22 silicosis and 18 asbestosis patients were studied. These patients were compared with 57 untreated and 36 treated sarcoidosis patients. In all groups significantly raised ACE and LZM mean values were noted. Untreated sarcoidosis patients had the highest values. Raised ACE activity in silicosis and asbestosis has not been reported before, and weakens the differential diagnostic value of this enzyme determination for sarcoidosis. The similar patterns of increased ACE and LZM mean values in all three diseases suggest that these enzymes have a common source.
An updated literature search was performed to evaluate the efficacy of rapid-acting β2-agonists d... more An updated literature search was performed to evaluate the efficacy of rapid-acting β2-agonists delivered via dry powder inhalers in the treatment of moderate-to-severe acute asthma. Databases were searched from 1985 up to December 2012. A total of 23 randomized, double-blind or open clinical studies in acute asthma comparing the efficacy of a dry powder inhaler with a pressurized metered-dose inhaler or a nebulizer, and performed under controlled hospital conditions, were identified. This review found that administration of β2-agonist bronchodilators via dry powder inhalers (formoterol, salbutamol, terbutaline and budesonide/formoterol) was effective during severe asthma worsening and acute asthma attacks, and was as effective as established therapies with a pressurized metered-dose inhaler with or without a spacer, or nebulization. These results ensure that patients can rely upon dry powder inhalers equally well as other inhaler devices during episodes of asthma worsening.
Current Medical Research and Opinion, Aug 25, 2004
The role of systemic corticosteroids in the treatment of exacerbations of chronic obstructive pul... more The role of systemic corticosteroids in the treatment of exacerbations of chronic obstructive pulmonary disease (COPD) is well established. However, despite being frequently prescribed for the treatment of COPD, the clinical utility of inhaled corticosteroids (ICS) is less clearly defined. This review article seeks to clarify the role of ICS in the clinical management of COPD through a review of key pivotal short-, medium- and long-term studies in this field. Studies for inclusion in this review were identified by means of a computerised search of several databases (including MEDLINE, BIOSIS and EMBASE) from 1980 to 2003. While individual clinical and epidemiological studies have yielded conflicting results, meta-analysis of available data suggests that ICS may reduce the frequency and severity of exacerbations, the number of hospitalisations and the mortality rate, as well as yielding improvements in lung function and health-related quality of life (HRQL) in some subgroups of COPD patients. More recently, clinical trials evaluating the effect of combination therapy with ICS and long-acting beta2-agonists (LABA) have shown significant effects on the prevention of exacerbations and HRQL. Emerging data are expected to clarify the role of ICS in the management of patients with COPD of different severities as well as the place of treatment with ICS/LABA combinations in the management of this chronic and disabling disorder.
Polymyalgia rheumatica developed in a 71-year-old patient within 2 years of the onset of acute sa... more Polymyalgia rheumatica developed in a 71-year-old patient within 2 years of the onset of acute sarcoidosis with biopsy-verified involvement of the thyroid, and concomitant autoimmune thyroiditis with hyperthyroid symptoms. Three years after the onset of muscle symptoms a non-metastasizing breast carcinoma was discovered and treated surgically. Neither the long interval between the onset of polymyalgia rheumatica and the discovery of the breast tumour, nor the good response of muscle symptoms to a one-year maintenance treatment with corticosteroids, was consistent with a paraneoplastic mechanism of the polymyalgia rheumatica syndrome. It was therefore hypothesized that the various disorders suffered by this patient might be related to a partly age-dependent depression of T-lymphocyte function, leading to an altered immunological reactivity to which the various clinical manifestations could be attributed. Such a hypothesis is supported by recent reports showing that in old people and in ageing experimental animals, a decrease in T-lymphocyte function and in the number of circulating T-cells occurs concomitantly with an increase in the incidence of a variety of neoplasms and autoimmune disorders.
