PubMed Health⌕ Search

Biomedical subjects

M Gebhardt

Publications and source records attributed to M Gebhardt.

At least 37 records · Page 2Linked to original sources

[Effects of the 1987 revision of the definition for an AIDS case in Switzerland].

AIDS cases diagnosed in Switzerland after the revision of 1987 and reported to the Swiss Federal Office of Public Health until 31.12.1992 were categorised according to whether they conformed to the diagnostic criteria valid before the revision (= "pre-87"-group) or only to the new criteria introduced with the revision (= "post-87"-group). Compared to the "pre-87"-group, the proportion of injecting drug users was higher, the proportion of homosexual men was lower, the patients were younger and Pneumocystis carinii pneumonia (PCP) and Kaposi-sarcoma were diagnosed less frequently in the "post-87"-group. The revision of the AIDS case-definition affected the proportion of Aids-diagnoses with PCP over time. It improved the surveillance of AIDS morbidity in Switzerland but its effects must be distinguished from true phenomena of the AIDS-epidemic.

Acquired Immunodeficiency Syndrome↗

Different growth factor requirements for human Th2 cells may reflect in vivo induced anergy.

We previously reported the isolation of allergen-specific Th2 lines and clones from atopy patch test (APT) sites of atopic dermatitis (AD) patients. Upon stimulation with allergen or anti-CD3+ phorbol myristate acetate (PMA) IL-4 was released with or without IL-5, while no (or extremely low concentrations of) IL-2 and interferon-gamma (IFN-gamma) were detectable. A high IL-4/IFN-gamma ratio facilitates production of allergen-specific IgE, of which high levels are observed in AD patients. Here we show that the above mentioned Th2 cells are notably different from murine Th2 cells. Not IL-4, which is the autocrine acting growth factor for murine Th2 cells, but IL-2 was needed for proliferation of these human APT-derived Th2 lines and clones. Of significance, unless exogenous IL-2 was added, no proliferative response to allergen, presented by Epstein-Barr virus-transformed B (EBV-B) cells, non-T cells or IgE-bearing Langerhans cells (LC), occurred. Lack of proliferation and IL-2 production after full T cell receptor (TCR) triggering is a characteristic first described for in vitro anergized T cells. However, like the clones we describe in this study, anergic T cells may retain production of cytokines other than IL-2. A further resemblance between anergic T cells and the human Th2 clones reported here is that IL-4 can enhance IL-2-driven proliferation, but is not capable of inducing T cell growth by itself. The absence of IL-4-driven proliferation differentiates human Th2 cells from murine Th2 cells. Both produce IL-4 when stimulated in a cognate fashion, but only murine Th2 cells will proliferate. We conclude that the presently reported human Th2 cells are different from murine Th2 cells, in that they need other T cells to produce IL-2 required for their expansion. Moreover, the Th2 cells phenotypically resemble anergic T cells. As yet, however, we have no clue as to whether these features account for the current Th2 cells only or for human Th2 cells in general. We hypothesize that the Th2 phenotype of AD skin-derived, allergen-specific T cells may be induced in vivo by LC, which lack CD80, and therefore do not provide secondary signals through CD28-CD80 interaction.

Adult↗

Magnetic source localization and morphological changes in temporal lobe epilepsy: comparison of MEG/EEG, ECoG and volumetric MRI in presurgical evaluation of operated patients.

Is MEG source analysis able to precisely locate the primary focal epileptic activity? 22 patients with pharmacoresistant temporal lobe epilepsy were recorded during presurgical evaluation simultaneously with multichannel MEG/EEG and invasive (subdural) electrodes to evaluate the increase of information gained by MEG concerning the localization of focal epileptic activity and lesions. With this systematic study it should become clearer how often MEG can establish a diagnostic bridge between function and morphology. In addition, MEG localization accuracy of focal epileptic activity was to be validated empirically by invasive EEG recordings and postsurgical outcome. Spikes in the MEG were used for magnetic source localization, and the result was combined with magnetic resonance imaging (MRI). All patients definitely suffered from temporal lobe epilepsy and revealed a structural abnormality in MRI. 17 patients with lesions in the temporal lobe were operated meanwhile and became markedly improved or seizure free. In 7 of 8 patients with a tumor and validated operation outcome, a very close correlation of the 3D-magnetic source localization and the border of the tumor in the brain was found (distance less than 10 mm). In 8 of 9 patients with a temporal/hippocampal atrophy and validated operation outcome, dipoles of epileptiform activity were located within the atrophic lobe.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

Characterization of murine monoclonal antibodies to phospholipase A2 and mellitin from bee venom.

