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Biomedical subjects

C Alberts

Publications and source records attributed to C Alberts.

At least 19 recordsLinked to original sources

[Sarcoidosis: immunopathogenesis and the potential of immunotherapy].

Sarcoidosis is a multi-systemic disease of unknown aetiology, immunopathologically and histologically characterised by a macrophage/T-helper I cell-mediated non-caseating granulomatous inflammation process. In the development of granulomas, an imbalance between pro-inflammatory and anti-inflammatory cytokines plays an important role, possibly initiated by an as yet unidentified (exogenous) stimulus. The clinical outcome of the disease process is unpredictable, and appears to be determined by the cytokine production of the inflammatory cells in the granuloma. Fifty to seventy percent of the patients recover without medication within a period of time which cannot be predicted, the other 30 to 50% of patients are treated during the course of the disease with corticosteroids (with varying degrees of success), either alone or in combination with cytostatic or immunosuppressive agents. Based on recent developments in the field of immunomodulation and on current knowledge of the immunopathogenesis of sarcoidosis, there appear to be opportunities for specific immunotherapy which should be evaluated in controlled studies.

Anti-Inflammatory Agents↗

[Non-specific inflammation of the respiratory tract in a female patient with inflammatory bowel disease and osteoporosis].

A 33-year-old woman presented with a non-specific inflammation of the respiratory passages, which occurred two months after partial colectomy and sigmoidectomy for local stenosis caused by an unclassified inflammatory bowel disease. After other causes of the respiratory symptoms had been ruled out, it was concluded that these were a complication of the bowel disease. Due to the osteoporosis, the patient was given a prolonged treatment with high doses of inhaled corticosteroids instead of systemic corticosteroids. She was treated successfully.

Administration, Inhalation↗

The role of laser assisted uvulopalatoplasty in snoring and sleep apnea.

1. A careful history and favorable physical exam is mandatory for consideration of LAUP. 2. Concurrent diseases must be addressed for optimal results. 3. A sleep study should be recommended with any evidence suggestive of sleep apnea. 4. LAUP cures snoring. 5. Primary treatment of severe sleep apnea is nasal continuous positive airway pressure (NCPAP). 6. Mild sleep apnea with appropriate physical exam can be expected to have acceptable results when treated by LAUP. 7. LAUP should be considered for moderate to severe sleep apnea only if NCPAF intolerance is intractible.

Adult↗

Inhaled budesonide in pulmonary sarcoidosis: a double-blind, placebo-controlled study. Dutch Study Group on Pulmonary Sarcoidosis.

In a double-blind, placebo-controlled study, we assessed the efficacy of inhaled budesonide on the course of newly diagnosed pulmonary sarcoidosis and whether budesonide treatment could postpone oral corticosteroid treatment. We evaluated: 1) symptoms; 2) chest radiography; 3) angiotensin-converting enzyme (ACE) in serum; and 4) lung function. Patients with histologically confirmed pulmonary sarcoidosis with chest radiographic stages I, II or III, and with an abnormal lung function (inspiratory vital capacity (IVC) < 79% of predicted or transfer factor of the lungs for carbon monoxide (TL,CO) < 77% pred) were included. Patients with radiographic stage II or III but with normal lung function were included when more than 20% of the total cell population in bronchoalveolar lavage fluid (BALF) was lymphocytes. Forty seven patients received placebo or budesonide (1.2 mg) once daily via a Nebuhaler for 6 months, followed by 6 months without treatment. Based on predetermined criteria, 11 patients were excluded during the blind treatment period as they needed oral prednisone: seven (28%) patients in the placebo group (n = 25) and four (18%) patients in the budesonide group (n = 22). Patient's Global Clinical Impression (GCI) score showed a significant difference in favour of budesonide. IVC showed a significant difference of 7.9% predicted between the two groups during the active treatment period. This difference persisted during follow-up, when the difference was 9.4% pred. TL,CO remained nearly unchanged over time, with no difference between the groups. Improvements in chest radiographic appearance and changes in serum ACE were similar for the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Soluble and cellular markers of T cell activation in patients with pulmonary sarcoidosis.

