De toekomst is aan de psychodynamische psychiatrie.

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[Reaction on 'The psychodynamic psychiatry has the future']. / Reactie op 'De toekomst is aan de psychodynamische psychiatrie'.

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Electrical stimulation of the upper limb in stroke: stimulation of the extensors of the hand vs. alternate stimulation of flexors and extensors.

OBJECTIVE: To investigate whether there is a difference in functional improvement in the affected arm of chronic stroke patients when comparing two methods of electrical stimulation. DESIGN: Explanatory trial in which 30 chronic stroke patients with impaired arm function were randomly allocated to either alternating electrical stimulation of the extensor and flexor muscles of the hand (group A) or electrical stimulation of the extensors only (group B). Primary outcome measure was the Action Research Arm test to assess arm function. Grip strength, Motricity Index, Ashworth Scale, and range of motion of the wrist were secondary outcome measures. RESULTS: Improvement on the Action Research Arm test was 1.0 point in group A and 3.3 points in group B; the difference in functional gain was 2.3 points (95% confidence interval, -1.06 to 5.60). The success rate (i.e., percentage of patients with a clinically relevant improvement of >5.7 points on the Action Research Arm test) was 27% in group B (four patients) and 8% in group A (one patient). The differences in functional gain and success rate were not statistically significant, neither were the differences between the two groups on the secondary outcome measures. CONCLUSION: The difference between the two stimulation strategies was not statistically significant.

Reasons for adopting technological innovations reducing physical workload in bricklaying.

In this paper the adoption of technological innovations to improve the work of bricklayers and bricklayers' assistants is evaluated. Two studies were performed among 323 subjects to determine the adoption of the working methods, the perceived workload, experiences with the working methods, and the reasons for adopting the working methods. Furthermore, a comparison of the results of the studies was made with those of two similar studies in the literature. The results show that more than half of the sector adopted the innovations. The perceived workload was reduced. The employees and employers are satisfied with the working methods and important reasons for adoption were cost/benefit advantages, improvement of work and health, and increase in productivity. Problems preventing the adoption were the use of the working methods at specific sites, for instance in renovation work. The adoption of the new working methods could perhaps have been higher or faster if more attention had been paid to the active participation of bricklayers and bricklayers' assistants during the development of the new working methods and to the use of modern media techniques, such as the Internet and CD/DVD.

Therapeutic electrical stimulation to improve motor control and functional abilities of the upper extremity after stroke: a systematic review.

BACKGROUND: Therapeutic electrical stimulation (TES) is a therapeutic strategy aimed at improving impairments of the upper extremity in stroke. OBJECTIVE: Assessment of the available evidence on the effect of TES of the affected upper extremity in improving motor control and functional abilities after stroke. METHODS: A systematic literature search was performed to identify randomized controlled trials (RCTs) that have studied the effect of TES on motor control and functional abilities. The methodological quality of the studies was assessed systematically by two raters. The reported outcomes were examined to evaluate the effect of TES and to identify a possible relationship with patient characteristics, method of stimulation and methodological quality. When possible, effect sizes were calculated (Hedges' g). RESULTS: Six RCTs were included. The methodological scores ranged from 7 to 16 (maximum 19). All studies assessed the effect on motor control, and four reported a positive effect. Effect sizes calculated in three studies ranged from 0.55 to 1.46. Only two studies assessed the effect on functional ability, one reported a positive effect. Subgroup analyses in two studies suggest a better response to stimulation in less severely affected patients. Apart from this, no relationship between effect and patient characteristics, method of stimulation or methodological quality could be detected. CONCLUSIONS: The present review suggests a positive effect of electrical stimulation on motor control. No conclusions can be drawn with regard to the effect on functional abilities.

Functional electrical stimulation by means of the 'Ness Handmaster Orthosis' in chronic stroke patients: an exploratory study.

