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1.
Sci Rep ; 9(1): 5605, 2019 04 03.
Article in English | MEDLINE | ID: mdl-30944353

ABSTRACT

Single-stranded DNA or RNA sequences rich in guanine (G) can adopt non-canonical structures known as G-quadruplexes (G4). Mitochondrial DNA (mtDNA) sequences that are predicted to form G4 are enriched on the heavy-strand and have been associated with formation of deletion breakpoints. Increasing evidence supports the ability of mtDNA to form G4 in cancer cells; however, the functional roles of G4 structures in regulating mitochondrial nucleic acid homeostasis in non-cancerous cells remain unclear. Here, we demonstrate by live cell imaging that the G4-ligand RHPS4 localizes primarily to mitochondria at low doses. We find that low doses of RHPS4 do not induce a nuclear DNA damage response but do cause an acute inhibition of mitochondrial transcript elongation, leading to respiratory complex depletion. We also observe that RHPS4 interferes with mtDNA levels or synthesis both in cells and isolated mitochondria. Importantly, a mtDNA variant that increases G4 stability and anti-parallel G4-forming character shows a stronger respiratory defect in response to RHPS4, supporting the conclusion that mitochondrial sensitivity to RHPS4 is G4-mediated. Taken together, our results indicate a direct role for G4 perturbation in mitochondrial genome replication, transcription processivity, and respiratory function in normal cells.


Subject(s)
Gene Expression/genetics , Genes, Mitochondrial/genetics , Genome, Mitochondrial/genetics , Mitochondria/genetics , Animals , Cell Line, Tumor , Cells, Cultured , DNA Replication/genetics , DNA, Mitochondrial/genetics , G-Quadruplexes , Guanine/metabolism , HeLa Cells , Humans , Mice , Mice, Inbred BALB C , Mitochondria/metabolism , Sequence Deletion/genetics
2.
Ophthalmologe ; 116(2): 127-137, 2019 Feb.
Article in German | MEDLINE | ID: mdl-30707284

ABSTRACT

NEUROTROPHIC KERATOPATHY: Neurotrophic keratopathy (NK) is a rare corneal disease caused by an impaired corneal innervation. It leads to spontaneous recurrent epithelial defects potentially leading to corneal ulcers and perforation. To avoid severe corneal damage, a prompt and stage-adjusted treatment is necessary. Treatment of NK is challenging. Due to the lack of direct causal treatment options, only a supportive therapy was previously possible. ESTABLISHED TREATMENT: The basic treatment of NK consists of intensive ocular surface lubrication with artificial tears free from preservatives. Medication toxic to the epithelium must be discontinued and associated ocular surface diseases must be treated in the best possible way. In advanced stages surgical options, such as amniotic membrane transplantation, tarsorrhaphy and conjunctival flaps are used but autologous serum can also be used to achieve closure of the epithelium. NOVEL AND EXPERIMENTAL TREATMENT OPTIONS: Cenegermin, a recombinant neurotrophic growth factor, has recently become available, which can be used for the causal treatment of advanced stages of NK. Clinical experience with this drug is, however, still limited. Corneal neurotization is an established procedure in other medical disciplines and is currently also being evaluated in the treatment of NK. Keratoplasty is only used in emergencies, such as corneal perforation, as it is associated with a high risk for recurrent neurotrophic corneal ulcers. The various techniques of keratoplasty and the absolutely necessary concomitant treatment are also discussed.


Subject(s)
Corneal Diseases , Keratitis , Trigeminal Nerve Diseases , Cornea , Humans
3.
Ophthalmologe ; 116(2): 109-119, 2019 Feb.
Article in German | MEDLINE | ID: mdl-30478498

