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Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 307 records · Page 17Linked to original sources
PubMed1996

Incidence of lower limb amputations and diabetes.

OBJECTIVE: We collected data on the incidence rates of amputations and their relative risk in diabetic subjects compared with the nondiabetic population. RESEARCH DESIGN AND METHODS: From all three hospitals in a city of approximately 160,000 inhabitants, we obtained complete lists of nontraumatic lower limb amputations. From each patient record, diabetic status was determined. We estimated age-specific and standardized incidence rates of amputations in the diabetic and nondiabetic populations and in the entire population, as well as the relative and attributable risks due to diabetes. RESULTS: Nontraumatic lower limb amputations were performed on 106 residents of Leverkusen (Germany) in 1990 and 1991. Of them, 82 (77.4%) had diabetes. Mean age was 72.0 years. In the case of multiple amputations, only the highest level was counted for the analysis. The following results were standardized to the German population. Incidence rates (100,000(-1) year-1) were determined to be as follows: for all amputations per total population, 33.8; for amputations in diabetic individuals per diabetic population, 209.2; for amputations in nondiabetic individuals per nondiabetic population, 9.4. Relative risk was 22.2; attributable risk among exposed, 0.96; population attributable risk, 0.72. When the study is repeated to monitor the St. Vincent targets (50% reduction), a reduction in the amputation rate in the diabetic population by 46% will be detected with 90% power. CONCLUSIONS: We found incidence rates similar to those in the non-Indian population of the U.S. Great relative and population-attributable risks indicate that improving foot care in diabetic individuals appears to be the main target for the reduction of amputations in the general population.

Adult↗
PubMed1996

Both adenosine A1- and A2-receptors are required to stimulate microglial proliferation.

The neuromodulator adenosine is one of the major endogenous inhibitors of overactive excitatory neurotransmission. Adenosine receptors have been identified on neuronal but also on glial surfaces, indicating a role of glial cells in mediation of adenosine effects. Microglia, the immunocompetent cells of the brain, typically respond with proliferation, migration and production of inflammatory substances to viral or bacterial stimuli or to cell damage and degeneration. Since adenosine is released in large amounts in conditions of, for example, hypoxic or ischemic stress, it might be involved in the activation process of microglia. Proliferation of microglia was determined by incorporation of [3H]thymidine into microglial DNA after stimulation with adenosine A1- and A2-receptor agonists. N6-Cyclopentyl adenosine (CPA) and CGS-21680, a specific adenosine A2-receptor agonist had no effect on microglial proliferation. However, combinations of CPA and CGS-21680 as well as the mixed agonist, N6-ethyl-carboxamido adenosine (NECA) increased incorporation of radiolabel above controls. The effect of NECA was inhibited by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). From these results, it is concluded that proliferation of microglia can be increased only by simultaneous stimulation of both adenosine A1- and A2-receptors. Targeted interference with the activation of A1-adenosine receptors by specific drugs appears to be sufficient to reduce microglial activation. The findings may have implications for the treatment of neurodegenerative diseases in which microglial activation is supposed to play a causative role.

Adenosine↗
PubMed1996

[Phase prevention in bipolar affective disorder with nimodipine. A case report].

A 56-year-old female patient had a history of more than 10 years' duration of a bipolar affective disorder manifest mainly as depressive episodes. These episodes used to occur once or twice each year, frequently leading to hospital admission. On average, the episodes lasted for about 2 months, and they tended to be followed by brief periods of hypomania. Only once, in 1986, did a manic episode make hospitalization necessary. Attempted prophylaxis with lithium at therapeutic plasma levels did not prove effective. Treatment with carbamazepine was discontinued because of leukopenia. The most recent stay in hospital became necessary because of a depressive episode that lasted for 5 months and did not respond to therapy. On admission the patient's score on the Hamilton depression scale was 23. When the calcium antagonist nimodipine was given at a dosage quickly escalated to 360 mg daily, the patient could be discharged in a state of complete remission after 26 days. For the first time in many years she has been emotionally stable for almost 1 year with single agent nimodipine therapy at 180 mg daily.

Bipolar Disorder↗
PubMed1996

[Differential diagnosis of resorptive tooth diseases and caries].

Feline Odontoclastic Resorptive Lesions (FORL, previously known as "neck lesions") on cat teeth are compared to caries and differentiated with the use of new methods. Radiological examination reveals typical odontoclastic resorptive processes, which take place at the dental root and at the periodontium. These lesions demonstrate the destruction on the desmodontium and the following ankylosing reaction. The rhodamine B stain which is selective for caries, stains regions which are softened by caries in a dark red way. Fuchsin/Acetic-Light Green stained histological preparations demonstrate the resorptive lacunae, resorptive lagoons and resorptive canals. Giant cells with multiple nuclei and reparative cementum can also be shown with the same stain. Hardness measurements using a Knoop diamond (KHN Knoop hardness number) give information about the degree of hardness of the different tissues. Electron microscopic investigations are performed to show the dentinal tubules and allowing the differentiation between FORL and caries. Since FORL also has been found in wild cats we deduced that alimentation has no effect on the pathogenesis of the disease.