We have characterized the activation state of T cells in the bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) from patients with sarcoidosis, to obtain more information about their mechanisms of activation. We analyzed the expression of activation markers (CD25, HLA-DR, Leu-8, and two recently defined markers, CD69 and CD27) on T cells by two-color flow cytometry. We also measured the levels of soluble CD27 and soluble CD25 in nonconcentrated BALF and in serum by ELISA. We found that most T cells in BALF from patients, but not in the peripheral blood, expressed CD69, whereas they did not express CD27. The phenotype (CD69+CD27-) of most BALF T cells and the coexpression of CD69 with HLA-DR and/or VLA-1 indicates that they are in a state of recent and persistent activation. We confirmed previous findings of expression of CD25, HLA-DR, and Leu-8 by T lymphocytes in BALF from patients. We also confirmed increased levels of soluble CD25 in the serum from these patients. The levels of sCD27 and sCD25 in the epithelial lining fluid (ELF) were calculated on the basis of urea in BALF and serum. They were increased in the patients compared with control subjects. In both patients and control subjects, levels in ELF were higher than in the peripheral blood. This indicates shedding of sCD27 (and sCD25) in the lung compartment, which likely contributes to levels in the serum. It is known that in vitro CD27+ cells become CD27- after repeated stimulation and that CD27- cells, after restimulation, do not shed sCD27.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Standardized quantitative 67Ga scintigraphy in relation to carbon monoxide diffusion capacity in pulmonary sarcoidosis.

67Ga lung uptake, obtained by a standardized computer-assisted quantitative method of 67Ga scintigraphy, was compared to carbon monoxide diffusion capacity (DLCO) in 45 patients with biopsy proven pulmonary sarcoidosis. Increased 67Ga lung uptake was found in 24 (53%) patients and DLCO was decreased in only 16 (36%) patients. An inverse relationship (r = -0.53; p < 0.001) was demonstrated between 67Ga lung uptake and DLCO. Eleven patients had an increased 67Ga lung uptake whereas the DLCO values were normal. There was no correlation between 67Ga lung uptake or DLCO and either chest radiographic stage or mode of clinical presentation. On the basis of the normal limits for 67Ga lung uptake and DLCO, 4 subgroups of patients could be identified. The use of the combined investigations may open an opportunity for an early identification of those patients who require therapy. An increased 67Ga accumulation within the lung seems to be considered as a factor indicating risk for pulmonary disability, which is supported by the follow-up of the 4 subgroups of patients.

Adult↗

ELISA of complement C3a in bronchoalveolar lavage fluid.

Activated complement factors within the lung may induce several local biological effects. In order to investigate local complement activation we have developed non-competitive two-site ELISAs of C3a and total C3 in bronchoalveolar lavage fluid (BALF). For the assay of C3a, both C3 and C3(H2O) were removed from the samples by precipitation with polyethylene glycol. It was necessary to add carrier proteins to BALF to remove C3 and C3(H2O) fully. The ELISA of C3a has the lowest limit of detection reported thus far, namely 0.045 nM (= 0.405 ng/ml). In BALF from healthy persons (n = 9) the C3a concentration was 0.20 nM (0.12-0.31 nM) (median, range). C3a was higher in BALF from patients with asthma or with sarcoidosis; asthma (n = 10), 0.45 nM (0.20-5.79 nM); sarcoidosis (n = 19), 1.31 nM (0.095-5.65 nM) (Mann-Whitney U test, p less than 0.005). In BALF from patients with Pneumocystis carinii pneumonitis (n = 10) the C3a concentration was 0.18 nM (0.07-0.57 nM). C3a concentrations in BALF may reflect local complement activation in the lung and/or diffusion into the lumen. This was studied by normalizing C3a concentrations in BALF into values for epithelial lining fluid (ELF), and calculating serum-to-ELF quotients of C3a, and C3a/total C3 quotients.

Adolescent↗

Uveitis and systemic disease.