ABSTRACT

Neurotrophic keratopathy (NK) is a degenerative corneal disease that is based on an impairment of the corneal innervation. The damage to the sensory innervation, which is delivered through the 1st branch of the trigeminal nerve (ophthalmic nerve), can occur throughout the entire length of the nerve from the nucleus in the brainstem, e.g. caused by brain tumors, to the terminal nerve fibers in the cornea, caused for example by refractive corneal surgery (e. g. LASIK). Due to the loss of the sensory innervation, a reduced lacrimation and a reduction in the secretion of trophic factors occur. This in turn inhibits the regeneration potential of the corneal epithelium. In the most severe cases of the disease, the reduction or loss of lacrimation, together with the impaired regeneration potential of the epithelial cells, can lead to persistent epithelial defects, ulcers and corneal perforation. The NK has a prevalence of 5 or fewer individuals per 10,000 and is classified as a rare, i. e. orphan disease (ORPHA137596). A fundamental understanding of the pathogenesis and epidemiology of NK supports the early diagnosis and therefore the initiation of a specific treatment.


Subject(s)
Corneal Dystrophies, Hereditary , Epithelium, Corneal , Keratitis , Trigeminal Nerve Diseases , Cornea , Humans
5.
Eur J Clin Microbiol Infect Dis ; 35(12): 1933-1939, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27677280

ABSTRACT

Tedizolid is an oxazolidinone with an antimicrobial in vitro potency advantage against Gram-positive bacterial pathogens compared to other currently marketed drugs in this class, including linezolid. Tedizolid was compared to linezolid when tested against Staphylococcus aureus and Streptococcus pneumoniae isolates collected from countries in Latin America and the Asia-Pacific. Isolates were tested by broth microdilution susceptibility methods against tedizolid, linezolid, and non-class comparators in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. The activity of tedizolid against S. aureus was potent and consistent in Latin America (MIC90, 0.5 mg/L), Australia and New Zealand (MIC90, 0.25 mg/L), and China (MIC90, 0.5 mg/L). Based on MIC90 results, tedizolid was four- to eight-fold more active than linezolid against S. aureus, including both methicillin-susceptible and -resistant isolates. Only two tedizolid non-susceptible strains were observed; both had intermediate minimum inhibitory concentration (MIC) values of 1 mg/L, for which the MICs of linezolid was higher (≥2 mg/L). Tedizolid (MIC90, 0.25 mg/L) was four-fold more potent than linezolid (MIC90, 1 mg/L) against S. pneumoniae in all countries that provided isolates. The findings from this study support the global clinical development of tedizolid for Gram-positive infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Organophosphates/pharmacology , Oxazoles/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus aureus/isolation & purification , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/isolation & purification , Australasia , China , Humans , Latin America , Linezolid/pharmacology , Microbial Sensitivity Tests
6.
J Psychosom Res ; 80: 37-43, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26721546

ABSTRACT

OBJECTIVE AND METHODS: Despite its value for the management of psychological burden, little is known about the efficacy of and patient satisfaction with internet-based cognitive behavioral stress management (IB-CBSM) for women with preterm labor. The present study sets out to analyze stress/anxiety reduction, patient satisfaction and patient's working alliance in a group of 58 women with preterm labor participating in an online psychological stress management project. As part of the project, women were randomly assigned to online stress management or a control condition. RESULTS: Levels of stress and anxiety decreased significantly in both conditions from pre- to post-treatment measure. Participants in IB-CBSM reported significant higher working alliance inventory (WAI) scores in the task and goal subscale (p<.001; p<.05) than women in the control condition. In Addition the IB-CBSM group showed significant correlations of the WAI subscale task and goal and the stress/anxiety outcome. Regarding patient satisfaction, women in the IB-CBSM reported significantly higher satisfaction scores (p<.001) than women in the control condition. WAI explained nearly 40% of the variance in patient satisfaction. Furthermore, WAI mediates, at least in part, the relationship between group condition and patient satisfaction. CONCLUSION: The current analysis indicated that participants in IB-CBSM had higher WAI scores and were more satisfied with the program. In addition only the IB-CBSM group showed significant correlations of the WAI with the stress/anxiety reduction outcome. Based on these findings, it can be presumed that measures of agreement with working alliance parameters, especially task and goal components, are substantially important for more effective and satisfactory therapeutic interventions.


