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P Junker

Publications and source records attributed to P Junker.

At least 37 records · Page 2Linked to original sources

YKL-40, a matrix protein of specific granules in neutrophils, is elevated in serum of patients with community-acquired pneumonia requiring hospitalization.

The serum concentration of YKL-40, a matrix protein of specific granules in neutrophils, was determined by RIA in 90 patients hospitalized with pneumonia of suspected bacterial origin. Of these, 64 were followed prospectively during antibiotic treatment with blood samples taken on day 0 (on admission and the start of treatment) and on days 1, 3, 5, 7, 10, and 21. Serum YKL-40 at admission was increased in patients with Streptococcus pneumoniae pneumonia (median, 893 microgram/L; 95% confidence interval [CI], 704-1560), compared with healthy subjects (median, 102 microgram/L; 95% CI, 64-247 microgram/L; P<.001) and in patients with pneumonia of unknown etiology (median, 448 microgram/L; 95% CI, 334-700; P<.05). Peak YKL-40 serum values were observed on day 1 and thereafter declined steeply to almost normal by day 3. During the first 10 days, there was a close relation between serum YKL-40 and markers of specific granules of neutrophils (serum lactoferrin and neutrophil gelatinase-associated lipocalin), which suggests that serum YKL-40 reflects exocytosis of specific granules of neutrophils in persons with acute bacterial pneumonia.

Adipokines↗

Diminished ability of erythrocytes from patients with systemic lupus erythematosus to limit opsonized immune complex deposition on leukocytes and activation of granulocytes.

OBJECTIVE: To compare the ability of normal erythrocytes and erythrocytes from systemic lupus erythematosus (SLE) patients to bind immune complexes (IC), thereby inhibiting IC deposition on polymorphonuclear leukocytes (PMN) and the consequent induction of a PMN respiratory burst (RB). METHODS: The binding of fluorescein isothiocyanate-labeled IC in 75% autologous serum to whole blood cells or isolated leukocytes from 17 SLE patients and 10 controls was assessed by flow cytometry. Reactive oxygen metabolite (ROM) production by PMN was measured as the intracellular oxidation of dihydrorhodamine 123, on stimulation with unlabeled IC. RESULTS: Erythrocyte-mediated inhibition of IC uptake by PMN reached a mean +/- SD maximum of 68 +/- 18% in controls and 29 +/- 51% in SLE patients (P < 0.05) and, in the patients, correlated inversely with disease activity. In the presence of erythrocytes from various donors, IC binding to a standard preparation of PMN and their ROM production were inversely proportional to the number of type 1 complement receptors (CR1) per donor erythrocyte. Thus, the ROM production was higher in the presence of SLE patients' erythrocytes (125 +/- 67 CR1/erythrocyte) than with erythrocytes from controls (235 +/- 118 CR1/erythrocyte). CONCLUSION: Erythrocytes from SLE patients are defective in protecting their PMN against IC deposition and induction of the RB.

Adolescent↗

A multicentre study of 513 Danish patients with systemic lupus erythematosus. I. Disease manifestations and analyses of clinical subsets.

A Danish multicentre study was undertaken of the manifestations, infections, thrombotic events, survival and predictive factors of survival in 513 Danish patients with systemic lupus erythematosus (SLE) according to the 1982 classification criteria of the American College of Rheumatology. The mean duration of follow-up was 8.2 years from diagnosis and 12.8 years from first symptom. This paper describes the most common clinical and laboratory manifestations and their relationship to sex and age at the time of onset and diagnosis. Cluster analysis revealed three clinically defined clusters at the time of disease onset. Cluster 1 (57% of patients) consisted of relatively elderly patients without nephropathy or malar rash, but with a high prevalence of discoid lesions. Cluster 2 (18%) consisted of patients with nephropathy, a third of whom also developed serositis and lymphopenia. The patients of the third cluster (25%) all had malar rash and half were photosensitive. Follow-up showed that the patients of cluster 2 developed azotaemia, large proteinuria, arterial hypertension and myositis significantly more often than did the rest of the patients, but the mortality was not increased. The risk of developing renal end-stage disease was highest in men with early-onset disease.

Adolescent↗

A multicentre study of 513 Danish patients with systemic lupus erythematosus. II. Disease mortality and clinical factors of prognostic value.

