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Biomedical subjects

G Hein

Publications and source records attributed to G Hein.

At least 37 records · Page 2Linked to original sources

Advanced glycation end-products pentosidine and N epsilon-carboxymethyllysine are elevated in serum of patients with osteoporosis.

OBJECTIVE: To investigate serum levels of the advanced glycation end-products (AGEs) pentosidine and N epsilon-carboxymethyllysine (CML) in patients classified into different osteoporosis subgroups according to histomorphometric data. METHOD: Serum samples were obtained from 116 osteoporotic patients (34 men, 82 women) classified by bone histomorphometry into subgroups with high turnover (HTO, n = 32), low turnover (LTO, n = 39), normal turnover (NTO, n = 9) and cellular uncoupled osteoporosis (CUO, n = 36). Pentosidine was measured by high-performance liquid chromatography, and CML by a competitive enzyme-linked immunoassay. RESULTS: The entire osteoporosis group had significantly higher pentosidine and CML serum concentrations than healthy subjects. In contrast to healthy subjects, no correlation between levels of AGEs and age could be found. In subgroups characterized by increased bone resorption (HTO, CUO), serum pentosidine correlated significantly with the histomorphometric marker reflecting osteoclast activity/bone resorption (eroded surface as a percentage of trabecular surface). Moreover, in CUO a strong correlation between pentosidine and the mineral apposition rate was found. Surprisingly, in HTO the levels of CML and percentage of eroded surface were significantly negatively correlated. CONCLUSION: AGE-modified proteins may be a cause of disturbed bone remodelling in osteoporosis. Our findings do not support the alternative hypothesis that increased AGEs in serum indicate only a more intensive releasing of AGEs in circumstances of increased bone resorption.

Adult↗

[Treatment of obstructive sleep apnea with a new vest preventing the supine position].

BACKGROUND AND OBJECTIVE: Prevention of the supine position has for decades been a well known treatment option in positional obstructive sleep apnea. It was the aim of this study to test the efficacy of a recently patented commercially available supine position preventing vest. PATIENTS AND METHODS: The vest is made of linen tissue with a half cylindrical piece of hard foam in its dorsal part. 12 male patients slightly overweight (body mass index 26.5 +/- 2.6 kg/m(2)) and 55.8 +/- 11.6 years old were investigated polysomnographically prospectively. RESULTS: The pretherapeutical respiratory-disturbance index (RDI) was 26.7+/-11.9/h increasing to 39.3+/-16.1/h in the supine position. When using the vest, patients no longer slept on their back and the RDI dropped to 7.6 +/- 5.1/h (p < 0.005). Total sleep time at an oxygen saturation below 90 % was reduced from 11.7 +/- 11.3 % to 1.5 +/- 2.1 %. 9 patients (75 %) were cured (RDI < 10/h and RDI reduction > 50 %), 2 patients (17 %) improved (RDI reduction > 50 %) and only the oldest patient (76 years old) remained unchanged. Even though snoring decreased from 180 +/- 125 minutes to 110 +/- 52 minutes, an increase was observed in 30 % of the patients. Sleep quality and structure did not change considerably. CONCLUSION: The supine position prevention vest is a safe and simple treatment alternative of high efficacy in positional sleep apnea. As a complete remission cannot be predicted, polygraphic or polysomnographic controls are necessary.

Adult↗

[Collagen breakdown in ankylosing spondylitis-relationship to disease related parameters].

