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Biomedical subjects

J Mayer

Publications and source records attributed to J Mayer.

At least 73 records · Page 4Linked to original sources

Ifosfamide- and etoposide-based chemotherapy as salvage and mobilizing regimens for poor prognosis lymphoma.

Treatment of early relapsing or resistant non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) remains problematic. High-dose chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation improves the prognosis for patients in response following standard dose regimens. We adopted the strategy of using salvage chemotherapy to debulk disease and simultaneously mobilize stem cells. We used regimens based on ifosfamide and etoposide because these drugs are not usually used as the front-line treatment. Twenty-seven patients with NHL received MINE chemotherapy (mesna and ifosfamide 1330 mg/m2 and etoposide 65 mg/m2 i.v. days 1-3, and mitoxantrone 8 mg/m2 i.v. day 1). The same schedule, but higher doses were used for PBSC stimulation (mesna, ifosfamide 1700 mg/m2, etoposide 175 mg/m2, mitoxantrone 10 mg/m2). Forty-six patients with HD received VIM chemotherapy (mesna, ifosfamide 1200 mg/m2 i.v. days 1-5, etoposide 90 mg/m2 i.v. days 1, 3, and 5, methotrexate 30 mg/m2 i.v. days 1 and 5). After both VIM and high dose MINE, chemotherapy for mobilization was followed by G-CSF administered at a dose 5-16 micrograms/kg/day depending on the clinicians judgement of the patient's pretreatment. Complete response after VIM and MINE were 39% and 38%, respectively; partial response (PR) rates were 17% and 29%, and stable disease (SD) 25% and 4%, respectively. In both groups, patients with relapsing disease had better responses than did those with primary progressive disease. Both regimens exhibited excellent mobilizing capacity. We performed 213 aphereses with a median 3 per patient starting on either day 13 as a median for VIM, or on day 12 as a median for MINE. In the majority of patients, the collection started in the time interval median +/- 1 day (n = 62, 85%). The median yields were 10.6 x 10(6) CD34+ cells/kg and 53.1 x 10(4) CFU-GM/kg for VIM, and 13.3 x 10(6) CD34+ cells/kg and 54.5 x 10(4) CFU-GM/kg for MINE. We collected at least 2.5 x 10(6) CD34+ cells/kg in all but six patients (8%), and the harvested amount of CD34+ cells was less than 1.0 x 10(6)/kg in only two patients (3%). The toxicity of VIM and MINE was minimal and chemotherapy-induced trombocytopenia did not occur with PBSC collection.

Adolescent↗

[Collection of peripheral hematopoietic stem cells for transplantation from volunteer donors--siblings of the patients].

Peripheral stem cells obtained by stimulation of haematopoiesis by administration of so-called growth factors are used for allogenic transplantations of haematopoietic cells only since the mid-nineties of the 20th century. So far however not all potential undesirable effects of growth factor administration to healthy subjects are known. The authors present the results of a programme of allogene transplantation of peripheral blood stem cells from related donors which was started in their department in 1996. From 11/1996 till 8/2000 the authors started 55 mobilizations of peripheral stem cells in donors before transplantation. The mobilization growth factor G-CSF was used for in a total dose of 16 micrograms/kg/day s.c. administered in two daily doses. During administration of G-CSF 19 donors had no complaints, 34 donors (64%) had pain in their bones, subfebrile temperatures and/or symptoms of flu. G-CSF produced dramatic changes in the haemogram--massive leucocytosis with dominant neutrophilia, after collection of the transplant thrombocytopenia developed. The changes of some biochemical parameters were also marked. A peripheral venous approach for collection of the transplant was applied in 23 instances (43%), in the remainder cannulation of a central vein was used. A total of 121 leukaophereses was performed in 53 donors (separator COBE Spectra) which were started on the 4th day of G-CSF administration. An automatic operation of PBSC collection was used in 28 leukaphereses, an operation of mononuclear collection in 93 leukaphereses. In leukaphereses only mild symptoms of hypocalcaemia were observed in 26 donors (48%). The mean total yield of leukaphereses was 9.39 x 10(6) CD34+ cells/kg of the recipient (3.48-23.13) and 76.54 x 10(4) CFU-GM/kg of the recipient (10.02-238.78), no mobilization failed. Of 36 donors 25 (69%) came for a check-up one year after collection of the transplant. No changes in the haemogram nor in biochemical parameters were recorded. In donors with hepatopathies pathological findings persisted in biochemical examinations without a deteriorating trend. Administration of G-CSF to healthy subjects is a new technology associated with certain advantages as well as some questions. Safety of donors holds the first place, detailed information is essential as well as examination and follow up not only on a short-term but also on a long-term basis.