Subject(s)
Cognitive Behavioral Therapy/methods , Obstetric Labor, Premature/therapy , Stress, Psychological/therapy , Adult , Anxiety/psychology , Anxiety/therapy , Female , Humans , Internet , Obstetric Labor, Premature/psychology , Patient Dropouts , Patient Satisfaction , Pregnancy , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Stress, Psychological/etiology , Surveys and Questionnaires , Treatment Outcome
7.
Infection ; 44(1): 65-76, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26370552

ABSTRACT

PURPOSE: Changes in sputum microbiology following antibiotic treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), including patterns of bacteriological relapse and superinfection are not well understood. Sputum microbiology at exacerbation is not routinely performed, but pathogen presence and species are determinants of outcomes. Therefore, we determined whether baseline clinical factors could predict the presence of bacterial pathogens at exacerbation. Bacterial eradication at end of treatment (EOT) is associated with clinical resolution of exacerbation. We determined the clinical, microbiological and therapeutic factors that were associated with bacteriological eradication in AECOPD at EOT and in the following 8 weeks. METHODS: Sputum bacteriological outcomes (i.e., eradication, persistence, superinfection, reinfection) from AECOPD patients (N = 1352) who were randomized to receive moxifloxacin or amoxicillin/clavulanate in the MAESTRAL study were compared. Independent predictors of bacterial presence in sputum at exacerbation and determinants for bacteriological eradication were analyzed by logistic regression and receiver operating characteristic (ROC) analyses. RESULTS: Significantly greater bacteriological eradication with moxifloxacin was mainly driven by superior Haemophilus influenzae eradication (P = 0.002, EOT). Baseline clinical factors were a weak predictor of the presence of pathogens in sputum (AUCROC = 0.593). On multivariate analysis, poorer bacterial eradication was associated with antibiotic resistance (P = 0.0001), systemic steroid use (P = 0.0024) and presence of P. aeruginosa (P = 0.0282). CONCLUSIONS: Since clinical prediction of bacterial presence in sputum at AECOPD is poor, sputum microbiological analysis should be considered for guiding antibiotic therapy in moderate-to-severe AECOPD, particularly in those who received concomitant systemic corticosteroids or are at risk for infection with antibiotic-resistant bacteria.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/microbiology , Pulmonary Disease, Chronic Obstructive/complications , Sputum/microbiology , Aged , Aged, 80 and over , Amoxicillin-Potassium Clavulanate Combination/therapeutic use , Bacteria/classification , Bacteria/isolation & purification , Double-Blind Method , Female , Fluoroquinolones/therapeutic use , Humans , Male , Middle Aged , Moxifloxacin , Prospective Studies , Treatment Outcome
8.
Article in English | MEDLINE | ID: mdl-29796423

ABSTRACT

AIMS: To assess neuronal depolarization evoked by autoantibodies in diabetic depression compared to depolarization evoked by autoantibodies in control patients. To determine whether a subset of severe (late-onset) diabetic complications may be mediated in part by toxic immunoglobulin light chains that may increase in diabetic nephropathy. METHODS: Protein-A eluates from plasma of 21 diabetic depression patients and 37 age-matched controls were tested for depolarization in hippocampal or immature neurons. Subsets of depolarizing or non-depolarizing autoantibodies were tested for neurite outgrowth inhibition in N2A neuroblastoma cells or the ability to modulate Ca2+ release in HL-1 atrial cardiomyocytes or in endothelial cells. The stability of depolarizing autoantibodies was investigated by heat treatment (56°C × 30 minutes) or following prolonged exposure to the pro-protein convertase, furin. Gel filtration of active depolarizing autoantibodies was performed to determine the apparent molecular mass of peak neurotoxicity associated with the autoantibodies. RESULTS: Diabetic depression (n = 21) autoantibodies caused significantly greater mean depolarization in neuroblastoma cells (P < 0.01) compared to autoantibodies in diabetic (n = 15) or non-diabetic (n = 11) patients without depression. Depolarizing autoantibodies caused significantly more (P=0.011) inhibition of neurite outgrowth in neuroblastoma cells than non-depolarizing autoantibodies (n = 10) and they evoked sustained, global intracellular Ca2+ release in atrial cardiomyocytes or in endothelial cells. A subset of older diabetic patients suffering with a cluster of nephropathy, non-ischemic cardiomyopathy and/or depression demonstrated the presence of stable light chain dimers having apparent MW of 46 kD and associated with peak neurotoxicity in neuroblastoma cells. CONCLUSION: These data suggest that autoantibodies in older adult diabetic depression cause long-lasting depolarization in hippocampal neurons including adult dentate gyrus neural progenitor cells. The autoantibodies may impair adult dentate gyrus neurogenesis associated with treatment-refractory depression via several mechanisms including suppression of neurite outgrowth, and alteration of membrane excitability. Stable, toxic light chain autoantibody components may contribute to a cluster of severe (late-onset) complications characterized by dysfunction in highly vascularized tissues.

