[Questionnaire for Investigating Therapeutic Alliance in Forensic Setting (FTBF): Results of a Pilot Study]. / Fragebogen zur therapeutischen Beziehung in der Forensik (FTBF): Ergebnisse einer Pilotstudie.

The relation between patient and therapist has a substantial effect on the success of psychotherapy. So far, in German-speaking regions questionnaires translated from English have been used, particularly for studying outpatients. Studies investigating and concerned with specialised features of hospitalised forensic psychiatry patients are sparse. The preliminary results of this study evaluating a recently developed questionnaire aimed to investigate the quality of the therapeutic relationship in forensic psychiatry ("Fragebogen zur therapeutischen Beziehung in der Forensik, FTBF") are reported. The data were collected both in general and forensic psychiatry departments. Factor analyses yielded two essential factors, namely "positive emotional aspects" (12 items, main features trust, respect, helpfulness, harmony, and sympathy; Cronbach's α = .933) and "negative emotional aspects" (4 items, main features power divide and punishment; Cronbach's α = .805). Forensic patients experienced power divide and punishment tendencies more intensively than general psychiatry patients (p < 0.001). Our questionnaire therefore demonstrates not only excellent reliabilities but also differential validity, enabling a differentiation between general and forensic psychiatry patients. Studies with larger samples would enable conclusions about the impact of the therapists' perspective, specific diagnostic subgroups and different psychotherapeutic orientations, on the patient-therapist relationship in forensic psychiatry.

Structural alterations in white-matter tracts connecting (para-)limbic and prefrontal brain regions in borderline personality disorder.

BACKGROUND: A dysfunctional network of prefrontal and (para-)limbic brain region has been suggested to underlie emotional dysregulation in borderline personality disorder (BPD). Abnormal activity in this network may be due to structural alterations in white-matter tracts connecting prefrontal and (para-)limbic brain regions. To test this hypothesis, we investigated the structural integrity of major white-matter tracts connecting these regions in BPD. METHOD: Using diffusion tensor imaging, we investigated fractional anisotropy (FA), axonal anisotropy (AD) and radial diffusivity (RD) in the uncinate fasciculus, the major white-matter tract connecting (para-)limbic and prefrontal brain regions, in 26 healthy controls (HC) and 26 BPD participants. To clarify the specificity of possible white-matter alterations among HC and BPD participants, FA, AD and RD were also investigated in the cingulum. RESULTS: We found distinct structural alterations in the uncinate fasciculus but not in the cingulum of BPD participants. Compared to HC participants, BPD participants showed lower FA and higher RD in the uncinate fasciculus. By contrast, AD did not differ in the uncinate fasciculus of HC and BPD participants. CONCLUSIONS: Our finding of abnormal FA and RD in the uncinate fasciculus indicates distinct white-matter alterations in BPD, presumably due to stress-induced myelin degeneration in the aftermath of stressful life events. Although these alterations may account for abnormal activity in brain regions implicated in emotion dysregulation, such as the amygdala, anterior cingulate cortex and prefrontal cortex, it remains to be determined whether these alterations are specific for BPD.

Antiviral activity of some plants used in Nepalese traditional medicine.

Methanolic extracts of 41 plant species belonging to 27 families used in the traditional medicine in Nepal have been investigated for in vitro antiviral activity against Herpes simplex virus type 1 (HSV-1) and influenza virus A by dye uptake assay in the systems HSV-1/Vero cells and influenza virus A/MDCK cells. The extracts of Astilbe rivularis, Bergenia ciliata, Cassiope fastigiata and Thymus linearis showed potent anti-herpes viral activity. The extracts of Allium oreoprasum, Androsace strigilosa, Asparagus filicinus, Astilbe rivularis, Bergenia ciliata and Verbascum thapsus exhibited strong anti-influenza viral activity. Only the extracts of A. rivularis and B. ciliata demonstrated remarkable activity against both viruses.

Antibacterial and antiviral naphthazarins from Maharanga bicolor.