Adult↗

[What is a non-myeloablative transplantation of hematopoietic cells?].

Transplantation of haematopoietic cells, dominantly peripheral stem cells, after a non-myeloablative regime is nowadays a very intensely investigated method. Its principle involves that the pretransplantation regime accentuates the immunosuppressive component to prevent transplant rejection but reduces the antitumourous component (chemotherapy or irradiation). It was demonstrated that the reaction of allogene transplanted lymphocytes against the residual tumour is the dominant anti-tumourous component of the whole allogene transplantation. Thus the acute toxicity of the whole procedure is reduced. The initial experience with this method is so far very promising. This is apparent from a review of the literature and 21 transplantations made by the authors. It appears also that this method will probably not be very suitable for patients with very advanced tumourous disease. There the antitumourous effects will not be sufficient. At present there are many pretransplantation regimes. This may be an advantage for seeking an optimal regime but it may also obscure the whole problem. Quite new horizons are offered by transplantation of allogenic T lymphocytes of HLA identical donors in the treatment of solid tumours. The first data were published for renal adenocarcinoma and are very promising.

Hematopoietic Stem Cell Transplantation↗

[Autologous transplantation of peripheral hematopoietic cells and subsequent maintenance therapy with interferon alpha or interferon alpha and dexamethasone in patients with multiple myeloma--results from the 4W randomized clinical trial of the Czech Myeloma Group].

In the clinical 4W study patients with newly diagnosed multiple myeloma are included where the state of the disease calls for treatment, while high dose chemotherapy is not contraindicated. Treatment according to protocol 4W comprises induction chemotherapy VAD, mobilization of haematopoietic cells (cyclophosphamide 5 g/m2). This is followed by autologous transplantation (as a conditioning regime melfalan 200 mg/m2 is administered). The patients are randomized into two groups, the first one is given interferon alpha as maintenance treatment, in the second group alternates cyclically interferon alpha and dexamethasone treatment. So far between 1996 and Aug. 31 2000 in the 4W clinical study 167 patients were included. 113 patients after transplantation were evaluated incl. 13 (12%) who achieved complete remission of the disease (absence of paraprotein, negative immunofixation), 63 patients (56%) with remission of the disease (decline of paraprotein, by more than 75%). Another 24 patients (21%) achieved partial remission (decline of paraprotein by more than 50% but less than 75%). The peritransplantation mortality is 2.67%. So far there is no significant difference between the two groups on maintenance treatment as regards the mean period before a relapse of the disease (p = 0.567). The median of the mean survival was not reached so far. The authors describe the results of the internal analysis of data incl. statistical processing.

Adolescent↗

[Comparison of the effectiveness of idarubicin (Zavedos) and mitoxantrone (Refador) in induction therapy of acute myeloid leukemia in elderly patients (55-75) (a prospective multicenter randomized study conducted 1998-2000].

