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DNase I hypersensitive sites in promoter elements associated with basal and vitamin D dependent transcription of the bone-specific osteocalcin gene (1994)

Montecino, M. ; Pockwinse, S. ; Lian, J. ; [et al.]

s.l. : American Chemical Society

Biochemistry 33 (1994), S. 348-353

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ISSN: 1520-4995

Source: ACS Legacy Archives

Topics: Biology , Chemistry and Pharmacology

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1021/bi00167a045

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2

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Serumspiegel und organablagerungen vonΒ 2-mikroglobulin bei dialysepatienten (1990)

Stein, G. ; Schneider, A. ; To\, H. ; [et al.]

Springer

Journal of molecular medicine 68 (1990), S. 1150-1155

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ISSN: 1432-1440

Keywords: Β 2-Mikroglobulin ; AB-Amyloid ; Dialysis ; Arthropathy ; Spondylarthropathy

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Summary In radioimmunological estimation ofΒ 2-microglobulin (Β 2m) significant higher serum values were found in 36 dialysis patients (44.4±20.3 mg/l) in comparison with healthy probands (1.5±0.2 mg/l). A significant relation to the duration of dialysis, diuresis, symptoms of the musculo-skeletal system, but not to radiologic changes or bone biopsy findings could be seen. Post mortem examinations carried out in 21 dialysis patients revealed AB-amyloid depositis in synovial tissue of different joints (particularly shoulder and hip joint) or intervertebral discs in eight patients (age 48 to 73 years, dialysis duration less than four years) without correlation to serumΒ 2m level or radiographically suspect areas. In the tissue of cervical spine or intervertebral discs of two patients suffering from destructive spondylarthropathy no amyloid could be detected. These results suggest that AB-amyloid may occur in elderly patients early in the course of hemodialysis and may be asymptomatic in most cases.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF01798067

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3

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Auswirkung von Aprotinin und Tranexamsäure auf die Fibrinolyse und Thrombinbildung bei extrakorporaler Zirkulation (2000)

Risch, A. ; Dorscheid, E. ; Stein, G. ; [et al.]

Springer

Der Anaesthesist 49 (2000), S. 279-285

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ISSN: 1432-055X

Keywords: Schlüsselwörter Aprotinin ; Tranexamsäure ; Extrakorporale Zirkulation ; Thrombosen ; Key words Aprotinin ; Tranexamic acid ; CPB ; Thrombosis

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Description / Table of Contents: Abstract Objective: Antifibrinolytic drug therapy has proved to be effective in reducing blood loss associated with cardiac surgery and cardiopulmonary bypass (CPB). Concerns remain regarding the risk of enhancing thrombosis. In the present study we investigated the effect of aprotinin (AP) and tranexamic acid (TA) on fibrinolysis and thrombin generation during CPB. Methods: 60 patients undergoing coronary artery bypass graft surgery were randomised in 3 groups. They received either aprotinin (“high-dose-scheme”), tranexamic acid (2 g/h) or no antifibrinolytic therapy (control group). Collection of blood was performed at 7 pre-, intra- and postoperatively predetermined intervals. Fibrinolytic activity was determined by measuring concentrations of D-dimer, thrombin generation by the measurement of thrombin-antithrombin III complex (TAT). Results: There was no significant increase of D-dimers in the AP or TA group. D-dimer concentration in the control group increased significantly after starting CPB. Comparing with the control group, thrombin generation in the AP group was significant less, while TA group produced significantly higher values. Conclusion: After the administration of AP for cardiac surgery we observed reductions in both intraoperative fibrinolysis and thrombin generation. In case of TA suppression of fibrinolytic activity in the absence of concomitant reduction in thrombin generation occurred. These results suggest that TA could potentiate a hypercoagulable state with the risk of thrombosis in the perioperative setting.

