PubMed Health⌕ Search

Biomedical subjects

A Scheja

Publications and source records attributed to A Scheja.

33 records · Page 2Linked to original sources

Long-term evaluation of penicillamine or cyclofenil in systemic sclerosis. Results from a two-year randomized study.

In a two-year prospective therapeutic trial 13 patients with systemic sclerosis (SSc) were treated with penicillamine, 9 with cyclofenil, and 7 with neither. At entry skin involvement and esophageal, lung, heart, and kidney function did not differ significantly between the groups. Reevaluation after one and two years did not show any significant changes in skin, esophageal, heart, and kidney manifestations, while lung function had slightly improved in both drug-treatment groups. This study thus shows little overall effect of penicillamine and cyclofenil, although both drugs may arrest worsening of pulmonary dysfunction.

Adult↗

Leukocyte migration in vivo and in vitro in patients with psoriasis.

Leukocyte migration in vivo was studied with a skin chamber technique in 21 patients with active psoriasis vulgaris and 18 with cleared psoriasis vulgaris. Measuring over 24 h, no difference was found between healthy volunteers and most patients with active psoriasis, although a subgroup of patients with long-lasting relapses showed subnormal migration values. In patients with cleared psoriasis on the other hand the in vivo leukocyte migration values were increased. In addition, leukocyte migration in vitro under agarose was studied, but no difference was found between healthy controls and patients with psoriasis, active or cleared.

Adult↗

Experience with a skin chamber technique for leucocyte migration studies.

An in vivo skin chamber method using lesions obtained by suction was evaluated. Neither dyspigmentation nor scarring were seen after 2 mth. The number of leucocytes accumulated in the collection chamber was correlated to the area of the lesion. Reproducibility remained essentially unchanged over an extended period and was 19% for one chamber and 13.6% for determinations with two chambers. No correlation was found between results obtained with the skin chamber technique and with chemotaxis or random migration as determined by an underagarose technique. When factors influencing in vivo and in vitro migration were studied, it was found that nonsteroidal anti-inflammatory drugs when given to arthritis patients or healthy volunteers inhibit leucocyte migration in vivo while in vitro migration was unchanged. Activated serum and LTB4 attracted leucocytes both in vivo and in vitro. The attraction by serum appeared at least partly to be caused by C5a. Polymorphonuclear leucocytes harvested from skin chambers were chemotactically deactivated and their bactericidal capacity reduced. The chemiluminescent response to formyl-methionyl-leucyl-phenylalanine and opsonized zymosan was increased. Exposed to zymosan activated serum, blood leucocytes showed a similar functional modification as leucocytes harvested from a skin chamber, and our findings suggest that the altered function of leucocytes in an inflammatory focus is largely the result of their exposure to chemotactic factors.

Anti-Inflammatory Agents↗

A skin chamber technique for leukocyte migration studies; description and reproducibility.

An in vivo skin chamber method, using lesions obtained by suction, was evaluated for studying leukocyte migration. No dyspigmentation or scar was seen after two months. The number of leukocytes accumulated in the collection chamber was 6.9 X 10(7)/cm2 and was correlated to the area of the lesion (r = 0.964). Reproducibility, essentially unchanged over an extended period, was 19% for one skin chamber and 13.6% for determinations with duplicate chambers; by comparison, with an under-agarose technique, the coefficient of variation for migration was low on consecutive days (6%), but much higher (29%) when determined over a longer period. No correlation was found between the skin chamber technique and chemotaxis or random migration determined with the under-agarose technique (r = -0.38 and 0.12 respectively). Zymosan-activated serum attracted a higher number of leukocytes than did fresh serum, whereas heat-inactivated serum attracted a lower number. This attraction seems to be partly caused by C5a, as a higher C5a-concentration was detected in zymosan-activated serum and in fresh serum after 24 hours in a collection chamber than in heat-inactivated serum.

Adult↗

Functional properties of polymorphonuclear leukocytes accumulated in a skin chamber.

Polymorphonuclear leukocytes harvested from a skin chamber were compared with peripheral blood leukocytes by examining their migration under agarose, their bactericidal capacity and their chemiluminescence. The chamber leukocytes were chemotactically de-activated and their bactericidal capacity reduced. The chemiluminescent response of chamber leukocytes was increased. In response to stimulation with formylmethionyl-leucyl-phenylalanine (first peak), chemiluminescence was far more marked in chamber leukocytes (10-30 times) than in blood leukocytes, whereas in response to stimulation with opsonized zymosan it was only moderately more marked (3-5 times). Exposed to zymosan activated serum, blood leukocytes showed a similar functional modification as leukocytes harvested from a skin chamber, and our findings suggest that the altered function of leukocytes at an inflammatory focus is largely the result of their exposure to chemotactic factors.