In this Danish multicentre study, predictive clinical factors of mortality and survival were calculated for 513 patients with systemic lupus erythematosus (SLE), 122 of whom died within a mean observation period of 8.2 years equalling a mortality rate of 2.9% per year. Survival rates were 97%, 91%, 76% and 64% after 1, 5, 10 and 15 years, respectively. The direct causes of death included SLE (n = 35), infections (n = 25), malignancy (n = 9), cardiovascular disease (n = 32) and other causes (n = 21). Uni- and multivariate analyses of survival and mortality were performed for all deaths and for SLE-related deaths. Azotaemia (one-fifth of the patients) was a strong predictor of increased overall and SLE-related mortality, but nephropathy per se (one-half of the patients) and large proteinuria (one-sixth of the patients) were unrelated to survival. Haemolytic anaemia had a significant negative influence on survival related to mortality caused by infections. Diffuse central nervous system disease and myocarditis were related to increased SLE-related mortality, whereas photosensitivity predicted a decreased mortality. Non-fatal infections and thrombotic events predicted a decreased overall survival. Since 1980 the mortality caused by SLE manifestations has decreased significantly.

Adolescent↗

Effects of short-term treatment with prednisolone and calcitriol on bone and mineral metabolism in normal men.

To study the effects of treatment with glucocorticoid and calcitriol on biochemical markers of calcium and bone metabolism, 48 normal male volunteers (aged 21-54 years) were randomized to treatment for 7 days with either (A) prednisolone, 10 mg twice daily, (B) prednisolone, 10 mg twice daily, and calcitriol, 1 microg twice daily, (C) calcitriol 1 mg twice daily, or (D) placebo. The study period was 28 days. Renal calcium excretion increased (mean maximal increase +44.7%, p < 0.01) as well as serum parathyroid hormone (PTH) (max. +18.5%, p < 0.01) during prednisolone treatment. Concomitant treatment with calcitriol or calcitriol alone equally enhanced renal calcium excretion (max. +185.2%, p < 0.001) and decreased serum PTH (max. -43.1%, p < 0.001). Prednisolone administration was followed by prompt declines in markers of bone formation [serum osteocalcin (max. -34.7%, p < 0.001) and serum procollagen type I C-terminal propeptide (PICP) (max. -25.9%, p < 0.05)], whereas serum bone alkaline phosphatase (bone AP) remained unchanged. Calcitriol in combination with prednisolone attenuated the decrease in PICP (max. -8.9%, not significant), but it had no effect on osteocalcin (max. -40.1%, p < 0.001), and decreased bone AP (max. -22.2%, p < 0.05). Calcitriol alone increased osteocalcin (max. +37.8%, p < 0.03) and PICP (max. +26.0%, p < 0.05). Among markers of bone degradation, prednisolone suppressed serum C-terminal telopeptide of type I collagen (ICTP) (max. -28.4%, p < 0.001), but not the fasting renal excretion of hydroxyproline (OHP) and collagen type I N-terminal telopeptide (NTx). Calcitriol partially antagonized the decrease in ICTP (max. -17.2%, p < 0.001). Calcitriol alone had no effect on resorptive markers. Extraosseous matrix synthesis was suppressed by prednisolone evaluated by serum procollagen type III N-terminal propeptide (max. -30.8%, p < 0.001) and was not affected by concomitant treatment with calcitriol or calcitriol alone. In conclusion, short-term administration of prednisolone to healthy men leads to fast and protracted suppression of biochemical markers of bone formation and extraosseous connective tissue metabolism. The effect on bone was partially antagonized by simultaneous calcitriol treatment, and points toward a potential role of calcitriol in the prevention of steroid induced osteoporosis.

Adult↗

Systemic lupus erythematosus in Denmark: clinical and epidemiological characterization of a county-based cohort.

A population based cohort of patients with systemic lupus erythematosus (SLE) was recruited from a for epidemiological purposes representative Danish region. Patients were ascertained from 4 different sources with a high degree of completeness as estimated by using capture-recapture analysis. The diagnosis was verified by means of case records, patient interviews, and clinical examinations. Patients were classified according to the 1982 revised ACR criteria as Definite SLE (D-SLE) fulfilling > or = 4 criteria and Incomplete SLE (I-SLE) with < 4 criteria. As of January 1, 1995, the point prevalences of D-SLE and I-SLE were 21.7 and 5.2 per 100000 respectively. The cohort comprised 98% white Europeans. The annual incidence of D-SLE increased from 1.0/100,000 to 3.6/100,000 during the study period 1980-94. D-SLE patients had clinical profiles comparable to other Western European study populations. The I-SLE subclass had milder disease manifested by lower criterial load and absence of cerebral and kidney involvement. Tissue and organ damage expressed as SLICC-score increased in the order of live I-SLE, live D-SLE, and deceased patients.

Adolescent↗

Shrinking spinal cord following transverse myelopathy in a patient with systemic lupus erythematosus and the phospholipid antibody syndrome.

