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P Junker

Publications and source records attributed to P Junker.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2004

IVIG treatment for progressive stroke in the primary antiphospholipid antibody syndrome.

A 32-year old woman with antiphospholipid antibody syndrome (APS) developed severe thrombocytopenia, elevated liver enzymes and progressive cerebral thrombosis a few days after preterm delivery by caesarean section. Her condition deteriorated despite treatment with low dose aspirin, anticoagulation by heparin and iv glucocorticoid administration. Intravenous immunoglobulin (IVIG) on three consecutive days was followed by rapid resolution of her neurological impairment and increasing platelets counts. The temporal association between IVIG and reversal of both neurological impairment and platelet number strongly indicates a specific effect of IVIG administration in this condition. It is proposed that IVIG therapy is considered as a therapeutic option in APS patients with progressive cerebral infarction despite optimal use of anticoagulant and immunomodulating agents.

Adult↗
PubMed2004

A putative regulatory polymorphism in PD-1 is associated with nephropathy in a population-based cohort of systemic lupus erythematosus patients.

The association between polymorphisms in the programmed death (PD-1) gene and susceptibility to systemic lupus erythematosus (SLE) was determined using genomic DNA, isolated from a population-based cohort of 95 SLE patients and 155 healthy controls. Polymorphisms in the complete PD-1 gene except the large intron 1 were detected by sequencing. Furthermore, the patients were stratified according to the presence or absence of lupus nephropathy. The influence of the detected single nuclear polymorphisms (SNPs) on this specific clinical disease parameter was determined. In total, we identified 12 single nucleotide polymorphisms, of which six were novel and eight were considered to be rare (the frequency of the minor allele of these was less than 1% in our study populations). We found a significant association of an intronic 6867C/G SNP in the PD-1 gene with the presence of lupus nephropathy. As the 6867C/G SNP is located in a putative binding site for the transcriptional repressor ZEB, the associated allele of this SNP potentially alters the transcriptional regulation of PD-1. This report, for the first time, indicates that a 6867C/G SNP of the PD-1 gene is associated with lupus nephropathy in Caucasian SLE patients.

Adolescent↗
PubMed2004

Autoantibodies and self-reported health complaints in relatives of systemic lupus erythematosus patients: a community based approach.

First-degree relatives (FDRs) and spouses to a population-derived cohort of lupus patients were investigated for the occurrence of selected autoantibodies and self-reported health complaints. A healthy reference population was included. The lupus population consisted of 103 index cases. A total of 275/375 available relatives accepted to enter the study. Two hundred and twenty-six/315 (72%) were FDRs and 49/60 (82%) were spouses. Serum was analysed for ANA using indirect immunofluorescence on Hep-2 cells at the following dilutions: 1:40, 1:80 and 1:160 and in addition sera were tested for anti-dsDNA, IgM RF, ACA (IgM, IgG), anti-beta2GPI (IgM, IgG) and antibodies to prothrombin. ANA positivity occurred more frequently in FDRs compared with spouses and controls at serum dilution 1:160 (10 versus 0% and 2.5%, respectively, P = 0.04 and P < 0.01), 1:80 (24 versus 4% and 5%, respectively, P = 0.003 and P < 0.001) and 1:40 (31 versus 10% and 10%, respectively, P = 0.006 and P < 0.0001). ANA positivity in FDRs occurred randomly, irrespective of family relationship. Fifty-three/184 versus 2/32 FDRs to patients with definite SLE (D-SLE) and incomplete SLE (I-SLE), respectively, tested ANA positive at 1:80 (P < 0.05). FDRs with ANA titer at 80 were affiliated to lupus probands with high SLICC scores (P < 0.05). Self-reported health complaints, cardiovascular/thromboembolic events in particular, were more frequent among FDRs than in spouses. The population-based approach adopted in the present study supports previous clinic-based evidence of an increased propensity for autoantibody occurrence in relatives to SLE patients. In FDRs, present ANA positivity was associated with increased prevalence of health complaints and ANA positivity in FDRs was related to the criterial burden and cumulated damage in corresponding lupus probands. The low ANA frequency among spouses of SLE patients argues against a significant autoantibody triggering effect of shared environment in adult life.

Adult↗
PubMed2003

Connective tissue responses in acute community-acquired pneumonia.