9.
Infection ; 41(1): 175-86, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23180507

ABSTRACT

OBJECTIVE: The aim was to compare the efficacy and safety of two antibiotic regimens in patients with diabetic foot infections (DFIs). METHODS: Data of a subset of patients enrolled in the RELIEF trial with DFIs requiring surgery and antibiotics were evaluated retrospectively. DFI was diagnosed on the basis of the modified Wagner, University of Texas, and PEDIS classification systems. Patients were randomized to receive either intravenous/oral moxifloxacin (MXF, N = 110) 400 mg q.d. or intravenous piperacillin/tazobactam 4.0/0.5 g t.d.s. followed by oral amoxicillin/clavulanate 875/125 mg b.d. (PIP/TAZ-AMC, N = 96), for 7-21 days until the end of treatment (EOT). The primary endpoint was clinical cure rates in the per-protocol (PP) population at the test-of-cure visit (TOC, 14-28 days after EOT). RESULTS: There were no significant differences between the demographic characteristics of PP patients in either treatment group. At TOC, MXF and PIP/TAZ-AMC had similar efficacy in both the PP and intent-to-treat (ITT) populations: MXF: 76.4 % versus PIP/TAZ-AMC: 78.1 %; 95 % confidence interval (CI) -14.5 %, 9.0 % in the PP population; MXF: 69.9 % versus PIP/TAZ-AMC: 69.1 %; 95 % CI -12.4 %, 12.1 % in the ITT population. The overall bacteriological success rates were similar in both treatment groups (MXF: 71.7 % versus PIP/TAZ-AMC: 71.8 %; 95 % CI -16.9 %, 10.7 %). A similar proportion of patients (ITT population) experienced any adverse events in both treatment groups (MXF: 30.9 % versus PIP/TAZ-AMC: 31.8 %, respectively). Death occurred in three MXF-treated patients and one PIP/TAZ-AMC-treated patient; these were unrelated to the study drugs. CONCLUSION: Moxifloxacin has shown favorable safety and efficacy profiles in DFI patients and could be an alternative antibiotic therapy in the management of DFI. CLINICAL TRIAL: NCT00402727.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/complications , Bacterial Infections/drug therapy , Diabetic Foot/complications , Administration, Intravenous , Administration, Oral , Aged , Amoxicillin-Potassium Clavulanate Combination/administration & dosage , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Aza Compounds/administration & dosage , Bacteria/classification , Bacteria/drug effects , Bacteria/isolation & purification , Female , Fluoroquinolones , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Moxifloxacin , Penicillanic Acid/administration & dosage , Penicillanic Acid/analogs & derivatives , Piperacillin/administration & dosage , Quinolines/administration & dosage , Tazobactam , Treatment Outcome
10.
Int J Antimicrob Agents ; 41(1): 57-64, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23153963