A 38-year-old woman with systemic lupus erythematosus and the phospholipid antibody syndrome was admitted because of rapidly evolving symptoms consistent with a transverse myelopathy at the TH9/10 level. Magnetic resonance imaging (MRI) showed slight diffuse swelling and increased signal intensity of the spinal cord. She was treated with high dose methylprednisolone plus azathioprine and aspirin. Four months later she had achieved almost complete remission with minimal residual sphincter disturbances. Despite the clinical recovery, repeated MRI at 4 months and 4 years showed diffuse and irreversible atrophy of the entire spinal cord.

Adult↗

Dose-response effect of short-term calcitriol treatment on bone and mineral metabolism in normal males.

To evaluate the effects of short-term treatment with calcitriol on biochemical markers of calcium and bone metabolism, 36 normal male volunteers (aged 21-54 years) were randomized to oral treatment for 7 days with either (A) calcitriol, 1 microgram twice daily, (B) calcitriol, 0.5 microgram twice daily, or (C) placebo twice daily. Serum calcium increased slightly in a dose-dependent manner (maximal increase 2.5%, p < 0.05) followed by a heavy increase in both 24 h (max. 156.1%, p < 0.001) and fasting urinary calcium excretion (max. 123.1%, p < 0.001), and a striking reduction in serum PTH (max. -43.1%, p < 0.001). Biochemical markers of osteoblast activity and bone formation increased immediately in a dose-dependent manner [serum osteocalcin (max. 37.8%, p < 0.03) and serum procollagen type I C-terminal propeptide (PICP) (max. 26.0%, p < 0.05)], whereas there was no effect on serum bone alkaline phosphatase. Calcitriol treatment had no effect on biochemical markers of bone resorption [serum C-terminal telopeptide of type I collagen (ICTP) and fasting urinary excretion of hydroxyproline/creatinine (OHP)]. Extraosseous collagen matrix synthesis was not affected evaluated by serum procollagen type III N-terminal propeptide (PIIINP). In the follow-up period (15 weeks) no unequivocal changes were observed. The fast and protracted increase in biochemical markers of osteoblast activity and bone formation, without affecting bone resorption and extraosseous connective tissue metabolism points toward a selective effect of calcitriol on bone matrix formation.

Administration, Oral↗

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Humans↗

Serum hyaluronan is increased in malignant lymphoma.

The serum concentration of hyaluronan (HYA) was measured in 41 patients with malignant lymphoma, including 21 patients with non-Hodgkin's malignant lymphoma and 20 patients with Hodgkin's disease. Thirty-four patients were studied at diagnosis. The remaining 7 patients had relapsing or resistant disease. The patients were categorized into four stages according to conventional staging procedures. The median serum HYA concentration in patients with malignant lymphoma was significantly higher (median 40.7 ng/ml; 95% confidence limits 26.1-57.6 ng/ml) than in an age-matched healthy reference group (median 14.5 ng/ml, 95% confidence limits 11-19.4 ng/ml) (P = 0.00032). The highest serum HYA levels were found in patients with relapsing/resistant disease, all being in stages III and IV (median 181.5; range 11.9-500 ng/ml), as compared to previously untreated patients (median 29.8; range 9.1-108) (P = 0.0002) and controls (median 14.2; range 6.7-51.2). Decreased uptake and degradation of HYA owing to malignant transformation of lymphatic tissue is the most plausible explanation to these findings.

Adolescent↗

Complement receptor expression and activation of the complement cascade on B lymphocytes from patients with systemic lupus erythematosus (SLE).

It has previously been reported that the expression of the complement receptors, CR1 on erythrocytes and blood leucocytes and CR2 on B cells, is reduced in patients with SLE, and that the reduced expression of CR1 on erythrocytes is related to disease activity. We have earlier demonstrated that normal B cells are capable of activating the alternative pathway (AP) of complement in a CR2-dependent fashion. In this study we have investigated whether disturbances in this activity may be related to the altered phenotype of SLE B cells. Flow cytometry was used to measure expression of complement receptors and regulatory proteins on B cells from SLE patients, as well as the deposition of C3 fragments occurring in vivo or after in vitro AP activation. We have confirmed, for a proportion of the patients studied, reduced expression of CR1 and CR2 on B cells, and shown a consistency between low CR2 expression and reduced in vitro AP activation in the presence of homologous, normal serum. In addition, the B cells, like erythrocytes, bear raised levels of in vivo-deposited C3dg, but not C3b fragments, compared with normal B cells. The erythrocytes from SLE patients were unable to inhibit in vitro AP activation by B cells in homologous serum. Finally, we demonstrated an inverse relationship between SLE disease activity index (SLEDAI) and the expression of complement receptor 2 (CR2) on SLE B cells. Thus, determination of CR2 on B cells may emerge as an additional laboratory tool in the assessment of SLE activity.

