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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 1,477 records · Page 82Linked to original sources
PubMedDate not supplied

Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs.

OBJECTIVE: The objective of this study was to establish the non-inferiority of an oral enzyme therapy (Phlogenzym-(PE)) as compared to the non-steroidal anti-inflammatory drug (NSAID) diclofenac (DC) in patients with osteoarthritis (OA) of the hip. METHODS: Ninety patients presenting with painful episodes of OA of the hip were treated for 6 weeks in one study centre in a phase III, randomised, double blind, parallel group trial. Altogether, 45 patients were treated in the PE group and 45 patients were treated in the DC group. Primary efficacy criteria were: WOMAC dimensions pain, joint stiffness and function, and Lequesne index as multiple endpoint according to O'Brien. The efficacy criteria were analysed applying the test of non-inferiority with regard to mean changes and frequencies, t-test, U test, ANCOVA and descriptive methods. RESULTS: Within the 6 weeks observation period, the adjusted changes from baseline to endpoint of the target parameters worked out as follows (adjusted differences, mean +/- SEM): WOMAC subscale pain (PE -10.3 +/- 1.2, DC -9.5 +/- 1.2), WOMAC subscale joint stiffness (PE -3.9 +/- 0.5, DC -3.6 +/- 0.5), WOMAC subscale physical function (PE -31.7 +/- 3.5, DC -29.7 +/- 3.5), Lequesne's index (PE -2.89 +/- 0.47, DC -2.27 +/- 0.47). Non-inferiority of PE as compared to DC with regard to the O'Brien's global sum of the standardised adjusted changes from baseline to endpoint in pain, stiffness, physical function, and Lequesne's index was established with p = 0.0025. PE was simultaneously non-inferior as compared to DC with regard to the 4 single endpoints: WOMAC subscale pain (p = 0.0033), WOMAC subscale joint stiffness (p = 0.0061), WOMAC subscale physical function (p = 0.0039), Lequesne's index (p = 0.0008) (closed test procedure). The equivalence tests remained insignificant due to comparatively lower effects of DC. For 71.1% of the PE patients and for 61.4% of the DC patients rates of good or very good global investigator assessments of efficacy were calculated (test of non-inferiority: p = 0.0011). In the majority of patients, tolerability was judged in both drug groups as very good or good. CONCLUSION: This trial showed significant non-inferiority from 6 weeks treatment with PE in patients with OA of the hip with regard to the WOMAC dimensions pain, stiffness and physical function, to Lequesne's index, to the investigator and patients assessments of efficacy, and to the responder rates based on pain, physical function, and patient assessment of efficacy. With regard to drug tolerability some tendencies in favour of PE were detected. However, in this study there was no real difference between PE and DC 100 mg/day, implying an equal benefit-risk relation between the substances. PE may well be recommended for the treatment of patients with osteoarthritis of the hip with signs of inflammation as indicated by a high pain level.

Activities of Daily Living↗
PubMedDate not supplied

The biology and serology of Epstein-Barr virus (EBV) infections.

The Epstein-Barr virus (EBV), carried by the majority of the world's adult human population, is closely associated with three known human diseases; infectious mononucleosis IM), Burkitts lymphoma (BL) and nasopharyngeal carcinoma (NPC). It is now generally accepted that EBV plays an active role in the etiology of BL and NPC rather than simply being a "passenger". Considerable evidence also argues for the participation of "co-factors" in these two diseases. Environmental co-factors appear needed to explain the peculiar geographical distribution of BL. Among various possibilities that must be considered are insect-transmitted agents that could lead to eventual immunosuppression and/or stimulate further proliferation of EBV-transformed cells, thereby permitting an additional cytogenetic evolution towards malignancy. Recent studies have uncovered a possible cytogenetic co-factor in the ethiology of BL; the 8-14 chromosomal translocation. Genetic co-factors, on the other hand, are likely to be involved in the etiology of NCP. EBV is a B-cell associated virus. Carrier lymphoid cell lines obtained either by in vitro "immortalization" of human cord-blood lymphocytes or by explants from IM and African BL donors harbor multiple copies of the EBV genome, and viral genetic sequences have also been directly detected in biopsies of African BL. The state of the viral genomes in the carrier cell appears to be such that some are integrated into the cellular DNA while others exist as free, covalently closed circular molecules.

Burkitt Lymphoma↗
PubMedDate not supplied

[Value of pepsinogen I in serum as a screening method for early detection of gastroduodenal lesions and follow-up in therapy with non-steroidal antirheumatic drugs].

Gastroduodenal lesions of the mucosa are known to be the most frequent side effect during therapy with non-steroidal antiinflammatory drugs (NSAIDs). We investigated the radioimmunological determination of serum-pepsinogen I as an indicator for the quality of the gastroduodenal mucosa. A good correlation was found between the endoscopy findings of 78 patients and contemporary determinations of serum-pepsinogen. Further, a follow-up of pepsinogen I was made during the treatment of 107 patients with degenerative rheumatic diseases with eight different NSAIDs. The results recommend the determination of pepsinogen I as an indicator of gastroduodenal mucosal changes under therapy with NSAIDs; this determination gives a deciding factor for the gastrolesive potency of an NSAID.

Adult↗
PubMedDate not supplied

Epstein Barr virus (EBV) carrying cells in blood of Hodgkin's disease (HD) and non-Hodgkin lymphoma (NHL) patients with high antibody titers against EBV capsid antigens (VCA).

