[Important aspects in pediatric care of children and adolescents with chronic disease using the example of bronchial asthma]. / Wichtige Aspekte bei der Betreuung chronisch kranker Kinder und Jugendlicher am Beispiel des Asthma bronchiale.

When treating children or adolescents with chronic disease one should take the specific age-related features of the course of disease, differential diagnosis, and the psychosocial environment, as well as the avoidance of complications and side effects of therapy into account. These may impair the patient's physical and psychosocial development and quality of life in the context of family, school and occupational life. Continued care of growing children from the start of the disease when they are infants to the point when they assume personal responsibility as adults is one of the major concerns of the pediatrician. This concept requires interdisciplinary cooperation and a large body of personnel which would include training programs, inclusion of family members and in some cases psychosomatic therapy. Given the increasing prevalence of chronic diseases in this age group and their sociopolitical significance it is important to activate preventive potentials in terms of content and structure - by quality assurance - especially to avoid long-term complications. Various care structures are used in Europe to achieve this goal. Asthma is the most common chronic disease in children and adolescents. It influences quality of life as well as the child's personal, educational and occupational development to a significant extent. The special aspects of the treatment of these patients will be addressed to illustrate the therapy of chronic disease.

Interactions between the Fusarium toxin deoxynivalenol and lipopolysaccharides on the in vivo protein synthesis of acute phase proteins, cytokines and metabolic activity of peripheral blood mononuclear cells in pigs.

The in vivo effects of the Fusarium toxin deoxynivalenol (DON) on albumin and fibrinogen synthesis in pigs and metabolic activity of porcine peripheral blood mononuclear cells (PBMCs) were studied alone or in combination with lipopolysaccharides (LPSs) in order to examine proposed synergistic effects of both substances. A total of 36 male castrated pigs (initial weight of 26 kg) were used. Uncontaminated (Control) and naturally DON-contaminated (chronic oral DON, 3.1mg/kg diet) wheat was fed for 37 days. On the day of protein synthesis measurement, pigs recruited from the Control group were treated once intravenously with (iv) DON (100 µg/kg live weight (LW)/h), iv LPS (7.5 µg/kgLW/h) or a combination of both substances, and six pigs from the chronic oral group were treated once with iv LPS. A treatment with DON alone exhibited no alterations of acute phase protein synthesis and metabolic activity of PBMC. There was no evidence that the chosen dosing regimen of DON had influences on the induced sub-acute stage of sepsis, as the LPS challenge, irrespective of DON co-exposure, mediated an acute phase reaction with a typical decrease of albumin synthesis, as well as changes in cytokine concentration and a loss of metabolic activity in PBMC.

Deoxynivalenol and E.coli lipopolysaccharide alter epithelial proliferation and spatial distribution of apical junction proteins along the small intestinal axis.