OBJECTIVE: Patients with ankylosing spondylitis (AS) often develop osteoporosis particularly of the axis skeleton. To investigate disease-related or therapeutic influence on bone catabolism, we quantified the total excretion of the collagen crosslinks (CL) pyridinoline (Pyd) and deoxypyridinoline (Dpyd) in 91 AS patients (26 f, 65 m) in relation to disease activity or stage and therapy with NSAID. METHODS: CL were determined by HPLC (High Performance Liquid Chromatography). RESULTS: The AS patients show a highly significant positive correlation between Pyd and the inflammatory activity (CrP, r = 0.36, p < 0.001: ESR, r = 0.379, p < 0.001). Also the quotient Pyd/Dpyd correlates positively to the inflammatory activity (CrP, r = 0.262, p < 0.001: ESR, r = 0.325, p < 0.002). In the case of increased inflammatory disease activity (CrP > or = 10 mg/l vs CrP < 10 mg/l or ESR > or = 10 30 mm vs ESR < 30 mm), Pyd excretion is raised significantly (p < 0.042 for CrP and p < 0.009 for ESR). Among those patients treated with NSAID therapy, significantly reduced levels for Dpyd (p < 0.001) and raised levels for the quotient Pyd/Dpyd (p < 0.002) appear. In the case of advanced radiological changes with evidence of syndesmophytes, Pyd (p = 0.014) and Dpyd (p < 0.004) were significantly raised in urine. Regarding the movement function (finger-floor distance, schober test), no significant correlation to crosslink excretion could be proven. CONCLUSION: From our investigations, we assume that osteoporosis in AS is primarily caused by an inflammatory-mediated degradation of bone.

Adolescent↗

Anti-C1q antibodies and antiendothelial cell antibodies in systemic lupus erythematosus - relationship with disease activity and renal involvement.

The aim of this study was to investigate the relationship between the presence and titre of antibodies against C1q (anti-C1q Ab) and disease activity and renal involvement in patients with systemic lupus erythematosus (SLE). Anti-C1q Ab were measured in 79 patients with SLE (70 women and 9 men; mean age 41.7 years; mean disease duration 8.4 years): 19 patients had active disease with lupus nephritis, 8 active disease without nephritis, 26 inactive disease with nephritis and 26 inactive disease without nephritis. Anti-dsDNA antibodies (EIA and immunofluorescence), antiendothelial cell antibodies (AECA) and complement levels (C3, C4, total haemolytic complement activity) were determined in parallel. Anti-C1q Ab were positive in 49%, anti-dsDNA Ab in 61% and AECA in 19% of the patients, respectively. Significantly higher titres of anti-C1q Ab were found in patients with active disease compared with those with inactive SLE ( P < 0.01). Serum levels of anti-C1q Ab showed a positive correlation with anti-dsDNA Ab and SLEDAI score ( P < 0.01) and a negative correlation with C3 ( P < 0.05), C4 ( P < 0.01) and CH50U ( P < 0.01). The presence of anti-C1q Ab was not different between patients with or without nephritis. In patients with ( P < 0.05) and without nephritis ( P < 0.01) the frequency of anti-C1q Ab was significantly higher in active patients compared with inactive patients. Both anti-C1q and anti-ds-DNA Ab were detectable in 74% of patients with active nephritis but only in 30% of all other patients ( P=0.001). None of the patients with active nephritis was negative for anti-C1q and anti-dsDNA Ab, whereas 37% of the patients without active nephritis were negative for both antibodies ( P < 0.01). Sensitivity, specificity, positive and negative predictive values for active lupus nephritis among SLE patients were 100%, 50%, 51.9% and 100% for anti-dsDNA Ab (EIA) and 74%, 70%, 57% and 89.4% for positive findings of both anti-dsDNA and anti-C1q Ab. The presence and titre of anti-C1q-Ab in SLE are related to disease activity. Absence of anti-dsDNA Ab excludes active nephritis; positive findings of both anti-dsDNA Ab and anti-C1q Ab are of relatively high specificity for active nephritis.

Adolescent↗

Hydroxypyridinium collagen crosslinks in serum, urine, synovial fluid and synovial tissue in patients with rheumatoid arthritis compared with osteoarthritis.