ABSTRACT

Antibiotic therapy for complicated intra-abdominal infections (cIAIs) should provide broad-spectrum coverage both Gram-positive and Gram-negative microorganisms. The PROMISE study compared the clinical and bacteriological efficacy and safety of moxifloxacin versus ertapenem for the treatment of cIAIs. This randomised, prospective, double-dummy, double-blind, multicentre trial was designed as a non-inferiority study. The safety and efficacy of 5-14 days of daily intravenous moxifloxacin (400mg) or ertapenem (1g) were compared in patients with cIAIs requiring surgery and parenteral antibiotic therapy. The primary and secondary endpoints included clinical and bacteriological responses at 21-28 days after the end of treatment (TOC), respectively. Of 830 enrolled patients, 699 were efficacy valid. Moxifloxacin was non-inferior to ertapenem regarding clinical success [89.5% (315/352) versus 93.4% (324/347); 95% confidence interval (CI) -7.9%, 0.4%]. There were no significant differences between groups for any of the primary causes or types of cIAI regarding clinical response. Bacteriological success was achieved in 86.5% (257/297) of moxifloxacin-treated patients and 90.2% (249/276) of ertapenem-treated patients (95% CI -9.0%, 1.5%). There were no major differences between groups regarding the frequency or types of organisms eradicated. The incidence of adverse events (AEs) was higher with moxifloxacin than ertapenem (P=0.039), however a similar number of drug-related AEs was seen in each group (P=1.000). Wound infections, nausea and increased lipase were the most commonly reported AEs with both agents. The results show that moxifloxacin is a valuable treatment option for a range of community-acquired cIAIs with mild-to-moderate severity.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Aza Compounds/administration & dosage , Intraabdominal Infections/drug therapy , Quinolines/administration & dosage , beta-Lactams/administration & dosage , Administration, Intravenous , Adult , Aged , Anti-Bacterial Agents/adverse effects , Aza Compounds/adverse effects , Double-Blind Method , Drug-Related Side Effects and Adverse Reactions/epidemiology , Ertapenem , Female , Fluoroquinolones , Humans , Incidence , Male , Middle Aged , Moxifloxacin , Prospective Studies , Quinolines/adverse effects , Treatment Outcome , beta-Lactams/adverse effects
12.
Ultraschall Med ; 32 Suppl 2: E100-7, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22187410

ABSTRACT

PURPOSE: Providing information about prenatal diagnosis (PND) that leads to an informed decision is ethically and psychologically challenging, especially in an intercultural context. The aim was to investigate cultural differences in information processing, test interpretation, evaluation of an established information leaflet, emotional response during screening and acceptance of PND. MATERIALS AND METHODS: This prospective study compared 30 pregnant Turkish immigrants with 30 women from Switzerland and countries within the European Union (EU). They completed a questionnaire prior to (T1) and after risk assessment between 11-14 weeks (T2) and after receiving the results (T3). The questionnaire focused on the perception of, experiences with and knowledge about the risk assessment and included the hospital anxiety and depression scale (HADS). χ(2) tests were used for dichotomous variables and Student's t-tests for scores on perception, experience, knowledge, depression and anxiety. Groups were compared over time by 2-factorial ANOVA. RESULTS: Regarding the 6 questions on knowledge, the rate of correct answers was between 32.2% and 62.5% at T1 and 35.1% and 75.0% at T2. The Turkish women's knowledge level was significantly lower. They rated the information leaflet as less helpful and found the counseling significantly more unsettling. The acceptance of PND was higher in Turkish women. CONCLUSION: Considering the information and knowledge deficits, informed consent was not given in every case, especially in Turkish women. Nevertheless, the acceptance of PND was good. Further studies will have to focus on counseling strategies that take into account the specific needs and expectations of pregnant women with different cultural backgrounds.


Subject(s)
Adaptation, Psychological , Counseling , Cross-Cultural Comparison , Emigrants and Immigrants/psychology , Emotions , Genetic Counseling/psychology , Patient Acceptance of Health Care/ethnology , Patient Acceptance of Health Care/psychology , Patient Education as Topic , Pregnancy/ethnology , Pregnancy/psychology , Prenatal Care/psychology , Prenatal Diagnosis/psychology , Ultrasonography, Prenatal/psychology , Adult , Anxiety/ethnology , Anxiety/psychology , Depression/ethnology , Depression/psychology , Europe/ethnology , Female , Health Knowledge, Attitudes, Practice/ethnology , Humans , Informed Consent/psychology , Multilingualism , Pregnancy Trimester, Second , Prospective Studies , Risk Assessment , Socioeconomic Factors , Surveys and Questionnaires , Switzerland , Turkey/ethnology
13.
Womens Health (Lond) ; 5(6): 629-36, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19863466