We investigated a proposed synergistic effect of deoxynivalenol (DON) and lipopolysaccharides (LPS) on small intestinal architecture and epithelial barrier integrity in pigs. Crypt depth and intestinal cell proliferation were analyzed, as well as expression of zonula occludens protein-1 (ZO-1) and ß-catenin of the apical junction complex along the small intestine. Barrows (26.2±4.1 kg) were fed restrictedly either a control diet (CON) or a diet naturally contaminated with 3.1 mg DON/kg feed (DON) for 37 d. At d 37, the control group was infused for 1 h either with 100 µg/kg BW of DON (CON-DON, n=6), 7.5 µg/kg BW of LPS (CON-LPS, n=6), a combination of both (CON-DON+LPS, n=7), or 0.9% NaCl (CON-CON, n=6) and the DON group with 7.5 µg/kg BW of LPS (DON-LPS, n=8) or 0.9% NaCl (DON-CON, n=6). Pigs were euthanized 3.25 h after start of infusion. Immunohistochemistry (5'-bromo-2'-deoxyuridine for proliferation) and immunofluorescence (ZO-1 and ß-catenin) from duodenum, proximal jejunum, mid-jejunum, proximal ileum, and terminal ileum were analyzed for crypt depth, cell proliferation, and apical junction proteins. Duodenal crypts were deeper compared with the other 4 intestinal regions, and proximal jejunal crypts were deeper than those of mid-jejunum and proximal ileum (P<0.001). Epithelial proliferation showed a bell-shaped distribution along the small intestinal axis. Duodenal proliferating cells had the least number compared with jejunal sections and proximal ileum (P<0.001). Neither DON nor LPS affected these variables. Zonula occludens-1 displayed a distinct spatial distribution in the epithelium with an apical and a cytosolic component. Apical expression of ZO-1 was severely damaged in the mid-jejunum (P<0.001) of CON-DON compared with animals treated with LPS. Also, in all animals receiving LPS systemically, the cytosolic ZO-1 fraction in the 3 upper gut sections disappeared completely. This effect was independent of DON presence. Control pigs had a greater basolateral ß-catenin accumulation (P<0.05) in the cells, whereas the protein distribution did not differ in CON-DON pigs. In conclusion, results of this experiment demonstrated that epithelial proliferation has a distinct pattern along the small intestine and is not necessarily positively linked to crypt depth in pigs. Furthermore, results indicate that LPS changed the spatial distribution of ZO-1. A synergistic effect of DON and LPS on intestinal architecture could not be verified in the present study.

Gender preferences and demand for preconception sex selection: a survey among pregnant women in Pakistan.

BACKGROUND: In its recent report 'Human Reproductive Technologies and the Law', the House of Commons' Select Committee on Science and Technology called for greater efforts to establish the potential demographic impact of sex selection across all sectors of UK society. Given the well-known preference for boys over girls among some communities, there is concern that a readily available service for social sex selection may upset the balance of the sexes. Of particular interest are the gender preferences and the demand for sex selection among Pakistanis. METHODS: We conducted a social survey on gender preferences and potential demand for preconception sex selection among 301 pregnant women in Karachi, Pakistan, using a self-report questionnaire consisting of 14 questions. RESULTS: About 41.5% wish to have a family with an equal number of boys and girls; 3.3% would like to have only boys, 1.0% only girls, 27.6% more boys than girls and 4.3% more girls than boys, and 22.3% stated that they do not care about the sex composition of their family. Whereas 6.3% could imagine employing cytometric sperm separation for social sex selection, 76.1% could not and 17.6% were undecided. About 27.2% felt that social sex selection ought to be legal, 48.8% thought it ought to be illegal and 23.9% were undecided. CONCLUSIONS: Although Pakistani women do show a statistically significant preference for boys over girls, the number of women willing to subject themselves to cytometric sperm separation appears to be too small to cause a severe imbalance of the sexes. However, further research among British citizens of Pakistani origin is needed to establish whether sex selection poses a serious threat to the sex ratio of UK communities.

Social sex selection and the balance of the sexes: empirical evidence from Germany, the UK, and the US.

Preconception sex selection for nonmedical reasons is one of the most controversial issues in bioethics today. The most powerful objection to social sex selection is based on the assumption that it may severely distort the natural sex ratio and lead to a socially disruptive imbalance of the sexes. Based on representative social surveys conducted in Germany, the United Kingdom, and the United States, this paper argues that the fear of an impending sex ratio distortion is unfounded. Given the predominant preference for a "gender balanced family," a widely available service for social sex selection is highly unlikely to upset the balance of the sexes in Western societies.

Attitudes towards preconception sex selection: a representative survey from Germany.

