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Biomedical subjects

G Hein

Publications and source records attributed to G Hein.

At least 73 records · Page 4Linked to original sources

Relationship between soluble markers of immune activation and bone turnover in post-menopausal women with rheumatoid arthritis.

OBJECTIVE: Regarding interactions between pro-inflammatory cytokines and bone metabolism in rheumatoid arthritis (RA), we investigated the relationship between the serum levels of interleukin (IL)-1beta, IL-6, soluble interleukin-2 receptor (sIL-2r), C-reactive protein (CRP), the vitamin D metabolites 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], intact parathyroid hormone (iPTH) as well as serum and urinary parameters of bone turnover in 74 post-menopausal women with RA. RESULTS: SIL-2r correlated negatively with 1,25(OH)2D3 (P < 0.01), whereas IL-6 showed a positive correlation with urinary excretion of deoxypyridinoline collagen cross-links (P < 0.01). 1,25(OH)2D3 (P < 0.01) and iPTH (P < 0.01) were negatively related to CRP, whereas the urinary excretion of pyridinoline (P < 0.01) and deoxypyridinoline (P < 0.01)-collagen cross-links showed a positive correlation with CRP. 1,25(OH)2D3 (P < 0.01) and iPTH (P < 0.05) were positively related to bone alkaline phosphatase as a marker of osteoblast function. CONCLUSION: Our data indicate that IL-6 is a critical determinant of increased bone resorption in post-menopausal RA women with high disease activity and that serum levels of 1,25(OH)2D3 are inversely related to T-cell activation.

Aged↗

PICP as bone formation and NTx as bone resorption marker in patients with chronic renal failure.

UNLABELLED: Renal bone disease which develops in patients with chronic renal failure (CRF) is not a uniform metabolic disorder. Although bone histomorphometry is accepted to be the gold standard for characterizing the state of disease progression, the techniques involved are cumbersome and expensive so that it cannot be used routinely. As a result, numerous biochemical markes have been developed to measure bone formation and resorption. The purpose of this study was to evaluate the suitability of procollagen type-I C-terminal peptide (PICP) in serum as an indicator of bone formation and cross-linked amino-terminal telopeptide of type I collagen (NTx) in urine as an indicator of bone degradation processes, and to investigate their relation to histomorphometric and other biochemical parameters. 77 patients with CRF and 49 patients on intermittent hemodialysis treatment (DT) were investigated. PICP was measured in serum and NTx in urine. In addition, iPTH, phosphate, calcium, alkaline phosphatase (APH), osteocalcin and creatinine in serum were determined. Bone biopsies were obtained from the anterior, superior iliac crest, and the histomorphometric parameters were measured and expressed according to the standardized nomenclature. Patients with CRF and DT had significantly higher PICP and NTx levels as compared to controls. In the CRF group significant correlations could be obtained between PICP and histomorphometric parameters of bone formation as well as between NTx and histomorphometric indices of bone resorption. In this group, PICP levels were positively correlated to iPTH, phosphate and creatinine levels and negatively to calcium concentrations. Furthermore, there were significant correlations between NTx values and those of both iPTH and APH. In the group of dialysis patients, levels of PICP and NTx did not correlate with any of the histomorphometric parameters or the classical humoral markers. CONCLUSIONS: The results suggest that PICP as bone formation and NTx as bone resorption markers are of potential use for screening bone turnover in predialysis chronic renal failure patients. But in patients undergoing dialysis, neither PICP nor NTx yielded any substantial information as noninvasive markers of bone histology.

Adult↗

Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis.

