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Biomedical subjects

I Lorenzen

Publications and source records attributed to I Lorenzen.

At least 37 records · Page 2Linked to original sources
PubMed1996

Serum YKL-40 levels in healthy children and adults. Comparison with serum and synovial fluid levels of YKL-40 in patients with osteoarthritis or trauma of the knee joint.

YKL-40 is a recently discovered human glycoprotein which is related in amino acid sequence to the chitinase protein family. YKL-40 is a major secretory protein of human chondrocytes and synoviocytes, and could play a role in tissue remodelling. The aim of the study was to establish the serum YKL-40 level in normal subjects and to evaluate serum YKL-40 as a marker for osteoarthritis. Serum YKL-40 was 80 micrograms/l in healthy children (n = 476) and 102 micrograms/l in healthy adults (n = 260). No age or sex differences were found in serum YKL-40 in subjects younger than 70 yr, but thereafter serum YKL-40 increased significantly. Patients with late-stage osteoarthritis of the knee (n = 37) had significantly higher serum YKL-40 (1.5-fold; P < 0.01) compared to healthy age-matched subjects, whereas patients with early-stage osteoarthritis of the knee or recent torn cruciate ligaments or menisci did not have elevated serum YKL-40. The level of YKL-40 in serum and synovial fluid correlated significantly, and 10-fold higher values were found in synovial fluid. YKL-40 levels in serum and synovial fluid of patients with acute severe synovial inflammation were significantly higher (P < 0.05-P < 0.001) than those in patients with no, light or moderate synovitis of the knee joint. Furthermore, YKL-40 correlated significantly (P < 0.01) with the amino-terminal propeptide of type III procollagen, but not with serum C-reactive protein. Our data indicate that YKL-40 in synovial fluid and serum may reflect human articular cartilage degradation and the degree of synovial inflammation in the knee joint.

Adipokines↗
PubMed1996

Bone loss in rheumatoid arthritis. Influence of disease activity, duration of the disease, functional capacity, and corticosteroid treatment.

Axial and appendicular bone mass were studied in 95 patients with rheumatoid arthritis. The aims were to quantify bone mineral density (BMD) and to evaluate the importance of disease activity, duration of disease, functional capacity, and corticosteroid treatment for bone loss in patients with rheumatoid arthritis. The BMD in the lumbar spine (BMDSPINE) did not differ from age-matched healthy controls, but distal forearm BMD (BMDARM) and metacarpal BMD (BMDMCB) were significantly lower in the patients (p < 0.01 and p < 0.001, respectively). Neither BMDSPINE nor BMDMCB were related to the disease activity at the time of investigation. By contrast, BMDARM was decreased in patients with active disease. BMD in any of the three measured locations was not directly correlated to duration of the disease. However, the bone mass in the appendicular skeleton was already decreased within the first two years after the start of the disease. The overall functional capacity in terms of physical activity increased BMD in the axial skeleton. The local functional capacity in terms of grip strength was positively related to BMD in the appendicular skeleton. Patients with severe functional impairment had the lowest BMDARM. The decreased BMD in patients with rheumatoid arthritis seems primarily to be caused by an impaired physical activity which may be related to disease activity. Corticosteroids did not decrease BMD in neither the axial nor the appendicular skeleton. The antiinflammatory effect of steroids lead to clinical improvement, which may counteract the expected negative effect of these drugs on bone in rheumatoid arthritis.

Absorptiometry, Photon↗
PubMed1996

Changes in synovial membrane and joint effusion volumes after intraarticular methylprednisolone. Quantitative assessment of inflammatory and destructive changes in arthritis by MRI.