Within the next parliamentary term, the German government is expected to replace the current Embryo Protection Act with a new Human Reproductive Technology Act. Before introducing new legislation, policy makers may want to survey public attitudes towards novel applications of reproductive technology. In order to assess opinions and concerns about preconception sex selection for non-medical reasons, a social survey has been conducted in Germany. As a representative sample of the German population, 1005 men and women 18 years and older were asked whether or not preconception sex selection should be made available. Of the respondents, 32% held that sex selection should be strictly prohibited, be it for medical or non-medical reasons, and 54% accepted the use of preconception sex selection for medical purposes. Only a minority of 11% approved of the use of preconception sex selection for non-medical reasons. The widespread opposition to a freely available service for non-medical sex selection is based on several claims: 87% of respondents hold that 'children are a gift and deserve to be loved regardless of any characteristics such as beauty, intelligence or sex'; 79% argue that choosing the sex of children is 'playing God'; 76% are opposed because it is seen as 'unnatural'; 49% are afraid that it is 'skewing the natural sex ratio'; and 40% consider it to be 'sexist'.

Preconception sex selection for non-medical reasons:a representative survey from Germany.

BACKGROUND: Preconception sex selection for non-medical reasons raises serious moral, legal and social issues. The main concern is based on the assumption that a freely available service for sex selection will distort the natural sex ratio and lead to a severe gender imbalance. However, for a severe gender imbalance to happen, at least two conditions have to be met. First, there must be a significant preference for children of a particular sex, and second, there must be a considerable demand for preconception sex selection. To ascertain whether or not these two conditions are met, we have conducted a survey in Germany. METHODS: As a representative sample of the German population, 1094 men and women aged 18-45 years were asked about their gender preferences and whether or not they could imagine selecting the sex of their children through flow cytometric separation of X- and Y-bearing sperm followed by intrauterine insemination. RESULTS: 58% of respondents stated that they do not care about the sex of their offspring. 30% wish to have a family with an equal number of boys and girls. 4% would like to have more boys than girls, 3% more girls than boys, 1% only boys and 1% only girls. For first-borns, however, there is still a preference for boys over girls. While 75.6% claimed to have no gender preference, 14.2% would like their first child to be a boy and 10.1% would like their first child to be a girl. Whereas 6% could imagine taking advantage of preconception sex selection, 92% found this to be out of the question. Even in the hypothetical case that a medication for sex selection were ever to become available, 90% stated that they would not want to use it. CONCLUSION: Given that a majority does not seem to care about the sex of their offspring and only a minority seem to be willing to select the sex of their children, a freely available service for preconception sex selection for non-medical reasons is rather unlikely to cause a severe gender imbalance in Germany.

Peptide mimics of SNARE transmembrane segments drive membrane fusion depending on their conformational plasticity.

SNARE proteins are essential for different types of intracellular membrane fusion. Whereas interaction between their cytoplasmic domains is held responsible for establishing membrane proximity, the role of the transmembrane segments in the fusion process is currently not clear. Here, we used an in vitro approach based on lipid mixing and electron microscopy to examine a potential fusogenic activity of the transmembrane segments. We show that the presence of synthetic peptides representing the transmembrane segments of the presynaptic soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) synaptobrevin II (also referred to as VAMP II) or syntaxin 1A, but not of an unrelated control peptide, in liposomal membranes drives their fusion. Liposome aggregation by millimolar Ca(2+) concentrations strongly potentiated the effect of the peptides; this indicates that juxtaposition of the bilayers favours their fusion in the absence of the cytoplasmic SNARE domains. Peptide-driven fusion is reminiscent of natural membrane fusion, since it was suppressed by lysolipid and involved both bilayer leaflets. This suggests transient presence of a hemifusion intermediate followed by complete membrane merger. Structural studies of the peptides in lipid bilayers performed by Fourier transform infrared spectroscopy indicated mixtures of alpha-helical and beta-sheet conformations. In isotropic solution, circular dichroism spectroscopy showed the peptides to exist in a concentration-dependent equilibrium of alpha-helical and beta-sheet structures. Interestingly, the fusogenic activity decreased with increasing stability of the alpha-helical solution structure for a panel of variant peptides. Thus, structural plasticity of transmembrane segments may be important for SNARE protein function at a late step in membrane fusion.