OBJECTIVE: To gain experience with 'Ness Handmaster Orthosis' treatment in chronic stroke patients, to identify suitable patients, and to study the effects of treatment. DESIGN: Exploratory, uncontrolled trial with measurement of motor functions and muscle tone of the upper extremity prior to, during, upon completion, and six weeks after a treatment period. SETTING: A rehabilitation centre in the Netherlands. SUBJECTS: Eighteen chronic stroke patients (more than six months post stroke), who exhibited upper extremity dysfunction due to spastic paresis. INTERVENTION: A 10-week therapy programme of functional electrical stimulation by means of the 'Ness Handmaster Orthosis'. RESULTS: The results of 15 patients were available for analysis. The differences in motor score and muscle tone before and at the end of treatment were statistically significant (p = 0.008 and 0.021, respectively). The follow-up measurements showed that the effects on motor functions and muscle tone decreased after therapy completion. Stratification of the patients in two subgroups indicated that patients with initial high motor scores benefited most during the intervention period. CONCLUSION: The present study suggests that Handmaster treatment possesses therapeutic opportunities in chronic stroke patients with spastic paresis of the upper extremity.

Characterization of a novel malignant B cell line with t(14;18) and t(4;11) established from a patient with acute monoblastic leukemia.

The severe combined immunodeficient (SCID) mouse model is an important tool with which to study new strategies for treating hematologic neoplasia. For these experiments, a large number of human cell lines growing in SCID mice are a prerequisite. We describe a new Epstein-Barr virus (EBV)-positive B cell line, designated BEVA, with a complex karyotype including translocations t(14:18)(q32;q21) and t(4;11) (q21;q23) that meets this need. As demonstrated by Southern blot analysis, BCL2 at 18q21, but not MLL/ALL1 at 11q23, was involved in these translocations. BEVA cells coexpressed lymphoid (IgG-kappa, CD19, CD20, CD21, and CD24) and myeloid (CD11b, CD15, and CDw65) markers. Interestingly, the cell line was established from the bone marrow culture of a patient with acute myeloid leukemia (AML). Examination of bone marrow biopsy specimens suggested the presence of non-Hodgkin's lymphoma (NHL) in this patient in addition to AML. In vitro and in vivo growth characteristics of the BEVA cell line were compared with the previously described EBV-positive B cell line DoHH2, also carrying a translocation t(14;18)(q32;q21). These DoHH2 cells additionally expressed CD10, whereas, in contrast to BEVA cells, only a small population of DoHH2 cells showed expression of CD44. Both cell lines showed similar growth characteristics in vitro, but reacted differently to cytokines, including interleukin (IL)-4, IL-6, IL-7, and alpha-interferon (IFN). Upon inoculation in SCID mice, marked differences were observed in the dissemination patterns of the BEVA or DoHH2 cells. Although both cell lines circulated in the blood and were predominantly found in murine bone marrow and lymphoid tissues, DoHH2 cells infiltrated the murine spleens, whereas BEVA cells could only rarely be detected in these tissues. In contrast to DoHH2 cells, BEVA cells gave rise to tumor masses in liver, kidney, and para-aortal or mesenteric lymph nodes. The relationship between these in vitro differences and the observed differences in dissemination of both cell lines is discussed.

Human cytotoxic CD8+ T-lymphocyte clones engraft in severe combined immunodeficient (SCID) mice but show diminished function.

Mice with severe combined immunodeficiency (SCID) provide an in vivo model for studying interactions between human tumor cells and effector cells of the immune system. We studied the behavior of human alloreactive cytotoxic T lymphocytes (CTLs) in SCID mice, including the migration pattern of CD8+ or CD4+ CTL clones to various murine tissues, their engraftment in the absence or presence of recombinant human interleukin 2 (rhIL-2) compared with the engraftment of lymphokine activated killer (LAK) cells, and the in vitro as well as the in vivo function of the engrafted CTL clones. The polymerase chain technique using T-cell-receptor-gamma specific primers revealed the presence of human CD8+ CTL clones in the blood, lungs, and liver of mice receiving rhIL-2 for 14 days, for at least 18 days after intravenous inoculation. Human T cells were transiently detected in the bone marrow, lymph nodes, thymus, and spleen. Although the three CD8+ CTL clones and two CTL lines tested required rhIL-2 for their engraftment, the four LAK cell populations also engrafted in the absence of rhIL-2. In contrast to CD8+ T cells, only low frequencies (<1%) of CD4+ cells could be detected in the blood of the SCID mouse. Engrafted human T cells recovered from the murine blood showed absent or diminished cytotoxicity in vitro against human target cells in five or six experiments, respectively. In addition, when the antitumor activity of engrafted CD8+ clones was investigated in vivo using a xenotransplantation model of human B-cell lymphoma in SCID mice, no significant prolongation of the mean survival time of six treated animals was observed compared with animals treated with rhIL-2 alone. Our results illustrate that although in vitro primed and cultured human CD8+ T cells engraft in SCID mice, their in vitro and in vivo function is impaired.

