[The situation of patients with dementia may be rectified by Gingko Biloba].
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Biomedical subjects
Publications and source records attributed to D Daniel.
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UNLABELLED: BACKGROUND AND ISSSUES: Ginkgo biloba-extracts are often used in therapy of patients with dementia. In this study, benefit and structure of Ginkgo biloba-extract EGb 761 in treatment of patients with dementia was examined. PATIENTS AND METHODS: For the assessment of quality of life of care-taking relatives and patients as well as treatment costs were documented. The study was conducted as a non-randomised, two-armed cohort study with an open design for 683 slightly or moderately demented patients, aged between 65 and 80 years. Society's perspective was taken. Barthel-Index and MMST were also documented. Because of significant differences at inclusion of both cohorts, a matched-pairs-analysis and multiple regression analysis conducted. RESULTS: According to PLC a significant improvement in quality-of-life of care-taking relatives (p < 0.001) and patients (positive mood p = 0.018, negative mood p < 0.001) was only observed in the Ginkgo-cohort. Also Barthel-Index indicated an improvement in the Ginkgo-cohort (p < or = 0,001). MMST-scores increased significantly only in the Ginkgo-cohort (p < 0.001). Average total cost per patient amounted to 3.614,75 euro in the standard-cohort, whereas these costs per patient in the Ginkgo-cohort amounted to 3.031,78 euro (p = 0.067). Results were confirmed by matched-pairs-analysis. RESULTS: Ginkgo treatment has a valid place in caretaking structure of health services. Gingko attributes to a higher quality of life for both care-takers and patients, the progression of disease is slowed down and treatment costs are lower.
Nucleosomes are the basic units of eukaryotic chromatin structure. By restricting factor access to regulatory DNA sequences, nucleosomes significantly impact genomic processes such as transcription, and various mechanisms to alter nucleosome structure to relieve this repression have evolved. Both nucleosomes and processes that alter them are inherently dynamic in nature. Thus, studies of dynamics will be necessary to truly understand these relief mechanisms. We describe here the characteristics of a novel fluorescence resonance energy transfer-based reporter that can clearly signal the formation of a canonical nucleosome structure and follow conformational and compositional changes in that structure, both at the ensemble-average (bulk) and at the single molecule level. Labeled nucleosomes behave conformationally and thermodynamically like typical nucleosomes; thus they are relevant reporters of nucleosome behavior. Nucleosomes and free DNA are readily distinguishable at the single-molecule level. Thus, these labeled nucleosomes are well suited to studies of dynamic changes in nucleosome structure including single-molecule dynamics.
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An open prospective cohort study was performed in Germany in order to evaluate the costs of treating alcohol dependence under real-world conditions. Eight hundred and fourteen recently detoxified alcohol-dependent patients were provided with psychosocial rehabilitation support. In addition, 540 alcohol-dependent patients treated with adjuvant acamprosate therapy were compared with 274 patients without pharmacotherapy. Real costs were assessed over a period of one year. Of the patients who were treated with acamprosate, 33.6% remained abstinent compared to only 21.1% in the standard cohort. The mean total costs per patient treated with acamprosate were EUR 1,631.49 per year. In the standard cohort, total costs were EUR 2,068.83. This difference is highly significant (p = 0.012). Direct costs amounted to 76.9% of the total costs, with a 27% difference between the cohorts (p < 0.001). There was no difference in indirect costs between the two groups (p = 0.324). This real-cost study confirms the favourable cost-effectiveness of acamprosate previously suggested by pharmaco-economic modelling studies.
OBJECTIVE: On the basis of several controlled clinical investigations the cost-effectiveness of acamprosate as adjuvant therapy of alcohol-dependent patients has yet been evaluated. These optimal conditions cannot be found in the daily ambulant practice and results in asking which of the alternatives, "standard plus acamprosate" or "standard without acamprosate", is more cost-effective in maintaining abstinence in alcohol dependent patients under realistic conditions. PATIENTS AND METHODS: In an open multi-centre study, medical care, costs and therapeutic outcome was prospectively documented. Prior to enrolling, all patients were obliged to undergo a detoxification procedure. At a mean age of 45 years the patients suffered an average of ten years from alcohol dependence. 521 patients were documented in the acamprosate cohort and 265 patients in the cohort "other therapy" over one year. Two thirds of the participating patients were male. RESULTS: At 33.6 % the rate of abstinence was remarkably higher in the acamprosate cohort in comparison to the cohort "other" at 21.1 % abstinent patients. The mean total costs per patient and year amounted to DM 3191 in the acamprosate-cohort and were significantly lower than in the cohort "other" with DM 4046. Effectiveness-adjusted costs of DM 9500 per successfully treated patient in the acamprosate-cohort were superior to the cohort "other", amounting to DM 19 148 per successfully treated patient. CONCLUSION: The described economic benefits may be utilised under conditions of an adequate disease management.