Three patients with Hodgkin's disease (HD) and 7 patients with non Hodgkin lymphoma (NHL) who had high antibody titers against Epstein Barr virus (EBV) capsid antigens (VCA) were studied for the occurrence of EBV carrying B cells in the blood. The outgrowth of lymphoblastoid cell lines (LCLs) in their blood lymphocyte culture was tested in the presence of Cyclosporin A, which abrogates the growth inhibitory effect of T cells. Transformation occurred in the cultures of 4/10 patients and 4/10 age matched healthy individuals. The frequency of transformation in wells seeded with identical cells number from these 4 individuals in each group did not differ. Thus the lymphoma patients with high anti VCA titers did not show elevated level of EBV carrying B cells in the blood.

Aged↗
PubMedDate not supplied

The role of viral transformation and cytogenetic changes in viral oncogenesis.

A wide variety of DNA viruses and a more restricted family of RNA viruses can transform normal cells in vitro. Transformation means either immortalization and/or the appearance of certain phenotypic changes. Although it has been often inferred that in vitro transformation can be essentially equated with malignant transformation, increasing evidence indicates that the latter, reflected by tumorigenicity in vivo, requires additional cytogenetic changes. The evidence will be reviewed for EB virus-associated human malignancy (Burkitt's lymphoma) and the role of the 14q + translocation marker in human B-cell neoplasia. These findings point to an initiating role of viral transformation, reflected by in vitro immortalization, followed by a cytogenetic evolution where chromosome 14-associated changes are essential for the liberation of B lymphocytes from super-imposed controls. The contrast of tissue-associated, specific chromosomal changes that bring about malignant transformation after the initiating impact of different agents will be illustrated experimentally for murine T-cell lymphoma. Here, X-ray, DMBA and different virus (RadLV, Gross virus)-induced T lymphomas show the same chromosomal change: trisomy 15. It may be questioned whether viral transformation can ever lead to neoplasia in the absence of subsequent cytogenetic changes.

Burkitt Lymphoma↗
PubMedDate not supplied

Cancer, viruses and environmental factors.

The genesis of Burkitt's lymphoma is visualized as proceeding in three steps: I. Primary EBV infection affects the young child, probably at a relatively high multiplicity. It immortalizes a certain number of B-lymphocytes in vivo. II. This is followed by the impact of an environmental promoting agent, perhaps chronic holoendemic malaria, providing a chronic stimulus to the proliferation of the EBV-carrying preneoplastic cells. III. Chromosomally abnormal variants appear in the stimulated tissue by chance. After certain types of changes, particularly the 8 to 14 translocation that leads to the 14q+ marker, the affected B lymphocyte would no longer obey the negative feedback controls that would otherwise restrict its proliferation in vivo.

Animals↗
PubMedDate not supplied

[Cytogenetic studies of human lymphocytes under the influence of oxicams].

The influence of the oxicams, a special group of non-steroidal anti-inflammatory drugs, to the sister chromatid exchange (SCE) was determined on human lymphocytes in vitro and in vivo. The analysis of SCE is a sensitive parameter indicating chromosomal damage. The cytogenetic examinations of Lornoxicam, Tenoxicam, and Piroxicam in vitro showed no influence on the SCE frequencies in therapeutic dosages. With addition of mitomycin C (MMC) to the cultures (a method which simulates an additional genotoxic stress) we found significant higher SCE rates in connection with the oxicams than in controls without an oxicam. A 14-day treatment with Tenoxicam and Lornoxicam changed the spontaneous SCE rates in vivo; Piroxicam did not. The raised SCE levels could indicate an antimutagenic effect of the oxicams if the repair of DNA damages is transferred to a more perfect pathway; however by an overloading of the repair, due to additional genotoxic factors (such as cytostatics, cigarette smoking, x-ray exposure) therapy with oxicams could point out a genotoxic risk.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

[Clinical effectiveness and tolerance of auranofin in patients with chronic polyarthritis. Results of a multicenter long-term study].

In an open multicenter trial, 90 patients with rheumatoid arthritis were treated with a daily dose of 6 mg auranofin. The duration of the treatment was 12 months. A significant improvement in the following parameters was observed: grip strength, number of swollen and painful joints after the 4th month, blood erythrocyte sedimentation rate decreased significantly after the 2nd month. Of the 90 patients, 56 (62.3%) completed the therapy, in 14 (15.5%) it was discontinued because of side effects and in 8 (8.9%) because of inefficacy. 12 patients (13.3%) stated other reasons for discontinuing the therapy (non compliance). The reported side-effects were mostly gastrointestinal, especially diarrhoea and loose stools. The evaluation of results referring to the duration of the disease shows that patients with a duration of less than 2 years reacted better to the improvement with auranofin therapy than patients with a longer sickness history.

Adult↗
PubMedDate not supplied

[Studies on the differentiation of chondrocytes in connection with poly ADP ribose synthesis].

Cell differentiation and the behaviour of poly-(ADP-ribose)-synthesis after treatment with methoxybenzamide and procaine was examined in chondrocytes of cell cultures from albino rats. In this study an increase in cell differentiation was connected with a higher level of poly(ADP-ribose)-synthesis. On the basis of an increase in poly(ADP-ribose)-synthesis in chondrocytes an improved scheme of treatment of some rheumatic diseases could be developed.

Animals↗