Effects of exercise on fitness and cognition in progressive MS: a randomized, controlled pilot trial.

BACKGROUND: Exercise may have beneficial effects on both well-being and walking ability in multiple sclerosis (MS). Exercise is shown to be neuroprotective in rodents and may also enhance cognitive function in humans. It may, therefore, be particularly useful for MS patients with pronounced neurodegeneration. OBJECTIVE: To investigate the potential of standardized exercise as a therapeutic intervention for progressive MS, in a randomized-controlled pilot trial. METHODS: Patients with progressive MS and moderate disability (Expanded Disability Status Scale (EDSS) of 4-6) were randomized to one of three exercise interventions (arm ergometry, rowing, bicycle ergometry) for 8-10 weeks or a waitlist control group. We analyzed the drop-out rate as a measure of feasibility. The primary endpoint of the study was aerobic fitness. Secondary endpoints were walking ability, cognitive function as measured by a neuropsychological test battery, depression and fatigue. RESULTS: A total of 42 patients completed the trial (10.6% drop-out rate). Significant improvements were seen in aerobic fitness. In addition, exercise improved walking ability, depressive symptoms, fatigue and several domains of cognitive function. CONCLUSION: This study indicated that aerobic training is feasible and could be beneficial for patients with progressive MS. Larger exercise studies are needed to confirm the effect on cognition. TRIAL REGISTRATION: ISRCTN (trial number 76467492) http://isrctn.org.

Family strain and its relation to psychosocial dysfunction in children and adolescents after liver transplantation.

Parental functioning is essential to children's development. Therefore, this cross-sectional single-center study examined the prevalence of family strain in 181 parents and its associations to psychosocial functioning in their children after LT. Median age at LT was one yr. Mean time elapsed since LT was 5.8 yr. The IFS, and the SDQ were applied to parents. Family strain in the present sample was comparable to that in the German normative group of families with a chronically ill or disabled child, but families of LT recipients showed a significantly higher financial impact, impact on coping, and impact on siblings (p < 0.001). Younger age of patients at survey, a more severe clinical course, child's restrictions, and financial losses following LT were determined as significant predictors of family strain (R(2)  = 0.42). Parents reported less family strain after living-related compared with deceased donation. Family strain was significantly correlated to psychosocial dysfunction in children post-LT. Present findings demonstrate a risk of maladjustment to the post-LT condition in families. They emphasize the importance of psychological assessment of parents and patients during transplant and follow-up to ensure the best achievable long-term outcome of patients.

Cognitive performance in pediatric liver transplant recipients.

To date, the course of cognitive development in children after liver transplantation (Ltx) is poorly understood. Cognitive performance, however, is crucial in all developmental stages and for educational achievement. This cross-sectional single-center study examined the prevalence of long-term cognitive impairment in a cohort of 64 pediatric patients after Ltx. Median age at Ltx was 12 months. The revised Wechsler Intelligence Scale IV was administered to assess cognitive performance. Patients were compared with an age- and gender-matched group of children without a chronic health condition. Liver transplanted children performed significantly worse in three of four cognitive domains as well as in the Total Intelligence Quotient (Total IQ) (p = 0.017 to p = 0.005). Liver transplant recipients showed substantially more "serious delays" (IQ < 70) compared to the reference group (9.4% vs. 4.7%). Children with a genetic-metabolic disease performed worse than the other groups in three of the four WISC Indices and in the Total IQ (p = 0.05 to p = 0.01). The strongest association was revealed between height at Ltx and Verbal Comprehension (R(2) = 0.21), Perceptual Reasoning (R(2) = 0.30), Working Memory (R(2) = 0.23) and Total IQ (R(2) = 0.25). Our results indicate a high impact of primary diagnosis and height percentile at Ltx even on children's long-term cognitive performance.

[Long-term outcome with end-stage renal disease - survival is not enough: does dialysis or kidney transplantation matter?]. / Langzeitüberleben bei chronischer Niereninsuffizienz.