Adult↗

Seromarkers of collagen I and III metabolism in active Crohn's disease. Relation to disease activity and response to therapy.

Crohn's disease is characterised by gradual development of intestinal fibrotic lesions containing large amounts of collagen type I, III, and V. Measurement of circulating connective tissue metabolites has emerged as a useful tool for assessment of fibroproliferative activity in various diseases. Serum concentrations of procollagen peptides, N-terminal propeptide of type III procollagen (PII-INP), and C-terminal propeptide of type I procollagen (PICP), reflect the synthesis rate of the parent collagens, while the C-terminal telopeptide of type I collagen (ICTP) reflects its degradation. S-PIIINP, S-PICP, and S-ICTP were measured by radioimmunoassays in 29 patients with active Crohn's disease. S-ICTP was significantly increased, median 6.2 micrograms/l (95% CI 5.2 to 8.7 micrograms/l) versus controls 2.6 micrograms/l (2.5 to 2.7 micrograms/l) (p < 0.0001), S-PICP reduced, 100 micrograms/l (80 to 110 micrograms/l) versus 132 micrograms/l (124 to 141 micrograms/l) (p = 0.001), and S-PIIINP did not differ from controls. Patients with sustained clinical remission during prednisolone therapy exhibited an increase in S-PICP (p = 0.0052). S-PIIINP changed significantly (p = 0.0002), however, exhibiting a biphasic pattern. S-ICTP decreased (p = 0.015) in treatment responders but remained above the upper normal limit even when clinical remission had been achieved. Non-responders showed no significant changes in any of the marker molecules of collagen synthesis or degradation. Correlations were found between S-PIIINP and S-PICP (p < 0.005) and S-ICTP (p < 0.02), and between S-ICTP and S-orosomucoid (p < 0.005) and S-C reactive protein (p < 0.02). By contrast, there was no relation between the connective tissue metabolites and Harvey Bradshaw Index. These data provide evidence that collagen I degradation is increased not only in active Crohn's disease, but also in patients entering clinical remission. The concurrent normal/low-normal values of markers of collagen formation may reflect a changed local or systemic elimination of the propeptides.

Adolescent↗

Type III procollagen N-peptide correlates with beta-2-microglobulin in myelomatosis.

The serum concentration of the N-terminal peptide of type III procollagen (PIIINP) was determined in 32 patients with myelomatosis (MM). Four subjects were studied at the time of diagnosis and the remaining patients at variable intervals from diagnosis. Serum concentration of beta-2-microglobulin (B2m) was measured in 31 patients. Serial measurements of both substances were performed in 20 patients. Serum PIIINP was increased in MM as compared with healthy control subjects (P < 0.001). Patients with active disease had significantly higher propeptide values (median 7.4; range 3.8-11.2) as compared to those with stable disease (median 4.3; range 2.2-9.6) (P < 0.009). A highly significant correlation existed between circulating PIIINP and B2m (P < 0.001). It is concluded that MM elicits a stromal reaction as reflected by parallel increases in serum PIIINP and serum B2m. In subsets of patients, e.g. those with non-secretory myeloma and in patients with smouldering disease, serum PIIINP may even be superior to B2m as an indicator of disease activity.

Aged↗

Serum laminin P1 in idiopathic myelofibrosis and related diseases.

The serum concentration of laminin P1 antigen was determined in 32 patients with various myeloproliferative disorders, including 19 patients with idiopathic myelofibrosis. The serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) was measured concomitantly in 27 patients. Serial laminin measurements were carried out in 25 patients. The median serum laminin concentration in patients with acute disease, i.e. acute myelofibrosis and patients in a transforming disease phase was significantly higher (1.58 U/ml; range 1.15-2.07) as compared with patients with chronic disease (1.02 U/ml; range 0.75-1.76; p = 0.012) and healthy control subjects (1.13 U/ml; range 0.75-1.67; p = 0.00015). In individual patients serum laminin covariated closely with serum PIIINP, the leucocyte count and LDH. The median serum laminin concentration in patients with a huge spleen was significantly lower than in the patient group with a normal spleen size/previous splenectomy. Pronounced splenomegaly was particularly prevalent in patients with chronic disease implicating splenic enlargement as a significant extrahepatic site of laminin uptake/degradation in myeloproliferative disorders.

Adult↗