OBJECTIVE: To evaluate synovial membrane volumes, effusion volumes, and cartilage and bone erosion scores determined by magnetic resonance imaging (MRI) as markers of disease activity and severity in arthritis. METHODS: Gadolinium-DTPA enhanced MRI of 18 arthritic knees was performed before and 1, 7, 30 and 180 days after intraarticular methylprednisolone injection until clinical relapse. Intraobserver, interobserver, and inter-MRI variations were determined from 2 successive MRI of another 6 knees. RESULTS: In all knees synovial membrane and effusion volumes decreased within the first posttreatment week (median decrease 49 and 65%, respectively), and remained low during remission. Synovial volumes, but not effusion volumes, increased to pretreatment levels in case of clinical relapse, indicating that synovial volumes were most important to the clinical appearance. The intraobserver + interobserver + inter-MRI variation was maximally 26%. Total volumes and volumes in a selected sagittal slice were highly statistically correlated. The duration of clinical remission in patients with rheumatoid arthritis (RA) was significantly inversely correlated to the pretreatment synovial volume (both total and "one slice" volumes), but not to the effusion volume, MRI or radiography scores of erosions or any clinical/laboratory variables. Cartilage and bone erosions, invisible by radiography, were visualized by MRI. No progressive erosive changes were observed. CONCLUSION: MRI-determined synovial and effusion volumes and MRI scores of cartilage and bone erosions are reproducible and may be sensitive measures of disease activity and severity in RA. The synovial volume may rather than the effusion volume determine clinical appearance. Both are influenced by the present inflammatory activity. The pretreatment synovial volume may have predictive value to treatment outcome in RA.

Adult↗
PubMed1995

Glucocorticoids inhibit the synthesis rate of type III collagen, but do not affect the hepatic clearance of its aminoterminal propeptide (PIIINP).

The aminoterminal propeptide of type III procollagen (PIIINP) is a marker of type III collagen metabolism. The serum concentration of PIIINP is increased during inflammation, probably reflecting stimulated biosynthesis of type III collagen. Serum PIIINP decreases during glucocorticoid treatment. This has been interpreted as an inhibited biosynthesis of type III collagen. However, circulating PIIINP is extracted by the liver, and the decrease in serum PIIINP may also be caused by an increased hepatic elimination. In the present study we investigated the influence of intravenous methylprednisolone on the serum PIIINP level in pigs combined with a simultaneous determination of the hepatic extraction of PIIINP. The serum level of PIIINP decreased by approximately 30% within 2 h following glucocorticoid injection (p < 0.01). The initial hepatic extraction ratio of PIIINP was 0.15 (range 0.05-0.33) and neither changed after administration of methylprednisolone nor differ from that of the controls. Injection of methylprednisolone did not influence the gel filtration profile. The results of this study confirm the previous finding of serum PIIINP being decreased following glucocorticoid administration, but disprove the hypothesis that alterations in the liver extraction of PIIINP explain the decrease.

Amino Acid Sequence↗
PubMed1995

The accuracy of MRI-determined synovial membrane and joint effusion volumes in arthritis. A comparison of pre- and post-aspiration volumes.

Magnetic resonance imaging (MRI) of 18 knees of patients with arthritis was performed before and immediately after arthrocentesis. Pre- and post-aspiration volumes were calculated by adding the outlined areas of synovium/effusion from a continuous series of gadolinium-DTPA-enhanced 5 mm transversal T1-weighted MR-images. The difference between MRI-determined and syringe-determined volumes of aspirated joint fluid was 0-7 ml, median 2 ml, corresponding to 0-18%, median 7%, of the pre-aspiration effusion volume. Synovial membrane volumes, determined before and after arthrocentesis varied 0-10 ml, median 3 ml (0-17%, median 7%). No significant systematic misinterpretation of the borderline between joint fluid and synovium was found. We conclude that effusion volumes and in all probability also synovial membrane volumes, can be determined by MRI with a maximal analytical error of approximately 20%. The acceptable accuracy of the method encourages further studies of the value of effusion and synovial membrane volumes as markers of the activity and/or severity of joint inflammation.

Adult↗
PubMed1995

Scoring of synovial membrane hypertrophy and bone erosions by MR imaging in clinically active and inactive rheumatoid arthritis of the wrist.

