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Biomedical subjects

A Scheja

Publications and source records attributed to A Scheja.

At least 19 recordsLinked to original sources
PubMed2006

BALF-derived fibroblasts differ from biopsy-derived fibroblasts in systemic sclerosis.

Growth of fibroblasts from bronchoalveolar lavage fluid (BALF) in patients with systemic sclerosis (SSc) has previously been described. The purpose of the present study was to characterise fibroblasts from BALF and bronchial biopsies from SSc patients with alveolitis and from controls, to analyse fibroblast proliferation, migration, stress fibres and proteoglycan production. BALF and bronchial biopsies were collected from 10 patients with SSc and alveolitis and from 15 controls. Outgrowth of fibroblasts was observed from the BALF of four patients, particularly in those with a markedly increased percentage of eosinophils in BALF, but not in any member of the control group. Increased levels of granulocyte-macrophage colony-stimulating factor, correlating with the percentage of eosinophils in BALF, were found in patients when compared with controls. Fibroblasts from BALF showed an elongated, mobile phenotype and increased proteoglycan production compared to the corresponding biopsy fibroblasts. In conclusion, outgrowth of fibroblasts with an altered phenotype is reported from bronchoalveolar lavage fluid in systemic sclerosis patients with alveolitis and an increased percentage of eosinophils in the bronchoalveolar lavage fluid. These findings indicate a possible role for eosinophil-fibroblast interaction in pulmonary fibrosis in systemic sclerosis.

Adult↗
PubMed2004

Screening for pulmonary hypertension in systemic sclerosis: the longitudinal development of tricuspid gradient in 227 consecutive patients, 1992-2001.

OBJECTIVE: To evaluate the longitudinal development of the tricuspid gradient (TG) for screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc). METHODS: Doppler echocardiography was performed 506 times in order to estimate TG in 227 consecutive patients with SSc. The value of biochemical markers for predicting TG levels and development was assessed through analyses of pro-brain natriuretic peptide (proBNP), calcitonin-gene related peptide, thrombomodulin and von Willebrand factor in 76 patients with a borderline increase in TG, defined as TG 24-38 mmHg, and for the purpose of comparison also in 10 patients with a normal TG (< 23 mmHg) and in 10 patients with increased TG (TG > 38 mmHg). RESULTS: TG > 23 mmHg was found in 102 patients (44.9%) at the first assessment point and in 139 patients (61.2%) respectively, cumulatively at follow-up. TG values > 33 mmHg were measured in 24 patients (10.6%) initially and in 38 patients (16.7%) cumulatively in a subsequent assessment. Age and the presence of interstitial lung disease (ILD) were associated with more frequent occurrence of TG > 23 and > 33 mmHg initially and at follow-up, but were not associated with progression rate. The change in TG (mean +/- S.D.) was 1.34 +/- 4.55 mmHg/yr. ProBNP correlated to TG. CONCLUSION: An increased TG, indicating possible PAH, is common and progressive in SSc. Age and ILD increase the risk of increased TG. Patients with or without ILD have similar progression of TG. ProBNP has potential as an adjunct to TG in selecting patients eligible for invasive treatment.

Age Factors↗
PubMed2004

Longitudinal development of skin involvement and reliability of high frequency ultrasound in systemic sclerosis.