[A patient with Gulf war syndrome. On discussion of an uncertain disease picture]. / Ein Patient mit Golfkriegssyndrom? Zur Diskussion eines unklaren Krankheitsbildes.

The Gulf War syndrome represents neurological and neuropsychological disorders in veterans of the Persian Gulf war. Until today, the various symptoms observed could not be attributed to any defined disease. As a possible cause, exposure to neurotoxic agents such as the organophosphates used during the war has been suggested by many authors. We report on a 29-year-old man who suffered from dysmnesia, disturbance of orientation, cognitive impairment, and double vision. His history revealed several front-line operations in 1990 and 1991 during the Gulf War. Physical examinations showed a complex eye-movement disturbance and a horizontal nystagmus, which was neuro-ophthalmologically confirmed. The early auditory potentials referred to a brainstem dysfunction and the cognitive disturbances correlated to changes in the late-appearing component of event-related potentials (P 300). Brain imaging with CCT, MRI, SPECT, PET, and EEG and CSF showed no pathologies. Neuropsychological tests disclosed severe cognitive impairment especially concerning memory. Three-month follow-up studies in a department of psychosomatic medicine excluded a dissociative disorder as a feature of a post-traumatic stress or a conversion disorder. This is the first case of Gulf War syndrome in Germany. We focus on an unfamiliar complication after the war. The recent literature is reviewed.

[Psychosocial predictors of metabolic instability in brittle diabetes--a multivariate time series analysis]. / Psychosoziale Prädiktoren der metabolischen Instabilität bei Brittle Diabetes. Eine multivariate Zeitreihenanalyse.

The term "brittle diabetes" denotes the unstable course of an insulin-dependent diabetes characterised by frequent hypo- or hyperglycaemic crises. The aim of this study is to demonstrate empirically how psychosocial parameters interact with metabolic instability in a paradigmatic case of juvenile brittle diabetes. By means of a structured diary study, blood sugar values, moods (SAM), body symptoms (GBB), the daily hustle and hassle, helping therapeutic alliance (HAQ) and the aspects of setting were registered. Resulting time series (112 days each) were ARIMA-analysed by a multivariate approach. It could be shown that the mean variance of daily blood sugar values as an indicator of brittleness was predicted by moods, body complaints and by a family session as setting factor (p < 0.05, for corresponding predictors). Feelings of dominance preceded an increase of blood sugar variance, whereas depressive moods, anger and body symptoms were associated with metabolic instability. A family therapy session also resulted in an increase of the mean blood sugar variance. The model accounted for almost 30% of the total variance of the dependent variable (R-square-adjusted, p < 0.0001). The potential of multivariate time-series as a means to demonstrate psychosomatic interrelations is discussed. We believe that the results may also contribute to an empirically rooted understanding of psychodynamic processes in psychosomatoses.

The "Dorian Gray Syndrome": psychodynamic need for hair growth restorers and other "fountains of youth.".

The psychic-dynamic factors underlying the hypochondriac disorder involving an obsessive preoccupation with physical attractiveness (dysmorphophobia) and the treatment possibilities for some manifestations of this syndrome have been examined. This psychosomatic illness frequently leads to the taking of finasteride, a medication that halts the balding process in cases of androgenetic alopecia or even stimulates renewed hair growth. The nosological demarcation of the disorder requires the differential diagnosis of depressive, hypochondriac and delusionary disorders. The psychodynamics involved, as deduced from 2 case studies, takes the form of an expansion of the patients' reductionist perspective, characterized by an emphasis on external types extending to a psychogenetic attitude with regression into narcissistic fixation. The authors seek eternal youth which is a "leitmotif' of the disorder, and they apply the term "Dorian Gray Syndrome" after Oscar Wilde's novel. The treatment recommended is a course of intensive psychotherapy; often the topic of "life-style medication" must be introduced before the specific narcissistic conflicts behind the current symptoms can be treated.