Maharanga bicolor, Boraginaceae, is used in the Nepalese ethnomedicine for the treatment of several diseases. In the course of screening investigations the dichloromethane extract of the roots of Maharanga bicolor was found to inhibit the growth of gram positive bacteria. Bio-assay directed fractionation led to the isolation of five active naphthazarins, deoxyalkannin (1), alkannin (2), acetylalkannin (3), alkannin beta-hydroxyisovalerate (4) and alkannin beta-acetoxyisovalerate (5). Compounds 2-5 showed antibacterial activity against multi resistant human pathogenic Staphylococcus and Enterococcus species and 1, 4 and 5 showed antiviral activity against herpes simplex virus type-1.

No influence of atopic diseases on antibody titres following tetanus, diphtheria and hepatitis B immunisation among adults.

Several studies have reported associations between reduced humoral immune response to vaccine antigens and diseases with modified reactions of the immune system. We have investigated the influence of atopic diseases on specific IgG levels to tetanus, diphtheria and hepatitis B (HB), following immunisation, in a general adult population. From the Study of Health in Pomerania, a total number of 3,920 subjects aged 20 to 79 years were included in the analyses. Information on immunisation history, as well as behavioural and socio-demographic characteristics were collected. Anti-tetanus IgG, anti-diphtheria IgG and anti-HBs IgG were measured by indirect enzyme-linked immunosorbent assay (ELISA). Odds ratios and 95% confidence intervals were calculated using logistic regression. Atopic diseases were reported by 14% of participants. Proportions of 67%, 34% and 10% had been vaccinated against tetanus, diphtheria and hepatitis B within the past ten years, respectively. Multi-variable analyses revealed no associations between the presence of atopic diseases and all of the three vaccine-specific antibody titres. We conclude that there is no reduced immune response related to antibody production following immunisations against tetanus, diphtheria and hepatitis B in adults with atopic diseases.

Enterovirus RNA sequences in sera of schoolchildren in the general population and their association with type 1-diabetes-associated autoantibodies.

Type 1 diabetes (T1D) is an autoimmune disease linked with genetic factors as well as with environmental triggers, such as virus infections, but the aetiology is still unclear. The authors analysed serum from autoantibody-positive (n=50) and autoantibody-negative (n=50) schoolchildren as well as children newly diagnosed with T1D (n=47; time from diagnosis, median 5 days, interquartile range 1-12 days) for the presence and frequency of enterovirus (EV) and adenovirus sequences. The autoantibody-positive and -negative groups were part of the Karlsburg Type 1 Diabetes Risk Study of a Normal Schoolchild Population, which represents a general population without T1D first-degree relatives. There was no significant seasonality of sampling in any of the three groups investigated. EV RNA sequences were detected in 10 of 50 (20%) autoantibody-positive children and in 17 of 47 (36%) children newly diagnosed with T1D, but only in two of 50 (4%) of the age- and sex-matched controls (P<0.05, P<0.001). Characterization of the EV amplicons by direct sequencing revealed high homology with coxsackievirus B group. For adenovirus we found no data to support an association with T1D. The data support the hypothesis that different enteroviruses may be aetiologically important as a trigger and/or accelerating factor in the process of T1D development.

Molecular and clinical characteristics of respiratory syncytial virus infections in hospitalized children.

The objective of this study was to determine the importance of respiratory syncytial virus (RSV) for hospitalization in the north east of Germany and to obtain molecular epidemiological data of the circulating strains. Using a rapid and sensitive reverse transcriptase-PCR, it was found that a quarter of pediatric respiratory disease admissions were due to RSV. Infections caused by RSV in hospitalized patients were determined over the whole year. Both RSV groups A and B were identified with a predominance of RSV A (86%) over the entire period. The analysis of the deduced amino acid sequences by direct sequencing showed that very similar RSV strains are circulating in the community.