BACKGROUND: Measurement of skin involvement is essential for diagnosis and prognosis in systemic sclerosis. Assessment by palpation skin score is the current method. OBJECTIVE: To explore high frequency ultrasound as an objective method to improve skin characterisation by combining measurements of skin thickness and echogenicity. METHODS: Skin thickness and echogenicity were measured at the proximal phalanx of the second digit, the back of the hand, the forearm, and the lower leg and, in order to separate limited (lSSc) from diffuse SSc (dSSc), at the chest in 16 patients with early disease and in 16 controls. Measurements were repeated in each patient three or four times with an interval of 1-2 years. Ultrasound measurements of skin thickness were compared with the palpation skin score. RESULTS: Compared with controls, the skin was thickened on the phalanx, hand, forearm, and chest of patients with dSSc, but not patients with lSSc, at the 1 year examination. In dSSc the degree of thickening tended to diminish with time, and at 4 years, thickness was significantly decreased on the forearm and chest compared with the 1 year measurements. Low reflectancy was most pronounced at the 1 year evaluation on the forearm, hand, and phalanx in dSSc, and on the phalanx in lSSc. CONCLUSION: Separate measurements of skin thickness and echogenicity by high frequency ultrasound add a new dimension to the assessment of skin involvement in SSc, and this seems to be an objective non-invasive tool for use in the study of disease development and in clinical trials.

Adult↗
PubMed2003

The association of antinuclear antibodies with organ involvement and survival in systemic sclerosis.

OBJECTIVES: To study the frequency and specificity of antinuclear antibodies (ANA) and their association with internal organ involvement and survival in systemic sclerosis (SSc). METHODS: Sera from 276 SSc patients were analysed by an indirect immunofluorescence (IIF) technique with HEp-2 cells as a substrate to categorize centromeric (ACA), nucleolar, speckled and homogeneous nuclear IIF patterns. Specific ANA were determined as follows: anti-DNA topoisomerase I (anti-topo I) by double immunodiffusion, anti-U1 RNP by passive haemagglutination, anti-RNA polymerase I, II and III (anti-RNAP) and anti-histone (AHA) antibodies by enzyme immunoassays. During the follow-up of 7.0+/-4.5 (mean+/-S.D.) yr the occurrence of clinical manifestations and internal organ involvement was registered. RESULTS: ANA were present in 84% of the patients. The most common patterns of the IIF were speckled (41%), homogeneous (25%), nucleolar (24%) and centromeric (18%). A nucleolar pattern was associated with pulmonary fibrosis (P < 0.01) and cardiomegaly (P < 0.05). ACA were related to organic vasculopathy (P < 0.05) and renal involvement (P < 0.01), but not to pulmonary fibrosis (P < 0.01). Anti-topo I were present in 9.4%, anti-U1 RNP in 21%, anti-RNAP in 22% and AHA in 16% of the patients. Pulmonary involvement was more common in patients with anti-topo I (P < 0.05), whereas AHA-positive patients were characterized by cardiac (P < 0.05), pulmonary (P < 0.05) and renal (P < 0.05) involvement. A nucleolar IIF pattern and AHA were both associated with a decreased survival [relative risk of death 1.71 (P < 0.05) and 2.36 (P < 0.01), respectively]. CONCLUSIONS: AHA and a nucleolar HEp-2 cell pattern may indicate critical organ involvement and predict a reduced survival in SSc patients.

Adult↗
PubMed2002

Correlation between plasma concentrations of calcitonin gene related peptide and pulmonary pressure in patients with systemic sclerosis.

OBJECTIVE: To examine plasma levels of calcitonin gene related peptide (p-CGRP) in patients with systemic sclerosis (SSc) and pulmonary hypertension (PH). MATERIAL AND METHODS: Twenty nine patients with SSc, 10 with diffuse form, 18 with limited form and one with overlapping systemic lupus erythematosus were examined. Twelve patients displayed normal systolic pulmonary artery pressure (PAPsyst) < or =30 mm Hg and 17 increased PAPsyst >30 mm Hg. Eight patients had isolated PH without interstitial lung disease (ILD) and nine had PH and ILD (secondary PH). PAPsyst was measured non-invasively by Doppler cardiography. CGRP was determined by radioimmunoassay. RESULTS: Patients with PH had higher p-CGRP than patients with normal pressure. A positive relation was found between p-CGRP and PAPsyst and between p-CGRP and erythrocyte sedimentation rate (ESR), particularly in patients with isolated PH. CONCLUSION: In patients with SSc p-CGRP correlates with pulmonary pressure and with ESR. Whether CGRP reflects disease activity or is released secondary to pulmonary vasoconstriction needs to be investigated further.

