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Biomedical subjects

M Gebhardt

Publications and source records attributed to M Gebhardt.

At least 19 recordsLinked to original sources

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

[Hysteria and psychosis].

The relationship between endogenous-psychotic and hysterical behavior is presented in this paper on the basis of typical patients' accounts. Various patterns of behavior are revealed: chronic hysterical psychotic syndromes, acute hysterical psychotic syndromes, hysterical exalted psychotic episodes, simulated hysterical psychotic syndromes, hysterical behavior in the attempt to cope with psychosis, and pseudohysterical behavior in endogenous psychoses. The specific aspects of the doctor-patient relationship in the case of these patients are described.

Adaptation, Psychological

[Results of short-term group psychotherapy of schizophrenic patients].

A seven-week group-centered dynamic therapy course was conducted with 12 patients within the framework of a long-term treatment for schizophrenic patients. The purpose and method of treatment and the course of the group sessions are described. Analysis of the Freiburg personality inventory yielded no changes; the degree of agreement between the group mean profile and that of neurotics was striking. Analysis of the Frankfurt complaint questionnaire (Suellwold) revealed a reduction in the number of affirmative answers during and after treatment. The treatment is considered to have had positive results, although it has to be embedded in a more comprehensive treatment plan with supportive individual psychotherapy, psychopharmaceutic treatment and sociotherapy.

Adult

Association between rapidly progressive glomerulonephritis and the properdin factor BfF and different HLA-D region products.

Frequencies of the HLA antigens ABC, DR and MT, as well as of the properdin factor alleles were determined in 24 unrelated patients presenting with immune complex mediated idiopathic rapidly progressive glomerulonephritis (RPGN) type II. As in Goodpasture syndrome (RPGN type I with pulmonary hemorrhage), a significant association with the B-cell alloantigen HLA-DR 2 was demonstrated (relative risk for HLA-DR 2 positive individuals was 3.54; P less than 0.01). In addition a marked increase of the HLA specificity MT 3 was shown, which is supposed to belong to an antigen system of a second HLA-D region locus. The highest relative risk of 14.67 (P less than 0.00001), however, was calculated for all patients carrying the BfF phenotype. Increased numbers of patients positive for HLA-DR 2 and -MT 3, as well as BfF suggested immune response genes or disease-related mutations on different haplotypes responsible for a MHC (major histocompatibility complex) associated predisposition of RPGN type II.

Adolescent

[Early changes in the microangiogram of the rabbit brain after experimental skull and cerebral trauma. Part 1 methods (author's transl)].

Experiments were performed in order to determine what changes occur in the microcirculation of the brain in animals following closed skull trauma, when these occur in relation to the trauma and what further changes are to be expected. In the first part of the paper suitable experimental methods are described. Skull trauma was inflicted to anaesthetised rabbits by means of a special apparatus by which impact speed, force, frequency, acceleration and period of contact could be determined. Three, five, ten and 15 minutes following the trauma, a special mixture was injected through a catheter in the aortic arch and the animals were decapitated. The brain was sectioned in three anatomically defined places and examined histologically and by microangiography. For the latter purpose glass plate coated with emulsion, a special exposure chamber and an x-ray tube with small focal spot were used. Exposures of five minutes permitted objects of 0.78 micrometers to be sharply resolved. Twenty-one defined areas were enlarged 360 times and compared with histologic sections. The normal microcirculation in the rabbit brain is described.

Angiography

Further observations on the inhibition of tumor growth by C. parvum with cyclophosphamide. VII. Effect of treatment prior to primary tumor removal on the growth of distant tumor.

The present investigations were directed toward determining whether primary tumor manipulation prior to its removal is advantageous for the control of metastases and survival. Studies were carried out to ascertain whether 1) there is justification for delaying surgical removal of a primary tumor to permit preoperative administration of cyclophosphamide (CY) and/or C. parvum (CP) and 2) there is an advantage to administering the immunotherapy directly into a primary tumor. After operation, in all investigations, systemic CP and CY was used. Despite the putative similarity of animals, tumors and treatment regimens there was marked variation in response of tumors to therapy. No benefit was derived from administering preoperative immunotherapy alone. When operation was delayed to employ systemic immuno-chemotherapy, a slight improvement in the control of distant tumor was noted. The employment of preoperative intratumor immunotherapy led to a greater prolongation of survival and more inhibition of distant tumor growth than did immediate primary tumor removal or the use of preoperative systemic immunotherapy. The results suggest that there may be an advantage to delaying removal of a primary tumor so that it may be employed in therapeutic strategies directed toward control of metastatic disease.

Animals

Urinary matrix calculi consisting of microfibrillar protein in patients on maintenance hemodialysis.

In seven patients on maintenance hemodialysis, de novo recurrent renal stone formation was observed. In all patients, the underlying disease was glomerulonephritis, with or without the nephrotic syndrome. All patients had considerable persistent proteinuria. The stones consisted predominantly of protein, as revealed by amino acid analysis, and had a negligible carbohydrate and lipid content. Only in some specimens, X-ray diffraction and scanning electron microscopy revealed the presence of small amounts of whewellit (calcium oxalate monohydrate) and/or uric acid. In semithin sections, the stones had a laminated texture and exhibited structural anisotropy under polarized light. With transmission electron microscopy, they were found to consist of peculair microfibrils. The proteinaceous material differed from fibrin or Tamm-Horsfall-protein, as indicated by ultrastructure, carbohydrate analysis, and amino acid analysis. Symptomatic de novo matrix stone formation constitutes another complication of dialyzed patients which has not been reported so far.

Adult