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Biomedical subjects

K Hørslev-Petersen

Publications and source records attributed to K Hørslev-Petersen.

At least 19 recordsLinked to original sources

Low-cost, low-field dedicated extremity magnetic resonance imaging in early rheumatoid arthritis: a 1-year follow-up study.

OBJECTIVE: To study the ability of low-cost low-field dedicated extremity magnetic resonance imaging (E-MRI) to assess and predict erosive joint damage in the wrist and metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis. METHODS: 24 previously untreated patients with rheumatoid arthritis with joint symptoms for <1 year were evaluated at the time of diagnosis and after 6 and 12 months of methotrexate treatment with conventional clinical or biochemical examinations, x rays of both hands and wrists, and E-MRI of the dominant wrist and MCP joints. RESULTS: At baseline, all patients showed magnetic resonance imaging (MRI) synovitis, and MRI erosions were detected in 21 bones (10 patients). 6 (29%) of these, distributed among two patients, were seen on x ray. One x ray erosion was not detected by MRI. At 1 year, MRI and x ray detected 15 and 8 new erosions, respectively, and 19% of MRI erosions at baseline had progressed to x ray erosions. In bones with MRI erosions at baseline, the relative risk of having x ray erosions at the 1-year follow-up was 12.1, compared with bones without baseline MRI erosions (lesion-centred analysis). If bones with baseline x ray erosions were excluded, the relative risk was 5.2. In patients with baseline MRI bone erosion or oedema, the relative risk of having x ray erosions at 1 year was 4.0, compared with patients without these signs at baseline (patient-centred analysis). CONCLUSION: In this group of patients with early rheumatoid arthritis who were treated uniformly, baseline E-MRI erosions in MCP or wrist bones markedly increased the risk of x ray erosions at the 1-year follow-up. Low-cost, low-field dedicated extremity MRI is promising for assessment and prognostication of early rheumatoid arthritis.

Adult↗

Low field dedicated magnetic resonance imaging in untreated rheumatoid arthritis of recent onset.

OBJECTIVE: To compare a low field dedicated extremity magnetic resonance imaging system (E-MRI) with x ray and clinical examination, in the detection of inflammation and erosive lesions in wrist and metacarpophalangeal (MCP) joints in newly diagnosed, untreated rheumatoid arthritis (RA). PATIENTS AND METHODS: Twenty five patients (disease duration < or =1 year) and three healthy controls entered the study. An x ray examination and MRI (before and after intravenous injection of a contrast agent) of the 2nd-5th MCP joints and the wrist was performed. The number of erosions on x ray examination and MRI was calculated, and synovitis in the MCP joints and wrists was graded semiquantitatively. RESULTS: E-MRI detected 57 bone erosions, whereas only six erosions were disclosed by x ray examination (ratio 9.5:1). Synovial hypertrophy grades were significantly higher in RA joints with clinical signs of joint inflammation-that is, swelling and/or tenderness (median 3, 5th-95th centile 1-4) than without these clinical signs (median 2, 5th-95th centile 1-3), p < 0.001. 51% of the joints without clinical signs of synovitis showed synovial hypertrophy on E-MRI. There was a positive correlation between MRI scores of synovitis and the number of erosions detected by MRI in the MCP joints (Spearman r(s) = 0.31, p < 0.01). No healthy controls had erosions or synovitis on MRI. CONCLUSION: Joint destruction starts very early in RA and E-MRI allows detailed evaluation of inflammatory and destructive changes in wrists and MCP joints in patients with incipient RA.

Adult↗

[Leflunomide for active rheumatoid arthritis].

In 1999, leflunomide was introduced for the treatment of active rheumatoid arthritis. Leflunomide is a reversible inhibitor of "de novo" synthesis of pyrimidine, resulting in a restriction of lymphocyte proliferation. The pharmacodynamics are characterized by slow elimination. Leflunomide has shown an efficacy and a pattern of mild and serious side effects similar to methotrexate and sulphasalazine. Treatment is started with a loading dose of 100 mg orally for three days followed by 20 (10) mg daily. Regular haematological measurements, determination of serum chemistry and blood pressure should be performed every second week the first six months, subsequently every sixth week. If the treatment is to be terminated abruptly, a drug elimination procedure must be performed. Leflunomide will find its place in the treatment of rheumatoid arthritis. Leflunomide should follow an unsuccessful treatment attempt with methotrexate or sulphasalazine.

Administration, Oral↗

Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease activity.