Notes: Zusammenfassung Fragestellung: Zur Reduktion des intra- und postoperativen Blutverlusts werden heute bei Eingriffen mit extrakorporaler Zirkulation (EKZ) in der Kardioanästhesie häufig antifibrinolytisch wirksame Substanzen eingesetzt. Es bestehen jedoch gleichzeitig Bedenken hinsichtlich ihres Potentials als Auslöser thrombotischer Komplikationen. Vorliegend sollte daher die Wirksamkeit von Aprotinin und Tranexamsäure auf die Fibrinolyse und Thrombingeneration während Herzoperationen unter EKZ miteinander verglichen werden. Methodik: 60 Patienten, die sich einer aortokoronaren Bypassoperation unterziehen mußten, wurden randomisiert in 3 Gruppen eingeteilt. Die erste Gruppe erhielt intraoperativ Aprotinin (“high-dose-Schema”), die zweite Gruppe Tranexamsäure (2 g/h), die dritte Gruppe diente als Kontrollgruppe und erhielt kein Antifibrinolytikum. Blutproben wurden zu 7 festgelegten Meßzeitpunkten prä-, intra- und postoperativ entnommen. Zur Kontrolle der Fibrinolyse wurden die D-Dimer-Konzentration, zur Bestimmung der Thrombingeneration die Konzentration der Thrombin-Antithrombin III-Komplexe (TAT) bestimmt. Ergebnisse: Zu keinem Meßzeitpunkt konnte weder unter Anwendung von Aprotinin noch von Tranexamsäure ein signifikanter Anstieg der D-Dimer-Konzentration verzeichnet werden, wogegen die D-Dimere in der Kontrollgruppe nach EKZ-Beginn signifikant anstiegen. Unter Aprotinin kam es außerdem zu einer signifikant geringeren Thrombingeneration im Vergleich zur Kontrollgruppe. Die Thrombingeneration in der Tranexamgruppe war im Gegensatz dazu signifikant höher als in der Kontrollgruppe. Schlußfolgerung: Aprotinin hemmt sowohl die Fibrinolyse als auch die Thrombingeneration und scheint damit eine Balance zwischen Blutgerinnung und Lyse herzustellen. Tranexamsäure hemmt zwar wirksam die Fibrinolyse, jedoch ohne gleichzeitige Reduktion der Thrombingeneration. Es könnte dadurch eine hyperkoagulabile Situation mit der Gefahr von thrombotischen Komplikationen in der perioperativen Phase entstehen.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/s001010050829

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High-dose clodronate therapy prevents joint destruction in chronic antigen-induced arthritis of the rat but inhibits bone formation at the axial skeleton (2000)

Oelzner, P. ; Kunze, A. ; Henzgen, S. ; [et al.]

Springer

Inflammation research 49 (2000), S. 424-433

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ISSN: 1420-908X

Keywords: Key words: Antigen-induced arthritis - Clodronate - Inflammation - Joint destruction - Osteoporosis

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Abstract: Objective: To investigate the effects of clodronate on clinical disease activity, inflammatory alterations and cartilage destruction, periarticular and axial bone volume and bone turnover in chronic antigen-induced arthritis (AIA; day 28).¶Methods: Rats with AIA were treated with clodronate (5 mg/kg/day continuously; 20 mg/kg/day intermittently or high-dose with 300 mg/kg 3 hours after arthritis induction +20 mg/kg/day continuously, respectively). Joint pathology was examined by histology. Bone volume and cellular turnover parameters of the right tibia head and the third lumbar vertebra were evaluated by histomorphometry. The findings were compared with those of healthy controls, sham-treated AIA and AIA treated continuously with 250 μg/kg of dexamethasone.¶Results: All three therapy regimens with clodronate resulted in a significant reduction of joint swelling, histopathological inflammatory changes and cartilage destruction in comparison with sham-treated AIA. The antiinflammatory effect of high-dose clodronate was comparable with dexamethasone. The intermittent administration of 20 mg/kg/day of clodronate completely prevented periarticular bone loss by reduction of bone resorption without affecting bone formation at the periarticular and axial bone. Both continuous treatment with 5 mg/kg/day of clodronate and high-dose clodronate therapy partially prevented periarticular bone loss and reduced parameters of bone formation at the axial bone to values below those of healthy controls.¶Conclusion: High-dose clodronate therapy exerts an excellent preventive effect on clinical disease activity and on joint destruction in AIA. However, continuous treatment with high doses of clodronate may result in a low turnover state of bone remodelling.¶

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/s000110050611

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5

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Responsiveness of gene expression markers of osteoblastic and osteoclastic activity to calcitonin in the appendicular and axial skeleton of the rat in vivo (1994)

Jenis, L. G. ; Ongphiphadhanakul, B. ; Braverman, L. E. ; [et al.]