9 murine monoclonal antibodies (MoAbs), 7 to phospholipase A2 (Pla2; Api m I) and two to mellitin (Api m III) have been produced. Specificities were demonstrated using immunoblotting and enzyme immunoassays (ELISA). Antibodies specific for Pla2 were characterized in detail. Epitope mapping of Pla2-specific MoAbs identified three independent binding regions. 5 selected MoAbs bound to one of these sites compete with specific human IgE. Two of MoAbs characterized are suitable tools to quantify Pla2 in a two-site binding assay.

Animals↗

The biliary and renal elimination of the new muscarinic-1-antagonist AWD 26-06 in volunteers with T-tube after cholecystectomy.

The biliary and renal elimination of the new muscarinic-1-antagonist AWD 26-06 were investigated in 6 female volunteers (age: 26-69 years) 9-14 days after cholecystectomy and T-tube construction. After a single oral dose of 50 mg AWD 26-06 as an aqueous solution the amount of the unchanged substance was determined in serum, T-tube bile and urine with a special HPLC-method. The concentration maximum was reached earlier and higher in bile (60 +/- 22 min; 10.8 +/- 5.7 micrograms/ml) than in serum (73 +/- 28 min; 0.98 +/- 0.53 micrograms/ml). During the whole observation time of 24 h the AWD 26-06 concentration in bile was 2-21-fold higher than in serum. In mean 2.3 +/- 1.5% of the administered dose were eliminated unchanged by bile and 12.2 +/- 5.9% by urine. More than 70% of the dose were metabolized. The results gave a hint at active liver transport processes and an enterohepatic recirculation. A drug interaction was observed with valproic acid on the metabolic level. The great interindividual variability of pharmacokinetic data can be caused by the heterogeneity of the subject group and a genetic polymorphism in the metabolism of AWD 26-06. The bile sampling by means of a T-tube is a simple but effective method under consideration of special conditions.

Adult↗

[Tumor diseases in families of 600 breast cancer patients with special reference to familial adenocarcinomatosis and the Li-Fraumeni-/SBLA syndrome].

In some families breast cancer aggregates as the predominant site-specific neoplasia and in others in association with defined malignancies. In the case of familial adenocarcinomatous (Lynch II-syndrome) it occurs together mainly with colorectal and endometrial carcinoma whereas in the case of the Li-Fraumeni/SBLA-syndrome it belongs to a wider spectrum including sarcoma, brain tumors, lung and laryngeal cancer, leukaemia and adrenocortical carcinoma. The occurrence of these malignancies is reported as they were observed in the families of 600 women suffering from breast cancer.

Adenocarcinoma↗

[Mast cells and basophilic granulocytes: their significance in allergic diseases].

Mast cells, and to a lesser extent basophilic granulocytes, have long determined models in the field of pathogenetic mechanisms in allergic disease. Unfortunately this has not resulted in adequate therapy for these diseases, and other cell types such as eosinophils and lymphocytes are now thought to influence allergic mechanisms too. However, knowledge of mast cells has increased to such an extent over the last decade that there may be a "revival" of their importance for allergic disease. In many organs in the body heterogeneity of mast cell morphology has been demonstrated. These different types of mast cells may also release different types of mediators. Moreover, mast cells have recently been shown to be capable of releasing cytokines, which may have a very important bearing on the pathogenesis of allergic diseases. Because mast cells and basophils are able to release a wide variety of mediators which may be responsible for many different physiological responses, they remain important cell types for allergy.

Basophils↗

Rotationplasty as a reconstructive operation after tumor resection.

Reconstruction in the skeletally immature patient following resection of osteosarcoma about the knee is a challenging problem. Salvaging of the limb with allogeneic or prosthetic replacement results in a shortened limb with functional limitations. Arthrodesis yields a stiff and shortened limb. The so-called growing prosthesis has a high complication rate and is still unproven. However, rotationplasty has been successfully used as a reconstructive technique following resection of these types of tumors in the skeletally immature patient. A limb with normal sensation and proprioceptions, adequate range of motion, and without leg-length discrepancies, functional limitations, or painful neuroma is to be expected. Although a prosthesis must be worn, these patients are active and participate in unrestricted physical activity. Cosmetic acceptance has not been a problem and complications are minimal. Thus, rotationplasty requires only a single operation and results in a highly functional limb.