Thirty-nine sarcoidosis patients with pulmonary infiltrations (stage II) of less than 5 years dur... more Thirty-nine sarcoidosis patients with pulmonary infiltrations (stage II) of less than 5 years duration and not treated earlier with corticosteroids were randomly allocated for treatment with methylprednisolone for 7 months or for observation without therapy. Every other treated patient was given the drugs daily and every other followed an alternate-day regimen. After 7 months the chest radiographic finding, the forced vital capacity and the diffusion capacity for carbon monoxide were superior in the treated group. There was no difference between the two drug regimens. After 24 and 48 months no statistically significant differences between the untreated and the treated groups were found.
Serial tuberculin skin tests with 0·1–100 TU of PPD were performed on 209 patients with chronic r... more Serial tuberculin skin tests with 0·1–100 TU of PPD were performed on 209 patients with chronic renal disease. Skin test reactivity decreased with the severity of uraemia. Lymphocytes from three out of four skin test negative patients showed a high PPD-induced blast response in vitro. Thus, the absence of skin reactivity in uraemia does not always depend on a lack of antigen-sensitive lymphocytes.
The once-daily oral bronchodilator bambuterol and the twice-daily inhaled bronchodilator salmeter... more The once-daily oral bronchodilator bambuterol and the twice-daily inhaled bronchodilator salmeterol have been compared in only a few studies. In placebo-controlled studies, both bronchodilators have been found clinically effective and with few side-effects. In a double-blind, randomized 6-week parallel-group study in 117 patients with nocturnal asthma and using inhaled or oral steroids, no difference was found in efficacy between bambuterol 20 mg once daily in the evening and salmeterol 50 µg b.i.d. (morning and evening PEF, nocturnal awakenings). Similar results were seen in a double-blind, crossover study in 12 patients comparing 10 mg bambuterol in the evening with salmeterol 50μg in the evening for 2 weeks each. In a small, double-blind crossover study in 15 patients with reversible airway obstruction, bambuterol 20 mg once daily in the morning was compared with placebo for one week each. The patients were thereafter treated openly for one week with 50 μg salmeterol b.i.d. In steady state, on day 8, the 12- and 24-hour FEV1 values and the maximum FEV1 values were not significantly different after treatment with bambuterol or salmeterol. No differences in side-effects were seen. Further comparative double-blind, controlled studies are warranted.
To determine the frequency of splenic involvement in sarcoidosis fine-needle aspiration biopsies ... more To determine the frequency of splenic involvement in sarcoidosis fine-needle aspiration biopsies of the spleen were performed in 77 patients with verified sarcoidosis. Splenic sarcoidosis was documented in 53% of the patients; in 67% of those with and in 47% of those without known extrathoracic manifestations. The majority of the patients had a normal spleen size. The results indicate that splenic involvement is common in sarcoidosis and even in the early stage of the disease. The splenic aspiration biopsy is a simple, safe, rapid and reliable diagnostic procedure.
The mean values of serum angiotensin-converting enzyme (ACE) activities and lysozyme (LZM) concen... more The mean values of serum angiotensin-converting enzyme (ACE) activities and lysozyme (LZM) concentrations measured during different phases of sarcoidosis coincided well with the clinical evaluation of the state of the disease. However, both enzymes, especially LZM, decreased before improvement was detected. Changes in these enzymes were in accord with the simultaneous clinical development in three fourths of cases. Incompatibility between clinical observations apnd LZM fluctuations was most frequently seen during active stable or inactive disease. LZM often decreased during the active stable phase and fluctuated irregularly during inactive disease. During the former phase LZM decrements possibly reflect decreasing activity of granulomatous macrophages and, in fact, precede detectable improvement. During inactive disease, on the other hand, cells were not connected with the disease process dominate LZM production. ACE changes paralleled the clinical development more often than corresponding LZM changes during stable sarcoidosis. This may have been misleading and due to a delayed reaction of serum ACE, compared with LZM, inreflecting the activity of granylomatous cells. This delayed reaction was also observed in connection with erythema nodosum. Stable ACE activity during inactive sarcoidosis indicated the usefulness of measurements when trying to predict a relapse. We conclude that ACE may be a secondary feature of sarcoidosis rather than a primary funtion of macrophage activity.