Anti-CD45 and anti-CD52 (Campath) monoclonal antibodies effectively eliminate systematically disseminated human non-Hodgkin's lymphoma B cells in Scid mice.

Severe combined immunodeficient (Scid) mice inoculated with the human (t(14;18)-positive B cell lines DoHH2 and BEVA develop lethal systemically disseminated lymphoma (de Kroon et al., Leukemia 8:1385, and Blood 80 [suppl 1]:436). These models were used to study the therapeutic effect of rat-anti-human CD52 (Campath-1G) or CD45 monoclonal antibodies (mAbs) on systemically disseminated tumor cells and on tumor cells present in solid tumor masses. Both mAbs were effective in inhibiting growth of systemically disseminated malignant cells. When treatment with anti-CD52 or anti-CD45 mAbs at a dose of 30 micrograms/mouse/d for 4 days was started 24 hours after intravenous inoculation of human DoHH2 or BEVA cells, a 3-log kill of tumor cells was observed as measured by prolonged survival. After treatment, surviving animals injected with high numbers of BEVA cells showed tumor masses in liver, kidney, and mesenteric lymph nodes. In contrast to nontreated animals, however, only low numbers of malignant cells were found in peripheral blood, and bone marrow was free of tumor cells. Similarly, after mAb treatment of mice inoculated subcutaneously (sc) with DoHH2 cells, no tumor cells could be found in the bone marrow, and few DoHH2 cells could be detected in the peripheral blood, spleen, liver, kidney, or lung. In contrast, tumor cells present in subcutaneous tumors and axillary lymph nodes were relatively unaffected by mAb therapy. The presence of rat immunoglobulin (Ig) could be demonstrated on surviving tumor cells. The presence of murine macrophages in areas in these tumors that were depleted of DoHH2 cells suggested that the mAb-mediated antitumor effect observed in the Scid mouse model is mediated by cellular mechanisms. Apparently these mechanisms were not sufficient to eliminate the fast-growing tumor cells present in the protected sites. Our results indicate that treatment with anti-CD52 or anti-CD45 mAbs potentially may be useful as adjuvant immunotherapy for systemically disseminated B cell lymphoma.

Homing and antigenic characterization of a human non-Hodgkin's lymphoma B cell line in severe combined immunodeficient (SCID) mice.

The dissemination pattern of a human non-Hodgkin's lymphoma (NHL) B cell line (DoHH2) carrying the t(14;18) translocation was analyzed in severe combined immunodeficient (SCID) mice, using different routes of administration. When engrafted intraperitoneally (i.p.) the DoHH2 cells showed a local infiltration into intra- and retroperitoneal mouse tissues, and disseminated to bone marrow and lymph nodes. In contrast, after subcutaneous (s.c.) or intravenous (i.v.) transfer the DoHH2 cells displayed a hematogenous spread, and disseminated predominantly to hematopoietic and lymphoid organs including bone marrow, peripheral blood, spleen, peripheral lymph nodes, and liver. No involvement of the gut and mesenteric lymph nodes was observed, suggesting a specific homing pattern, bypassing the mucosa-associated lymphoid tissue (MALT). This pattern is reminiscent of the human disease. Phenotypic analysis, cytogenetic analysis, and minor histocompatibility antigen (mHA) typing using mHA-specific cytotoxic T-lymphocyte (CTL) clones performed on the original DoHH2 cell line and on DoHH2 cells recovered from mouse tissue, showed that in vivo passage did not alter the characteristics of the DoHH2 cells. After i.v. administration, the survival time of the SCID mice directly correlated with the number of DoHH2 cells inoculated. This model of dissemination of the DoHH2 cell line may be useful for studying the efficacy of (immunotherapeutic) treatment of human lymphoproliferative disorders in vivo.