Animals↗
PubMed1996

Performing CAPD independently with one hand using an assist device.

When a patient with only one functioning hand and learning disabilities experienced difficulty using the Baxter Ultrabag disconnect system, the CAPD staff at an Indiana unit conceived and designed a single-handed assist device to help their patient. Along with staff input from the Indiana unit, Baxter engineers used this design to help create the EZ-Aide Assist Device to help meet the needs of this particular patient population.

Activities of Daily Living↗
PubMed1996

[Goals, content and evaluation of training seminars for quality circle moderators].

In this paper, our experience with training courses for quality circle moderators is reported. Basic principles of the peer review method in general and the specific model of the topic-oriented quality circle approach in the ambulatory care in Sudbaden is described. Peer review in quality circle groups demands specific participants' skills. Thus, training courses for quality circle leaders have been set up to prepare moderators for their task. Attention is given to the goals and contents of training courses for physicians. Key elements are the supervisory role of the moderator and specific tasks in handling the group dicussions. Evaluation questionnaires after the courses showed that the participants (n = 41) judged the programme very positively.

Curriculum↗
PubMed1996

[Organization of practice oriented knowledge structures by the "cognitive apprenticeship" method].

The introduction of the new German specialist for psychiatry and psychotherapy increased the requirement for more integrated and flexible clinical training programs for residents. The integration of this multitude of more sophisticated diagnostic and therapeutic strategies in an individualized treatment plan for each patient requires new teaching strategies. The instructional method "Cognitive Apprenticeship" in acquisition of treatment planning-competence is discussed within a curriculum framework.

Curriculum↗
PubMed1996

Adenovirus-enhanced receptor-mediated transferrinfection for the generation of tumor vaccines.

Cancer vaccines are genetically modified tumor cells that, by cytokine secretion or by expression of costimulatory molecules, are capable of mobilizing the host's immune system to destroy tumor cells. We have used adenovirus-enhanced transferrinfection (AVET) for the generation of cancer vaccines. This is a highly efficient method to deliver various genes into a large proportion of tumor cells, making further selection unnecessary. We found in the mouse M-3 melanoma model that two consecutive vaccinations with transfected cells secreting IL-2 protect animals from tumor development by a subsequent challenge, and result in long-lasting tumor-specific immunity dependent on both CD4+ and CD8+ T cells. Patterns of lymphocyte recirculation and the need for CD4+ T cells indicated that the role of IL-2 is not merely local 'replacement of help', as has been proposed before. Instead, our findings suggest a three-stage process for the generation of effector T cells after vaccination with IL-2 secreting tumor cells: (1) tumor antigen uptake and processing at the site of injection by APCs, (2) migration of APCs into the regional draining lymph nodes where T-cell priming occurs, and (3) recirculation of activated cytotoxic T cells, that recognize and eliminate distant tumor cells. This model also implies that allogeneic tumor cells or synthetic tumor antigens may be used with success in future cancer vaccines.

Adenoviridae↗
PubMed1995

Stimulation of the sphingomyelin pathway induces interleukin-6 gene expression in human astrocytoma cells.

Interleukin-6 (IL-6) has previously been shown to participate in neurodegenerative processes including Alzheimer's disease. However, the mechanisms leading to increased IL-6 expression in the brain remain largely unknown. We have studied the effects of synthetic ceramides and sphingomyelinase as possible regulators of IL-6 gene expression in a human astrocytoma cell line. The synthetic ceramides C2- and C6-ceramide as well as the enzyme sphingomyelinase were able to induce IL-6 gene transcription and protein synthesis in a dose-dependent manner with maximal IL-6 mRNA levels being reached after 4 h of ceramide treatment. We propose that the sphingomyelin pathway is part of the signal transduction cascade leading to IL-6 gene expression in astrocytes, and that this pathway may be involved in IL-6-mediated neurodegenerative processes.

Astrocytes↗
PubMed1995

T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years.

In 1990, a clinical trial was started using retroviral-mediated transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA- SCID). The number of blood T cells normalized as did many cellular and humoral immune responses. Gene treatment ended after 2 years, but integrated vector and ADA gene expression in T cells persisted. Although many components remain to be perfected, it is concluded here that gene therapy can be a safe and effective addition to treatment for some patients with this severe immunodeficiency disease.

Adenosine Deaminase↗
PubMed1995

Growth hormone response to growth hormone-releasing hormone and clonidine in depression.