MRI-scores of synovial membrane hypertrophy and bone erosions of the RA-wrist are introduced. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) and conventional radiography (CR) of the wrist were performed in 16 patients with rheumatoid arthritis (RA) and 3 healthy controls. A MRI-score of synovial membrane hypertrophy was obtained by summation of gradings of synovial hypertrophy in 6 regions of the wrist. The score was significantly higher in wrists with than in wrists without clinical signs of active arthritis. The score was 0 in all healthy controls. Each bone of the wrist was assessed by MRI and CR with respect to bone erosions. Bone erosions were detected by MRI in 14 wrists in contrast to only 6 wrists by CR. In all patients the erosions were more numerous on MRI. The introduced methods may be useful quantitative measures of synovitis and early joint destruction in RA.

Adult↗
PubMed1995

Ultrasonography in arthritis of the knee. A comparison with MR imaging.

Ultrasonography (US) of the knee in gonarthritis was evaluated with gadolinium-DTPA-enhanced MR imaging as a reference. The study included 13 patients with gonarthritis, 2 patients with osteoarthritis and 5 healthy controls. Compared to MR, US identified 100% (12/12) of joint effusions, 100% (5/5) of Baker's cysts, 57% (8/14) of the synovial membranes of the suprapatellar recess and 38% (3/8) of bone erosions. No MR or clinical findings characterized the patients with ultrasonographically identifiable synovial membranes. Quantitative MR- and US-estimates of effusion, synovial membrane and cartilage thicknesses were correlated. The Spearman correlation coefficients were 0.87, 0.86 and 0.82, respectively. US reliably demonstrated joint effusions and Baker's cysts but showed lack of sensitivity for demonstration of the synovial membrane and bone erosions. When the synovial membrane was identifiable, the measurements of synovial thickness by US appeared precise. Cartilage evaluation by US seemed dependable. The clinical value was limited, because the weight-bearing areas were inaccessible.

Arthritis, Rheumatoid↗
PubMed1994

Fibromyalgia: a clinical challenge.

The syndrome of fibromyalgia includes an unusually large and heterogeneous number of symptoms apart from the core features of generalized pain and widespread tenderness. Widespread tenderness is the only objective criterion. There is no evidence that fibromyalgia is a disease of the muscles or a rheumatic syndrome. The experience from an Australian epidemic of fibromyalgia indicates that there is an important psychosomatic component in the pathogenesis. Probably, fibromyalgia is not a disease entity; rather, the symptoms reflect difficulties in coping with various types of environmental stress. Secondary to this, sleep disturbances, fatigue, a low level of physical activity and poor physical fitness may develop, rendering the patients susceptible to muscle pain and tenderness elicited by sleep disturbances. A vicious circle may be responsible for the chronicity of the syndrome. Identification of environmental factors and early intervention should be given a high priority.

Fatigue↗
PubMed1994

Synovial volume--a marker of disease severity in rheumatoid arthritis? Quantification by MRI.

Volumes of synovial membrane and joint effusion were determined by magnetic resonance imaging (MRI) in patients with inflammatory gonarthritis. Volumes were calculated by adding the outlined areas of synovium/effusion from a continuous series of gadolinium-DTPA-enhanced 5 mm transversal T1-weighted MR-images. Ten knees with clinically active gonarthritis (CAG), 8 knees with clinically inactive gonarthritis (CIG) and 5 healthy controls (HC) were examined. The synovial volume of CAG-, CIG- and HC-knees were significantly different. The median volumes were 79 ml, 21 ml and 3 ml, respectively. Synovial and effusion volumes were highly correlated. A selected sagittal one-slice volume showed a high correlation to the total volumes. The reliable quantification of synovial and effusion volumes could be useful in the assessment of disease severity and as an outcome measure to treatment.

Arthritis, Rheumatoid↗
PubMed1994

Dynamic gadolinium-enhanced MR imaging in active and inactive immunoinflammatory gonarthritis.