A prospective study was conducted of 865 patients with uveitis to determine the frequency of associated systemic diseases and to assess the value of limited laboratory screening of these patients. All patients underwent a standard diagnostic protocol followed--when indicated--by special tests and procedures performed in order of likelihood ('tailored approach'). For 628 patients (73%) a specific diagnosis was established based on history, ophthalmologic examination, and laboratory and radiographic studies. A definite association with systemic disease was determined for 220 patients (26%). A relationship with a subclinical systemic disorder could be presumed in 201 cases (23%) and a well-established clinical uveitis entity without a recognisable systemic disorder was present in 207 cases (24%). For 237 patients (27%) a diagnosis could not be determined. The most frequently observed systemic diseases were sarcoidosis (7%) and HLA-B27-associated seronegative spondylarthropathies (6%). Presumed or definite toxoplasmosis was encountered in 10% of cases. HLA-B27-associated acute anterior uveitis was the most common clinical entity (17%). In the majority of cases the presence of a systemic disease was not suspected prior to eye involvement and was only recognised after the subsequent diagnostic procedures.

Adolescent↗

Surfactant protein A in bronchoalveolar lavage fluid.

We measured surfactant protein A and phosphatidylcholine in the bronchoalveolar lavage fluid from healthy volunteers and several groups of patients with lung diseases to obtain information on surfactant in the lung. We developed three types of enzyme-linked immunosorbent assays that used combinations of polyclonal antiserum and monoclonal antibodies. Phosphatidylcholine was assessed by enzymatic measurement. The median amounts of surfactant protein A in bronchoalveolar lavage fluid determined by the enzyme-linked immunosorbent assay with monoclonal antibodies were as follows: control subjects (n = 10), 2.82 mg/L (range, 0.92 to 5.17 mg/L); patients with asthma (n = 13), 1.89 mg/L (range, 0.45 to 2.95 mg/L); and patients with pulmonary sarcoidosis (n = 20), 2.98 mg/L (range, 0.68 to 7.02 mg/L). The median phosphatidylcholine concentrations in the bronchoalveolar lavage fluid were as follows: control subjects (n = 10), 20 mumol/L (range, 3 to 37 mumol/L); patients with asthma (n = 12), 24 mumol/L (range, 3 to 55 mumol/L); and patients with pulmonary sarcoidosis (n = 20), 26 mumol/L (range, 4 to 76 mumol/L). As a group, the patients with asthma had less surfactant protein A in bronchoalveolar lavage fluid than did the control subjects (Mann-Whitney U test, p less than 0.05). The surfactant protein A levels measured by the enzyme-linked immunosorbent assay with polyclonal antiserum and by a competitive enzyme-linked immunosorbent assay were also lower in bronchoalveolar lavage fluid from patients with asthma than in that from control subjects. The phosphatidylcholine concentrations in all groups were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Sarcoidosis of the heart].

In 2 patients arrhythmias and conduction disorders were the first symptoms at presentation of cardiac sarcoidosis. One patient with severe conduction disorders showed normalisation of the EKG during steroid treatment. The other patient developed an overall cardiomyopathy and the arrhythmia was treated with conventional drugs. The frequency of cardiac involvement in sarcoidosis is much higher than that of clinical symptoms of sarcoid heart disease. Cardiac sarcoidosis is increasingly diagnosed in the last few decades. In most cases, it presents with sudden death, arrhythmia, conduction disorders or cardiomyopathy. The main diagnostic pathological feature is evidence of noncaseating granulomas, but mononuclear cell infiltration and focal interstitial fibrosis have also been found. The basal part of the interventricular septum is particularly prone to involvement. If conventional therapy in clinically important cases proves inadequate, steroid therapy should be added. It is recommended to make an EKG in every patient presenting with sarcoidosis even in the absence of cardiac symptoms. Sarcoid heart disease should be considered in every patient with diagnostic sarcoidosis and heart disease but also in every case of difficult heart disease without an obvious aetiology. Because of the relatively early age at onset, life expectancy is shortened.

Adult↗

Cochlear implant.

Cochlear implantation to restore some of the hearing in the profound or totally cochlear deaf patient has been briefly presented. An approximate two year follow up has not shown any complications. The Nucleus 22 channel cochlear implant, as presently manufactured, is a very useful device to rehabilitate profoundly or totally cochlear deaf patients.

