Competence of mentally ill patients: a comparative empirical study

BACKGROUND: This study investigates the competence of patients with dementia, depression and schizophrenia to make treatment decisions. The outcome of an objective test instrument is presented and compared with clinical assessment of competence by the attending physician. METHOD: The MacArthur Competence Assessment Tool-Treatment (MacCAT-T), a test instrument to assess abilities in different standards of competence, was administered to patients with diagnoses of dementia (N = 31), depression (N = 35) and schizophrenia (N = 43). Statistical significance of group differences in the MacCAT-T results were tested with the chi-square test. The concordance of the test and clinical assessment of competence by the attending physician were evaluated by Cohen's kappa coefficient. RESULTS: Patients with dementia, as a group, showed significantly more often impaired performance than those with schizophrenia who were still more impaired than depressed patients. Patients were classified as impaired or not depending on the standards used. By combination of all standards substantially more patients were classified as impaired than by clinical assessment (67.7 v. 48.4% of patients with dementia, 20.0 v. 2.9% of patients with depression, 53.5 v. 18.4% of patients with schizophrenia). CONCLUSIONS: Using different standards of competence the study showed substantial differences among patients with dementia, depression and schizophrenia. The high proportion of patients identified as incompetent raises several ethical questions, in particular, those referring to the selection of standards or the definition of cut-offs for incompetence. The discrepancy between clinical and formal evaluations points out the influence of the used procedure on competence judgements.     

Auditory Discrimination and the Eyeblink

This experiment evaluated the association between blinking and cognitive activities. Subjects received 200 and 400 ms tones (1 KHz) at fixed intervals in a duration discrimination paradigm. One group (“Task”) was instructed to respond to the stimuli on the basis of duration and another (“No-Task”) was instructed to ignore the stimuli. Blink activity (latency, rate, duration) and performance (RT, hit and false alarm rates) measures were evaluated. A first analysis (Task subjects only) indicated that stimulus duration had significant effects on RT and blink latency; both were generally longer following the 400-ms than the 200-ms stimuli. In a second analysis, involving Task and No-Task subjects, blink latencies were shorter in the Task group. Blink and eyelid closure durations increased over the task period in both analyses. These effects suggest that blinks occur when attentional processes wane.     

Analytical technique for quantification of selected resorbable calcium phosphate bone void fillers with the use of polarized-light microscopy

Synthetic calcium phosphate bone void fillers promote varying rates of bone formation and material resorption depending on chemistry, porosity, pore structure, and implant site. The objective of this study was to quantify the resorption of a novel ultraporous beta-tricalcium phosphate cancellous bone void filler with simultaneous quantification of bone formation in a canine humerus model. Potential measurement error involved in conventional histomorphometry using Von Kossa stains inspired the development of a new technique. This technique utilizes bright-field and polarized-light microscopy in conjunction with image analysis software, allowing more accurate histomorphometry. This technique was validated with two separate controlled experiments. Scanning electron microscopy further supported the results. The findings suggest that the use of polarized-light microscopy combined with image analysis software can be an effective tool in simultaneously quantifying calcium phosphate resorption and bone formation.     

Clara cell protein 16 (CC16) gene polymorphism influences the degree of airway responsiveness in asthmatic children

