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Biomedical subjects

K Stricker

Publications and source records attributed to K Stricker.

14 recordsLinked to original sources

Resource use in the ICU: short- vs. long-term patients.

BACKGROUND: Intensive care medicine uses a disproportionate share of medical resources, and little is known about the distribution of resources between different patient groups. METHODS: In this prospective observational study, all patients admitted between 1 January 1998 and 31 December 1999 to our medical-surgical university's ICU were assigned to one of two groups according to length of stay (LOS): patients staying more than 7 days in the unit (group L) and those staying a maximum of 7 days (group S). Resource use was estimated using TISS-28, number of nursing shifts, use of mechanical ventilation, and use of renal replacement therapy. Further, SAPS II and ICU and hospital mortalities were recorded. RESULTS: Of 5481 patients, 583 (10.6%) were in group L and 4898 in group S (89.4%). Patients in group L were more severely sick upon admission than those in group S. Patients in group L stayed a total of 9726 days in the ICU (52.5% of the total LOS). In group L, 69.2% of all shifts with respiratory support and 80.1% of all shifts with renal replacement were used. Further, group L patients consumed 53.4% (909225) of all TISS points provided. The ICU-mortality rates were 14.4% in group L and 7.2% in group S, and the hospital mortality rates were 19.9% and 9.8%, respectively. A mean of 1898 TISS points was used per patient surviving the hospital stay in group L compared with 190 points in group S. CONCLUSIONS: In this university-based, medical-surgical adult ICU, 11% of all patients stayed more than 7 days in the unit and consumed more than 50% of all resources. Thus, a highly disproportionate amount of resources were used per survivor in group L compared with those in group S.

Adolescent↗

Anti-CD95 (APO-1/Fas) autoantibodies and T cell depletion in human immunodeficiency virus type 1 (HIV-1)-infected children.

Advanced stages of HIV-1-infection are characterized by progressive CD4+ T cell depletion. Peripheral T cells from HIV-1+ donors show accelerated apoptosis in vitro. The CD95 (APO-1/Fas) receptor/ligand system is involved in this process. To further study deregulation of the CD95 system in peripheral T cells during HIV-1-infection, we measured CD95-expression on CD4+ and CD8+ T cells together with serum levels of soluble CD95 (sCD95) and anti-CD95 autoantibodies in HIV-1+ children and healthy controls. Anti-CD95 levels in HIV-1+ children were significantly elevated when compared to uninfected controls, whereas serum levels of sCD95 were not different. In HIV-1+ children, CD95-expression on CD4+ and CD8+ T cells increased with age. A strong correlation between depletion of CD4+ cells in vivo and increase in CD95-expression on CD4+ T cells was observed. In contrast, such a correlation was not found for CD8+ T cells. A negative correlation between anti-CD95 autoantibody levels and CD4+ T cell counts, that was predicted by multiple linear regression analysis of pooled data, was found in individual patients observed longitudinally by repeated measurements. Since anti-CD95 autoantibodies isolated from HIV-infected adults have previously been shown to induce apoptosis of sensitive target cells in vitro, we speculate that the interaction of these antibodies with CD95-positive and CD95-sensitive T cells in vivo might be involved in progressive T cell loss during HIV-1-infection.

Adult↗

Expressed-emotion development and course of schizophrenic illness: considerations based on results of a CFI replication.

This study examines the correlation between development of expressed emotion (EE) in relatives and course of illness of 99 DSM-III schizophrenic patients. Patients whose relatives were high EE at baseline and at the 2nd CFI approximately 20 months later had a poor prognosis at the very outset of the study and an unfavourable course of illness. They had a higher rehospitalisation rate, more symptoms, lower psychosocial assessment, and a poorer 2-year and even 8-year outcome. Patients from families with a fluctuating EE or a consistently low EE had better courses. Expressed emotion is therefore a valid predictor not only of symptomatic relapses, but also of other important aspects of schizophrenia. The connection between EE index and course of illness seems not to be simply reactive or causal, but complex and non-uniform.

Adult↗

Family interaction and the course of schizophrenic illness. Results of a multivariate prospective study.