BACKGROUND AND OBJECTIVE: Prospectively determined data on costs of chronic bronchitis were not yet available for the Federal Republic of Germany. The purpose of the burden-of-illness-study conducted in the Federal Republic of Germany from October 1996 to March 1998 was to calculate direct and indirect costs of chronic bronchitis as well as its acute exacerbations per patient and year. Furthermore, the health-related quality of life of the patients was determined. PATIENTS AND METHODS: The burden-of-illness-study was conducted as an open, not randomised surveillance study. The evaluation based on 785 patients (55.4% male, 44.2% female, 0.4% unknown; mean age 60 years) who were treated by 147 general practitioners. 755 patients could be included into the cost analysis. RESULTS: Per patient and year direct costs of chronic bronchitis amounted to DM 1112.27, the calculation of indirect costs resulted in DM 959.09. 41.4% of direct costs were due to drug acquisition, hospitalisation costs shared 31.6% and costs for physicians' fee amounted to 20.6%. The severity of chronic bronchitis revealed significantly different results in cost analysis: per patient, mild disease lead to direct costs of DM 387.86, moderate disease to DM 802.62 and severe disease to DM 2224.40. This result was caused by higher costs for drug acquisition and hospitalisation costs due to chronic bronchitis in higher stages of severity. Indirect costs were calculated by applying the human-capital-approach: 45.8% of indirect costs were due to time-off-work, nursing costs amounted to 23.7%. CONCLUSION: The costs of chronic bronchitis have a considerable impact on the total costs of the health care system of Germany.
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BACKGROUND & OBJECTIVES: Human T lymphotropic virus-I (HTLV-I) has been associated with adult T cell lymphoma/leukemia (ATLL). There are Indian studies on HTLV-I infection among people with sexually transmitted infection, but no large study has been conducted on individuals with haematological malignancies. In this group of individuals, serology is known to under-diagnose HTLV-I infection. This study was carried out to identify serologically and where possible with molecular techniques, HTLV-I infection in individuals with haematological malignancies. To understand the modes of transmission, family members of individuals with proven HTLV-I infection were also studied. Individuals with sexually transmitted infection (STI), blood donors and pregnant women were also studied. METHODS: Particle agglutination test was used to detect antibody to HTLV-I. HTLV genome was amplified by polymerase chain reaction (PCR) and detected with probes by digoxiginin (Dig) ELISA. RESULTS: There was no serological evidence of HTLV-I infection among the healthy blood donors and pregnant women studied. High prevalence of anti-HTLV-I antibody was identified in the patients with haematological malignancies (8 of 86 patients, 9.3%) and a lower prevalence in individuals with STI (8 of 670 individuals, 1.2%). In the STI group, all 8 individuals seroreactive to HTLV-I were coinfected with human immunodeficiency virus (HIV). In the group with haematological malignancies, three of 22 (13.6%) patients with leukemia, 3 of 11 (27.3%) with cutaneous T-cell lymphoma (CTCL) and 2 of 53 (3.8%) with lymphoma were reactive for anti-HTLV-I antibody. In this group, PCR identified all the seroreactive individuals tested. There were also seronegative infected individuals who were only identified by PCR. There was also a large number of seronegative family members who were only positive by PCR. INTERPRETATION & CONCLUSION: The study revealed a strong disease association of HTLV-I with haematological malignancies and evidence for both horizontal and vertical transmission of the infection in the Indian population. HTLV-I infection appears to be common among family members of individuals with HTLV-I associated haematological malignancies.
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We compared the effects of reinforcing compliance with either positive reinforcement (edible items) or negative reinforcement (a break) on 5 participants' escape-maintained problem behavior. Both procedures were assessed with or without extinction. Results showed that compliance was higher and problem behavior was lower for all participants when compliance produced an edible item rather than a break. Treatment gains were achieved without the use of extinction. Results are discussed regarding the use of positive reinforcement to treat escape behavior.
Impulsivity and self-control involve a choice between a smaller, more immediate reinforcer and a larger, more delayed reinforcer. Impulsive behavior occurs when responding produces the more immediate, relatively smaller reinforcers at the expense of delayed larger reinforcers. Self-control occurs when responding produces delayed larger reinforcers at the expense of immediate smaller reinforcers. Recently, researchers in applied behavior analysis have suggested that evaluations of self-control and impulsivity are relevant to socially important behaviors. Further, common behavioral treatments such as differential reinforcement may be influenced by variables such as reinforcer delay. In this study, we showed that aggression, reinforced by access to food, could be maintained as impulsive behavior. The participants were 2 young boys with severe developmental disabilities. For both participants, descriptive observations, care provider report, and functional analyses suggested that aggression was reinforced by food access (and television access for 1 participant). Next, we introduced a differential reinforcement procedure in which appropriate mands were reinforced. After various manipulations, we showed that aggression occurred when it produced immediate but small reinforcers even though mands produced larger, more delayed reinforcers. However, both participants displayed self-control when the delay to reinforcement was signaled (with a hand gesture or a timer).