Growth hormone (GH) responses to the alpha 2-adrenoceptor agonist clonidine and to GH-releasing hormone (GHRH) were measured in 12 patients fulfilling DSM-III-R criteria for major depressive disorder and in 12 age- and sex-matched controls. GH responses to clonidine correlated significantly with the GH responses to GHRH in the depressed patients as well as in the controls. Neither the responses to clonidine nor the responses to GHRH were significantly lower in depressed patients than in controls. Similarly, somatomedin-C (Sm-C) plasma concentrations and baseline GH concentrations were not different between the two groups. The data do not suggest that blunted GH responses to clonidine and/or GHRH represent specific features of depression.

Adrenergic alpha-Agonists↗
PubMed1995

Priming of tumor-specific T cells in the draining lymph nodes after immunization with interleukin 2-secreting tumor cells: three consecutive stages may be required for successful tumor vaccination.

Although both CD4+ and CD8+ T cells are clearly required to generate long-lasting anti-tumor immunity induced by s.c. vaccination with interleukin 2 (IL-2)-transfected, irradiated M-3 clone murine melanoma cells, some controversy continues about the site and mode of T-cell activation in this system. Macrophages, granulocytes, and natural killer cells infiltrate the vaccination site early after injection into either syngeneic euthymic DBA/2 mice or athymic nude mice and eliminate the inoculum within 48 hr. We could not find T cells at the vaccination site, which argues against the concept that T-cell priming by the IL-2-secreting cancer cells occurs directly at that location. However, reverse transcription-PCR revealed transcripts indicative of T-cell activation and expansion in the draining lymph nodes of mice immunized with the IL-2-secreting vaccine but not in mice vaccinated with untransfected, irradiated M-3 cells. We therefore propose that the antigen-presenting cells, which invade the vaccination site, process tumor-derived antigens and, subsequently, initiate priming of tumor-specific T lymphocytes in lymphoid organs. These findings suggest a three-stage process for the generation of effector T cells after vaccination with IL-2-secreting tumor cells: (i) tumor-antigen uptake and processing at the site of injection by antigen-presenting cells, (ii) migration of antigen-presenting cells into the regional draining lymph nodes, where T-cell priming occurs, and (iii) circulation of activated T cells that either perform or initiate effector mechanisms leading to tumor cell destruction.

Animals↗
PubMed1995

Cancer vaccines: the interleukin 2 dosage effect.

Cancer vaccines genetically engineered to produce interleukin 2 have been investigated intensively in a series of animal models and are at the point of entering into clinical trials. In this study we demonstrate a strong correlation between the rate of interleukin 2 production and the protection efficiency of murine S91 melanoma cell (clone M-3) vaccines. Best immunization is achieved with vaccines producing medium interleukin 2 levels of 1000-3000 units per 10(5) cells per day. Reduced interleukin 2 production evokes a corresponding decline in the number of successfully treated animals. Unexpectedly, when interleukin 2 expression is raised to high levels of 5000-7500 units per 10(5) cells per day, protection is completely absent because of impaired generation of tumor-specific cytotoxic T lymphocytes. In comparison, granulocyte-macrophage colony-stimulating factor as immunomodulator induces substantial immunization even at a moderate level of secretion and protects all animals at the maximal obtainable level of secretion. Our findings demonstrate the importance of the interleukin 2 level produced by genetically modified tumor cells and may have substantial impact for the clinical application of cancer vaccines.

Animals↗
PubMed1995

Elicitation of a systemic and protective anti-melanoma immune response by an IL-2-based vaccine. Assessment of critical cellular and molecular parameters.

We have established a model for the immunologic rejection of melanoma cells. Using a receptor-mediated, adenovirus-augmented gene delivery system (transferrinfection) we have shown that, upon transfection with an IL-2 gene construct, MHC class I+/class II- murine M-3 cells lose their tumorigenicity in both athymic and euthymic mice. More importantly, we found that these melanoma cells, which produce high levels of IL-2, can be used to induce a long-lasting anti-tumor immune response in syngeneic euthymic DBA/2 mice but not in athymic animals. This immune response, which can also be elicited by coadministration of nonmodified, irradiated M-3 cells and IL-2-transduced fibroblasts, results in the rejection of a subsequent challenge with M-3 cells or, in the elimination of preexisting M-3 cancer cell deposits. We found that transfer of T cell-enriched, but not of T cell-depleted, splenocytes from immunized mice conferred protection against M-3 cells, but not against unrelated KLN 205 cancer cells. Transfer of either CD4+ or CD8+ T cells led to only partial protection against challenge with wild-type M-3 cells. Our further observations that T cell-enriched, but not T cell-depleted splenocytes of immunized animals are capable of tumor-specific lytic activity and that this activity resides in the CD8+ cell population are compatible with the assumption that MHC class I-restricted T cell cytotoxicity is a biologically relevant effector mechanism in this model. That other mechanisms also contribute to melanoma cell destruction is evidenced by the presence of large numbers of macrophages and granulocytes in addition to T cells at the challenge sites of immunized mice.

Animals↗