Springer

Calcified tissue international 54 (1994), S. 511-515

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ISSN: 1432-0827

Keywords: Collagen ; Osteocalcin ; Bone mineral density ; Skeletal heterogeneity ; TRAP ; Cell proliferation

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine , Physics

Notes: Abstract We have previously shown that calcitonin (CT), an inhibitor of bone resorption, increases vertebral, but not femoral bone density in the rat [3]. To address the physiologic responses associated with these effects on bone mineral density (BMD), we assessed mRNA transcripts reflecting activities of osteoblasts (type I collagen, osteocalcin, osteopontin, and alkaline phosphatase), osteoclasts [tartrate-resistant acid phosphatase (TRAP)], and cell proliferation (histone H4) in the spine and femur of these rats. CT increased spine BMD while increasing type I collagen and decreasing TRAP and histone mRNAs. In the femur, where CT had no effect on BMD, it decreased type I collagen and histone H4 mRNA but did not affect TRAP. CT had no effect on the gene expression of osteocalcin, osteopontin, or alkaline phosphatase at either site. The results indicate that selective alterations in gene expression, as reflected by steady state mRNA levels, are consistent with the changes observed by BMD measurement, and can more clearly define the specific contribution from osteoblast and osteoclast activity. This study demonstrates a heterogeneity in response of the axial and appendicular skeleton to CT, reflected by alterations in gene expression that provide a basis for understanding the observed BMD responses to various pharmacologic interventions.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00334334

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6

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Do limited changes in phosphate intake modulate 1,25(OH)2D3 levels in early renal failure? (1992)

Seidel, A. ; Stein, G. ; Schneider, S. ; [et al.]

Springer

Pediatric nephrology 6 (1992), S. 564-564

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ISSN: 1432-198X

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00866509

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7

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Non-lectin component in a fermented extract from Viscum album L. grown on pines induces proliferation of lymphocytes from healthy and allergic individuals in vitro (1994)

Stein, G. ; Berg, P. A.

Springer

European journal of clinical pharmacology 47 (1994), S. 33-38

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ISSN: 1432-1041

Keywords: Viscum album ; Iscador Pini ; Lactobacillus plantarum ; lectins ; mistletoe extracts

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Abstract Mistletoe preparations have been shown to express immunomodulatory properties. In order to evaluate the stimulatory potency of different mistletoe extracts, peripheral blood mononuclear cells (PBMC) from healthy and allergic/atopic individuals were exposed to aqueous or fermented extracts derived from Viscum album L. grown on apple trees (Mali-extracts) or on pines (Pini-extracts). None of them had received any mistletoe treatment. Iscador Pini was the only extract which strongly induced proliferation of PBMC in contrast to the other five preparations. On testing these extracts by Western blotting with anti-mistletoe lectin-1 (ML-1) antibody positive sera from mistletoe-treated patients, it became evident that Iscador Pini was almost devoid of lectins. The stimulatory potency of Iscador Pini for PBMC from three different groups was examined: PBMC from 35 normal controls (Group I), 23 patients with drug-induced adverse effects (Group II) and 16 individuals with allergic manifestations (Group III). Cells were exposed in 7-day cultures to the extract at concentrations between 1 and 10,000 μg/ml. PBMC from 63% of Group III individuals showed strong stimulation (SI varying from 6 to 97) in contrast to only 9% from Group I and 22% from Group II individuals. Anti-ML-1 antibodies were detected in 5% and anti-IP antibodies in 11% of subjects in the three groups. They were either of the IgA or IgM type but not of the IgG type. Our findings strongly imply that a non-lectin associated antigen from Iscador Pini is able to activate PBMC from healthy and allergic/atopic individuals, thereby demonstrating sensitization to probably highly conserved plant antigens.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00193475

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High thiamine diphosphate concentrations in erythrocytes can be achieved in dialysis patients by oral administration of benfotiamine (2000)

Frank, T. ; Bitsch, R. ; Maiwald, J. ; [et al.]