ABSTRACT

Sexual function in female diabetic patients is much less investigated than in males. Empirical studies do not show uniform results, but it appears that diabetic women experience more frequent sexual dysfunction in general than age-matched healthy controls, independent of the sociocultural environment. The most frequently cited dysfunctions are desire and arousal disorders, such as lubrication difficulties, while orgasmic capacity appears to be less affected. Direct pathophysiological effects on lubrication are proven, but the impact on mental arousal is unclear. The role of diabetic complications is controversial. The comorbidity with depression plays a major role. Individual coping with the disease and the quality of the relationship are also contributing factors. Patients should be encouraged to talk about their sexual problems, as both biomedical and psychosocial factors have to be explored. Therapeutic interventions include basic counseling, biomedical treatment of atrophy and lubrication difficulties, as well as treatment of comorbidities and/or sex therapy.


Subject(s)
Depression/complications , Diabetes Complications , Sexual Dysfunction, Physiological/etiology , Sexual Dysfunction, Physiological/therapy , Age Factors , Antidepressive Agents/therapeutic use , Counseling , Estrogen Replacement Therapy , Female , Humans , Phosphodiesterase 5 Inhibitors , Prevalence , Risk Factors
14.
Antimicrob Agents Chemother ; 53(4): 1463-7, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19171803

ABSTRACT

Daptomycin is approved for treatment of Staphylococcus aureus bacteremia and right-sided endocarditis. Increases in daptomycin MICs have been associated with failure. A rabbit model of aortic valve endocarditis was used to determine whether MIC correlates with activity in vivo and whether a higher daptomycin dose can improve efficacy. Two related clinical S. aureus strains, one with a daptomycin MIC of 0.5 microg/ml and the other with a MIC of 2 microg/ml, were used to establish aortic valve endocarditis in rabbits. Daptomycin was administered once a day for 4 days at 12 mg/kg of body weight or 18 mg/kg to simulate doses in humans of 6 mg/kg and 10 mg/kg, respectively. Endocardial vegetations, spleens, and kidneys were harvested and quantitatively cultured. The strain with a MIC of 2 microg/ml had a survival advantage over the strain with a MIC of 0.5 microg/ml with >100 times more organisms of the former in endocardial vegetations at the 12-mg/kg dose in a dual-infection model. Both the 12-mg/kg dose and the 18-mg/kg dose completely eradicated the strain with a MIC of 0.5 from vegetations, spleens, and kidneys. The 12-mg/kg dose was ineffective against the strain with a MIC of 2 in vegetations; the 18-mg/kg dose produced a reduction of 3 log(10) units in CFU in vegetations compared to the controls, although in no rabbit were organisms completely eliminated. Increasing the dose of daptomycin may improve its efficacy for infections caused by strains with reduced daptomycin susceptibility.


Subject(s)
Anti-Bacterial Agents/pharmacology , Daptomycin/pharmacology , Endocarditis, Bacterial/drug therapy , Staphylococcal Infections/drug therapy , Animals , Aortic Valve , Area Under Curve , Daptomycin/pharmacokinetics , Daptomycin/therapeutic use , Disease Models, Animal , Dose-Response Relationship, Drug , Heart Valve Diseases/drug therapy , Microbial Sensitivity Tests , Rabbits , Staphylococcus aureus/drug effects
15.
Ultraschall Med ; 30(2): 157-62, 2009 Apr.
Article in German | MEDLINE | ID: mdl-18484059