Adolescent↗

p53 functions as a cell cycle control protein in osteosarcomas.

Mutations in the p53 gene have been associated with a wide range of human tumors, including osteosarcomas. Although it has been shown that wild-type p53 can block the ability of E1a and ras to cotransform primary rodent cells, it is poorly understood why inactivation of the p53 gene is important for tumor formation. We show that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells. The growth arrest was determined to be due to an inability of the transfected cells to progress into S phase. This suggests that the role of the p53 gene as an antioncogene may be in controlling the cell cycle in a fashion analogous to the check-point control genes in Saccharomyces cerevisiae.

Amino Acid Sequence↗

Effects of propane-2, 2-diphosphonate (PDP) on matrix-induced ectopic bone formation in comparison to ethane-1-hydroxy-1, 1-diphosphonate (EHDP).

The most prominent effect of propane-2, 2-diphosphonate (PDP) and ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on matrix-induced ectopic bone in the rat was a dose-dependent inhibition of osteogenesis in the early phases of development. The delay was seen as a consequence of osteoprogenitor cell inhibition. Additionally, later phases of bone maturation were disturbed by interference with the mineralization and remodeling processes. However, direct effects on the calcium phosphates of bone are only of minor additional value, which remains of lesser importance in comparison to the cellular impairment. After withdrawal of diphosphonates, the effects were nearly completely remitted. Neither PDP nor EHDP, even given in high doses, resulted in a lasting reduction in ectopic mass. The remission may be referred to the recovery of cell activities, whereas the mineral impregnation of osteoidosis was, if at all, of little importance. For treatment of ectopic osteogenesis PDP proved inefficient.

Animals↗

Postradiation multicentric osteosarcoma.

The oncogenic effects of radiation are well-established. Osteosarcomas and fibrosarcomas are the two most common histologic types of secondary sarcoma. In this article a case of postradiation osteosarcoma is presented in which four discrete foci of sarcomatous transformation have occurred in the tibia and fibula after irradiation for a rhabdomyosarcoma of the calf 8 years earlier. A review of the literature reveals no similar case. Although synchronous, multifocal osteosarcoma without prior radiation has been described, this case differs in clinical, radiographic, and pathologic features; it best fits the description of postradiation multicentric osteosarcoma.

Bone Neoplasms↗

Spontaneous rupture of the extensor pollicis longus tendon.

An extensor pollicis longus tendon, ruptured after treatment of a giant cell tumor of the distal radius by packing the cavity with polymethylmethacrylate cement. The lack of extension was treated successfully with tendon transfer of the extensor indicis proprius to the extensor pollicis longus. Pathophysiology of the rupture is discussed.

Adult↗

Weekly high-dose methotrexate and doxorubicin for osteosarcoma: the Dana-Farber Cancer Institute/the Children's Hospital--study III.

Weekly high-dose methotrexate with leucovorin rescue and vincristine (HDMTX) and doxorubicin was administered as adjuvant postoperative therapy to 46 patients with a diagnosis of conventional high-grade nonmetastatic osteosarcoma of an extremity between July 1976 and December 1981. The primary lesions were managed by wide or radical amputation (26 patients) or by limb-sparing resection in 20 selected patients. The margins of the resections were retrospectively classified as marginal in three, wide in 16, and radical in one. The 5-year relapse-free survival (RFS) for all patients is 59% (95% confidence interval [CI], 43%, 74%) and overall survival is 78% (95% CI, 65%, 91%). The RFS for patients initially having a limb resection procedure is 55% (95% CI, 32%, 77%) compared with 62% (95% CI, 43%, 81%) for those initially having amputations (P = .52). Using multivariate analysis, the only significant prognostic variables that predicted RFS of greater than or equal to 3 years, were the presence of moderate to marked lymphocytic infiltration of the primary tumor (P less than .002), primary site outside of the proximal humerus (P less than .005), and the absence of a predominance of osteoblastic pattern in the primary tumor (P less than .03).

Actuarial Analysis↗