In several studies on patients with rheumatoid arthritis, an association of bone loss with a persistently high disease activity has been found. The aim of our study was to investigate the relation between disease activity and serum levels of vitamin D metabolites, parathyroid hormone (PTH), and parameters of bone turnover in patients with rheumatoid arthritis. A total of 96 patients (83 women and 13 men) were divided into three groups according to disease activity measured by serum levels of C-reactive protein (CRP). In the whole group, serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (P < 0.001) and PTH (P < 0.05) were negatively correlated to disease activity. The urinary excretion of collagen crosslinks--pyridinoline (Pyd) (P < 0.001) and deoxypyridinoline (Dpd) (P < 0.05)--showed a positive correlation with disease activity. The inverse correlation between serum 1,25(OH)2D3 and disease activity was separately evident in patients with (P < 0.001) and without (P < 0.01) glucocorticoid treatment, in pre- (P < 0.01) and postmenopausal (P < 0.001) women, and in men (P < 0.01). 1,25(OH)2D3 and PTH serum levels were positively correlated to serum bone alkaline phosphatase (ALP) (P < 0.01). The results indicate that high disease activity in patients with rheumatoid arthritis is associated with an alteration in vitamin D metabolism and increased bone resorption. The decrease of 1,25(OH)2D3 levels in these patients may contribute to a negative calcium balance and inhibition of bone formation. Furthermore, low levels of 1,25(OH)2D3 as an endogenous immunomodulator suppressing activated T cells and the proliferation of cells may accelerate the arthritic process in rheumatoid arthritis.

Adolescent↗

Pain treatment of fibromyalgia by acupuncture.

The lack of objective parameters makes the measurement of pain and the efficacy of pain treatment in patients with chronic pain very difficult. We performed acupuncture therapy in fibromyalgia patients and established a combination of methods to objectify pain measurement before and after therapy. The parameters corresponded to patients' self-report. Twenty-nine fibromyalgia patients as defined by ACR-criteria (25 women, 4 men) with a mean age of 48.2 +/- 2.0 years and a mean disease duration of 6.1 +/- 1.0 years participated in the study. Pain levels and positive tender points were assessed using the visual analogue scale (VAS, i.e., range 0-100 mm) and dolorimetry. Serotonin and substance P levels in serum and the serotonin concentration in platelets were measured concomitantly. During acupuncture therapy no analgesic medication was allowed. The VAS scores decreased from 64.0 +/- 3.4 mm before therapy to 34.5 +/- 4.3 mm after therapy (P < 0.001). Dolorimetry revealed a decreased number of tender points after therapy from 16.0 +/- 0.6 to 11.8 +/- 1.0, P < 0.01. Serotonin levels decreased from 715.8 +/- 225.8 micrograms/10(12) platelets to 352.4 +/- 47.9 micrograms/10(12) platelets (P < 0.01), whereas the serum concentration increased from 134.0 +/- 14.3 ng/ml to 171.2 +/- 14.6 ng/ml (P < 0.01). Substance P levels in serum increased from 43.4 +/- 3.5 pg/ml to 66.9 +/- 8.8 pg/ml (P < 0.01). Acupuncture treatment of patients with fibromyalgia was associated with decreased pain levels and fewer positive tender points as measured by VAS and dolorimetry. This was accompanied by decreased serotonin concentration in platelets and an increase of serotonin and substance P levels in serum. These results suggest that acupuncture therapy is associated with changes in the concentrations of pain-modulating substances in serum. The preliminary results are objective parameters for acupuncture efficacy in patients with fibromyalgia.

Acupuncture Therapy↗

[Recurrent panuveitis. First manifestation of Behçet disease in childhood].