Serum angiotensin-converting enzyme (ACE) was studied in 51 patients with early or newly diagnose... more Serum angiotensin-converting enzyme (ACE) was studied in 51 patients with early or newly diagnosed sarcoidosis. Only 45% of these patients had increased ACE activity when their diagnosis was established, which diminishes the diagnostic value of this enzyme measurement. On the other hand, ACE accurately reflected disease activity, and it proved a useful tool for assessing of need for corticosteroid treatment. Patients with acute sarcoidosis associated with erythema nodosum (EN) had low ACE activity compared with the other patients with active, but less acute disease. Serum ACE was not significantly correlated with blood lymphocytes or the immunoglobulins, but there was a positive correlation between the enzyme and serum lysozyme, which strengthens the hypothesis of both enzymes being produced by the epithelioid cells of sarcoid granulomas.
The activity of serum angiotensin converting enzyme (ACE) was repeatedly measured together with s... more The activity of serum angiotensin converting enzyme (ACE) was repeatedly measured together with serum lysozyme (LZM) in patients with untreated sarcoidosis. Changes in the clinical picture were registered using chest X-ray, forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and appearance of extrapulmonary lesions. During a clinically unchanged period the highest ACE activity and the corresponding LZM value (not the highest value) were used for the calculation. A statistically significant change in ACE was noted when a normal chest X-ray changed to a stage II lesion or vice versa, and when a signficant change in FVC occurred. All other changes were insignificant. On the other hand, statistically significant changes in ACE were found during stable periods according to chest X-ray, FVC or DLCO. ACE is frequently elevated in serum of patients with active sarcoidosis. The fluctuations in activity mostly parallel the clinical course of the disease. The behaviour and metabolism of the enzyme need further investigation. An increased concentration of serum LZM is frequent in patients with active sarcoidosis. The highest LZM values are not always seen simultaneously with the highest ACE values, indicating that they probably express different dimensions of the disturbances in the sarcoid granuloma.
Serum angiotensin-converting enzyme (ACE) activity and lysozyme (LZM) concentration in 22 silicos... more Serum angiotensin-converting enzyme (ACE) activity and lysozyme (LZM) concentration in 22 silicosis and 18 asbestosis patients were studied. These patients were compared with 57 untreated and 36 treated sarcoidosis patients. In all groups significantly raised ACE and LZM mean values were noted. Untreated sarcoidosis patients had the highest values. Raised ACE activity in silicosis and asbestosis has not been reported before, and weakens the differential diagnostic value of this enzyme determination for sarcoidosis. The similar patterns of increased ACE and LZM mean values in all three diseases suggest that these enzymes have a common source.
An updated literature search was performed to evaluate the efficacy of rapid-acting β2-agonists d... more An updated literature search was performed to evaluate the efficacy of rapid-acting β2-agonists delivered via dry powder inhalers in the treatment of moderate-to-severe acute asthma. Databases were searched from 1985 up to December 2012. A total of 23 randomized, double-blind or open clinical studies in acute asthma comparing the efficacy of a dry powder inhaler with a pressurized metered-dose inhaler or a nebulizer, and performed under controlled hospital conditions, were identified. This review found that administration of β2-agonist bronchodilators via dry powder inhalers (formoterol, salbutamol, terbutaline and budesonide/formoterol) was effective during severe asthma worsening and acute asthma attacks, and was as effective as established therapies with a pressurized metered-dose inhaler with or without a spacer, or nebulization. These results ensure that patients can rely upon dry powder inhalers equally well as other inhaler devices during episodes of asthma worsening.
Current Medical Research and Opinion, Aug 25, 2004
The role of systemic corticosteroids in the treatment of exacerbations of chronic obstructive pul... more The role of systemic corticosteroids in the treatment of exacerbations of chronic obstructive pulmonary disease (COPD) is well established. However, despite being frequently prescribed for the treatment of COPD, the clinical utility of inhaled corticosteroids (ICS) is less clearly defined. This review article seeks to clarify the role of ICS in the clinical management of COPD through a review of key pivotal short-, medium- and long-term studies in this field. Studies for inclusion in this review were identified by means of a computerised search of several databases (including MEDLINE, BIOSIS and EMBASE) from 1980 to 2003. While individual clinical and epidemiological studies have yielded conflicting results, meta-analysis of available data suggests that ICS may reduce the frequency and severity of exacerbations, the number of hospitalisations and the mortality rate, as well as yielding improvements in lung function and health-related quality of life (HRQL) in some subgroups of COPD patients. More recently, clinical trials evaluating the effect of combination therapy with ICS and long-acting beta2-agonists (LABA) have shown significant effects on the prevention of exacerbations and HRQL. Emerging data are expected to clarify the role of ICS in the management of patients with COPD of different severities as well as the place of treatment with ICS/LABA combinations in the management of this chronic and disabling disorder.