ABSTRACT

PURPOSE: Informed decision making and informed consent prior to any intervention are crucial in the ethically and psychologically complex field of prenatal diagnosis (PND). The aim of this study was to investigate whether and to what extent pregnant women understand the information provided by their physicians. MATERIALS AND METHODS: Fifty pregnant women in the first trimester answered a structured questionnaire after their first visit between 7 to 10 weeks of gestation that routinely includes basic prenatal counseling. A special focus was put on information transfer, knowledge about and understanding of prenatal tests, as well as previous experiences with PND. The results were analyzed with regard to differences due to background, educational level and previous experiences with PND. RESULTS: The maternal mean age was 31.1 years (SD 6.7). 38 patients (76 %) had at least one previous pregnancy and two thirds of them had experiences with PND. Their experience was mainly positive. About three quarters of the women stated that they had been informed about the test methods during the consultation and had understood the explanations. Uncertainty was reported in 12.2 % and 23.3 % of the women said they had further questions. The percentage of questions related to appropriate understanding that were answered correctly was only 44 % to 77.5 %. The percentage of correct answers was lower in women without experience with PND, with a lower educational level and born in countries outside the EU and Switzerland. CONCLUSION: Pregnant women are relatively well informed about prenatal tests. Their actual knowledge of the meaning of the tests, however, seems to be incomplete. Especially in the case of immigrants and women without previous experience with PND, it is therefore doubtful whether the preconditions for an informed consent are met. Further research needs to focus on more helpful information and individually adapted counseling concepts for decision making in PND.


Subject(s)
Counseling , Health Knowledge, Attitudes, Practice , Informed Consent/psychology , Prenatal Diagnosis/psychology , Adult , Comprehension , Decision Support Techniques , Educational Status , Emigrants and Immigrants/psychology , Female , Humans , Informed Consent/legislation & jurisprudence , Multilingualism , Nuchal Translucency Measurement , Pregnancy , Pregnancy Trimester, First , Socioeconomic Factors , Ultrasonography, Prenatal
17.
Neurosci Lett ; 420(1): 58-60, 2007 Jun 08.
Article in English | MEDLINE | ID: mdl-17481814

ABSTRACT

A common intronic single nucleotide polymorphism (T102C) in the 5-HT2A receptor gene is associated with the development of different neuropsychiatric symptoms, including hallucinations and depressive symptoms in Alzheimer's disease (AD). Differential 5-HT2A receptor binding has also been associated with the development of these symptoms in AD. However, the relationship between 5-HT2A (T102C) genotype and 5-HT2A receptor binding in AD and control human brains has not been examined. We examined the association between different 5-HT2A (T102C) genotypes and [(3)H] ketanserin binding in the temporal and frontal cortex of 20 AD and 14 control human brains. In homozygotes, but not heterozygotes, there was a significant reduction in B(max) values for [(3)H] ketanserin binding in both areas of cortex in AD compared with control subjects. This study suggests a mechanism for the generation of different neuropsychiatric symptoms in AD from a single nucleotide polymorphism with reduced receptor binding in T102C 5-HT2A receptor gene homozygotes correlating with susceptibility to depressive symptoms, whereas the relative preservation of receptor binding in heterozygotes with AD correlating with susceptibility to hallucinations.


Subject(s)
Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Ketanserin/metabolism , Neocortex/metabolism , Receptor, Serotonin, 5-HT2A/genetics , Receptor, Serotonin, 5-HT2A/metabolism , Serotonin Antagonists/metabolism , Aged , Alzheimer Disease/psychology , Female , Genetic Variation , Genotype , Hallucinations/etiology , Hallucinations/genetics , Hallucinations/psychology , Humans , In Vitro Techniques , Kinetics , Male , Polymorphism, Single Nucleotide , Prefrontal Cortex/metabolism , Temporal Lobe/metabolism
18.
Scand J Immunol ; 63(2): 90-6, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16476007