Dynamic T1-weighted FLASH MR imaging, obtained just after i.v. gadopentetate dimeglumine injection, and pre- and postcontrast T1-weighted spin-echo (T1-SE) MR imaging were performed to compare their information value with respect to inflammatory activity in immunoinflammatory gonarthritis. We examined 16 clinically active (CAG), 7 clinically inactive (CIG) and 4 healthy knees. The synovium of a preselected slice was outlined. Its area and relative signal intensity increase after gadopentetate dimeglumine on T1-SE and FLASH (at each time t) were calculated. The CAG knees showed a mean signal intensity increase on early dynamic FLASH images higher by far than the CIG knees, while no significant difference was found on spin-echo images obtained 5 to 15 min after contrast injection. The early signal enhancement probably reflects the perfusion and capillary permeability of the synovium. The area of synovium could differentiate between healthy and arthritic knees. Gadolinium-enhanced dynamic FLASH imaging may provide clinically useful information about the actual inflammatory activity of arthritic joints.

Adult↗
PubMed1993

Lymphatic clearance of synovial fluid in conscious pigs: the aminoterminal propeptide of type III procollagen.

The aminoterminal propeptide of type III procollagen (PIIINP) in serum is employed as a direct marker of fibrillogenesis. The balance between local fibrillogenesis and serum PIIINP is governed by the transport and possible degradation en route from tissue to circulation. In conscious pigs, we investigated the transport of PIIINP from the knee cavity into the circulation after intra-articular injection of radiolabelled PIIINP followed by sequential sampling of thoracic duct lymph, serum and urine. Clearance from the joint space was evaluated by external detection of 131I-HSA, used as co-tracer. Lymph samples were gel filtrated to assess possible lymphatic degradation of the intact PIIINP. 125I-PIIINP and 131I-HSA were found in thoracic duct lymph within 20 min of the intra-articular injection. Both isotopes had a biphasic appearance, with the first peak after 60 min and a larger peak after 150 min. During the 6 h observational period 18% of the injected PIIINP was found in the lymph. Gel chromatography of lymph showed the fast formation of a small fraction with a lower MW than that of PIIINP, which suggests that some degradation of PIIINP may occur through the lymphatics. The half-life of the joint clearance of HSA by bulk flow was assessed to be 8.3 h. The clearance of PIIINP from the joint was estimated to be equal to that of HSA, which indicates that PIIINP leaves the joint space by bulk flow as has been proposed for HSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Collagen metabolism during wound healing in rats. The aminoterminal propeptide of type III procollagen in serum and wound fluid in relation to formation of granulation tissue.

The aminoterminal propeptide of type III procollagen (PIIINP) in serum has been shown to correlate with fibrillogenesis, and thus to be a potential direct marker of type III collagen deposition. The aim of the study was to investigate the correlation between changes in serum PIIINP and formation of granulation tissue during pharmacological suppression. Granulation tissue was induced in rats by the implantation of viscose cellulose sponges. Pharmacological suppression was achieved by cyclophosphamide treatment. To distinguish between the isolated effect of cyclophosphamide and the influence of the weight loss caused by treatment, weight loss caused by starvation was investigated. In untreated rats, serum PIIINP and wound fluid PIIINP were related to formation of granulation tissue (serum: r = 0.58, p < 0.05; wound fluid: r = 0.56, p < 0.05). In rats treated with cyclophosphamide, collagen deposition and formation of granulation tissue were markedly reduced, as compared within the untreated rats (6% vs 33%, p = 0.01). Wound fluid PIIINP reflected the sparse collagen deposition (r = 0.48, p < 0.05), whereas serum PIIINP decreased (-35%, p < 0.01) and was not correlated with the formation of granulation tissue. In starved rats, with a weight loss of 8%, formation of granulation tissue, vascular density, and collagen deposition were not reduced. Wound fluid PIIINP reflected the formation of granulation tissue (r = 0.52, p < 0.05), whereas serum PIIINP remained unchanged despite normal formation of granulation tissue. Starvation of rats without implants caused a decrease in serum PIIINP (-33%(-)-48%, p < 0.01). We conclude that during cyclophosphamide treatment and after a moderate weight loss, serum PIIINP is not a valid marker of fibrillogenesis. However, in normal rats with free access to food, changes in serum PIIINP mirror fibrillogenesis. Furthermore, our study provides experimental evidence consistent with the hypothesis that wound fluid PIIINP directly mirrors the local formation of granulation tissue, independent of weight loss and cyclophosphamide treatment.