BACKGROUND: Behçet's disease is a rare systemic vasculitis of unknown etiology. The typical symptoms include recurrent oral and/or genital aphthous lesions, iridocyclitis (historically with hypopyon) and various skin lessions. The number of young adults and children which are diagnosed with Behçet-syndrome is increasing in recent years and the mean age of manifestation has decreased to 25 years in German patients. The disease is generally diagnosed later in German (48.5 months) than in Turkish patients (25.5 months). Ocular manifestation has been confirmed as a marker of severe prognosis. In 15-25% of affected patients it leads to blindness. PATIENT: We describe a 19-year-old Caucasian woman who has suffered from the typical symptoms (oral aphthous lesions, recurrent uveitis posterior, various skin lesions) since the 16th year of age. RESULTS: After three years the patient was finally be diagnosed with Behçet's disease (using the criteria of the "International Study Group for Behçet's Disease"). Visual acuity was stabilized with an immunosuppressive therapy, although there was no complete remission in disease activity. In addition a cerebral vasculitis was manifested. CONCLUSIONS: Ophthalmologists should be familiar with Behçet's disease. In cases of recurrent uveitis Behçet's disease should be included in the differential diagnosis because timely immunosuppressive therapy can prevent irrevocable changes in the corpus vitreum and retina and preserve complete visual acuity.

Adolescent↗

Dysregulation of insulin-like growth factors in a case of generalized acquired lipoatrophic diabetes mellitus (Lawrence Syndrome) connected with autoantibodies against adipocyte membranes.

We report on a 33-year-old male patient with generalized acquired lipodystrophy, insulin resistant diabetes mellitus and acanthosis nigricans (Lawrence Syndrome). First probable symptoms of lipodystrophy (weight loss, shrinkage of subcutaneous fatty tissue, and loss of muscular strength) became evident three years ago, with the onset of diabetes mellitus occurring about six months later. The patient suffered from the following clinical symptoms: IDDM with increasing insulin-requirement, extreme reduction of fatty tissue, fatty liver hepatitis with elevated liver enzymes, glomerulopathy, muscular and neuropathic pains, as well as hypertriglyceridaemia. A basal C-peptide concentration is rather high. Definitely, the endogenous insulin secretion is increased. In other words, insulin resistance is documented. In an effort to identify the pathogenetic mechanisms of lipoatrophic diabetes mellitus in this patient and to develop a therapeutic strategy, antibodies against different tissues and endocrinologic regulation were investigated. It was possible to demonstrate the presence of serum autoantibodies against lipocytes of the subcutis and other tissues, against hepatic stellate cells, together with autoantibodies against different endocrine organs. By studying the basis of diabetic abnormalities relating to the growth hormone (GH), the insulin-like growth factor (IGF) dynamics in this patient, i.e. reductions of GH, IGF-I, IGF-II, IGF-Binding protein (IGF-BP) 2 and IGF-BP 3, were detected. An immunosuppressive treatment strategy was not beneficial.

Adipocytes↗

[ETICS Study: Empirical therapy of idiopathic chronic singultus].

Idiopathic chronic singultus (ICS) describes recurring episodes of persistent hiccuping lasting longer than an arbitrary time limit (e.g. one month) for which no organic cause or consistently effective treatment can be found. It has been suggested that ICS may result from chronic stimulation of a supraspinal "hiccup center" by impulses originating from receptors in the gastrointestinaltract. This hypotesis implies the possibility of treating ICS by reducing gastric acid (via omeprazole), facilitating gastric emptying (via cisapride), or suppressing of the "hiccup centre" (via GABA-ergic offects of baclofen or gabapentin). 29 patients (28 male, one female; age 71 +/- 10 years) suffering from ICS for four to 564 months were treated with a combination of cisapride (30 mg/d), omeprazole (20 mg/d) and baclofen (45 mg/d) (COB). The patients rated the severity of hiccuping on a subjective assessment scale (SAS) that ranged from 0 (= no hiccuping) to 10 (= unbearable hiccuping). Hiccuping ceased in 38% (11/29) of the treated patients and decreased in severity in an additional 24% (7/29). Mean SAS-scores following 20 to 24 weeks of therapy (3.7 +/- 3.4) were significantly lower compared to before therapy (8.8 +/- 1.3) (Mann-Whitney rank order test [p < 0.02]). In the patients that failed to respond to COB, gabapentin (1.200 mg/d) was substituted for baclofen. Hiccuping ceased in one and improved in two of these ten subjects. We conclude that COB is an effective empirical therapy in the majority of patients with ICS. It may be useful to substitute gabapentin for baclofen in those not responding to COB.