Springer

European journal of clinical pharmacology 56 (2000), S. 251-257

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ISSN: 1432-1041

Keywords: Key words Thiamine diphosphate ; Transketolase ; Benfotiamine

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Abstract Objective: The influence of either orally administered S-benzoylthiamine-O-monophosphate (benfotiamine) or thiamine nitrate on the thiamine status was tested in a randomised, two-group comparison study in 20 end-stage renal disease (ESRD) patients. Main outcome measures were the pharmacokinetics of thiamine diphosphate (TDP) in blood, the in vitro erythrocyte transketolase activity, its activation coefficient (α-ETK) and the TDP concentration in erythrocytes. Methods: After ingestion of a single dose of either 100 mg thiamine nitrate (corresponding to 305 μmol thiamine) or 100 mg benfotiamine (corresponding to 214 μmol thiamine), the blood levels of thiamine phosphate esters were analysed by means of high-performance liquid chromatography for a 24-h period. The TDP concentration in erythrocytes was calculated using the haematocrit and TDP concentration in blood. Erythrocyte transketolase activity and α-ETK were measured before and 10 h after administration. The pharmacokinetics of TDP in blood were compared with healthy subjects of other studies retrieved from database query. Results: Regarding the blood concentrations of TDP, the patients with ESRD had a 4.3 times higher area under the concentration–time curve after benfotiamine administration than after thiamine nitrate. After benfotiamine administration, the peak plasma concentration of TDP exceeded that in healthy subjects by 51%. In the ESRD patients, after 24 h, the mean TDP concentration in erythrocytes increased from 158.7 ± 30.9 ng/ml initially to 325.8 ± 50.9 ng/ml after administration of benfotiamine and from 166.2 ± 51.9 ng/ml to 200.5 ± 50.0 ng/ml after thiamine nitrate administration. The ratio between the maximum erythrocyte TDP concentration and basal concentration was 2.66 ± 0.6 in the benfotiamine group and 1.44 ± 0.2 in the group receiving thiamine nitrate (P 〈 0.001). After 24 h, it was 2.11 ± 0.4 and 1.23 ± 0.2, respectively. The transketolase activity increased from 3.54 ± 0.7 μkat/l initially to 3.84 ± 0.6 μkat/l after benfotiamine intake (P=0.02) and from 3.71 ± 0.8 μkat/l to 4.02 ± 0.7 μkat/l after thiamine nitrate intake (P=0.08). Likewise, α-ETK decreased from initially 1.10 ± 0.07 to 1.04 ± 0.04 (P=0.04) and from 1.12 ± 0.05 to 1.08 ± 0.06 (P=0.09). After 24 h, the phosphorylation ratio in whole blood decreased from 12.9 ± 6.9 initially to 5.6 ± 3.2 after benfotiamine administration (P=0.02) and from 13.5 ± 7.3 to 9.0 ± 4.8 (P=0.03) after administration of thiamine nitrate. No correlation between erythrocyte TDP concentration and transketolase activity and/or α-ETK was observed in ESRD patients, either before or 10 h after administration. Conclusion: Compared with thiamine nitrate, the oral administration of benfotiamine leads to higher TDP concentrations in erythrocytes accompanied with a significant improvement of the erythrocyte transketolase activity in ESRD patients.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/s002280000131

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Treatment of acute uncomplicated urinary tract infection with ceftibuten (1991)

Stein, G. E. ; Christensen, S. ; Mummaw, N.