Adult↗

Mecillinam and ampicillin separately or combined in gram-negative septicemia.

Of 20 patients with gram-negative septicemia treated with mecillinam alone or in combination with ampicillin, successful therapeutic results were obtained in 16. In 11 patients treated with ampicillin alone, three failures responded successfully to a combination of mecillinam and ampicillin. Mecillinam MIC values of isolated Enterobacteriaceae were 0.05-0.4 micrograms/ml. In patients receiving 5 mg/kg mecillinam intravenously every six hours, the mean 0.5 hour concentration was 11.0 micrograms/ml and in those given 10 mg/kg 23.3 migcrograms/ml. No serious side effects were recorded. One patient on mecillinam developed an exanthema, as did three patients on combined therapy.

Adult↗

Capillary density in patients with systemic sclerosis, as determined by microscopy counts and compared with computer-based analysis.

OBJECTIVE: To develop a method enabling capillary density to be determined rapidly and accurately in patients with systemic sclerosis. METHOD: Capillary density was determined in 11 controls and 22 patients: 5 with diffuse cutaneous systemic sclerosis (dSSc), 12 with limited cutaneous systemic sclerosis (lSSc), two with suspected systemic sclerosis (suspSSc), 2 with sclerodermatomyositis, and one with undifferentiated connective tissue disease. Using a microscope equipped with a graticule, nailfold capillaries were counted within a 3 mm length of the nailfold; these counts were made by 4 different observers. The results were compared with the corresponding values obtained by the computerbased analysis of photographs. RESULTS: The median capillary density according to the direct counts was 8.0 loops/mm (6.7-10.0) in the controls, 6.0 loops/mm (range 4.8-8.8) in the dSSc subgroup, 5.6 loops/mm (4.2-6.5) in the lSSc subgroup, and 7.2 loops/mm (6.2-8.2) in the suspSSc subgroup. In the series as a whole, there was no significant difference between the median values for the left hands and those for the right hands, nor between the median value for all digit IVs and the median value for all four digits analysed (II, III, IV, and V). Interobserver variation was small between the 4 different observers. Direct microscopy counts were slightly higher than the corresponding values obtained by computer-based analysis. CONCLUSION: Direct microscopy counting is a rapid, simple, and reliable means of determining capillary density for screening purposes.

Adult↗

The association between changes in skin echogenicity and the fibroblast production of biglycan and versican in systemic sclerosis.

OBJECTIVE: To investigate a possible association between the longitudinal changes in skin involvement and the fibroblast production of proteoglycans in vitro, among patients with early and untreated systemic sclerosis (SSc). METHODS: In 11 patients, 6 with diffuse cutaneous systemic sclerosis (dSSc) and 5 with limited cutaneous systemic sclerosis (ISSc), and in 6 controls skin thickness and skin echogenicity of the forearm was measured by high frequency (20 MHz) ultrasound. A skin biopsy was taken from the area of the ultrasound measurements, and from cultivated fibroblasts the production of the proteoglycans versican, perlecan, biglycan and decorin were measured. To investigate longitudinal changes in skin involvement, the ultrasound examination was repeated after 1-3 years. RESULTS: Compared to controls, SSc patients had increased skin thickness at the first evaluation. Patients with dSSc had lower skin echogenicity than both patients with lSSc and the controls. Patients with greater changes in skin thickness and skin echogenicity produced more versican, whereas the production of biglycan and decorin was higher only in patients with greater changes in skin echogenicity. There was a negative correlation between fibroblast production of biglycan and disease duration. CONCLUSION: High fibroblast synthesis of the proteoglycans versican and biglycan is associated with changes in skin echogenicity and may predict more progressive skin sclerosis in SSc.

Adult↗

Effect of LTB4 and its isomers on human leucocyte migration into skin chambers.

The in vivo chemotactic effect of LTB4 and of its isomers, 6-trans-LTB4, 12 epi-6-trans-LTB4 and 5S, 12S-DHETE, was tested with a skin chamber technique in healthy volunteers and in parallel in vitro with an under-agarose technique. LTB4 had an in vivo chemotactic effect at 10(-7) mol/l in 24-hour experiments, while its isomers had no in vivo chemotactic effect at this concentration. LTB4 was also in vitro a more effective attractant than its isomers. In addition, C5ades Arg was tested using zymosan-activated serum, and was found to have an in vivo chemotactic effect at 1.5 X 10(-10) mol/l. However, when LTB4 and C5ades Arg were studied in 6-hour experiments in skin chambers there was an alteration in relative potency, LTB4 being relatively more potent at shorter test durations. This is most likely due to metabolisation of LTB4 in the presence of PMN:s and precludes a strict comparison of the in vivo chemotactic effects of LTB4 and C5ades Arg. When zymosan-activated serum or LTB4 was replaced by PBS after six hours in skin chamber experiments more leukocytes accumulated in the chambers at 24 hours than in chambers containing PBS for the whole 24 hour period. The reason for the increased migration even after the removal of the chemo-attractants as well as the relevance of LTB4 and C5a as chemo-attractants in the inflammatory process is discussed.