Patients with end-stage renal disease require renal replacement therapy with either dialysis or kidney transplantation. Survival and quality of life (QoL) after transplantation are superior to chronic dialysis. Early living donor kidney transplantation is best for patient and graft survival. Preemptive living-related kidney transplantation therefore is the best medical treatment option for these patients. Patients with end-stage renal disease suffer from multiple physical and psychological complaints. The prevalence of depressive disorders is 20-25% in this population. Studies on QoL in children after kidney transplantation show a reduced physical QoL, but an overall good psychological QoL. Alarming results of numerous studies are the high non-adherence rates in adolescents. Especially exercise interventions during dialysis and after kidney transplantation show promising results. Whether QoL of patients will improve with new approaches to immunosuppressive therapy remains to be evaluated in future studies.

[Exercise and psychological well-being]. / Körperliche Aktivität und psychische Gesundheit.

Research on the association between physical activity and mental health addresses the beneficial effects of physical activity on emotional and cognitive functioning. With regard to emotional functioning, most studies focus on the influence of physical activity on depressive symptoms or affective disorders. These studies show that the beneficial effects of aerobic exercise and pharmacotherapy on depressive symptoms seem to be comparable and discuss a variety of neurobiological mechanisms that improve symptoms. The positive effects of physical activity on anxious mood and anxiety disorders are also well documented. Desensitization to physiological changes, improved self-esteem, and self-efficacy seem to play an important part. However, aerobic exercise does not improve mental health in every case, as seen for instance in over-trained athletes. Research on the relationship between physical activity and cognitive functioning reveals that physical activity can prevent the age-related cognitive decline and can delay the onset of dementia. Physical activity has beneficial effects not only on adults but also on children's and adolescents' mental health and cognitive performance, particularly on their executive functions that are still developing throughout adolescence. Finally, physical activity also affects the endocrine stress-regulation system: trained people reveal stronger reactivity and quicker regeneration when faced with stressful events.

Correlates of cognitive dysfunction in multiple sclerosis.

Cognitive impairment is one of the most frequent symptoms in patients with multiple sclerosis (MS) but its underlying mechanisms are poorly understood. A number of pathogenetic correlates have previously been proposed including psychosocial factors (such as depression and fatigue), inflammation, neurodegeneration, and neuroendocrine dysregulation. However, these different systems have never been studied in parallel and their differential contributions to cognitive impairment in MS are unknown. We studied a well-characterized cohort of cognitively impaired (CI, n=25) and cognitively preserved (CP, n=25) MS patients based on a comprehensive neuropsychological testing battery, a test of hypothalamo-pituitary-adrenal axis functioning (dexamethasone-corticotropin-releasing hormone suppression test, Dex-CRH test) as well as peripheral blood and MRI markers of inflammatory activity. CI patients had significantly higher disability. In addition, CI patients showed higher levels of fatigue and depression. Fatigue was more closely associated with measures of attention while depression showed strongest correlations with memory tests. Furthermore, percentage of IFNγ-positive CD4+ and CD8+ T cells showed modest correlations with processing speed and working memory. MRI markers of inflammation or global atrophy were not associated with neuropsychological function. Compared to previous studies, the number of patients exhibiting HPA axis hyperactivity was very low and no correlations were found with neuropsychological function. We conclude that fatigue and depression are the main correlates of cognitive impairment, which show domain-specific associations with measures of attention and memory.

Cognitive abilities, behaviour and quality of life in children after liver transplantation.

AIMS: We investigated interrelations between cognitive abilities, behavioural problems, quality of life and disease-related variables of children after LTX. METHODS: Our sample consisted of 25 children. They were 8.5/2.8 (M/SD) years old and had received the transplant 5.5/3.1 years previously. For assessment we used well-established instruments. RESULTS: Liver transplanted children scored below the population mean on the cognitive as well as on the behavioural instrument and showed scores below average in the scales Self-esteem, Friends and Total Score regarding QoL. Behavioural problems were associated with poorer cognitive performance (r=-0.38 to -0.63). QoL regarding physical well-being was correlated with sequential processing (r=0.41). Lower sequential processing scores were associated with lower QoL. Also between behavioural parameters and QoL correlations could be determined. Children with more behavioural problems experienced lower QoL (r=-0.40 to r=-0.76). Age at onset of disease showed correlations with behavioural and QoL parameters (r=-0.49 resp. r=0.44). Cognitive functioning was associated with medical complications (r=-0.44). CONCLUSIONS: High interrelations between cognitive functioning, behavioural deficits and QoL were obtained. Especially noticeable are correlations between sequential processing and internalized behavioural functions as both are associated with left lateralized brain functioning. This relationship could indicate differential effects on brain development during the preoperative phase.