Adult↗
PubMed2001

Von Willebrand factor propeptide as a marker of disease activity in systemic sclerosis (scleroderma).

In 44 consecutive patients with systemic sclerosis (SSc), plasma concentrations of von Willebrand factor (vWf) were higher than those of the vWf propeptide, but the propeptide showed less variability within patient subgroups. Higher values of the propeptide were observed in patients with early pulmonary involvement. A closer correlation of the propeptide than of vWf to biochemical markers of activity was also evident. Our results suggest that the propeptide, despite a shorter circulating half-time and lower plasma concentrations than vWf, is more useful in the assessment of disease activity in SSc.

Adult↗
PubMed2000

Circulating collagen metabolites in systemic sclerosis. Differences between limited and diffuse form and relationship with pulmonary involvement.

OBJECTIVE: To study collagen metabolites in systemic sclerosis (SSc) and their relationship with clinical manifestations of the disease. METHODS: Forty-eight SSc patients, 13 with a diffuse form (dcSSc), 23 with a limited form (lcSSc) and 12 with suspected SSc not fulfilling the ACR criteria, and 31 healthy controls were examined. Serum concentrations of aminoterminal type III procollagen peptide (PIIINP), aminoterminal and carboxyterminal type I procollagen peptides (PINP and PICP) and cross-linked carboxyterminal telopeptide of collagen I (ICTP) were determined by radioimmunoassay. RESULTS: Increased serum concentrations of ICTP were found in SSc patients compared with controls. Distinctly higher levels of ICTP were observed in dcSSc than in lcSSc. High serum ICTP was correlated with skin score and acute phase reactants, and with reduced pulmonary function. Serum PIIINP concentration was elevated in both lcSSc and dcSSc. CONCLUSION: Augmented collagen catabolism accompanies the increased collagen synthesis in SSc. Serum ICTP concentration is a marker of this feature and also reflects clinical severity.

Adult↗
PubMed1999

Decreased capillary density in juvenile dermatomyositis and in mixed connective tissue disease.

OBJECTIVE: To assess whether quantitative capillary microscopy is a useful tool to evaluate capillary abnormalities in children with connective tissue diseases. METHODS: Eight children with juvenile dermatomyositis (JDM), 6 with mixed connective tissue disease (MCTD) and 23 healthy children were investigated with computer based quantitative capillary microscopy. Median disease duration was 1 year among JDM (1-4) and 3 years (1-7) among MCTD. RESULTS: Capillary density was decreased in JDM [median 2.5 (1.4-4.3) loops/mm (p < 0.001)] and in MCTD [median 5.0 (4.1-7.0) loops/mm (p < 0.05)] compared to healthy controls [median 6.8 (5.3-8.0) loops/mm]. Median capillary loop area was increased in JDM [median 8.5 (3.0-15.8) 10(-3) mm2 (p < 0.001)] and in MCTD [median 4.5 (3.0-6.0) 10(-3) mm2 (p < 0.02)] compared to controls [median 2.5 (1.0-4.0) 10(-3) mm2]. CONCLUSION: Quantitative nailfold capillary microscopy is a sensitive indicator of JDM. In MCTD this technique is less discriminative.

Adolescent↗
PubMed1998

Mortality and causes of death in a Swedish series of systemic sclerosis patients.