OBJECTIVE: YKL-40, also called human cartilage glycoprotein-39, is secreted by chondrocytes, synovial cells, macrophages and neutrophils. Studies have shown that YKL-40 is an autoantigen in rheumatoid arthritis (RA). We evaluated whether serum YKL-40 was related to disease activity in patients with RA. METHODS: Serum YKL-40 was determined by radioimmunoassay in 156 patients with RA during a 1 yr longitudinal study. RESULTS: Serum YKL-40 was increased in 54% of the patients with clinically active disease. Patients with clinically active disease initially who became inactive after 12 months had a significant decrease in serum YKL-40 (-30%, P < 0.002) and patients who changed from inactive to active disease had an increase in serum YKL-40. Patients who remained active had unchanged serum YKL-40 during the study. Serum YKL-40 decreased rapidly (-24% after 7 days, P < 0.01) during prednisolone therapy, and more slowly in patients treated with methotrexate only (-15% after 60 days, P < 0.01). Patients with early RA (disease duration < 3 yr, n = 50) and a persistently elevated serum YKL-40 were at risk of radiological disease progression as determined by Larsen score. CONCLUSION: Serum YKL-40 varies according to disease activity in RA, but provides in some respect information different from conventional markers. Our previous studies are consistent with a local release of YKL-40 in the arthritic joint followed by a secondary increase in serum YKL-40. YKL-40 may prove to be a new tool for the study of disease activity and pathophysiology of RA.

Adipokines↗

Blood levels of CD11b+ memory T lymphocytes are selectively upregulated in patients with active rheumatoid arthritis.

The adhesion molecules CD11b (a beta2-integrin component) and CD54 (ICAM-1) on blood leukocytes were studied by flow cytometry in patients with rheumatoid arthritis (RA). The fractions of CD4+ cells co-expressing CD11b were elevated in 16 patients with active RA compared with those in 16 RA patients who improved during therapy and 8 healthy controls: 0.8+/-0.12% (mean+/-SEM) versus 0.3+/-0.06% (p<0.002) and 0.3+/-0.06% (p<0.005), respectively. Increased levels of CD11b+CD45R0+ cells were observed in patients with active RA compared to those with improved RA and controls: 12.6+/-3.9% versus 4.8+/-2.7% (p<0.002) and 6.1+/-1.2% (p<0.003), respectively. Disease activity, determined by C-reactive protein, correlated with the numbers of CD11b+CD45R0+ cells: r=0.62 (p<0.001). Seven patients were followed during induction of remission with methotrexate and glucocorticoids. The numbers of CD11b+CD4+ and CD11b+CD45R0+ cells fell significantly after clinical improvement. The levels of CD11b+CD14+ cells (monocytes) did not differ between the groups. The number of CD11b+CD15+ cells (neutrophils) was elevated in patients with RA irrespective of disease activity. The levels of CD54+ cells were not different between the RA and control groups. We conclude that the increased numbers of CD11b+ memory T cells may arise from exposure to stimuli outside the synovial compartment.

Adult↗

Bone metabolism in patients with systemic lupus erythematosus. Effect of disease activity and glucocorticoid treatment.

The bone metabolism in patients with systemic lupus erythematosus (SLE) has previously been examined, but the results are conflicting. In the present study the bone mineral density (BMD) of the axial and the appendicular skeleton was examined by means of dual energy x-ray absorptiometry. The bone turnover was evaluated by means of biochemical markers in serum and urine in a prospective cohort consisting of 36 female and male SLE patients. Repeated measurements of BMD were performed for up to two years. The BMD was decreased in the hand and in the femoral neck but normal in the spine and in the distal forearm. A weak correlation was found between the BMD of the femoral neck and the total consumption of glucocorticoids. Apart from this finding the BMD was uninfluenced by treatment with glucocorticoids and cyclophosphamide. No significant changes of BMD were found during the follow-up period. The serum concentration of the carboxyterminal cross-linked telopeptide of type I collagen was increased in almost all patients, but no other biochemical markers of bone metabolism were abnormal.

Absorptiometry, Photon↗

Serum aminoterminal propeptide of type III procollagen after cardiac transplantation and the effect of rejection.