Chemotaxis, Leukocyte↗

Reduced in vivo leucocyte migration and elastase and lysozyme concentrations in skin chamber experiments with piroxicam in healthy volunteers.

Leucocyte migration in vivo, studied with a skin chamber technique was inhibited in eight healthy volunteers after six days' medication with piroxicam, 20 mg a day, but not after only one day's medication. The inhibition was not correlated to the serum content of the drug. The median trough values of piroxicam in serum were 2.5 mg/l and in blister fluid 1.2 mg/l after six days' medication. Leucocyte migration in vitro under agarose was not inhibited after six days' medication with piroxicam. When normal polymorphonuclear leucocytes were incubated with piroxicam in vitro migration under agarose was inhibited but only at piroxicam concentrations higher than those attainable in clinical therapy. The concentrations of elastase and lysozyme in the skin chamber decreased after six days' medication with piroxicam.

Adult↗

Kinetics of enzymes released from polymorphonuclear leucocytes in a skin chamber.

Ten healthy volunteers were investigated with a skin chamber technique developed for leucocyte migration studies. Chambers, filled with autologous serum, were harvested at 4, 8, 12, 22, and 30 hours. A marked increase was found both in the concentration of elastase in chamber serum as measured by RIA, and of lysozyme as measured both with lysoplate and electroimmuno assays. The immuno-reactive elastase was shown to consist exclusively of elastase-alpha 1-proteinase-inhibitor complexes. During the first 22 hours the concentrations of elastase and lysozyme were roughly proportional to the number of cells in the skin chamber (r = 0.92 and 0.85). At longer incubation times there was a decrease of relative concentration of elastase but not of lysozyme. Lactate dehydrogenase (LDH) was measured as a marker of the lysis of chamber leucocytes. Lysis was less than 1.5% at all incubation times. The present study shows a release of elastase from primary granules and of lysozyme when polymorphonuclear leucocytes migrate into a skin chamber.

Adult↗

Inhibition of in vivo leucocyte migration by NSAIDs.

Leucocyte migration was studied in vivo using a skin window technique, and in vitro by migration under agarose. No difference was found between 28 patients with rheumatoid arthritis (RA), 10 patients with psoriatic arthritis (PA) and 30 healthy controls. Most patients were under treatment with anti-rheumatic drugs. Patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) had significantly lower values (p less than 0.01) than untreated patients. In vivo but not in vitro migration decreased during short-term treatment with diclofenac and naproxen, an effect observed both in patients and in healthy individuals. After pre-incubation of normal polymorphonuclear leucocytes with diclofenac, in vitro migration was diminished only at concentrations of 50 micrograms/ml and above, which are at least 10 times higher than those attained clinically. The in vivo effect of NSAIDs on leucocyte migration may imply a long-term disease modifying influence in chronic arthritides.

Adult↗

Comparison of high frequency (20 MHz) ultrasound and palpation for the assessment of skin involvement in systemic sclerosis (scleroderma).

BACKGROUND AND OBJECTIVES: Systemic sclerosis (SSc) is a connective tissue disease characterized by microvascular changes and fibrosis of the skin and internal organs. Increased skin thickness proximal to the metacarpophalangeal joints is the single major diagnostic criterion. The aim of this study was to evaluate high frequency (20 MHz) ultrasound for the assessment of skin thickness in patients with SSc of different disease durations. METHODS: Skin thickness was measured with high frequency (20 MHz) ultrasound equipment (Dermascan) in 41 patients with SSc (23 women and 18 men) and in 41 controls. Twenty-five patients had limited cutaneous systemic sclerosis (ISSc), 12 had diffuse cutaneous systemic sclerosis (dSSc) and 4 had suspected SSc. RESULTS: Skin thickness of the forearm was inversely correlated to disease duration. Compared to controls, skin thickness was increased over the proximal phalanx of the right second finger and over the forearm in patients with a disease duration of 2 years or less. Assessments of skin thickness in 10 controls by 2 independent investigators showed an inter-observer variability of 1.0% for the proximal phalanx and 0.0016% for the forearm. Patients whose ultrasound showed increased skin thickness on the hand and forearm also had thickened skin by palpation. CONCLUSION: High frequency (20MHz) ultrasound is a feasible method for measuring skin thickness in SSc, and may be useful for diagnosis, long-term follow-up, and assessment in therapeutic studies.

Adult↗