OBJECTIVES: To analyse survival rates and the causes of death in a systemic sclerosis (SSc) population, and to evaluate the occurrence of fatal malignant neoplasms and their possible association with oral cyclophosphamide (CYC) treatment. METHODS: Survival was calculated for 249 SSc patients followed up for up to 13 years. Mean (SD) follow up was 5.8 (4.2) years. The 49 decreased patients were subdivided according to causes of death and its relation to SSc. Fatal malignancies in CYC treated patients were compared with those occurring in non-CYC treated patients. RESULTS: The overall 5 and 10 year survival rates were 86% and 69% respectively. There was a 4.6-fold increased risk of death, as compared with the general population. Prognosis was worse in the diffuse cutaneous involvement (dSSc) and male subgroups than in the limited cutaneous involvement (1SSc) and female subgroups. Of the 49 deaths, 24 were attributable to pulmonary complications such as pulmonary fibrosis, pulmonary hypertension, pneumonia or pulmonary malignancy. Treatment with oral CYC did not increase the risk of dying of cancer. CONCLUSIONS: Mortality is increased both in the SSc population as a whole and in its different subsets (dSSc and 1SSc). Prognosis is worst among male patients with dSSc. However, the 5 year survival rate was better than those reported from earlier studies. Most patients die of cardiopulmonary disease. Five of seven fatal lung cancers were adenocarcinomas, possibly caused by chronic inflammatory disease of the lung. In this study, CYC treatment was not associated with an increased incidence of fatal malignant neoplasms.

Adenocarcinoma↗
PubMed1996

Computer based quantitative analysis of capillary abnormalities in systemic sclerosis and its relation to plasma concentration of von Willebrand factor.

OBJECTIVES: To evaluate an objective and quantitative method for assessment of capillary abnormalities in systemic sclerosis (SSc). METHODS: Nailfold capillaries were investigated by capillary microscopy and photographed in 17 consecutive SSc patients (five with diffuse cutaneous systemic sclerosis (dSSc) and 12 with limited cutaneous systemic sclerosis (lSSc)) and in 17 healthy controls. Investigators having no access to clinical data made drawings from magnified projections of coded photographs and analysed them using a computer program. Capillary density (capillary loops/mm in the distal row) and median capillary loop area were calculated. Presence of functional or organic arterial changes was evaluated by measurement of finger pressure with finger cooling. Plasma concentration of von Willebrand factor (VWF) was analysed using an enzyme linked immunosorbent assay (ELISA). RESULTS: In 16 of 17 SSc patients and 13 of 17 controls the technical quality of the photographs was sufficient for computer analysis. Capillary density was decreased in dSSc (median 6.9 loops/mm) and in lSSc (median 3.8 loops/mm) compared with healthy controls (8.9 loops/mm) and median capillary loop area was increased in dSSc (7.3 x 10(-3) mm2) and in lSSc (8.5 x 10(-3) mm2) compared with healthy controls (5.0 x 10(-3) mm2). An inverse relation was found between capillary density and median capillary loop area in SSc patients. Plasma VWF was increased in patients (median 401 IE/l in dSSc and 409 IE/l in lSSc) compared with controls matched for age and sex (median 276 IE/l). Computer based analysis showed capillary density below the control range and median capillary loop area above the control range in 14 of 16 SSc patients. Measurement of finger pressure with finger cooling showed organic vascular changes in nine of 13 SSc patients. CONCLUSION: Computer based quantitative analysis has low interobserver variability and is a quantitative and sensitive method of assessing capillary abnormalities in SSc.

Adolescent↗
PubMed1996

Occurrence and distribution of peptidergic nerve fibers in skin biopsies from patients with systemic sclerosis.

Systemic sclerosis is characterized by vascular dysfunction. Itch is sometimes present in early stages of the disease. This prompted us to study the innervation of the skin by immunocytochemistry. Antibodies to neuropeptide Y and vasoactive intestinal peptide were used for autonomic nerves. Sensory innervation was studied using antibodies to substance P and calcitonin gene-related peptide. Protein gene product 9.5 was used as a general neuronal marker. Skin biopsies from affected (lower arm) and non-affected (upper back) sites on 10 patients with systemic sclerosis and from corresponding sites on 10 sex- and age-matched healthy controls were studied. Regional variations were found in the occurrence of peptidergic nerve fibers. In the patients the density of nerve fibers (measured semiquantitatively) stained by the panneuronal marker was lower in affected than in unaffected skin (p < 0.05). There were no significant differences in peptidergic innervation between patients and controls. However, there was a tendency to higher density of neuropeptide Y-positive nerve fibers in the forearm skin in 6 to 10 patients, as compared to only 1 of 10 healthy controls.