The presented study compares the efficacy and the toxicity of idarubicine and mitoxantrone in combination with cytosar (3 + 7) in induction treatment of the patients with AML aged 55-75. 31 patients at the age of 55-75 (median 62) were evaluated in the arm with idarubicine and 29 patients at the age of 57-74 (median 64) in the arm with mithoxantrone. Complete haematological remission was achieved in 13 patients (41.9%) in the arm with idarubicine and 15 patients (51.7%) in the arm with mitoxantrone. The medians of overall survival time (OS) and disease free survival time (DFS) were 22 and 44 weeks in the idarubicine arm and 35 and 40 weeks in the mitoxantrone arm, respectively. Statistical analysis did not prove any significant difference in the complete remission rates, in the number of deaths during cytopenia, in the OS or DFS, in the duration of hospitalisation, severe neutropenia and thrombopenia, in the number of days with febrile neutropenia, or in the consumption of platelets and erythrocytes transfusion units between both arms. Despite the fact that these results are not statistically significant in favour of any treatment arm, which is probably influenced also by the small number of evaluated patients, more favourable results were achieved in the arm with mithoxantrone with the respect to the evaluated parameters. From the point of view of cost-effectiveness, the difference could be observed when considering the price of both intercalating cytostatics. The use of mitoxantrone (Refador, Lachema) is 15x times cheaper per course of treatment than the use of idarubicine (Zavedos, Pharmacia). Autologous peripheral blood stem cells transplantation (APBSC) was carried out only in 4 patients younger than 60. No one of them was cured by APBSC but the median of OS of these patients was longer than the median in the other patients of the group. The results achieved are comparable with those of other trials conducted by various foreign groups. The possible causes of our unfavourable treatment results in this high-risk category of aged patients and the ways how to individualize the treatment with the use of prognostic factors analysis and how to improve the quality of life of the patients has been discussed.

Acute Disease↗

[Non-cytostatic treatment of malignancies. Anti-CD20 monoclonal antibody (Rituximab, Mabthera) in the treatment of non-Hodgkin's lymphoma].

Some types of non-Hodgkin lymphomas cannot be treated by contemporary preparations. After repeated relapses and chemotherapy moreover damage of bone marrow occurs and further intense cytostatic treatment is not possible. Monoclonal antibodies against structures on tumour cells are an interesting alternative of cytostatic treatment. In 2000 the authors administered anti CD20 monoclonal antibody (rituximab, Mabthera Roche), 375 mg/m2, on the 1st, 8th, 15th and 22nd day i.v. to a total of 24 patients with relapsing non-Hodgkin lymphoma. In five patients the relapse developed after high dosage chemotherapy and autologous transplantation of peripheral stem cells. Treatment was well tolerated with minimal side-effects. Favourable therapeutic results were recorded in patients with follicular lymphoma (70% of the therapeutic responses), small lymphocyte lymphomas (64% of therapeutic responses) and in patients with a relapse after autologous transplantations (80% of therapeutic responses). Anti CD20 monoclonal antibody is a new effective alternative of cytostatic treatment. Its position in the therapeutic strategy in patients with non-Hodgkin lymphoma awaits elaboration.

Adult↗

Metastatic neuroendocrine tumor presenting as spinal cord compression--a case report and brief comment.

Gastrointestinal neuroendocrine tumors are derived from the diffuse neuroendocrine system of the gastrointestinal tract which is composed of amine and acid producing cells with different hormonal profiles, depending on the site of origin. The tumors they produce can be divided into carcinoid tumors and pancreatic endocrine tumors. We believe this to be only the fourth case in the literature of a patient presenting with cord compression as a result of a metastatic neuroendocrine tumor (MEDLINE 1966-2000).

Aged↗

Status of HERV in human cells: expression and coding capacity of human proviruses.

Human endogenous retroviruses (HERVs) comprise a significant portion of the human genome. They are expressed in a variety of human tissues and some encode intact retroviral proteins. HERV expression seems to be upregulated in certain tissues and tumour types. The HERV-K(HML-2) family is an important exception from the vast majority of defective HERVs in that it encodes all essential retroviral proteins and functional enzymes, respectively. Furthermore, several intact HERV-K(HML-2) gag and env genes as well as an almost intact HERV-K(HML-2) provirus could be demonstrated within the human genome. However, none of the HERVs described so far seems to produce infectious virus.

Defective Viruses↗

[High-dosage chemotherapy with support of autologous haematopoietic cells in the treatment of multiple myeloma--review of contemporary possibilities].