Circulating connective tissue components including the aminoterminal propeptides of type III collagen (PIIINP), type I collagen (PINP) and hyaluronan were determined in patients hospitalised for pneumonia of suspected bacterial origin. Ninety patients were included, 64 of these were followed prospectively for up to 21 days after initiation of therapy. Serum PIIINP was determined by RIA, s-PINP by ELISA, and s-hyaluronan by a radiometric assay. S-PIIINP rose significantly above the zero value within 24 h in both pneumococcal pneumonia (T0: 5.3 microg/l, 95% CI: 2.7-8.1 microg/l vs. T1: 6.7 microg/l, 95% CI: 3.8-9.1, P<0.01) and in pneumonia of unknown aetiology (T0: 4.0 microg/l, 95% CI: 3.6-4.8 vs. T1: 4.5 microg/l, 95% CI: 3.8-5.1, P<0.05) followed by a gradual decline. At T1, S-PIIINP was higher in pneumococcal pneumonia compared with pneumonia of unknown aetiology (P<0.05). By contrast, s-PINP tended to decline within 24 h in both pneumococcal pneumonia (T1: 30 microg/l, 95% CI: 23-40, ns) and in pneumonia of unknown aetiology (T1: 32 microg/l, 95% CI: 22-42, ns) followed by a steady increase. The PINP antigen size distribution remained constant throughout the follow-up period. S-hyaluronan in pneumococcal pneumonia paralleled s-PIIINP reaching a peak value on day 1 (121 microg/l, 95% CI: 65-191, P=0.38). There was a positive correlation between s-PIIINP and C-reactive protein (CRP). The study demonstrates, that community-acquired pneumonia elicits a differentiated mesenchymal response, which is turned down in response to successful antibiotic therapy.

Acute Disease↗
PubMed2002

Evaluation of the optimum dose of growth hormone (GH) for restoring bone mass in adult-onset GH deficiency: results from two 12-month randomized studies.

OBJECTIVE: To establish the optimum GH dose for restoring bone mineral density (BMD) in adult-onset GH deficiency (GHDA). DESIGN: Two separate randomized, controlled clinical trials. PATIENTS: Fifty-eight adults aged 45.1 (20-64) years with severe GHDA were followed in two 12-month studies. In the first study, patients were randomized to placebo or GH 1.7 IU/m2/day and in the second study GH 0.5 IU/m2/day or 1.0 IU/m2/day. MEASUREMENTS: BMD of the spine, hip, forearm and whole body was measured at 0 and 12 months. Alkaline phosphatase (AP) and collagen markers serum C-terminal propeptide of type I collagen (PICP), type I collagen telopeptide (ICTP) and N-terminal propeptide of type III collagen (PIIINP) were measured at baseline and every 3 months. RESULTS: Biochemical markers of skeletal and soft tissue collagen increased significantly and remained elevated throughout the study period. BMD changes depended on site, dose and gender. In placebo-treated patients, spinal BMD declined by 2.5%. At the low and medium doses, BMD increased by 2.4 and 3.1%, respectively, while a nonsignificant 0.2% decrease was seen with high dose. Forearm BMD decreased by 4.9% (P < 0.05) with high-dose treatment but remained unchanged at lower doses. Males showed larger gains in BMD, but the dose-response relationship was similar in males and females. CONCLUSION: A GH dose of 0.5-1.0 IU/m2/day (4-9 micro g/kg/day) stimulated bone remodelling and increased BMD over 12 months in patients with severe GHDA, irrespective of gender. A higher dose (1.7 IU/m2/day congruent with 15 micro g/kg/day) was associated with initial declines in forearm and whole-body BMD.

Adenoma↗
PubMed2001

Association of mannose-binding lectin gene variation with disease severity and infections in a population-based cohort of systemic lupus erythematosus patients.

This study describes the importance of mannose-binding lectin (MBL) variant alleles for systemic lupus erythematosus (SLE) and accompanying infections in a population-based cohort. MBL alleles were determined in 99 SLE patients recruited from a representative Danish region. Patients were classified according to the 1982 revised ACR criteria as definite SLE (D-SLE) (n = 77) fulfilling > or =4 criteria and incomplete SLE (I-SLE) (n = 22) with 0.99, respectively). A meta-analysis of eight previously published studies suggested that the presence of MBL variant alleles confer a 1.6 times overall increased risk for D-SLE (P < 0.00001). MBL variant allele carriers had higher disease activity (SLEDAI-index) in a 2-year follow-up period (P = 0.02) and had an increased risk of acquiring complicating infections in general (P = 0.03) and respiratory infections in particular (P = 0.0006). Only in SLE patients fulfilling > or =4 ACR criteria an increased frequency of MBL variant alleles was found. MBL variant alleles were also associated with increased risk of disease activity and of complicating infections indicating that the MBL gene is an SLE disease modifier locus.