The present study examines serum concentrations of the aminoterminal propeptide of type III procollagen (S-PIIINP), a marker of type III collagen synthesis, after heart transplantation, and assesses changes induced by rejection. Fourteen transplant patients were included with 12 coronary artery bypass patients serving as controls. Mild to moderate rejection was found in 44 biopsies, and severe rejection in 6. Two severe rejection incidents occurred before postoperative day 10, the remainder at postoperative days 23 to 57. S-PIIINP was elevated in transplant patients at postoperative days 1 to 7 (p < or = 0.01), with return to baseline at postoperative day 60 (p = 0.14, n = 6). S-PIIINP remained unchanged after mild to moderate rejection, but increased 1 to 2 weeks following severe rejection occurring after postoperative day 10. S-PIIINP was elevated in bypass patients from postoperative day 2 throughout the study period of 360 days (p < or = 0.01). Thus, type III collagen turnover after heart transplant and coronary artery bypass grafting resembles wound healing. Collagen synthesis after severe rejection is reflected by S-PIIINP approximately 2 weeks after transplant. The findings may prove to be significant concerning the prognosis of heart transplant patients.

Adult↗

Procollagen type I N-terminal propeptide (PINP) as an indicator of type I collagen metabolism: ELISA development, reference interval, and hypovitaminosis D induced hyperparathyroidism.

A sandwich enzyme-linked immunosorbent assay (ELISA) for quantification of the N-terminal propeptide of human procollagen type I (PINP) utilizing purified alpha 1-chain specific rabbit antibodies is described. The ELISA measured the content of the alpha 1-chain of PINP independent of the molecular form of the molecule. A parallelism was found between amniotic fluid (calibrator), normal and patient serum, and purified PINP (alpha 1), as well as the high and low molecular weight forms of PINP (alpha 1). The concentration of PINP in the calibrator (second trimester amniotic fluid) was determined to 25 micrograms/mL and the detection limit was 62 pg/mL measured in amniotic fluid, and 41 pg/mL measured in serum. The interassay coefficients of variation were 4.6% (low control) and 5.3% (high control), and the corresponding intraassay parameters were 2.9% and 4.9%. Recovery studies revealed an accuracy between 93% and 105%. The normal range (n = 57) for PINP was 56 ng/mL (median) the 10th and 90th centiles being 30 and 82 ng/mL, respectively. Patients with hyperparathyroidism due to hypovitaminosis D had median serum level of 168 ng/mL with a 10th centile of 44 ng/mL and a 90th centile of 450 ng/mL, these values being significantly different from the normal range (p < 0.001). The PINP-ELISA was superior to commercially available assays for PICP and osteocalcin in separation between healthy controls and patients with osteomalaci.

Adult↗

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↗

Urinary hydroxypyridinium cross-links of collagen in rheumatoid arthritis. Relation to disease activity and effects of methylprednisolone.

Pyridinoline (Pyr) and deoxypyridinoline (Dpyr) are new markers of type I and II collagen degradation. Dpyr is a specific marker of type I collagen resorption in bone, whereas Pyr is released from type I and II collagen in bone and cartilage. We assessed the effect of six repeated iv methylprednisolone (MP) pulses or placebo at 4 week intervals in combination with DMARDs, on the excretion of Pyr and Dpyr in 86 patients with active RA. Pyr and Dpyr correlated significantly with clinical and biochemical markers of disease activity. After an initial decrease in Pyr on day 7 in the MP treated group, Pyr was significantly increased in both treatment groups at day 28. Dpyr remained unchanged after a single MP pulse in contrast to significant increases after 7 and 28 days in the placebo group. Pyr and Dpyr were significantly decreased after 24 and 52 weeks in the MP group, whereas no changes were observed in the placebo group. Pyr and Dpyr correlate with clinical and biochemical markers of disease activity in patients with active RA. Repeated MP pulses in combination with DMARDs in RA, do not seem to have a deleterious effect on bone resorption measured by Dpyr excretion, on the contrary MP pulses may even prevent an increase in bone resorption, as indicated by the decreased Dpyr observed in this group.

Adult↗

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↗

Collagen types I and III propeptides as markers of healing in chronic leg ulcers. A noninvasive method for the determination of procollagen propeptides in wound fluid--influence of growth hormone.

A noninvasive method allowing measurements of the propeptides of collagen type III (PIIINP) and type I (PICP) in ulcer washings was developed. The response to topical human growth hormone was examined. Fourteen patients with venous ulcers were treated sequentially with human growth hormone (0.1, 0.25, and 1 IU/cm2/day), each dose for 1 week, followed by 1 week washout. On alternate days, three and two times during treatment and washout periods, respectively, the ulcers were washed and incubated for 30 minutes with sterile water. No changes in healing rates in relation to growth hormone application were observed. In contrast, PIIINP increased significantly to 168% (154% to 184%) (mean, 95% confidence interval) and 195% (179% to 218%) 5 and 9 days, respectively, after start of treatment, (p < 0.01). Propeptides of collagen type I reached a significant increase, to 196% (172% to 232%), in the fourth week, (p < 0.01). The areas under the curves of PICP and PIIINP correlated significantly with the healing rates (r = 0.57, p = 0.04; and r = 0.64, p = 0.01, respectively). The authors conclude that propeptide measurements may be useful markers of healing in clinical studies.