Cochlear Implants↗

Comparison of the effectiveness of slow-release propranolol (Inderal LA) 80, 160 and 320 mg orally daily in the treatment of angina pectoris.

Doses of 80, 160 and 320 mg of Inderal LA (slow-release propranolol) were compared in 12 patients with stable angina pectoris. There was an unpredictable and variable individual response to treatment and hence no differences were detected between the effects of the three doses on mean treadmill exercise duration, time to angina, frequency of angina or glyceryl/trinitrate consumption. There was a marked deterioration in two patients whilst on 320 mg Inderal LA. In these patients, the time to angina fell by 2 minutes 50 seconds and 4 minutes 20 seconds on 320 mg daily and 160 mg daily respectively. Given the inter-patient variability in response to Inderal LA, the dose for each patient should be individually titrated according to response. Two patients reported here suggest that some subjects may benefit from lower doses, although further work is required to clarify this point. Possible explanations for this finding are discussed.

Administration, Oral↗

Risk factors for ocular sarcoidosis.

We reviewed 121 consecutive patients with biopsy-proven sarcoidosis who visited the sarcoidosis clinic of the University Hospital in Amsterdam, to determine the risk factors for the development of ocular manifestations. Of 121 patients 52 (43%) were black. Ocular disease developed in 50 (41%) patients and was more common in female and in black patients. uveitis was the most frequent manifestation of ocular sarcoidosis (29 out of 50 or 58%). There were no differences in the extra-ocular manifestations of the sarcoidosis between patients with and without ocular disease or between uveitis and non-uveitis patients. This study covered a mixed racial population and shows that different types of uveitis are seen in white and black patients. Anterior uveitis was more frequent in black patients (P less than .001), whereas posterior uveitis was more common in white patients (P less than .01). Chronic posterior uveitis with complications occurred most frequently in white female patients with late onset of the systemic disease. Uveitis was an early feature of sarcoidosis (25 out of 29 or 86%); moreover in 9 out of 29 (31%) cases, uveitis preceded the non-ocular detectable signs of sarcoidosis by more than one year. This emphasizes the importance of periodic re-evaluation of uveitis patients for sarcoidosis.

Adolescent↗

Standardized quantitative 67Ga scintigraphy in pulmonary sarcoidosis.

A method of standardized quantitative 67Ga scintigraphy in the evaluation of pulmonary sarcoidosis is described. Standardization of 67Ga activity measurements was achieved by using an external attenuated 67Ga standard for comparison. The method was applied to control subjects (n = 24), and to patients (n = 88) suffering from biopsy-proven pulmonary sarcoidosis, whether or not treated with systemic or inhaled corticosteroids. The quantitative 67Ga activity values for pulmonary hili and parenchyma were found to be increased in patients, especially in those patients who were recently diagnosed and untreated. 67Ga accumulation in the liver showed normally a wide variation and appeared to be increased in patients with sarcoidosis, so that use of the liver radioactivity as the standard for comparison may lead to misinterpretation of the intrathoracic 67Ga activity distribution. Standardized quantitative 67Ga scintigraphy appeared to be a valuable tool in the management of pulmonary sarcoidosis and also opens up the possibility for results from different institutions to be compared. Supplementary digitized functional images improved the accuracy of the interpretation of routine analogue unprocessed images. Diffuse or local 67Ga accumulation in the chest was more readily discernible on digitized functional images than on analogue images.

Female↗

Distribution of ventilation-perfusion ratios in pulmonary sarcoidosis.

In 14 patients with advanced stage pulmonary sarcoidosis the distribution of regional ventilation-perfusion ratios (V/Q) was obtained by quantitative analysis of ventilation-perfusion single photon emission computed tomography (SPECT) of the lungs. In 6 patients normal V/Q distributions were found with a decreased DLCO in only one of them. In 8 patients abnormal distributions of V/Q ratios were found. Six of these patients also had a decrease in diffusing capacity for CO (DLCO). It is suggested that the decrease in DLCO in these patients is partly a result of uneven distribution of V/Q ratios.

Adult↗