BACKGROUND: Several studies have indicated linkage of chromosome 11q12-13 to asthma and associated traits. Among other candidate genes, the Clara cell protein 16 (CC16) gene maps to this region. CC16 is expressed in the bronchial epithelium and exhibits potent anti-inflammatory properties. A single-nucleotide polymorphism (SNP) in the CC16 gene (A38G) was previously associated with asthma. OBJECTIVE: We evaluated the role of the CC16 SNP in pediatric asthma and asthma severity in 2 German study populations. METHODS: The German Multicenter Allergy Study (MAS) cohort (n = 872, 94 asthmatic patients) and 112 allergic asthmatic children recruited in Freiburg, Germany, were included in the present study. Histamine provocations were performed at the age of 7 years in the MAS cohort to determine bronchial hyperreactivity; in the Freiburg study population a standardized exercise-induced decrease in FEV1 was evaluated. For genotyping, melting-curve analysis and restriction enzyme digestion were applied. RESULTS: No association of the CC16*38A allele with asthma could be observed in either study population. However, in asthmatic subjects (MAS cohort) PC(20)FEV(1) values were significantly lower in individuals homozygous or heterozygous for the CC16*38A allele compared with those in subjects with the CC16*38GG genotype (P <.05 and P <.03, respectively). Similarly, allergic asthmatic patients in the Freiburg cohort showed a significantly greater decrease in FEV1 after exercise when homozygous for the CC16*38A allele compared with that seen in asthmatic patients with the *38AG or *38GG genotype (P <.04 and P =.006, respectively). CONCLUSION: We conclude that the CC16*A38G SNP influences bronchial hyperreactivity and might be a genetic determinant of asthma severity in German children.     

Toll-like receptor 9 contributes to recognition of Mycobacterium bovis Bacillus Calmette-Guérin by Flt3-ligand generated dendritic cells

Recognition of mycobacteria by the innate immune system is essential for the development of an adaptive immune response. Mycobacterial antigens stimulate antigen presenting cells (APCs) through distinct Toll-like receptors (TLRs) resulting in rapid activation of the innate immune system. The role of TLRs during infection with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) has been evaluated for TLR2 and TLR4 only. Surprisingly, despite the fact that immune stimulatory CpG-motifs have been originally derived from BCG, for the vaccine strain the role of TLR9 has not been addressed before. To identify the set of TLRs involved in the recognition of BCG, we infected bone marrow-derived macrophages and bone marrow-derived dendritic cells (Flt3-ligand generated DCs) from TLR2, TLR3, TLR4, TLR7, TLR9, MyD88 knockout, TLR2/4 and TLR2/4/9 multiple knockout mice. The degree of activation and stimulation was determined by TNFα, IL-6 and IL-12p40 ELISA. Activation of DCs was measured by surface expression of the costimulatory molecule CD86. We observed the most dramatic reduction of the inflammatory response for TLR2-deficient antigen presenting cells. Both macrophages and DCs produce markedly decreased amounts of TNFα and IL-6 in the absence of TLR2 whereas no significant reduction could be observed for TLR3, 4, 7, 9 single TLR-knockouts. However, IL-12 production in DCs appears not exclusively dependent on TLR2 and only in TLR2/4/9-deficient DCs BCG-induced IL-12 is reduced to background levels. Similarly, up-regulation of CD86 is abolished only in TLR2/4/9-deficient DCs supporting a role of TLR9 in the recognition of M. bovis BCG by murine dendritic cells.     

Selective inhibition of the transmembrane Ca conductivity of mammalian myocardial fibres by Ni,Co and Mn ions

Pflügers Archiv - European Journal of Physiology - According to earlier studies on mammalian papillary muscles, Ni and Co ions reduce the Ca dependent mechanical response whilst the action...     

Regulation and chance in the ontogeny of B and T cell antigen receptor repertoires

The adaptive immune system has to economically generate a large array of T and B cell antigen receptors (T cell receptors [TCRs], B cell receptors [BCRs]) that eliminate both longstanding and novel antigens from the host while preventing the production of deleterious (e.g., autoreactive) antigen receptors. Our studies focus on the mechanisms that shape the development of these antigen receptor repertoies during human ontogeny. The key to BCR and TCR diversity is the third complementarity determining region (CDR3) of the variable domain, which in the immunoglobulin heavy chain and TCR β chain, is created by the junction between the variable, diversity, and joining gene segments. The CDR3 diversity is constrained by overrepresentation of gene segments and lack of N regions during the first trimester of gestation and then increases exponentially during ontogeny until it reaches adult levels months after birth. This process parallels, and may contribute to, the stepwise acquisition of the ability to respond to specific antigens. Recent studies indicate that maturation of the CDR 3 repertoire is not accelerated by premature exposition to extrauterine antigen and thus appears to follow a strictly developmentally regulated program whose pacemaker(s) is still unknown.