OBJECTIVE: To investigate the relationship between inflammation markers and content of pyridinium crosslinks in hydrolysates of synovial tissue and to specify the significance of urinary excreted pyridinoline, released primarily from collagen I and II of bone and cartilage, and deoxypyridinoline released especially from collagen I of bone and dentin, dependent on disease activity in rheumatoid arthritis (RA). METHODS: Synovial tissue and fluid from knee endoprosthesis surgery, as well as simultaneously obtained serum and urine, were collected from 12 patients with inactive RA or RA with low disease activity [iRA: C-reactive protein (CRP) <28 mg/l], 10 with active RA (aRA: CRP > or =28 mg/l) and 21 with OA. After preparation of the synovial tissue, including hydrolysis, completely released synovial pyridinoline and deoxypyridinoline crosslinks as well as those from synovial fluid, serum and urine were investigated using a gradient ion-paired reversed-phase HPLC method. Crosslink levels in synovial tissue are expressed as mol/mol collagen, assuming 300 residues of hydroxyproline per collagen molecule, also measured by HPLC. RESULTS: In the synovial tissue of aRA patients we found significantly elevated total pyridinoline concentrations and pyridinoline/deoxypyridinoline (Pyr/Dpyr) quotients compared with the iRA and OA controls, indicating an elevated crosslinking density of mature synovial tissue collagen with increased activity of RA. Pyridinoline levels and the Pyr/Dpyr ratio were correlated with those of urine and with acute-phase reactants in RA patients. Compared with serum crosslink levels, which were unrelated to disease activity, the urinary concentration of pyridinoline was increased by a factor of 2 and showed a simultaneous increase with increasing synovitis. CONCLUSION: Both crosslinking density and degradation of mature collagen from synovial tissue depend on the disease activity in RA. Urinary excretion of associated crosslinks, expressed as the Pyr/Dpyr ratio, correlates with those in synovial tissue and may be confirmed as a marker of synovial tissue collagen degradation. We suggest that increased crosslinking of mature collagen in the synovial tissue of RA is related to an inflammation-dependent regulation of collagen synthesis in activated synovial fibroblasts, in which lysyl oxidase represents the final enzymatic step for crosslinking.

Adult↗

Medical THz imaging: an investigation of histo-pathological samples.

We present a THz investigation of histo-pathological samples including the larynx of a pig and a human liver with metastasis. Our measurements show that different types of tissue can be clearly distinguished in THz transmission images, either within a single image or by a comparison of images obtained for different frequency windows. This leads to the problem that images obtained for different frequencies inherently have a different spatial resolution. An image obtained from two such images by a simple mathematical operation may contain artefacts. We discuss measures to deal with this problem. Furthermore, we investigate the possibility of improving the spatial resolution of THz images. Finally, we present a cw THz imaging system based on a photomixer and an external cavity semiconductor laser that allows for simultaneous two-mode operation. The cw system is less expensive and more compact than conventional time-domain imaging systems.

Algorithms↗

Are advanced glycation end-product-modified proteins of pathogenetic importance in fibromyalgia?

OBJECTIVE: To quantify the serum levels of the advanced glycation end-product (AGE) pentosidine in 41 patients with fibromyalgia (FM) and 46 healthy controls. The formation of pentosidine is closely related to oxidative stress. METHODS: Pentosidine was measured by reverse-phased high-performance liquid chromatography with gradient separation on a RP-18 column. RESULTS: Patients with FM have significantly higher pentosidine serum levels than healthy subjects. CONCLUSION: AGE modification of proteins leads to reduced solubility and high resistance to proteolytic digestion of such altered proteins (e.g. AGE-modified collagens). AGEs are also able to stimulate different kinds of cells via activation of the NFkappaB, mediated by specific receptors of AGEs (e.g. RAGE) on the cell surface. Both mechanisms may contribute to the development, perpetuation and spreading of pain phenomena in FM patients.

Adult↗

Identification of the advanced glycation end products N(epsilon)-carboxymethyllysine in the synovial tissue of patients with rheumatoid arthritis.

