Expression and function of histamine receptors 1 and 2 on human monocyte-derived dendritic cells

BACKGROUND: Histamine is a well-known mediator of inflammatory and allergic reactions and has immunomodulatory capacities. There is increasing evidence that dendritic cells as professional antigen-presenting cells play a major role in the development of allergic reactions. However, a possible link between histamine and dendritic cells has not been investigated thus far. OBJECTIVE: We investigated the effect of histamine on human monocyte-derived dendritic cells (MoDCs). METHODS: Expression of histamine H1 and H2 receptors (H1R and H2R) on MoDCs was assessed by means of RT-PCR and flow cytometry. Functional exploration of these receptors was performed by monitoring the increase of intracellular calcium levels (H1R), cyclic adenosine monophosphate formation (H2R), F-actin polymerization, and IL-12p70 production. RESULTS: MoDCs express both H1R and H2R. Stimulation of dendritic cells with histamine resulted in F-actin polymerization and cyclic adenosine monophosphate production through H2R. Influx of calcium could not be detected after stimulation of dendritic cells with histamine under conditions in which histamine induced calcium influx in monocytes. Histamine and H1R and H2R agonists downregulated IL-12p70 production of prestimulated MoDCs. CONCLUSION: MoDCs express histamine H1 and H2 receptors. Our results indicate chemotactic (F-actin polymerization) and immunomodulatory (inhibition of IL-12p70 production) effects of histamine on MoDCs. Therefore histamine might represent a link between immediate-type hypersensitivity reactions and cellular inflammation in allergic disease (eg, in atopic dermatitis).     

Writing the proposal for a qualitative research methodology project

Writing the proposal for a qualitative research methodology study is a double challenge because of the emergent nature of qualitative research design and because a methodology study entails describing a process to produce a process. How the authors addressed this challenge is shown in the annotated text of the grant proposal--"Analytic Techniques for Qualitative Metasynthesis"--funded by the National Institute of Nursing Research. Appealing qualitative research proposals adhere to principles that engage writers and readers in an informative and mutually respectful interaction.     

Gender in medical ethics: Re-examining the conceptual basis of empirical research

Conducting empirical research on gender in medical ethics is a challenge from a theoretical as well as a practical point of view. It still has to be clarified how gender aspects can be integrated without sustaining gender stereotypes. The developmental psychologist Carol Gilligan was among the first to question ethics from a gendered point of view. The notion of care introduced by her challenged conventional developmental psychology as well as moral philosophy. Gilligan was criticised, however, because her concept of two different voices may reinforce gender stereotypes. Moreover, although Gilligan stressed relatedness, this is not reflected in her own empirical approach, which still focuses on individual moral reflection. Concepts from social psychology can help overcome both problems. Social categories like gender shape moral identity and moral decisions. If morality is understood as being lived through actions of persons in social relationships, gender becomes a helpful category of moral analysis. Our findings will provide a conceptual basis for the question how empirical research in medical ethics can successfully embrace a gendered perspective.This revised version was published online in October 2005 with corrections to the Cover Date.     

Pili trianguli et canaliculi

We report on a child with pili trianguli et canaliculi. This hair shaft abnormality belongs to a heterogeneous group of diseases which are included under the synonym uncombable hair. The diagnosis was confirmed by scanning electron microscopy, revealing hair shafts with a characteristic longitudinal groove. In addition the girl suffered from atopic eczema and tooth anomalies. Our findings suggest that this disorder could represent a tricho-odontal subtype of ectodermal dysplasia.     