Induction of contact dermatitis in guinea pigs by quaternary ammonium compounds: the mechanism of antigen formation.

Eight quaternary ammonium compounds were tested for their ability to induce contact dermatitis in guinea pigs by using a modified Freund's complete adjuvant test together with the guinea pig maximization test. Only two quaternary ammonium salts of the eight tested could be designated as strong allergens. These two active substances were shown to be capable of stable association with membrane lipids in forming immunogenic complexes. This surface complexation phenomenon was confirmed by using a spin-labeled quaternary ammonium salt which competed for binding sites at the surface of epidermal cells in vivo. Electron spin resonance was used to demonstrate that stable "ion-pairs" are formed between binding sites and the two allergenic preservatives. Furthermore, information was obtained on the kinetics of immunogenic complex formation as well as on the position and orientation of the quaternary ammonium ion at the cell surface.

The sensitizing capacity of naturally occurring quinones. Experimental studies in guinea pigs. II. Benzoquinones.

Experimental studies on the sensitizing capacity of naturally occurring benzoquinones, isolated from plants and woods have been carried out in guinea pigs of the Pirbright white strain. Seven compounds were available: primin, three dalbergiones, mansonia quinone (mansonone A), 2,6-dimethoxybenzoquinone and rapanone. With five of these substances (primin, mansonone A, three dalbergiones) guinea pigs could be sensitized. Primin, the allergen of Primula obconica Hance (primrose) proved to be the most effective one of all quinones tested in this and the preceding studies. As a similar but weaker sensitizer R-3, 4-dimethoxydalbergione from Machaerium scleroxylon Tul. (Pao ferro, Caviuna vermelha) could be identified. The results obtained with mansonone A, a sesquiterpenoid quinone from Mansonia altissima A. Chev. demonstrate that even naturally occurring orthoquinones are capable of inducing contact allergy. Allergic cross reactions could be obtained between all chemically related mansonones A-F. The results are in good accordance with the view that the sensitizing capacity of naturally occurring quinones depends on the fundamental quinoid structure and the length, position and configuration of the aliphatic side-chain.

Sensitivity to aspirin: a new serological diagnostic method.

Certain adverse reactions to aspirin (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs) and pyrazolone derivatives resemble IgE-mediated hypersensitivity. However, convincing evidence of antigen-antibody interactions or inhibition of the cyclooxygenase pathway of arachidonic acid metabolism, stimulating the production of leukotrienes (LTs) and decreasing the production of prostaglandins (PGs), has not been presented. In this study, two types of specific IgE antibodies have been found in six serum samples from eight ASA-sensitive patients with salicyloyl and O-methylsalicyloyl disks using the Radio Allergo Sorbent Test (RAST), whereas no positive result could be found with acetylsalicyloyl disks. Further investigation on the specificity of these IgE antibodies and the chemical structure of their epitopes were performed by cross-inhibition studies. The results are in favor of an IgE-dependent mechanism involved in ASA sensitivity, and suggest that determination of specific IgE antibodies would be a safe diagnostic method for ASA sensitivity in vitro.

Activated Fc alpha T cells in Crohn's disease are involved in regulation of IgA.

Activated peripheral T cells (APT) of patients with Crohn's disease (CD) have been analysed for the expression of IgA-Fc receptors and for competence of IgA regulation. It was found that within the subset of APT an increased number of cells express binding sites for IgA (IgA-Fc), that was not found in other diseases with elevated numbers of APT. Moreover the number of IgA-Fc receptor expressing T cells was found to be increased in the inflamed mucosa too. Cocultures with autologous B cells revealed that isolated IgA-Fc receptor bearing T cells of patients with CD suppress IgA secretion. These data support the hypothesis that APT are involved in the immunopathogenesis of CD.

When should a substance be designated as sensitizing for the skin ('Sh') or for the airways ('Sa')?