Peptide mimics of the vesicular stomatitis virus G-protein transmembrane segment drive membrane fusion in vitro.

The efficiency of cell-cell fusion mediated by heterologously expressed vesicular stomatitis virus G-protein has previously been shown to be affected by mutating its transmembrane segment. Here, we show that a synthetic peptide modeled after this transmembrane segment drives liposome-liposome fusion. Addition of millimolar Ca(2+) concentrations strongly potentiated the effect of the peptides suggesting that Ca(2+)-mediated liposome aggregation supports the activity of the peptide. Peptide-driven fusion was suppressed by lysolipid, an established inhibitor of natural membrane fusion, and involved inner and outer leaflets of the liposomal bilayer. Thus, transmembrane segment peptide-driven liposome fusion exhibits important hallmarks characteristic of natural membrane fusion. Importantly, the mutations previously shown to attenuate the function of full-length G-protein in cell-cell fusion also attenuated the fusogenicity of the peptide, albeit in a less pronounced fashion. Therefore, the function of the peptide mimic is dependent on its primary structure, similar to full-length G-protein. Together, our data suggest that the G-protein transmembrane segment is an autonomous functional domain. We propose that it acts at a late step in membrane fusion elicited by vesicular stomatitis virus.

[Psychosomatic dermatology in Germany: a survey of 69 dermatologic clinics]. / Psychosomatische Dermatologie in Deutschland. Eine Umfrage an 69 Hautkliniken.

BACKGROUND AND OBJECTIVE: A questionnaire study of German dermatological clinics was designed to show the situation and development of psychosomatic dermatology 10 years after a similar study. PATIENTS/METHODS: A questionnaire was sent to 170 dermatological clinics. 76 were send back; 69 of them (40.6%) were evaluable. The questionnaires were mostly answered by the heads of the dermatological clinics (38/69 = 55.1%). RESULTS: Nearly 85% of the dermatological clinics answered that they take psychosomatic aspects into consideration in the therapy. 5.1% of the dermatologists working in clinics have additional psychotherapeutic certification. The improvement of coping behaviour seems to be the main goal of psychosomatic interventions. The importance of psychic factors increased in the last 10 years in comparison to a former study in regard to most of the dermatological diseases. CONCLUSIONS: Psychosomatic aspects seem to be an obligatory part of inpatient dermatological therapy. The frequency of some diseases was underestimated in comparison with results from literature.

A conserved membrane-spanning amino acid motif drives homomeric and supports heteromeric assembly of presynaptic SNARE proteins.

Assembly of the SNARE proteins synaptobrevin/VAMP, syntaxin, and SNAP-25 to binary and ternary complexes is important for docking and/or fusion of presynaptic vesicles to the neuronal plasma membrane prior to regulated neurotransmitter release. Despite the well characterized structure of their cytoplasmic assembly domains, little is known about the role of the transmembrane segments in SNARE protein assembly and function. Here, we identified conserved amino acid motifs within the transmembrane segments that are required for homodimerization of synaptobrevin II and syntaxin 1A. Minimal motifs of 6-8 residues grafted onto an otherwise monomeric oligoalanine host sequence were sufficient for self-interaction of both transmembrane segments in detergent solution or membranes. These motifs constitute contiguous areas of interfacial residues assuming alpha-helical secondary structures. Since the motifs are conserved, they also contributed to heterodimerization of synaptobrevin II and syntaxin 1A and therefore appear to constitute interaction domains independent of the cytoplasmic coiled coil regions. Interactions between the transmembrane segments may stabilize the SNARE complex, cause its multimerization to previously observed multimeric superstructures, and/or be required for the fusogenic activity of SNARE proteins.

A heptad motif of leucine residues found in membrane proteins can drive self-assembly of artificial transmembrane segments.