Acetates↗

[Inflammation and bone metabolism in rheumatoid arthritis. Pathogenetic viewpoints and therapeutic possibilities].

BACKGROUND: Systemic osteoporosis is a common and pathogenetically heterogenous complication in rheumatoid arthritis. Various factors such as disease activity, dosage and duration of glucocorticoid treatment and immobilization are involved in pathogenesis of osteoporosis in rheumatoid arthritis. INFLAMMATION AND BONE METABOLISM: Proinflammatory cytokines secreted by immunocompetent cells have a role in the regulation of the activity of osteoblasts and osteoclasts. The effects of these proinflammatory cytokines include the inhibition of bone formation and an increase in bone resorption. Interleukin-6 and nitric oxide induced in osteoblasts by proinflammatory cytokines are likely to be important mediators between these cytokines and the function of osteoblasts and osteoclasts. Furthermore, disease activity dependent changes in the secretion of glucocorticoids and in vitamin D metabolism may be involved in the pathogenesis of osteoporosis in this disease. Alteration of bone remodeling associated with immobilization is an important factor of systemic bone loss in rheumatoid arthritis. CONCLUSION: The inflammatory process in rheumatoid arthritis may cause penarticular and systemic bone loss by various cytokine and hormone mediated mechanisms. Concluding from these pathogenetic mechanisms, bisphosphonates and active vitamin D metabolites are likely to be effective therapeutic options in osteoporosis associated with rheumatoid arthritis.

Arthritis, Rheumatoid↗

Interleukin-6, soluble interleukin-2-receptor and soluble interleukin-6-receptor in sera of patients with rheumatoid arthritis: influences of disease activity and drug therapy.

Cytokines and their receptors play a fundamental role in the development and maintenance of the inflammatory process in rheumatoid arthritis (RA). The purpose of this study was to evaluate sIL-2R, sIL-6R and IL-6 levels in the sera of 48 RA patients and to correlate them with disease activity, indicators of inflammatory process as ESR and CRP, and drug treatment modalities. IL-6 and sIL-2R levels were positively correlated with disease activity, ESR and CRP. No correlation between sIL-6R levels and these markers were observed. Our results suggest that different drug therapies have a decisive influence on the levels of selected cytokines. All investigated disease-modifying antirheumatic drugs (DMARDs) were able to reduce the IL-6 level significantly. Non-immunosuppressive DMARDs decreased the amount of circulating sIL-2R more than immunosuppressive drugs. Treatment with methotrexate resulted in a significant reduction of circulating levels of sIL-6R compared to azathioprine therapy. Under low dose glucocorticoid therapy, significantly lower levels of sIL-6R were found than in patients without glucocorticoids. In conclusion, the results provide some arguments in favour of combined drug therapies, which might possibly enhance the effectiveness of RA therapy.

Adult↗

[Still's syndrome in the adult. A report of 8 cases with special reference to diagnostic value of ferritin].

BACKGROUND: Adult onset Still's disease (AOSD) is an uncommon, systemic, inflammatory disorder of unknown etiology, characterized by the triad of fever, arthritis and rash. PATIENTS AND RESULTS: We describe 8 cases of AOSD (3 male, 5 female) diagnosed and treated in the Department of Rheumatology from 1980 to 1996. The delay in reaching a firm diagnosis was between 2 and 86 months, due to both lack of specific serum markers and the abundance of possible differential diagnoses. Our therapeutic strategies and results are presented and the value of obtaining serum ferritin levels for both diagnosis and follow-up studies is discussed. The patients data are compared to those of the world's literature on AOSD. CONCLUSION: The differential diagnosis of fever of unknown origin should always include AOSD, because these patients could be spared from invasive and unnecessary diagnostic measures. Increased serum ferritin levels are of particular value in the diagnosis of acute AOSD and the normalization of the serum ferritin value is a reliable indicator of therapeutic success.