Adolescent↗
PubMed2001

Collagen metabolites in the peripheral and splanchnic circulation of patients with Crohn disease.

BACKGROUND: Fragments of collagen arising during synthesis and breakdown have been suggested as markers of fibrous tissue remodelling in Crohn disease. We compared serum concentrations of the C-terminal propeptide of collagen I (PICP), the N-terminal propeptide of collagen III (PIIINP) and the C-terminal telopeptide of type I collagen (ICTP) in the splanchnic and systemic circulation in Crohn disease requiring segmental intestinal resection. METHOD: 15 consecutive patients undergoing surgery due to strictures or continuous inflammation. Male:female ratio was 6:9. Blood was drawn from a peripheral vein prior to surgery. Immediately before intestinal resection, additional samples were drawn from the antecubital vein and from a mesenteric vein draining the affected intestinal segment. PIIINP, PICP and ICTP were measured with radioimmunoassays. RESULTS: Pre-surgery S-ICTP (median 5.5 microg/L; range 3.2-17.2 microg/L) was significantly increased in peripheral blood compared with healthy controls (median 2.6 microg/L; range 0.6-5.7 microg/L), P < or = 0.05. By contrast, S-PICP (median 98 microg/L; range 62-137 microg/L) and S-PIIINP (median 2.5 microg/L; range 1.2-7.4 microg/L) were significantly lower than S-PICP (median 133 microg/L; range 66-284 microg/L) and S-PIIINP (median 3.4 microg/L; range 1.0-7.1 microg/L) in healthy controls, P < or = 0.05. During surgery. no difference in S-PICP and S-PIIINP was documented between peripheral blood and splanchnic blood. In contrast, S-ICTP was increased in splanchnic blood (median 6.2 microg/L; range 2.7-17.4) compared to peripheral blood (median 5.0 microg/L; range 3.1-13.4) (P=0.05). CONCLUSION: The present study provides further evidence that the altered intestinal collagen metabolism in Crohn disease is reflected in the local and systemic circulation.

Adult↗
PubMed2001

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↗
PubMed2001

Renal crisis in asclerodermic scleroderma--lupus overlap syndrome.

A 24-year-old woman with overlapping features of sclerodermia sine scleroderma and systemic lupus erythematosus (SLE) presented with rapidly accelerating hypertension accompanied by neuropsychological deficits and tonic-clonic seizures. Kidney biopsy showed severe intimal hyperplasia of small renal arteries but no glomerulonephritis. Following treatment with ACE inhibitor, prednisolone and cyclophosphamide complete remission was achieved with minimal brain damage and normal kidney function. Anti-RNA polymerase I, II and III antibodies have remained positive during follow-up for 2 years, suggesting a linkage with the underlying pathogenetic pathway.

Adult↗
PubMed2000

Willingness to pay for arthritis symptom alleviation. Comparison of closed-ended questions with and without follow-up.

OBJECTIVE: To compare two methods of measuring willingness to pay (WTP): closed-ended questions with and without follow-up. METHODS: A measurement experiment based on dichotomous choice contingent valuation survey data is reported. Marginal WTP estimates for alleviation of rheumatoid arthritis symptoms resulting from treatment with a novel anti-rheumatic agent, cA2 (TNF-alpha blockade), were calculated. Monte Carlo simulations were undertaken to evaluate the methods with respect to their statistical power. RESULTS: The estimated marginal WTP values using closed-ended questions with and without follow-up were DKK 637 (US $91) and DKK 1,268 (US $181), respectively. A Wilcoxon's signed-rank test showed that the difference of DKK 631 was significant. Moreover, including a follow-up question increases the precision of the result. Monte Carlo simulations showed that trade-offs between power (i.e., the probability of a correct rejection of a false null hypothesis), efficiency, and size may exist in the two models. CONCLUSIONS: There was a significant difference between the WTP estimates when using closed-ended questions with and without follow-up. When choosing between the models, however, power, efficiency, and size could be used as selection criteria.

Adult↗
PubMed1999

[Systemic lupus erythematosus in the county of Fynen. An epidemiologic study].