ABSTRACT

Transfusions of high-dose (> or =10,000 Joule/m(2)) ultraviolet-B (UVB)-irradiated allogeneic leukocytes in rodent models have been shown to induce immunologic tolerance that is mediated by allospecific regulatory CD4(+) T cells. Whether these regulatory T cells recognize alloantigens through the direct or indirect pathway of allorecognition is controversial. Here, we demonstrate that the proliferative response obtained in standard primary mixed leukocyte reactions (MLRs) with human peripheral blood mononuclear cells (PBMCs) reflected a CD4(+) T-cell-dependent direct pathway of allorecognition and that high-dose UVB irradiation of PBMCs totally inhibited their capacity to induce a proliferative alloresponse. Re-stimulation with gamma-irradiated PBMCs from the same allogeneic donor (secondary MLR) elicited a proliferative and Th1-deviated response that was similar to the response induced in unprimed PBMCs. Finally, high-dose UVB was found to induce a rapid and massive apoptosis of irradiated PBMCs. Collectively, these data indicate that leukocytes irradiated with high-dose UVB are unable to prime for unresponsiveness or immune deviation in T cells directly recognizing allogeneic major histocompatibility complex molecules. Because it is well-established that antigens within transfused apoptotic cells are captured by resident tolerogenic spleen dendritic cells, we propose that tolerance induced by transfusions of high-dose UVB-irradiated leukocytes primarily involve T cells indirectly recognizing alloantigens.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/radiation effects , Immune Tolerance/radiation effects , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/radiation effects , Apoptosis , Blood Transfusion , CD4-Positive T-Lymphocytes/cytology , Cells, Cultured , Humans , Immune Tolerance/immunology , Interferon-gamma/immunology , Leukocytes, Mononuclear/cytology , Lymphocyte Activation/radiation effects , Lymphocyte Culture Test, Mixed , Ultraviolet Rays
19.
Environ Pollut ; 141(3): 519-25, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16246476

ABSTRACT

The relevance of germination trials for screening plants that may have potential for use in the phytoremediation of PAH contaminated land was evaluated. The germination and subsequent growth of 7 grass and legume species were evaluated in soil spiked with a pure PAH mixture or coal tar and soil from a former coking plant heavily contaminated with aged PAHs. None of these treatments adversely affected germination of the plants. However, apart from Lolium perenne all species exhibited reduced growth in the coking plant soil after 12 weeks growth when compared to the untreated soil. In the coal tar spiked soil 4 out of the 7 species showed reduced growth, as did 3 out of the 7 in the soil spiked with a mixture of 7 PAHs. Therefore, germination studies alone would not predict the success of subsequent growth of the species tested in the ranges of soil PAH levels studied.


Subject(s)
Environmental Monitoring/methods , Environmental Pollution , Fabaceae/growth & development , Poaceae/growth & development , Polycyclic Aromatic Hydrocarbons/pharmacology , Soil Pollutants/pharmacology , Biodegradation, Environmental , Coal Tar , Coke , Fabaceae/drug effects , Germination/drug effects , Poaceae/drug effects , Time
20.
Ther Umsch ; 62(4): 245-9, 2005 Apr.
Article in German | MEDLINE | ID: mdl-15884447

ABSTRACT

Domestic violence differs from the nonrecurring trauma e.g. in the context of rape by a stranger in different aspects, emphasising the complexity of the victim's reaction and the enmeshment of the perpetrator The violence takes place in an established system of an intimate relationship which the woman was contracting voluntarily. Violence happens repeatedly and often several individuals (partner, children are directly and indirectly involved, which abide a relationship with the perpetrator Therefore the treatment of the posttraumatic stress disorder outstands in several aspects. The victims initially shows difficulties in talking about the experienced violence and are afraid to become unloyal; a therapeutic approach is often possible only after a fairly long time. Most authors agree that trauma therap the three phases (1 security and protection, psychoeducation and stabilisation, (2 trauma confrontation and (3 reintegration. Establishing a secure environment and intrapsychic stabilisation are a requirement for the therapeutic confrontation with the traumata in order to avoid re-traumatisation. Working with domestic violence victims is complex and demanding, experience in the work with trauma victims and regular supervision are fundamental.


Subject(s)
Crime Victims/rehabilitation , Domestic Violence/prevention & control , Rape/rehabilitation , Sex Offenses/prevention & control , Stress Disorders, Post-Traumatic/rehabilitation , Adolescent , Adult , Aged , Child , Child, Preschool , Crime Victims/psychology , Female , Germany , Humans , Middle Aged , Time
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