Adolescent↗

The determination of pyridinium crosslinks in urine and serum as a possible marker of cartilage degradation in rheumatoid arthritis.

The determination of the collagen crosslinks pyridinoline (Pyd) and deoxypyridinoline (Dpyd) seems to be a successful way of characterizing topic destructive processes in rheumatoid arthritis (RA). Dpyd is a specific marker of collagen I resorption in bone, whereas Pyd is released from types I and II collagen in bone and cartilage. Both crosslinks were examined in 38 RA patients concurrently by RP-gradient-HPLC in urine and serum. A positive correlation was found between the inflammatory activity (measured by CrP) and the level of collagen crosslinks in urine. A correlation between serum and urine concentrations was demonstrable for Pyd, but not for Dpyd. Different elimination kinetics for fragments containing either Pyd or Dpyd are a possible explanation for this observation. The ratio of Pyd/Dpyd is known to be a useful marker to distinguish between destruction of cartilage and bone collagen. Because the Pyd/Dpyd ratio in urine does not necessarily correspond to that in serum, probably as a result of metabolic or elimination processes, the usefulness of the relationship between the crosslinks in urine as a method of differentiating between cartilage and bone degradation must be questioned.

Adult↗

[Enthesopathies--diagnosis and therapy].

Problems are frequently encountered regarding the terminology, diagnosis, differential diagnosis, and therapy of diseases of thes tendons insertion point (enthesis): Terms such as tendinosis, tenopathy, tendinitis, tendovaginitis, tendoperiostitis, insertions tenopathy, tendomyosis, etc. often are used interchangeably even through they describe anatomically and pathophysiologically different conditions. The term enthesiopathy is used as a generic term in this overview article irrespective of the causality.

Combined Modality Therapy↗

Predictors of flares and long-term outcome of systemic lupus erythematosus during combined treatment with azathioprine and low-dose prednisolone.

Many patients with systemic lupus erythematosus (SLE) receive long-term treatment with azathioprine and prednisolone to control disease activity. In a retrospective study we evaluated the efficacy of combined treatment with azathioprine (2 mg/kg body weight/d) and low-dose prednisolone (7-12 mg/d) and the predictors of disease flares during this therapy regimen in 61 patients with SLE. We found three predictors of flares: renal disease, persistence of dsDNA antibodies for at least 1 year after the beginning of treatment and reduction in azathioprine dosage to below 2 mg/kg/d. The occurrence of flares was significantly associated with a higher rate of disease-related death. Furthermore, the persistence of dsDNA antibodies for at least 2 years was associated with progression of renal disease. We concluded that suppression of production of dsDNA antibodies with high avidity is a suitable parameter to determine efficacy of treatment and long-term outcome during combined therapy with azathioprine and low-dose prednisolone in SLE.

Adolescent↗

Quantitative analysis of pyridinium crosslinks of collagen in the synovial fluid of patients with rheumatoid arthritis using high-performance liquid chromatography.

The pyridinium crosslinks are important and definite biomarkers of mature hard tissue collagen degradation. A gradient ion-paired reversed-phase high-performance liquid chromatographic method was used for the simultaneous determination of both crosslinks in synovial fluid (SF) samples of 25 patients with rheumatoid arthritis (RA). The mean +/- SD levels of pyridinoline (Pyd) and deoxypyridinoline (Dpyd) in SF were 107.7 +/- 182.3 nmol/l and 4.8 +/- 8.3 nmol/l, respectively. The Pyd/Dpyd ratio, which indicates the amount of Pyd released from cartilage rather than bone, amounted to 30.8 +/- 29.5. This value is significantly higher than in urine or serum of the same patients. These data suggest increased destruction of joint cartilage in patients with RA and the release of collagen II fragments in SF. In addition, the levels of the crosslinks in SF reflect considerable interindividual variation, indicating substantial individual differences in the amount of collagenous material that is degraded.

Adolescent↗