The aim of the present study was to assess the prognostic relevance of relatives' interactive behaviour towards the patient, as covered by the Münster Family Interview (MFI), to the further course of the schizophrenic illness. The MFI is a family interview (of the whole family, including the patient) designed to record the emotional family atmosphere based on the concept of expressed emotion (EE). The ratings take place directly after the interview on five scales (criticism, hostility, overinvolvement, resignation and warmth), the resignation scale being added to the 'classic' EE scales. Ninety-nine families of outpatients diagnosed with schizophrenia according to the DSM-III were examined with the MFI during a home visit. The patients were seen 1 and 2 years after the first examination. The target criteria selected for the prognostic significance of the interaction measurements were: rehospitalisation within 2 years; extent of symptoms after 1 year, and psychosocial skills after 1 year. The significance of the interaction dimensions was verified in regression models. The control variable used in the regression models was the Strauss-Carpenter scale. Regression models were produced for the total group and for a subgroup of moderately ill patients. All target criteria yielded serviceable prediction models. The most important variable for prediction was the control variable, the Strauss-Carpenter scale. However the interaction variables made additional contributions to the prognosis, especially in the subgroup of moderately ill patients. The best MFI scale for all the outcome criteria was resignation; criticism predicted only the symptomatology, and emotional overinvolvement the level of social functioning after 1 year. In conclusion, practical work with families of schizophrenic patients should emphasise the protective function of relatives towards patients more strongly.

Adolescent↗

Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120.

The depletion of CD4+ T cells in AIDS is correlated with high turnover of the human immunodeficiency virus HIV-1 and associated with apoptosis. The molecular mechanism of apoptosis in HIV infection, however, is largely unknown. T-cell apoptosis might be affected by viral proteins such as HIV-1 Tat and gp120 (refs 10, 11). T-cell-receptor (TCR)-induced apoptosis was recently shown to involve the CD95 (APO-1/Fas) receptor. We show here that HIV-1 Tat strongly sensitizes TCR- and CD4(gp120)-induced apoptosis by upregulation of CD95 ligand expression. Concentrations of Tat found to be effective in cultures of HIV-1-infected cells were also observed in sera from HIV-1-infected individuals. Taken together, our results indicate that HIV-1 Tat and gp120 accelerate CD95-mediated, activation-induced T-cell apoptosis, a mechanism that may contribute to CD4+ T-cell depletion in AIDS.

Antigens, Surface↗

Identification of soluble APO-1 in supernatants of human B- and T-cell lines and increased serum levels in B- and T-cell leukemias.

The cell-surface protein APO-1 is a member of the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor superfamily. APO-1 mediates apoptosis in susceptible cells upon stimulation with the monoclonal antibody anti-APO-1 or upon binding of its natural ligand. Soluble receptors had previously been identified for most members of the NGF/TNF receptor superfamily. Recently, a soluble form of APO-1 (sAPO-1) was described. We established a sandwich enzyme-linked immunosorbent assay to detect sAPO-1 in culture supernatants of human cell lines and in human sera. sAPO-1 was found in culture supernatants of different human B- and T-cell lines. Molecular weights of sAPO-1 and membrane APO-1 were similar. In addition, in comparison to healthy donors, sera from patients with different high- and low-grade malignant B- and T-cell leukemias and lymphomas contained increased levels of sAPO-1. These findings may have implications for the growth of leukemias and the diagnostic monitoring of individual patients.

Animals↗

Hydrogen peroxide as a potent activator of T lymphocyte functions.

During inflammatory processes infiltrating cells produce large amounts of reactive oxygen intermediates (ROI). Increasing evidence suggests that ROI besides being cytotoxic may act as important mediators influencing various cellular and immunological processes. In this study, we have investigated the effects of hydrogen peroxide on several aspects of lymphocyte activation. In ESb-L T lymphoma cells, micromolar concentrations of hydrogen peroxide rapidly induced activation of the transcription factor NF-kappa B, whereas DNA-binding activity of the transcription factor AP-1 was virtually not affected. In addition, hydrogen peroxide induced early gene expression of interleukin-2 (IL-2) and the IL-2 receptor alpha chain. The stimulation of IL-2 expression was found to be conferred by a kappa B-like cis-regulatory region within the IL-2 gene promoter. In contrast to these activating effects, addition of hydrogen peroxide was largely inhibitory on cell proliferation which is consistent with a general requirement of thiol compounds for lymphocyte proliferation. However, hydrogen peroxide significantly increased T cell proliferation when applied for a short period under reducing conditions. These data indicate that ROI may act as an important competence signal in T lymphocytes inducing early gene expression as well as cell proliferation.