Animals↗
PubMed1993

Fate of circulating amino-terminal propeptide of type III procollagen in conscious pigs.

The amino-terminal propeptide of type III procollagen (PIIINP, M(r) 42,000) is a promising marker for the formation of type III collagen of granulation tissue in experimental and clinical studies. The disposal kinetics of circulating PIIINP is, however, almost unknown. In conscious pigs with a thoracic duct-venous shunt, 125I-labeled PIIINP was injected intravenously. The initial distribution volume was 2.2 liters, which was 1.7 times the plasma volume (P < 0.01). The disappearance curve was three-phased, with an initial steep decline (t1/2 58 min), followed by two slower phases (t1/2 239 min and 289 h). Consecutive gel filtrations showed that the initial slope of the plasma disappearance curve corresponded to the plasma clearance of the intact PIIINP. The initial plasma clearance was 26.5 ml plasma/min, whereas the urinary clearance was 8.7 ml plasma/min (P < 0.01). The other components of the plasma disappearance curve originated from the formation and disappearance of a high and a low molecular weight (MW) fraction as part of the degradation of PIIINP. The high MW fraction (approximately M(r) 90,000) was similar to a previously described, but not further characterized, PIIINP immunoreactive component. The existence of the low MW fraction (approximately M(r) 20,000) has not been reported before. The lymphatic recirculation of intact PIIINP was rapid, and the lymph-serum ratio was almost constant within 1 h of injection. We conclude that the t1/2 of circulating PIIINP is 58 min, that PIIINP escapes the circulation very quickly, and that the degradation of PIIINP includes at least two intermediary steps.

Animals↗
PubMed1993

Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate.

Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s-PIIINP changed significantly with age and pubertal development stages. For s-PIIINP, a peak was seen at 12 yr for girls and 13 yr for boys; no peak could be discerned for s-PICP. The prepubertal (Tanner stage 1) s-PICP value (mean +/- SD) for girls was 374 +/- 132 micrograms/L, the midpubertal value (stage 3) was 442 +/- 135 micrograms/L, and the postpubertal value (stage 5) was 203 +/- 103 micrograms/L. The mean s-PIIINP levels for girls were 9.1 +/- 2.4, 15.0 +/- 4.3, and 6.8 +/- 3.1 micrograms/L, respectively. For boys, levels were 362 +/- 119, 544 +/- 138, and 359 +/- 256 micrograms/L for s-PICP and 8.5 +/- 2.2, 14.5 +/- 5.0, and 8.6 +/- 3.8 micrograms/L for s-PIIINP (P < 0.001 for both propeptides in both boys and girls). There was, however, a large variation in normal values for both propeptides within the age groups and pubertal stages. There was a significant correlation of s-PICP and s-PIIINP levels to height velocity in girls (r = 0.35; P < 0.001 and r = 0.33; P < 0.001, respectively), while in boys, only s-PIIINP showed significant correlation to height velocity (r = 0.40; P < 0.001). In untreated girls with CPP, serum levels of s-PIIINP were elevated [PIIINP SD score (SDS), 2.13]. Levels of s-PICP were normal (PICP SDS, 0.39). Levels of both propeptides decreased within 2 months after initiation of therapy and remained below initial values (P < 0.01). The decrease in s-PIIINP after 2 months of therapy showed a significant correlation with the fall in height velocity SDS for chronological age after 6 months of therapy (r = 0.64; P < 0.01). We conclude that s-PIIINP and, to a lesser degree, s-PICP reflect growth in normal children, but due to the large variation, both propeptides seem unsuitable as markers for screening of growth disorders in children.

Adolescent↗
PubMed1992

Purification of porcine aminoterminal propeptide of type III procollagen from lymph and use for lymphatic clearance studies in pigs.