BACKGROUND: Generation of advanced glycation end products (AGEs) is an inevitable process in vivo and can be accelerated under pathological conditions such as oxidative stress. In serum and synovial fluid of patients with rheumatoid arthritis (RA) raised AGE levels have been found. OBJECTIVE: To determine the presence of N(epsilon)-carboxymethyllysine (CML; marker of oxidative stress) in RA synovial tissue by immunohistology. METHODS: Frozen synovial tissue samples from 10 patients with RA and eight controls (four patients without joint disease and four patients with osteoarthritis (OA)) were treated with rabbit-anti-CML-IgG and goat-antirabbit-IgG. Immunostaining was visualised by streptavidine-alkaline phosphatase (chromogen fuchsin). Cell differentiation was performed with antibodies against CD68, CD45RO, and CD20. RESULTS: CML was detected in the synovial lining, sublining, and endothelium in 10/10 RA and 4/4 OA synovial specimens. In RA some macrophages (CD68+) and T cells (CD45RO+) showed positive immunostaining for CML, whereas B cells were negative. Staining in OA synovial sublining was weak compared with RA. CONCLUSIONS: CML was detected for the first time in RA and OA synovial tissue. Different patterns of immunostaining in RA and OA and the presence of CML on macrophages and T cells, suggest a role for CML in the pathogenesis of RA. This might be due to presentation of new epitopes which can maintain or even trigger an autoimmune response.

Adult↗

Mosaic chromosomal aberrations in synovial fibroblasts of patients with rheumatoid arthritis, osteoarthritis, and other inflammatory joint diseases.

Chromosomal aberrations were comparatively assessed in nuclei extracted from synovial tissue, primary-culture (P-0) synovial cells, and early-passage synovial fibroblasts (SFB; 98% enrichment; P-1, P-4 [passage 1, passage 4]) from patients with rheumatoid arthritis (RA; n = 21), osteoarthritis (OA; n = 24), and other rheumatic diseases. Peripheral blood lymphocytes (PBL) and skin fibroblasts (FB) (P-1, P-4) from the same patients, as well as SFB from normal joints and patients with joint trauma (JT) (n = 4), were used as controls. Analyses proceeded by standard GTG-banding and interphase centromere fluorescence in situ hybridization. Structural chromosomal aberrations were observed in SFB (P-1 or P-4) from 4 of 21 RA patients (19%), with involvement of chromosome 1 [e.g. del(1)(q12)] in 3 of 4 cases. In 10 of the 21 RA cases (48%), polysomy 7 was observed in P-1 SFB. In addition, aneusomies of chromosomes 4, 6, 8, 9, 12, 18, and Y were present. The percentage of polysomies was increased in P-4. Similar chromosomal aberrations were detected in SFB of OA and spondylarthropathy patients. No aberrations were detected in i) PBL or skin FB from the same patients (except for one OA patient with a karyotype 45,X[10]/46,XX[17] in PBL and variable polysomies in long-term culture skin FB); or ii) synovial tissue and/or P-1 SFB of normal joints or of patients with joint trauma. In conclusion, qualitatively comparable chromosomal aberrations were observed in synovial tissue and early-passage SFB of patients with RA, OA, and other inflammatory joint diseases. Thus, although of possible functional relevance for the pathologic role of SFB in RA, these alterations probably reflect a common response to chronic inflammatory stress in rheumatic diseases.

Arthritis, Psoriatic↗

Clinical manifestation of POEMS syndrome with features of connective tissue disease.

The POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome is a rare plasma cell disease with multiorgan involvement and varying clinical manifestations. We report a 38-year-old man who presented with scleroderma-like skin changes of the hands and feet, sicca and Raynaud's syndrome, pleural effusions, glomerulopathy, polyneuropathy, hepatosplenomegaly and lymphadenopathy. Steroid treatment was started on the assumption of a connective tissue disease and led to a temporary improvement. During the further course of the disease, hypothyreosis, monoclonal gammopathy and osteosclerotic bone lesions were detected, leading to the diagnosis of POEMS syndrome. This case emphasises the need to consider POEMS syndrome as a differential diagnosis in patients with signs of connective tissue disease and polyneuropathy.

Adult↗

[IV: Small group workshop for developing future measures and projects. Evidence-based therapy in rheumatology with special reference to applications of new drugs--formulation of possible goals and possibilities for meeting them. Osteoporosis in rheumatic diseases].