Adult↗
PubMed1995

Esophageal scintigraphy of systemic sclerosis.

UNLABELLED: Esophageal involvement is common in systemic sclerosis, and esophageal scintigraphy can be used to detect and follow esophageal dysfunction. This study assesses the value of visual and quantitative analysis of esophageal scintigraphy performed as a multiple swallow test in normals and patients with systemic sclerosis. METHODS: Forty patients with systemic sclerosis and 40 sex- and age-matched healthy subjects (controls) were studied. A multiple swallow technique was used and both quantitative and qualitative analyses were performed. Visual analysis of condensed images was performed independently by two physicians. Each swallow was assigned a score on a scale from 1 to 4. In the quantitative analysis, time-activity curves based on the mean condensed images were used to calculate the following 3 parameters: residual activity 12 or 25 sec after the beginning of the swallow, measured with or without baseline correction, respectively, and time from onset of swallow to 50% of peak activity. RESULTS: Both visual and quantitative analysis showed a highly significant (p < 0.001) difference between the patient group and the control group. Visual analysis was best reflected by the residual activity 25 sec after the beginning of the swallow without correction for background. Receiver operating characteristic curves were used to study the ability to separate the two groups using visual or quantitative analysis. A high rate of positive tests in the patient group was achieved only at the cost of a relatively high rate of positive tests in the control group. CONCLUSION: Our results indicate high variability in esophageal motility in controls. This variability impairs the possibilities of developing a screening test to identify asymptomatic patients early in the disease course.

Adult↗
PubMed1994

Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide.

OBJECTIVE: Pulmonary fibrosis is a common feature of systemic sclerosis (SSc) and a major cause of morbidity and mortality. Since alveolitis may be an essential step in the development of pulmonary fibrosis, we investigated the use of immunosuppressive drug therapy to improve pulmonary function in patients with SSc. METHODS: Eighteen patients with progressive pulmonary dysfunction, diminished vital capacity (VC), and/or decreased static lung compliance (Cst) were treated with cyclophosphamide and corticosteroids for 1 year. Eight patients had diffuse cutaneous SSc and 10 had limited cutaneous SSc. The median disease duration was 2.5 years (range 0.5-17 years). RESULTS: VC increased in 14 of 18 patients and the median VC rose from 74% to 80% of predicted. Cst improved in 8 of 12 patients and the median Cst increased from 59% to 66% of predicted. Pulmonary nonfibrotic opacities disappeared in 9 of 12 patients. The erythrocyte sedimentation rate (ESR) and serum concentrations of orosomucoid, C-reactive protein, and aminopropeptide type III collagen all improved. The patients were divided into 2 groups based on the presence or absence of elevations in acute-phase protein levels and ESR before therapy. Among the 12 patients with biochemical signs of inflammation, VC increased in 11, and Cst improved or was unchanged in 7 of the 8 who were tested. The median VC in this subgroup increased from 73% to 80% of predicted and the median Cst increased from 57% to 60% of predicted. In the group of 18 patients overall, the skin score decreased, while esophageal and renal function remained stable. CONCLUSION: Cyclophosphamide may have a beneficial effect on pulmonary fibrosis in patients with SSc and elevated levels of acute-phase proteins. Controlled trials of cyclophosphamide in pulmonary SSc should be performed and should focus on such patients.

Adult↗
PubMed1994

Inverse relation between plasma concentration of von Willebrand factor and CrEDTA clearance in systemic sclerosis.