Polymyalgia rheumatica developed in a 71-year-old patient within 2 years of the onset of acute sa... more Polymyalgia rheumatica developed in a 71-year-old patient within 2 years of the onset of acute sarcoidosis with biopsy-verified involvement of the thyroid, and concomitant autoimmune thyroiditis with hyperthyroid symptoms. Three years after the onset of muscle symptoms a non-metastasizing breast carcinoma was discovered and treated surgically. Neither the long interval between the onset of polymyalgia rheumatica and the discovery of the breast tumour, nor the good response of muscle symptoms to a one-year maintenance treatment with corticosteroids, was consistent with a paraneoplastic mechanism of the polymyalgia rheumatica syndrome. It was therefore hypothesized that the various disorders suffered by this patient might be related to a partly age-dependent depression of T-lymphocyte function, leading to an altered immunological reactivity to which the various clinical manifestations could be attributed. Such a hypothesis is supported by recent reports showing that in old people and in ageing experimental animals, a decrease in T-lymphocyte function and in the number of circulating T-cells occurs concomitantly with an increase in the incidence of a variety of neoplasms and autoimmune disorders.
Thirty-nine sarcoidosis patients with pulmonary infiltrations (stage II) of less than 5 years dur... more Thirty-nine sarcoidosis patients with pulmonary infiltrations (stage II) of less than 5 years duration and not treated earlier with corticosteroids were randomly allocated for treatment with methylprednisolone for 7 months or for observation without therapy. Every other treated patient was given the drugs daily and every other followed an alternate-day regimen. After 7 months the chest radiographic finding, the forced vital capacity and the diffusion capacity for carbon monoxide were superior in the treated group. There was no difference between the two drug regimens. After 24 and 48 months no statistically significant differences between the untreated and the treated groups were found.
Serial tuberculin skin tests with 0·1–100 TU of PPD were performed on 209 patients with chronic r... more Serial tuberculin skin tests with 0·1–100 TU of PPD were performed on 209 patients with chronic renal disease. Skin test reactivity decreased with the severity of uraemia. Lymphocytes from three out of four skin test negative patients showed a high PPD-induced blast response in vitro. Thus, the absence of skin reactivity in uraemia does not always depend on a lack of antigen-sensitive lymphocytes.
The once-daily oral bronchodilator bambuterol and the twice-daily inhaled bronchodilator salmeter... more The once-daily oral bronchodilator bambuterol and the twice-daily inhaled bronchodilator salmeterol have been compared in only a few studies. In placebo-controlled studies, both bronchodilators have been found clinically effective and with few side-effects. In a double-blind, randomized 6-week parallel-group study in 117 patients with nocturnal asthma and using inhaled or oral steroids, no difference was found in efficacy between bambuterol 20 mg once daily in the evening and salmeterol 50 µg b.i.d. (morning and evening PEF, nocturnal awakenings). Similar results were seen in a double-blind, crossover study in 12 patients comparing 10 mg bambuterol in the evening with salmeterol 50μg in the evening for 2 weeks each. In a small, double-blind crossover study in 15 patients with reversible airway obstruction, bambuterol 20 mg once daily in the morning was compared with placebo for one week each. The patients were thereafter treated openly for one week with 50 μg salmeterol b.i.d. In steady state, on day 8, the 12- and 24-hour FEV1 values and the maximum FEV1 values were not significantly different after treatment with bambuterol or salmeterol. No differences in side-effects were seen. Further comparative double-blind, controlled studies are warranted.
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