Secondary osteoporosis is a common, late complication of inflammatory rheumatic diseases. Despite its great socio-economic implications for the individual, there is still a lack of appreciation of this problem. This may result in an inadequate or insufficient prophylaxis and therapy. The participants of this discussion group, therefore, approve of further investigations in this field to gather new relevant data, e.g., for our core documentation on rheumatic diseases. Of special importance is the registration of long-term patients obtaining documented, individual long-term therapy (e.g., cortisone). As well as epidemiologic and clinical research projects, it is imperative to do basic research into the pathogenesis of secondary osteoporosis and find new therapeutic approaches for curing rheumatic disease.

Anti-Inflammatory Agents↗

[Rare association of acute febrile neutrophilic dermatosis (Sweet syndrome) with rheumatoid arthritis].

We report on a 57 year old women with a long-standing course of severe rheumatoid arthritis, developing acute febrile neutrophilic dermatosis (Sweet's syndrome) in an active phase of the arthritis. Sweet's syndrome has been reported with hematologic and solid malignancies, infections and several autoimmunopathies, but in only three cases is there a coincidence with rheumatoid arthritis. We review Sweet's syndrome with regard to pathogenesis and associated disorders.

Arthritis, Rheumatoid↗

High phosphorus intake only slightly affects serum minerals, urinary pyridinium crosslinks and renal function in young women.

OBJECTIVE: Assessment of the physiological effects of a diet rich in phosphorus in young women. DESIGN: Control period I--commercial basic diet containing 1700 mg P and 1500 mg Ca/day for 4 weeks. Supplementation period--a 6 week high-phosphorus period of 3008 mg P and 1995 mg Ca/day. Control period II--4 weeks washout with basic diet as in period I. SETTING: Institute of Nutritional Science, Friedrich Schiller University, Jena. SUBJECTS: Ten healthy women, aged 20-30y. INTERVENTIONS: Orange juice and tablets, containing supplements of Ca5(PO4)3OH and NaH2PO4, totalling 1436 mg elemental phosphorus per day. RESULTS: There was an increase of 10.7+/-13.7 pg/ml in serum PTH, a decrease of 0.6+/-0.6 ng/ml in serum osteocalcin, an increase of 73.6+/-136.6 nmol/mmol creatinine in urinary pyridinoline and of 19.3+/-36.0 nmol/ mmol creatinine in urinary deoxypyridinoline, and a decrease of 2.6+/-9.3 mg/l in urinary microalbumin. All changes were insignificant. There were no changes in serum levels of Ca, PO4 or Zn, in serum concentration of 1,25-(OH)2D3, and in urinary beta-2-microglobulin excretion. Phosphorus supplementation caused intestinal distress, soft stools or mild diarrhoea. CONCLUSIONS: In spite of a high phosphorus supplementation no significant changes in bone-related hormones, pyridinium crosslinks as markers of bone resorption and parameters of renal function in young women were found.

Adult↗

Pseudoainhum of all fingers associated with Reynolds' syndrome and breast cancer: report of a case and review of the literature.

Pseudoainhum is a rare disorder characterized by digital constrictions leading to autoamputation. We report a bilateral pseudoainhum of all fingers in a 64-year-old fair-skinned woman with breast cancer, systemic scleroderma, and primary biliary cirrhosis. The overlap between scleroderma and primary biliary cirrhosis with antimitochondrial antibodies M2 is also known as Reynolds' syndrome. Although pseudoainhum has been associated with many conditions, this particular association is exceptional and has yet not been described.

Ainhum↗

Monarthritis of the ankle as manifestation of a calcaneal metastasis of bronchogenic carcinoma.

We report a case of bronchiogenic carcinoma metastasizing to the calcaneus and clinically manifesting itself as a therapy-refractory monarthritis in the right ankle. There is a wide spectrum of possible diagnoses of acute ankle monarthritis including different forms of inflammatory rheumatic diseases, sarcoidosis, osteoarthritis, or septic arthritis. Primary or metastatic malignancies of the hand or foot bones are considered to be rare. Persistent monarthritis as a sole symptom of a calcaneal metastasis has never been reported. This case demonstrates possible difficulties in the early differential diagnosis of acute monarthritis, and will be discussed with respect to the few reports on foot acrometastases.

Aged↗