Growth inhibition of clonogenic leukemic precursor cells by minor histocompatibility antigen-specific cytotoxic T lymphocytes.

Minor histocompatibility (mH) antigens appear to play a major role in bone marrow transplantation (BMT) using HLA-identical donors. Previously, we reported the isolation of major histocompatibility complex (MHC)-restricted mH antigen-specific cytotoxic T lymphocytes (CTL) from patients with graft-vs.-host disease or rejection after HLA-identical BMT. We have demonstrated that mH antigens can be recognized on hematopoietic progenitor cells, and residual recipient CTL specific for mH antigens expressed on donor hematopoietic progenitor cells may be responsible for graft rejection in spite of intensive conditioning regimens in HLA-identical BMT. Here, we investigated whether mH antigen-specific CTL directed against the mH antigens HA-1 to HA-5 and the male-specific antigen H-Y were capable of antigen-specific inhibition of in vitro growth of clonogenic leukemic precursor cells. We demonstrate that mH antigen-specific CTL against all mH antigens tested can lyse freshly obtained myeloid leukemic cells, that these mH antigen-specific CTL can inhibit their clonogenic leukemic growth in vitro, and that this recognition is MHC restricted. We illustrate that leukemic (precursor) cells can escape elimination by mH antigen-specific CTL by impaired expression of the relevant MHC restriction molecule. We suggest that mH antigen-specific MHC-restricted CTL may be involved in vivo in the graft-vs.-leukemia reactivity after BMT.

The indirect fluorescent antibody test for bovine anaplasmosis.

An indirect fluorescent antibody test was used successfully for the serodiagnosis of experimental Anaplasma infections in cattle. Specific antibodies were detected three to ten days after anaplasma bodies were found in the blood, and persisted at least 15 weeks post-infection. An American and an African stock of A. marginale were used to prepare antigens, and gave comparable results when tested on sera positive to either of these stocks, as well as to an A. central-like stock from Korea. There were no cross-reactions with several Theileria, Babesia, Trypanosoma and Eperythrozoon species.

Ligand-induced association of epidermal growth factor receptor to the cytoskeleton of A431 cells.

Recently, we have obtained evidence in favor of a structural interaction between the epidermal growth factor (EGF) receptor and the Triton X-100-insoluble cytoskeleton of epidermoid carcinoma A431 cells. Here we present a further analysis of the properties of EGF receptors attached to the cytoskeleton. Steady-state EGF binding studies, analyzed according to the Scatchard method, showed that A431 cells contain two classes of EGF-binding sites: a high-affinity site with an apparent dissociation constant (KD) of 0.7 nM (7.5 x 10(4) sites per cell) and a low-affinity site with a KD of 8.5 nM (1.9 x 10(6) sites per cell). Non-equilibrium binding studies revealed the existence of two kinetically distinguishable sites: a fast-dissociating site, with a dissociation rate constant (k-1) of 1.1 x 10(-3) s-1 (1.0-1.3 x 10(6) sites per cell) and a slow-dissociating site, with a k-1 of 3.5 x 10(-5) s-1 (0.6-0.7 x 10(6) sites per cell). The cytoskeleton of A431 cells was isolated by Triton X-100 extraction. Scatchard analysis revealed that approximately 5% of the original number of receptors were associated with the cytoskeleton predominantly via high-affinity sites (KD = 1.5 nM). This class of receptors is further characterized by the presence of a fast-dissociating component (k-1 = 2.0 x 10(-3) s-1) and a slow-dissociating component (k-1 = 9.1 x 10(-5) s-1). The distribution between fast and slow sites of the cytoskeleton was similar to that of intact cells (65% fast and 35% slow sites). Incubation of A431 cells for 2 h at 4 degrees C in the presence of EGF resulted in a dramatic increase in the number of EGF receptors associated to the cytoskeleton. These newly cytoskeleton-associated receptors appeared to represent low-affinity binding sites (KD = 7 nM). Dissociation kinetics also revealed an increase of fast-dissociating sites. These results indicate that at 4 degrees C EGF induces the binding of low-affinity, fast-dissociating sites to the cytoskeleton of A431 cells.