To investigate the lymphatic transport of the aminoterminal propeptide of type III procollagen (PIIINP) we established a thoracic duct-venous shunt in 6 pigs. Porcine PIIINP was purified, characterised, and compared with human PIIINP to ensure the suitability of the radioimmunoassay of human PIIINP for measurements in pigs. SDS-PAGE and radioimmunoinhibition assays show human and porcine PIIINP to be similar, thus indicating that the assay of human PIIINP is also reliable for determinations on pig serum and lymph. Intact PIIINP, as identified by gel filtration, accounted for 60% and 40% of the total PIIINP immunoreactivity in lymph and serum, respectively. The higher amount of total immunoreactivity and proportion of intact PIIINP in lymph compared with serum support the hypothesis that intact PIIINP is transported from peripheral tissue into the circulation by lymph. Two days after the shunt was established, the lymph was collected quantitatively hour-by-hour for 24 h. The flow was higher during the light periods than in the dark (p less than 0.01). The PIIINP concentration varied inversely with the flow, being higher in the dark hours (p less than 0.03). However, the total collected amount of PIIINP in lymph did not differ during the light and dark periods. Serum PIIINP remained unchanged over the 24 h. The lymphatic clearance of total PIIINP immunoreactive components was 6.2 ml serum/min and the lymphatic clearance of intact PIIINP was 9.1 ml serum/min, equal to 7 and 10 times the plasma volume/24 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Prognosis in glomerulonephritis. III. A longitudinal analysis of changes in serum creatinine and proteinuria during the course of disease: effect of immunosuppressive treatment. Report from Copenhagen Study Group of Renal Diseases.

A total of 395 consecutive patients with biopsy-proven glomerulonephritis were followed up for 14 years. At the time of entry to the study the patients were classified as having one of nine states of kidney disease according to serum creatinine levels and proteinuria. The transitions of the patients between the nine states were analysed. The influence of 14 independent variables including treatment with cytostatic drugs and prednisolone was estimated by the Cox proportional hazard model. Treatment with immunosuppressive drugs had an influence that emerged within the first month and continued for the next 2 months. Subsequent treatment with cytostatic drugs in combination with prednisolone delayed further improvement. Treatment with prednisolone or cytostatic drugs as single therapy for up to 6 months increased the risk of improvement of the disease, and had no significant effect on deterioration. The beneficial effect of the treatment persisted after withdrawal of the immunosuppressive drugs. The analysis revealed only a slight influence of the histological character of the glomerular changes. Post-streptococcal glomerulonephritis carried an increased tendency for improvement. Arterial hypertension affected the process in several states of kidney disease. Heavy proteinuria increased the risk of increasing serum creatinine levels.

Azathioprine↗
PubMed1992

Metabolism of the aminoterminal propeptide of type III procollagen in cultures of human proximal tubular cells.

Degradation of the intact form of the aminoterminal propeptide of type III procollagen (PIIINP) has been established in the liver, whereas the col 1 domain of PIIINP is extracted by the kidneys. We used native human PIIINP and col 1 domain of PIIINP to investigate the degradation of PIIINP in cultures of human proximal tubular cells. Normal renal tissue was obtained from the healthy part of kidneys surgically removed and from biopsies from a total of 10 patients. The degradation was characterized by incubation of [125I]-PIIINP followed by gel filtration. We found that in physiological concentrations (4.4 micrograms l-1 and 11.9 micrograms l-1 intact PIIINP was almost totally degraded, but not col 1 domain. High concentrations of PIIINP (20-50 micrograms l-1) had a non-linear, non-monoexponential degradation over time, which suggests several steps. Gel filtration of [125I]-PIIINP after 1 h, 3 h, 6 h and 24 h of incubation confirmed the observation by showing the rapid formation of a high-molecular-weight fraction, followed by the slower formation of a low-molecular-weight fraction. The high-molecular-weight fraction was PIIINP immunoreactive, but not the low-molecular-weight fraction. We conclude that cultures of human proximal tubular cells degrade intact human PIIINP by the formation of high- and low-molecular-weight fractions. Earlier findings that extraction of the PIIINP col 1 domain takes place in the kidneys, cannot be explained by degradation by the proximal tubular cells.

Cells, Cultured↗