Animals↗

Molecular mechanisms of APO-1/Fas(CD95)-mediated apoptosis in tolerance and AIDS.

The cell surface molecule APO-1/Fas(CD95), a member of the Tumor Necrosis Factor (TNF) receptor/Nerve Growth Factor (NGF) receptor superfamily mediates apoptosis upon cross-linking by agonistic antibodies or its ligand. Recent findings suggest that APO-1/Fas(CD95) and its ligand are the key molecules for antigen receptor-induced apoptosis in activated mature T cells. Here we propose a mechanism for antigen receptor-induced apoptosis of activated T cells via APO-1 ligand mediated autocrine suicide. This mechanism may also contribute to the depletion of CD4+ T cells in AIDS.

Acquired Immunodeficiency Syndrome↗

Activation of the mouse IL-2 gene by okadaic acid: synergy with interleukin-1.

Interleukin-1 (IL-1) has potent immunoregulatory and inflammatory functions. Its activity is mediated by an 80-kDa receptor on the cell surface and leads to activation of other genes. The underlying molecular events are largely unknown. We investigated the role of phosphatases in activation of the IL-2 gene in EL4 thymoma cells. We found that the protein phosphatase PP1 and PP2A inhibitor okadaic acid (OA) alone was able to significantly stimulate IL-2 production by the IL-1-responsive EL4 subline EL4 5D3 and also by the IL-1-nonresponsive EL4 subline EL4D6/76. In the IL-1-responsive cell line OA strongly synergized with phorbol myristate acetate (PMA) and IL-1. In the IL-1-nonresponsive cell line OA synergized with PMA but not with IL-1. Under suboptimal conditions of PMA/OA synergy an additional synergistic effect of IL-1 was shown. This was true for IL-2 and IL-6 production. Sphingomyelinase or sphingosine had no detectable effect. The kinetics of OA- and PMA-induced expression of IL-2 mRNA and IL-2 protein was different. PMA induced maximal expression between 6 and 12 h and was almost undetectable at 24 h. OA-induced expression was first obvious at 12 h and continued longer than 36 h. In both cases IL-1 caused no shift in kinetics, but potentiated the effects of the different tumor promoters. Utilizing IL-2 promoter-CAT constructs we showed in transfection experiments that the synergistic effect was also evident on the transcriptional level. We conclude from the data that phosphatases play an important role for IL-2 expression and that IL-1 can use additional pathways of activation that are different from events induced by PMA or OA.

Animals↗

An NF-kappa B-like element plays an essential role in interleukin-1-mediated costimulation of the mouse interleukin-2 promoter.

Interleukin-1 (IL-1) costimulation is required for efficient IL-2 synthesis and IL-2 receptor (IL-2R) expression of T cells. The molecular events leading to these effects are largely unknown. We utilized an IL-1-responsive and an IL-1-non-responsive subclone of the mouse thymoma cell line EL4 to investigate how IL-1 activates IL-2 gene expression. We correlated IL-2 promoter activity with the activity of the endogenous IL-2 gene, thereby showing the biological significance of our results. Our experiments provide new functional data showing that a major target of IL-1 mediated costimulation is the chi B-like site, T cell element distal TCEd (GGGATTTCAC), of the IL-2 promoter. Thus, deletion or mutation of TCEd within a complete IL-2 promoter abrogated IL-1 costimulation in the IL-1 responsive EL4 subclone. Therefore, the TCEd element is functionally essential for the effect of IL-1. We also identified a nuclear factor (NF), IL-1 NF, that binds to the TCEd site after IL-1 stimulation. This factor was only present in the IL-1-responsive EL4 subclone and not in the IL-1-non-responsive subclone after IL-1 stimulation and did not appear after phytohemagglutinin (PHA)-treatment. Binding of IL-1 NF to the TCEd site was competed by a typical chi B oligonucleotide, suggesting that it is similar to NF-chi B in its DNA-binding properties. However, the TCEd element was only activated by costimulation with PHA and IL-1 whereas a typical chi B element was already activated by IL-1 alone. These data suggest that the biological function of the TCEd element of the IL-2 promoter differs from that of a canonical chi B element. Our data provide new evidence that IL-1 acts on the IL-2 promoter by activating the TCEd element via the transcription factor IL-1 NF. Furthermore, activation of this element requires two signals, delivered by IL-1 and PHA, in this way reflecting the activation requirement for the endogenous IL-2 gene.