High-dosage chemotherapy with autologous transplantation of haematopietic stem cells prolonged the survival of patients with multiple myeloma as compared with results of standard chemotherapy, on average by 1.5 years. Nowadays this method is the standard treatment for suitable patients. Findings assembled recently are discussed by the authors.

Antineoplastic Agents↗

Impact of different clinical variables on pregnancy outcome following embryo cryopreservation.

In our program's 13 years of experience, more than 9000 embryos have been cryopreserved in gonadotropin-stimulated IVF cycles. Over 1500 thaw and transfer cycles have yielded a pregnancy rate of approximately 25%. Different ovarian stimulation regimens (various preparations of FSH. alone or in combination with hMG, with or without concomitant use of a GnRH agonist) did not influence embryo survival or pregnancy rate. Likewise, the application of oocyte/embryo micromanipulation techniques for assisted fertilization (ICSI for male infertility) or assisted hatching (performed selectively) did not have an impact on pregnancy results. Survival and transfer rates of embryos cryopreserved at pronuclear or cleaving stage did not differ significantly. However, implantation and pregnancy rates were higher with pronuclear embryo freezing (day-2 transfers) when compared to embryos frozen at the cleavage stage (day-3 transfers). This may be the result of patient selection and transfer policies. Similar implantation and pregnancy results were achieved in natural and estrogen progesterone supplemented transfer cycles. Initial experience with pronuclear freezing followed by transfer at the blastocyst stage appears to offer a very successful alternative for selected patients.

Adult↗

Human endogenous retrovirus protein cORF supports cell transformation and associates with the promyelocytic leukemia zinc finger protein.

Human endogenous retrovirus sequences (HERVs) reside in the genomes of primates and humans for several million years. The majority of HERVs is non-coding but a limited set is intact and can express proteins. We have recently identified an almost intact HERV-K(HML-2) provirus on chromosome 7 and have documented that most patients with germ cell tumors (GCTs) display antibodies directed against proteins of HERV-K(HML-2). To address whether these proteins merely represent tumor markers or contribute to neoplastic transformation, we examined the transforming potential of various HERV sequences and studied physical interactions between HERV and cellular proteins by yeast two-hybrid and biochemical assays. cORF, a protein encoded by the C-terminal open reading frame within the env gene, supports tumor growth in nude mice and associates with the promyelocytic leukemia zinc finger protein (PLZF). The interaction domains map between amino acid residues 21 and 87 of cORF, and between residues 245 and 543 of PLZF. PLZF is critical for spermatogenesis in mice. Abnormal spermatogenesis or maturation of gonocytes is thought to predispose humans to the development of germ cell tumors. Thus, cORF of human endogenous retroviruses may contribute to tumor development by interfering with processes during spermatogenesis that involve PLZF.

Animals↗

Matrices for tissue engineering-scaffold structure for a bioartificial liver support system.

This study proposes a new composite scaffold system. A woven polyethylenterephtalate (PET) fabric was coated on one side with a biodegradable PLGA film, in order to obtain a geometrically polarized scaffold structure for an bioartificial liver support system. The composite structure ensures the stability of the membrane during degradation of the membrane polymer. The mesh size of the composite does not significantly influence the degradation behavior. Hepatocyte culturing studies reveal that the formation of aggregates depends on the mesh size and on the pretreatment: The largest aggregates could be observed after 48 h when PVLA coating, large mesh size and EGF were combined. Thus, the combination of a geometrically structured, partially degradable scaffold with receptor-mediated cell attachment sites offers promising possibilities in liver tissue engineering.

Animals↗

[Scabies epidemic in a sheltered workshop--what should be done?].