Administration, Topical↗

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↗

Hepatic extraction of the aminoterminal propeptide of type III procollagen before and after bile duct ligation in pigs.

The aminoterminal propeptide of type III procollagen is extracted from the circulation by the liver, and PIIINP is found in bile. This study was performed in order to investigate whether biliary excretion contributes substantially to the hepatic extraction of circulating PIIINP. Hepatic extraction before and during a 4-h period after ligation of the common bile duct was assessed from serum PIIINP concentrations in a systemic artery, the portal vein and a hepatic vein of seven healthy anaesthetized pigs. Seven sham-operated anaesthetized pigs served as controls. Ligation of the bile duct did not cause a decrease in the hepatic extraction ratio of circulating PIIINP. The PIIINP serum levels of the cholestatic pigs and of the controls were similar throughout the investigation period. The PIIINP concentrations in bile were only 10% of the corresponding serum values. Gel filtration of sera showed that the lower PIIINP concentration in the hepatic vein, as compared to the artery and the portal vein was due to a selective decrease in the concentration of the intact propeptide. The study shows that biliary excretion does not contribute significantly to the hepatic extraction of circulating PIIINP in the normal liver. Furthermore, the hepatic extraction of circulating PIIINP preferentially affects the intact propeptide, rather than the somewhat larger PIIINP related molecule in serum.

Animals↗

Procollagen type III aminoterminal peptide in serum in idiopathic myelofibrosis and allied conditions: relation to disease activity and effect of chemotherapy.

The serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) was measured serially in patients with idiopathic myelofibrosis and other myeloproliferative syndromes. Two different assays were applied, the RIA-gnost assay (Hoechst, Frankfurt, FRG) and a new equilibrium RIA for the N-terminal propeptide of human type III procollagen (Farmos Diagnostica, Oulu, Finland). A positive correlation was found between the results obtained by the two RIA's (rho = 0.90, P less than 0.001). The highest propeptide levels were recorded in patients with idiopathic myelofibrosis, particularly in those with active disease. Elevated serum PIIINP levels decreased during treatment with various cytotoxic drugs, including intensive chemotherapy. By contrast, serum PIIINP was unchanged or increased in patients undergoing interferon alpha-2b therapy. Gel filtration of sera on Sephacryl S-300 column (Pharmacia, Sweden) showed that smaller PIIINP related peptides dominated in healthy subjects and in osteomyelosclerosis with stable disease. Conversely, the relative proportion of intact propeptide increased in accelerating disease stages and acute myelofibrosis. In conclusion, the present study implicates serum PIIINP as a useful indicator of disease activity in idiopathic myelofibrosis. The propeptide also appears to be a sensitive sero-marker of chemotherapy effect on fibrogenesis related to clonal myeloproliferation. Finally, the propeptide is suggested as an early predictor of relapse during cytotoxic therapy.

Acute Disease↗

Splanchnic and renal extraction of circulating type III procollagen aminoterminal propeptide in patients with normal liver function and in patients with alcoholic cirrhosis.

Splanchnic and renal extraction of circulating aminoterminal propeptide of type III procollagen and related antigens were studied in 12 patients with normal liver function and in 19 patients with alcoholic cirrhosis during catheterization. Type III procollagen peptide in serum was measured in two assays: the Type III Procollagen Peptide Radioimmunoassay Kit, a new assay that selectively determines the intact propeptide (and larger type III propeptide-holding antigens) and the Type III procollagen Fab assay that measures both the intact propeptide and the smaller fragments that quantitatively dominate in serum. A significant decrease in the concentration of the intact propeptide between the artery and the hepatic vein was found in the group with normal liver function (p less than 0.01) and in patients with cirrhosis (p less than 0.01). In patients with cirrhosis, however, the splanchnic extraction ratio of the intact propeptide (median = 0.04, range = -0.03 to 0.16) was significantly lower than in patients with normal liver function (median = 0.17, range = 0.05 to 0.36, p less than 0.01). The concentration of the intact propeptide in the hepatic vein was positively correlated to hepatic pressure (n = 18, r = 0.51, p less than 0.05) and inversely correlated to indocyanine green clearance (n = 15, r = -0.61, p less than 0.05). No splanchnic extraction could be demonstrated in the Type III propeptide Fab assay. A significant renal extraction was found in the Fab assay, but not in Type III Procollagen Peptide Radioimmunoassay Kit.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