In the List of MAK and BAT Values compounds are designated with 'Sa' ('sensitizing for the airways') or 'Sh' ('sensitizing for the skin') if, according to scientific evidence, they are allergens. Mainly based on suggestions by a WHO working group and based on our own experience, extended criteria have been elaborated by the working group 'skin and allergy' of the Commission of the Deutsche Forschungsgemeinschaft for the Investigation of Health Hazards of Chemical Compounds in the Work Area, which are presented in this article. They serve as guidelines for deciding which substances have to be labelled 'Sa' and 'Sh', respectively, for the prevention of sensitization and subsequent allergic diseases in workers. Although in some special cases their strict application may not be deemed necessary or possible, the proposed new criteria should be used to make the procedure of classification of substances: 1) more rational, 2) more consistent, 3) more comprehensible, and 4) more transparent. This paper informs readers working scientifically or administratively in this field and invites a critical discussion of the issue.

The presence of specific IgE to salicyloyl and O-methylsalicyloyl in aspirin-sensitive patients.

Certain adverse reactions to aspirin (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs) and pyrazoline derivatives resemble IgE-mediated hypersensitivity. However, convincing evidence of antigen-antibody interactions or of the inhibition of the cyclooxygenase pathway of arachidonic acid metabolism leading to an increase in the generation of leukotrienes (LTs) and a decrease in the generation of prostaglandins (PGs) was not fully demonstrated. In this study, two types of specific IgE antibodies have been found in 27 serum samples from 28 ASA-sensitive patients with salicyloyl-discs and O-methylsalicyloyl-discs by Radio Allergo Sorbent Tests (RAST). The positive rates were 96.4% and 71.4%, respectively. In contrast, no positive results could be found in 10 normal donors without ASA sensitivity after ingestion of ASA 500 mg/day for 14 days. Further investigation of the chemical structure of epitopes was done by cross inhibition studies. Our results are an increasing evidence in favour of an IgE-dependent mechanism in patients suffering from ASA sensitivity. Hopefully, the determination of specific IgE antibodies will be a safe diagnostic method of ASA sensitivity in vitro.

Detection of IgE antibodies specific for 1-phenyl-2,3-dimethyl-3-pyrazoline-5-one by RAST: a serological diagnostic method for sensitivity to pyrazoline drugs.

Certain adverse reactions to pyrazoline drugs resemble IgE-mediated hypersensitivity. However, convincing evidence of antigen-antibody interactions is not fully demonstrated. In this study, IgE antibodies specific for 1-phenyl-2,3-dimethyl-3-pyrazoline-5-one have been found in 17 out of 19 serum samples from individuals sensitive to pyrazoline drugs with 4-aminoantipyrine discs by Radio Allergo Sorbent Test (RAST). In contrast, we have not found any positive results from 10 normal donors without sensitivity to pyrazoline drugs after ingestion of metamizol 500 mg/day for 14 days. Therefore, our results provide further evidence in favor of an IgE-dependent mechanism in patients suffering from sensitivity to pyrazoline drugs. The determination of specific IgE antibodies could be used as a serodiagnostics method.

[Psychological stress, immune function and disease development. The psychoneuroimmunologic perspective]. / Psychische Belastung, Immunfunktionen und Krankheitsentwicklungen Die psychoneuroimmunologische Perspektive.

Interdisciplinary psychoneuroimmunological (PNI) research increasingly demonstrates clinically relevant interrelations between psychological stressors and the onset or progression of chronic diseases. Disturbances of the bi-directional interaction between the nervous system, the immune system and the endocrine system have been hypothesized to be implicated in several diseases. Here, we review evidence from psychoneuroimmunology within the theoretical framework of allostatic load to conceptualize some of these associations. Interdisciplinary PNI research investigating the importance of psychological stress for the higher incidence of infections, decreased responses to vaccinations and delayed wound healing is reviewed. Furthermore, the literature supporting similar associations with regard to progression of oncological diseases and autoimmune disorders is reviewed with a focus on breast cancer and multiple sclerosis. The accumulating evidence regarding the importance of neuroendocrine-immune interaction in these diseases may thus lead to novel insights into pathogenetic mechanisms and could contribute to the development of novel preventive and therapeutic strategies.