Cognitive strategies versus self-management skills as adjunct to vocational rehabilitation

Cognitive dysfunctions and negative symptoms are "rate-limiting factors" for community outcome and response to psychosocial intervention in people with schizophrenia. Therefore, two cognitive-behavioral group therapies were developed-computer-assisted cognitive strategy training (CAST) and training of self-management skills for negative symptoms (TSSN)-to target these barriers to rehabilitation readiness. One hundred thirty-eight DSM-IV schizophrenia inpatients on a rehabilitation ward were randomly assigned to CAST plus vocational rehabilitation, TSSN plus vocational rehabilitation, or vocational rehabilitation alone. CAST included computer-based training in coping strategies focusing on deficits in attention, verbal memory, and planning. TSSN focused on social withdrawal/social anhedonia, lack of drive/volition, and affect flattening using techniques such as time scheduling, mastery, and pleasure techniques. Treatment outcome was assessed at intake and at discharge after 8 weeks. Analyses of covariance controlling for basis-level functioning demonstrated that patients receiving CAST plus vocational rehabilitation showed greater improvement on attention and verbal memory but not on planning ability. Patients receiving TSSN plus vocational rehabilitation failed to demonstrate improvement in negative symptoms. CAST plus vocational rehabilitation was found to be associated with a higher rate of successful job placement at the 12-month followup interval. Hierarchical logistic regression analyses demonstrated that improvement in short- and long-term verbal memory predicted a higher proportion of variance of successful job placement in the followup than pretreatment history of employment alone. Cognitive training as an adjunct to inpatient vocational rehabilitation demonstrated cognitive improvement, which was found to be associated with successful job placement in the followup. TSSN's efficacy was less clear; reasons for this uncertainty are provided.     

Systematic review of anaemia and inflammatory markers in chronic obstructive pulmonary disease

This systematic review synthesizes the relevant published articles on the prevalence of anaemia in patients with chronic obstructive pulmonary disease (COPD) and its relationship with inflammatory markers. The upregulation of erythropoietin in anaemia maintains homeostasis. However, anaemic COPD patients do not respond to increased levels of erythropoietin. The increased levels could be an indicator of the peripheral erythropoietin resistance in COPD. Anaemia and inflammation are associated with an increased risk of hospitalization and mortality in these patients. The understanding of anaemia in chronic inflammation is that anaemia is at least partially due to the excessive production of inflammatory cytokines, which can contribute to improvements in the management, prognosis, and survival of patients with COPD and anaemia.     

Basal Ganglia Lesions and the Theory of Fronto-Subcortical Loops: Neuropsychological Findings in Two Patients with Left Caudate Lesions

Basal ganglia lesions have a high prevalence for associated behavioural impairments. However, the exact pattern of cognitive impairments and its relationship to individual basal ganglia lesion have rarely been investigated by means of a detailed neuropsychological and lesion study. Furthermore, different mechanisms have been proposed as relevant for the observed cognitive deficits; among these, the hypothesis of fronto-subcortical loops (Alexander et al., 1986) has made predictions regarding the relationship between the damage of particular striato-frontal circuits and the resulting behavioural impairment which await clinical confirmation. We present a study of two subjects who suffered a MRI-documented focal left basal ganglia hematoma. The two patients differed in their lesions; in one patient (PJ) large parts of the caudate nucleus were destroyed whereas in the other (AS) mainly the pallidum and putamen were lesioned and the caudate suffered only minor damage. In the acute phase, the behavioural and neuropsychological abnormalities were similar in both cases and included mainly abulia, an impairment of executive and attentional functions, and a severe amnestic syndrome. After several months many functions were restored in AS, whereas PJ’s abilities remained largely defective. Based on these data and on previous case studies several conclusions are drawn. Left caudate lesions induce marked and long-lasting behavioural and neuropsychological impairments comprising predominantly drive, executive control, attention, and memory. The extent of lesion in the head of the caudate nucleus is the critical factor regarding the severity and the outcome of the syndrome, whereas damage to the putamen and pallidum is less crucial for cognitive functions. A subset of behavioural alterations, among them abulia, attentional and frontal-executive dysfunctions, can well be attributed to lesions of the anterior cingulate circuit and the dorsolateral-frontal circuit at the basal ganglia level. Other impairments, most importantly the prominent amnestic syndrome, are more difficult to interpret on the grounds of this hypothesis and may be related to other pathomechanisms.