Animals↗

The predictability of relapses in schizophrenic patients.

The objective of this study was to identify clinically relevant predictors of short-term (2 years) outcome in schizophrenic patients and to gather these predictors into one simple prognosis model for the course of the disease. Ninety-nine schizophrenic outpatients classified according to DSM-III criteria were observed for 3 years with regard to their relapse (rehospitalization) frequency. Predictors of both a high and a low relapse risk permitting a prognostic assessment of the individual case were based on various sources: case history data, especially those relating to the previous course of the disease: social and therapeutic situation; psychopathological findings; emotional family atmosphere; and prognosis scales.

Adult↗

[Postoperative urinary retention].

In 359 patients 371 operations were performed under general or regional anesthesia, and these were followed up with regard to anesthesiological technique, postoperative course and voiding of the bladder. Patients under 15 years of age, with severe incontinence or with a bladder catheter were excluded from the study. The surgical specialties were general surgery, orthopaedics, gynecology, ENT and ophthalmology. If any patient had not urinated by 6-10 h postoperatively and was found to have a full bladder on palpation, urinary retention was diagnosed. There were 75 patients (20%) who had urinary retention, significantly fewer women than men (p less than 0.025), and men under 35 years old had significantly less retention than older men (p less than 0.0025). The anesthesiological technique is an important factor in postoperative urinary retention: spinal anesthesia with tetracaine and adrenaline caused significantly more retention than spinal anesthesia with lidocaine 5% (p less than 0.005), and more than epidural or general anesthesia (p less than 0.005). No significant difference concerning urinary retention was found regarding surgical specialty, emergency operations, morphine or adrenaline added to tetracaine for spinal anesthesia, amount of local anesthetics used for epidural anesthesia or between spinal anesthesia with lidocaine 5% and epidural anesthesia with mepivacaine. Once urinary retention is diagnosed, conservative (privacy, relaxation exercises, getting up) or medical treatment (propyphenazone + hexahydroadiphenine (Spasmocibalgin), carbamoyl choline chloride) should be given. Catheterization should be performed only as a last resort.

Adolescent↗

[Family groups and family self-help groups for schizophrenic patients. Concepts, establishment, problems in implementation].

In Münster/W.-Germany the effect of therapeutical work with relatives of young schizophrenic patients is investigated in a government supported prospective study. In this paper we reveal therapeutical concepts and difficulties dealing with the formation and guidance of the relatives groups. After a personal interview about one third of the relatives was interested in relatives groups (151 relatives of 99 patients). Relatives of younger patients with a shorter duration of illness were somewhat more interested. During the one-year-period of group-work about one third of the relatives left the groups. The motivation for a regular participation dependent on the symptoms of the patients. A special training produced better motivation for taking part in long-term self-help-groups.

Adult↗

In vitro T cell hyperreactivity in Obese strain (OS) chickens is due to a defect in nonspecific suppressor mechanism(s).

Spontaneous autoimmune thyroiditis of OS chickens is associated with a marked hyperreactivity of the T cell system. The purpose of the present study was to investigate the underlying regulatory mechanisms. Co-cultivation experiments between Con A-stimulated OS and NWL lymphocytes in communicating cultures revealed soluble regulatory factors to be responsible for the observed functional differences: the high proliferative response to Con A and hyperproduction of IL 2 of OS cells was found to be due to a deficiency in the conditioned medium of dialyzable inhibitory factor(s) that regulate IL 2 secretion of NWL lymphocytes. Furthermore, sera of young NWL chickens were found to profoundly inhibit the IL 2-promoted lymphoblast proliferation. This IL 2 antagonizing activity is lost with age (3 to 6 yr) and was found to be significantly diminished in OS birds throughout ontogeny, thus pointing to possible parallels between immune regulatory dysfunction in autoimmunity and in physiologic aging. Both enhanced T cell response and the defect in serum suppressor were inherited by (OS X CB)F1 animals, indicating that these two aberrations may be related to each other.

Animals↗