Scabies is an infectious parasitic skin disease with a notable rising incidence in Germany. The disease is usually transmitted by close physical contact, but indirect spread e.g. by bedding is also possible. Due to its contagiousness, introduction of scabies into crowding living facilities, such as dormitories or kindergartens, can easily cause an epidemic outbreak. We describe an epidemic of scabies in a workshop for handicapped people in February 1998. A worker with severe scabies reported that numerous colleagues in both workshop and the associated hostel had complained of pruritus for months and that some of them already had undergone scabicide treatment. The number of contacts (staff, colleagues, friends, attendants, family) of our patient and the other already affected people was more than 460. The management of the workshop asked for help in handling the epidemic. We describe the cooperative efforts of the management, as well as hospital and private dermatologists, to evaluate all potential contacts and present a concept of treatment for the termination of such an epidemic outbreak of scabies.

Animals↗

Preparation and in vivo testing of porous alumina ceramics for cell carrier applications.

Microporous alumina was used to develop implantable cell carriers shaped as a hollow-sphere with a central opening to allow ingrowth of vascularised tissues. The carriers were produced by suspending the ceramic raw materials in water, homogenising and dropping the resulting slurry onto a heated plate (hot plate moulding, HPM). Morphological characteristics of the cell carriers were investigated by SEM and optical microscopy. Produced carriers had an average diameter of 4.9 mm. The material was highly porous (56 +/- 8%). For in vivo testing the cell carriers were implanted into abdominal wall of Zur: SIV rats for up to 50 weeks and investigated by light microscopy, SEM and TEM. The surface of the hollow carriers was in close contact with unirritated muscle tissue; no inflammation or capsule formation was observed. Loose connective tissue had grown into the hollow cell carrier, and after prolonged implantation >20 weeks adipocytes were observed. The absence of scar tissue formation around the implant and the vitality within the cavity of the hollow carriers indicate that porous alumina may be used for cell transplantation devices.

Aluminum Oxide↗

Titanium containing amorphous hydrogenated carbon films (a-C: H/Ti): surface analysis and evaluation of cellular reactions using bone marrow cell cultures in vitro.

Amorphous hydrogenated carbon (a-C : H) coatings, also called diamond-like carbon (DLC), have many properties required for a protective coating material in biomedical applications. The purpose of this study is to evaluate a new surface coating for bone-related implants by combining the hardness and inertness of a-C : H films with the biological acceptance of titanium. For this purpose, different amounts of titanium were incorporated into a-C : H films by a combined radio frequency (rf) and magnetron sputtering set-up. The X-ray photoelectron spectroscopy (XPS) of air-exposed a-C : H/titanium (a-C : H/Ti) films revealed that the films were composed of TiO2 and TiC embedded in and connected to an a-C : H matrix. Cell culture tests using primary adult rat bone marrow cell cultures (BMC) were performed to determine effects on cell number and on osteoblast and osteoclast differentiation. By adding titanium to the carbon matrix, cellular reactions such as increased proliferation and reduced osteoclast-like cell activity could be obtained, while these reactions were not seen on pure a-C : H films and on glass control samples. In summary, a-C : H/Ti could be a valuable coating for bone implants, by supporting bone cell proliferation while reducing osteoclast-like cell activation.

Analysis of Variance↗

Analysis of local strain in aluminium interconnects by energy filtered CBED

Energy filtered convergent beam electron diffraction (CBED) was used to investigate localised strain in aluminium interconnects. The quantitative analysis of the experimental patterns is based on a multi-step evaluation procedure which is the main subject of the present paper. The improvements which were made to the analysis method aim at increasing both the automation and the accuracy. The detection of the higher order Laue zone (HOLZ) line positions is performed by means of the Hough transform. The required sub-pixel resolution can be achieved routinely and the achievable accuracy is only limited by the line width and the amount of noise in the patterns. The determination of the strain state is performed via a refinement algorithm which is based on varying the strain state in the sample coordinate system and simulating the patterns for the individual grains until a best fit with the experiment is obtained. For the simulation we have developed a new correction scheme in which the dynamical effects are treated separately for each individual HOLZ line. The results show that the main source of the observed strains is the difference in thermal expansion coefficients. The strain is substantially reduced underneath a hillock in the interconnect. Asymmetries in the strain distribution around the hillock show that the unidirectional diffusion during electromigration tests causes peak strains in areas next to the hillock which may be possible failure sites.

Journal Article↗