Springer

Infection 19 (1991), S. 124-126

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ISSN: 1439-0973

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Description / Table of Contents: Zusammenfassung Ceftibuten ist ein Oralcephalosporin der dritten Generation mit erhöhter Aktivität gegenEnterobacteriaceae-Arten. Die Wirksamkeit und Sicherheit dieses neuen Antibiotikums wurden in einer offenen Studie bei 74 Frauen mit akuter, unkomplizierter Harnwegsinfektion geprüft. Die Patientinnen erhielten sieben Tage lang eine einmal tägliche Dosis von 400 mg Ceftibuten oral. Nach Ende der Therapie wurden vier bis sechs Wochen lang Nachuntersuchungen vorgenommen. In allen Fällen war eine Erregereradikation nachzuweisen, darunter waren auch fünf Fälle, bei denen koagulase-negative Staphylokokken mit Resistenz gegen Ceftibuten aus dem Urin isoliert worden waren. Eine Heilung war fünf bis neun Tage nach Behandlungsende bei 93% der Patientinnen eingetreten. Rezidive wurden in einem von fünf Fällen auf eine Reinfektion zurückgeführt, in vier Fällen durch den ursprünglichen Keim. Vier bis sechs Wochen nach Therapie hatten weitere fünf Patientinnen erneut Infektionsschübe entwickelt. Insgesamt kam es in dieser Studie zu einer Heilungsrate von 85%. Nebenwirkungen, die unter der Therapie mit Ceftibuten auftraten, waren meistens leicht und betrafen den Gastrointestinaltrakt. Die häufigste Nebenwirkung war Diarrhoe. Der Latex-Agglutinationstest fürClostridium difficile war in drei von acht Fällen mit Diarrhoe (11% des Gesamtkollektivs) positiv. Bei Frauen mit akuter, unkomplizierter Harnwegsinfektion erwies sich die Therapie mit Ceftibuten als wirksam und im allgemeinen sicher. Bedenken ergeben sich aus der hohen Diarrhoerate in dieser Studie.

Notes: Summary Ceftibuten is an orally active third generation cephalosporin with increased potency against members of theEnterobacteriaceae. In this study, 74 women with acute uncomplicated urinary tract infection (UTI) were enrolled in an open study to evaluate the safety and efficacy of this new antibiotic. Patients were treated with 400 mg ceftibuten once daily for seven days and followed for four to six weeks after cessation of therapy. All pathogens were eradicated during treatment, including five coagulase-negative staphylococci that were resistant to ceftibuten. At five to nine days posttreatment, 93% of patients were cured. Of the five recurrent infections, four patients had a relapse and one had a reinfection. By four to six weeks post-treatment, five additional patients had recurrent infections. The overall cure rate was 85% in this study. Most ceftibuten-associated adverse effects were mild and involved the gastrointestinal tract. Diarrhea was the most commonly reported side effect. Of the eight (11%) patients who developed diarrhea, three had a positive latex agglutination test forClostridium difficile. The diarrhea resolved in all patients without sequelae. Ceftibuten was effective and generally safe in the treatment of women with acute uncomplicated UTI. The high incidence of diarrhea observed in this study is a concern.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF01645584

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Comparative study of clarithromycin and penicillin V in the treatment of streptococcal pharyngitis (1991)

Stein, G. E. ; Christensen, S. ; Mummaw, N.

Springer

European journal of clinical microbiology & infectious diseases 10 (1991), S. 949-953

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ISSN: 1435-4373

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Abstract This study evaluated the safety and efficacy of clarithromycin in the treatment of patients with Group A beta-hemolytic streptococcal pharyngitis. Subjects were treated with either 250 mg clarithromycin twice daily or 250 mg penicillin V four times a day for 10 days and followed for approximately three weeks post-treatment. At the completion of therapy, 96 % (45/47) of patients treated with clarithromycin and 89 % (43/48) of patients treated with penicillin V were clinically cured or improved. Recurrence of symptoms occurred in 7 and 5 patients who were treated with clarithromycin and penicillin V respectively. Initial bacteriologic eradication was observed in all but one patient. Recurrence ofStreptococcus pyogenes occurred in 5 (11 %) patients who received clarithromycin and 7 (15 %) patients who received penicillin V. The majority of adverse events reported during this study were mild and involved the gastrointestinal tract. Diarrhea was more frequent in patients who received clarithromycin. In this multicenter, randomized, double-blind trial, clarithromycin was as safe and effective as penicillin V in the treatment ofStreptococcus pyogenes throat infections.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF02005450

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