The incidence and prevalence of systemic lupus erythematosus (SLE) has never been investigated in Denmark, whereas international studies have reached divergent results. In the study patients were ascertained from diagnosis-based registers of inpatients and outpatients, notifications from physicians, and an autoimmune register. Diagnoses were validated and patients classified according to the American College of Rheumatology criteria: definite SLE (D-SLE) > or = 4 and incomplete SLE (I-SLE) < 4 criteria. The point prevalence as of Jan. 1, 1995, was 21.7/100,000 (CI 95% 17.3-26.8) for D-SLE and 5.2/ 100,000 (CI 95% 3.2-8.0) for I-SLE. The mean annual incidence in 1990-94 was 2.5/100,000 (CI 95% 1.8-3.3). Figures for annual incidence and prevalence were in accordance with recent British reports but considerably lower than Swedish and Icelandic results. Although methodological issues should be considered, the results point to a different distribution of SLE in otherwise closely related nationalities.

Adult↗
PubMed1999

Hepatic and renal extraction of circulating type I procollagen aminopropeptide in patients with normal liver function and in patients with alcoholic cirrhosis.

The circulating level and splanchnic and renal extraction of serum type I procollagen aminoterminal propeptide (PINP) was studied in 20 patients with normal liver function and in 15 patients with alcoholic liver cirrhosis. In patients with alcoholic cirrhosis, the concentration of PINP in the femoral artery blood was significantly higher than in the group of patients with normal liver function (median 145 microg/l, 95% CI 98-195 versus 57 microg/l, 95% CI 42-92, p<0.001). A significant decrease in the concentration of PINP between the femoral artery (median 57 microg/l, 95% CI 42-92) and the hepatic vein (median 45 microg/l, 95% CI 40-70, p<0.001) was found in patients with normal liver function. In this group we also observed a significantly higher concentration of PINP in femoral artery blood (median 60 microg/l, 95% CI 45-87) as compared with that in renal vein (median 50 microg/l, 95% CI 40-65, p<0.001). In contrast, serum-PINP did not differ between arterial and hepatic or venous venous blood in patients with alcoholic cirrhosis. Size-chromatography revealed no significant change in the ratio of the high and low molecular forms of PINP following extraction in liver and kidney. It is concluded that circulating PINP is extracted in the normal liver and kidney, and that the serum concentration of PINP is significantly higher in patients with alcoholic cirrhosis than in patients with normal liver function. Both the hepatic and the renal clearance of PINP are seriously impaired/reduced in patients with alcoholic cirrhosis.

Adult↗
PubMed1999

Mortality and causes of death of 513 Danish patients with systemic lupus erythematosus.

A multicentre cohort of 513 clinic attenders with systemic lupus erythematosus (SLE) was retrospectively identified, representing 4185 patient-years of follow-up. Expected numbers of death were calculated by means of age- and sex-specific mortality rates of the general Danish population. The observed number of deaths was 122. The survival rates were 97%, 91%, 76%, 64% and 53% after 1, 5, 10, 15, and 20 years respectively. The overall mortality rate was 2.9% per year (95% CI 2.4-3.5), and the standardized mortality rate (SMR) was 4.6 (95% CI 3.8-5.5). The causes of death included active SLE (n = 19), end stage organ failure due to SLE (n = 16), infections (n = 25), malignancy (n = 9), cardiovascular disease (n = 32), and other causes (n = 21). SLE was directly related to one third of the excess mortality. In conclusion, SLE patients in the present cohort had a 4.6-fold increased mortality compared with the general population and half of the deaths were caused by SLE manifestations or infections, especially in young patients during the early period of the disease.

Adolescent↗
PubMed1999

Prognostic value of renal biopsy and clinical variables in patients with lupus nephritis and normal serum creatinine.

OBJECTIVE: To evaluate factors with possible influence on the renal outcome in patients with lupus nephritis but without chronic renal insufficiency (CRI). METHODS: Renal biopsies from 94 patients were re-assessed with regard to WHO class, activity, chronicity and tubulointerstitial indices without knowledge of clinical features. The outcome parameters were CRI defined as irreversibly increased serum creatinine and renal end stage disease. RESULTS: The risk ratios (RR) of developing CRI were 2.6 for active urinary sediment, 3.1 for hyaline thrombi and 7.3 for glomerular leukocyte exudation. The RR of renal end stage disease was 5.0 when the duration of renal disease exceeded one year at the time of biopsy and 4.3 when biopsy disclosed a class IV lesion. Glomerular sclerosis was also associated to renal end stage disease. CONCLUSION: Early renal biopsy and the abovementioned signs of active renal disease carry prognostic information that may have significant therapeutic implications.

Adolescent↗