Restricted use of T cell receptor (TCR) gene segments is characteristic of several induced autoimmune disease models. TCR sequences have previously been unavailable for pathogenic T cells which react with a defined autoantigen in a spontaneous autoimmune disease. The majority of T cell clones, derived from islets of NOD mice which spontaneously develop type I diabetes, react with insulin peptide B-(9-23). We have sequenced the alpha and beta chains of TCRs from these B-(9-23)-reactive T cell clones. No TCR beta chain restriction was found. In contrast, the clones (10 of 13) used V alpha13 coupled with one of two homologous J alpha segments (J alpha45 or J alpha34 in 8 of 13 clones). Furthermore, 9 of 10 of the V alpha13 segments are a novel NOD sequence that we have tentatively termed V alpha13.3. This dramatic alpha chain restriction, similar to the beta chain restriction of other autoimmune models, provides a target for diagnostics and immunomodulatory therapy.
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The observation that overt type I diabetes is often preceded by the appearance of insulin autoantibodies and the reports that prophylactic administration of insulin to biobreeding diabetes-prone (BB-DP) rats, nonobese diabetic (NOD) mice, and human subjects results in protection from diabetes suggest that an immune response to insulin is involved in the process of beta cell destruction. We have recently reported that islet-infiltrating cells isolated from NOD mice are enriched for insulin-specific T cells, that insulin-specific T cell clones are capable of adoptive transfer of diabetes, and that epitopes present on residues 9-23 of the B chain appear to be dominant in this spontaneous response. In the experiments described in this report, the epitope specificity of 312 independently isolated insulin-specific T cell clones was determined and B-(9-23) was found to be dominant, with 93% of the clones exhibiting specificity toward this peptide and the remainder to an epitope on residues 7-21 of the A chain. On the basis of these observations, the effect of either subcutaneous or intranasal administration of B-(9-23) on the incidence of diabetes in NOD mice was determined. The results presented here indicate that both subcutaneous and intranasal administration of B-(9-23) resulted in a marked delay in the onset and a decrease in the incidence of diabetes relative to mice given the control peptide, tetanus toxin-(830-843). This protective effect is associated with reduced T-cell proliferative response to B-(9-23) in B-(9-23)-treated mice.
The non-obese diabetic (NOD) mouse develops diabetes as a result of spontaneous T cell mediated destruction of the insulin-producing beta-cells. Tolerization to glutamic acid decarboxylase (GAD65) has been reported to inhibit spontaneous T cell proliferative responses to GAD65 and GAD65 peptides and prevent insulitis and diabetes in NOD mice. To evaluate the role of T cells responsive to GAD65 in induction of diabetes in NOD mice we generated T cell clones from spleen cells of three prediabetic NOD mice using the reported immunodominant human GAD65 peptides nos. 17, 34 and 35, which are spontaneously recognized by NOD spleen cells. The ten T cell clones established from two female and one male NOD mice recognized either the GAD65 peptide no. 35 which has an identical amino acid sequence in mice and humans or recognized the human GAD65 peptide no. 17 which is different in two amino acids from murine GAD65 peptide no. 17. None of the clones exhibited responses to islet cells, and GAD65 peptide no. 17 responsive clones did not cross react with the murine GAD65 peptide no. 17. All clones were CD4 positive and expressed the alpha/beta T cell receptor, but differed in their V beta usage. Analysis of in vitro production of IFN gamma, IL-2 and IL-4 demonstrated a TH1 and TH0 like functional subset of the individual clones. In vivo, neither the autoreactive T cell clones specific for GAD65 peptide no. 35 nor the xenoreactive clones specific for GAD65 peptide no. 17 were able to accelerate diabetes in young NOD mice or transfer diabetes into NODscid mice.
T cells are known to play an important role in beta cell destruction in the nonobese diabetic (NOD) mouse model of Type I diabetes and islet-specific T cell clones have been demonstrated to be capable of adoptive transfer of diabetes. One important issue involves the identity of beta cell antigens that are recognized by nominally islet cell-specific T cell clones. We have previously reported that insulin-specific T cells are a predominant component of islet-specific T cells isolated from islet infiltrates of pre-diabetic NOD mice. In this report we examine six independently derived insulin-specific T cell clones established from islet infiltrates of pre-diabetic NOD mice in detail. All six clones were found to be specific to a region of the insulin molecule defined by a synthetic peptide encompassing residues 9-23 of the B chain. Despite this restricted specificity, each member of this panel exhibited a distinct receptor specificity defined either by V beta usage or antigen fine specificity. Five clones produced interferon (IFN)-gamma but not interleukin (IL)-4, placing them in the T helper type 1 (TH1)-like category whereas one clone produced both IL-4 and IFN-gamma, a characteristic of TH0 cells. All six clones were capable of either acceleration of diabetes in young NOD mice or adoptive transfer to NODscid mice. Taken together, these results suggest that spontaneously arising insulin-specific T cells participate in beta cell destruction during development of diabetes in NOD mice.