OBJECTIVE: Microvascular abnormalities involving endothelial cell dysfunction occur as an early event in systemic sclerosis. We studied plasma concentrations of von Willebrand factor (vWf), a substance released from injured endothelial cells, and its relation to pulmonary and renal dysfunction. METHODS: vWf was determined by immunoelectrophoresis. Renal function was assessed by CrEDTA clearance, an accurate measure of glomerular filtration rate and pulmonary function by spirometry and carbon monoxide diffusing capacity. Pulmonary pressure was measured by Doppler cardiography. RESULTS: In 22 patients with scleroderma, vWf concentrations related inversely to CrEDTA clearance. In contrast, no relationship between plasma vWf and pulmonary function was found; 9/10 patients with pulmonary hypertension and 9/12 patients with normal pulmonary pressure showed elevated levels of vWf. However in 5 patients with pulmonary hypertension without radiographic evidence of pulmonary fibrosis there was a strong correlation between plasma vWf and pulmonary pressure (rho = 0.90) which fell short of statistical significance due most likely to small population size. CONCLUSION: Renal but not pulmonary dysfunction was associated with elevated plasma levels of vWf.

Adult↗
PubMed1993

Carboxyterminal type I procollagen peptide concentrations in systemic sclerosis: higher levels in early diffuse disease.

Systemic sclerosis (SSc) is characterized by increased collagen deposition in skin and internal organs, and increased serum concentrations of different connective tissue metabolites have been reported. In this study serum concentrations of carboxyterminal type I (PICP) and aminoterminal type III procollagen peptide (PIIINP) were higher in 24 patients with diffuse cutaneous systemic sclerosis (dSSc), than in 30 patients with limited cutaneous systemic sclerosis (lSSc). Thirty patients with advanced and progressing disease had higher serum concentrations of both peptides than 24 patients with milder disease. In patients with advanced disease, both peptides showed a negative correlation to disease duration. Despite being relatively higher both in early, widespread and advanced disease, serum PICP concentrations varied only within the normal range for healthy controls. Thus PICP is of limited value as a marker of disease activity in SSc.

Adult↗
PubMed1993

Early pulmonary disease in systemic sclerosis: a comparison between carbon monoxide transfer factor and static lung compliance.

OBJECTIVES: Pulmonary disease is responsible for considerable morbidity and mortality in systemic sclerosis (SSc). Static lung compliance (Cst) has been observed to be decreased more often in SSc than the vital capacity, indicating that it is a sensitive measure of lung restriction. In this study Cst was compared with the carbon monoxide transfer factor (TLCO), a widely used measure of the function of the alveolar capillary unit, and with lung volumes in 59 patients with confirmed or suspected SSc. METHODS: Cst was calculated from the oesophageal pressure at different lung volumes and the TLCO was measured with the single breath method. RESULTS: The TLCO was found to be the earliest sign of pulmonary disease and was already decreased at a disease duration of one year or less. Surprisingly, no relation was found between the TLCO and smoking habits, nor the degree of peripheral vascular disease. The TLCO correlated with the Cst and vital capacity. CONCLUSIONS: An early pulmonary lesion can be identified in patients with SSc with decreased TLCO at a time when no fibrotic changes are manifested.

Acute-Phase Proteins↗
PubMed1992

Serum levels of aminoterminal type III procollagen peptide and hyaluronan predict mortality in systemic sclerosis.

Systemic sclerosis (SSc) is characterized by an excessive accumulation of collagen in skin and internal organs and increased serum concentrations of different connective tissue metabolites have been reported. In this study of 82 patients with SSc, serum concentrations of aminoterminal type III procollagen peptide (PIIINP), smaller PIIINP-related antigens (Fab PIIINP) and hyaluronan (HA) were increased as compared to healthy controls matched for age and sex. Patients with a shorter disease duration (less than 3 years) had higher serum levels of PIIINP and Fab PIIINP than patients with a longer disease duration. The highest serum concentrations of PIIINP and HA were seen in seven patients who died within 2 years.

Cyclofenil↗