Specific interactions between alpha-helical transmembrane segments are important for folding and/or oligomerization of membrane proteins. Previously, we have shown that most transmembrane helix-helix interfaces of a set of crystallized membrane proteins are structurally equivalent to soluble leucine zipper interaction domains. To establish a simplified model of these membrane-spanning leucine zippers, we studied the homophilic interactions of artificial transmembrane segments using different experimental approaches. Importantly, an oligoleucine, but not an oligoalanine, se- quence efficiently self-assembled in membranes as well as in detergent solution. Self-assembly was maintained when a leucine zipper type of heptad motif consisting of leucine residues was grafted onto an alanine host sequence. Analysis of point mutants or of a random sequence confirmed that the heptad motif of leucines mediates self-recognition of our artificial transmembrane segments. Further, a data base search identified degenerate versions of this leucine motif within transmembrane segments of a variety of functionally different proteins. For several of these natural transmembrane segments, self-interaction was experimentally verified. These results support various lines of previously reported evidence where these transmembrane segments were implicated in the oligomeric assembly of the corresponding proteins.

The dimerization motif of the glycophorin A transmembrane segment in membranes: importance of glycine residues.

The glycophorin A transmembrane segment homo-dimerizes to a right-handed pair of alpha-helices. Here, we identified the amino acid motif mediating this interaction within a natural membrane environment. Critical residues were grafted onto two different hydrophobic host sequences in a stepwise manner and self-assembly of the hybrid sequences was determined with the ToxR transcription activator system. Our results show that the motif LIxxGxxxGxxxT elicits a level of self-association equivalent to that of the original glycophorin A transmembrane segment. This motif is very similar to the one previously established in detergent solution. Interestingly, the central GxxxG motif by itself already induced strong self-assembly of host sequences and the three-residue spacing between both glycines proved to be optimal for the interaction. The GxxxG element thus appears to be the most crucial part of the interaction motif.

Dimerisation of the glycophorin A transmembrane segment in membranes probed with the ToxR transcription activator.

Specific interactions between membrane spanning polypeptide segments are important for folding and oligomerisation of integral membrane proteins. Previously the dimerisation of glycophorin A has been shown to depend on interactions between its transmembrane segment by studying chimeric proteins in detergent solution. Here, we examined dimerisation of the glycophorin A transmembrane segment in a natural membrane employing the ToxR transcription activator from Vibrio cholerae. The ToxR protein is integral to the bacterial inner membrane and its activity requires a dimeric state. Therefore, the ToxR protein is suited to monitor quantitative homophilic interactions. We replaced the ToxR transmembrane segment with parts of the glycophorin A transmembrane segment containing the amino acid motif LIxxGVxxGVxxT previously shown to be sufficient for dimerisation in detergent solution. Expression of these chimeric proteins in an indicator strain resulted in strong transcription activation. This is indicative of efficient dimerisation mediated by the glycophorin transmembrane segment inserted into the inner membrane. Analysis of individual point mutants revealed that at least four residues out of this motif are critical for dimer formation in membranes. However, dimerisation of the glycophorin A transmembrane segment appears to be less sensitive to mutations when localised within a natural lipid bilayer compared to measurements in detergent solution. This may be related to a slightly altered structure of the dimer and/or to a higher local concentration and preorientation of the interacting molecules in a membrane. This makes the ToxR system well suited for probing low-affinity interactions between the transmembrane segments of other proteins.

[Psychosocial problems in Huntington chorea. 1: Overview, project description. social and illness-related data]. / Psychosoziale Probleme bei Huntingtonscher Chorea. Teil 1: Ubersicht, Projektbeschreibung, soziale und krankheitsbezogene Daten.

Huntington's Disease, a neuropsychiatric disorder with dominant inheritance and late manifestation is related to multiple psychosocial problems of the affected person, his life partner as well as their children (so-called individuals at risk). During a five years project the authors contacted 131 persons, directly and indirectly involved in problems with H.D. In the first part the authors present after a general survey sociodemographic and clinical data of the project.