Real-time PCR to improve the diagnosis of respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is one of the most important virus respiratory pathogens in infants and young children. A rapid and sensitive diagnosis is essential to focus any outbreak due to this virus. A real-time RT-PCR method was designed using a primer/probe pair from the F gene. Simultaneously with nested RT-PCR and antigen ELISA, 71 consecutive specimens from hospitalized children with clinical symptoms of acute respiratory distress were evaluated to confirm the incidence of RSV infection. RSV was detected in 25 (35.2 %) specimens by real-time RT-PCR and in 19 (26.7 %) by nested RT-PCR. The assay was specific for RSV. The procedure offers a rapid and sensitive alternative to conventional RT-PCR. Closed-tube detection eliminates the risk of contamination.

Inhibitory effect of Bergenia ligulata on influenza virus A.

Methanol water extract from rhizomes of Bergenia ligulata, a plant used in Nepalese ethnomedicine, inhibited in vitro the replication of influenza virus in a dose dependent manner and did not show virucidal activity at effective concentration. Pretreatment of cells with B. ligulata extract was shown to be most effective to prevent cell destruction. The extract inhibited viral RNA synthesis and reduced viral peptide synthesis at 10 microg/ml. The virus inhibitory effect is related to the presence of condensed tannins in the extract.

Antiviral lanostanoid triterpenes from the fungus Ganoderma pfeifferi.

Ganodermadiol, lucidadiol and applanoxidic acid G were isolated as first triterpenes from the European Basidiomycete Ganoderma pfeifferi. The compounds show antiviral activity against influenza virus type A and HSV type 1.

Cyanobacteria a potential source of antiviral substances against influenza virus.

Aqueous and methanolic extracts of cultured cyanobacteria of several genera, Microcystis, Nodularia, Oscillatoria, Scytonema, Lyngbya and Calothrix were evaluated for their in vitro antiviral activity against influenza A virus in Madin Darby canine kidney cells. None of the methanolic extracts showed cytotoxic effects. The inhibitory concentration (IC(50)) of antiviral activity ranged between 20.0 micro g to 79.0 micro g extract/ml. The most active extract in this screening derived from genus Microcystis. The further analysis of methanolic extracts of cultured strains of genus Microcystis revealed a remarkable antiviral activity against influenza A virus for M. aeruginosa, M. ichthyoblabe and M. wesenbergii. The observed antiviral activity was associated with protease inhibitory activity of approximately 90% and suggest that protease inhibitory activity may be responsible for reducing virus replication. These results show that cyanobacteria are able to produce compounds with biological activity that may be of potential clinical interest.

Screening of Nepalese medicinal plants for antiviral activity.

In an ethnopharmacological screening, plants used in Nepalese traditional medicine were evaluated for antiviral activity. Methanolic and methanolic-aqueous extracts derived of 23 species were assayed in two in vitro viral systems, influenza virus/MDCK cells and herpes simplex virus/Vero cells. Two species, Bergenia ligulata and Nerium indicum showed the highest antiinfluenzaviral activity with 50% inhibitory dose of 10 microg/ml. Holoptelia integrifolia and N. indicum exhibited considerable antiviral activity against herpes simplex virus. None of these extracts showed cytotoxic effects. Additionally for B. ligulata and H. integrifolia partial protease inhibitory activity was estimated.

Mapping of linear epitopes on fibre knob of human adenovirus serotype 5.

Linear antigenic epitopes on the Ad5 fibre knob (FK5) were characterised with fibre- and virion-specific antisera, using 15-mer overlapping peptides covering the knob of the fibre. They were compared with epitopes on the Ad2 fibre knob (FK2) domain. The stronger reactive FK5 epitopes were represented by peptides P3 (amino acids (aa A419-L433)), P6 (aa S449-E463), P7 (aa I459-L473), P12 (aa G509-N523), P14 (aa P529-G543) and P16 (aa A549-Y563). P3 spans the B beta-strand and the left portion of the C beta-strand, P6 and P7 the D beta-strand and the adjacent parts of the CD and DE loops, P12, P14 and P16 the G, H and I beta strands and the adjacent parts of the loops, respectively. The stronger reactive epitopes on FK2 were located in P2 (aa P409-L423), P6 (aa T449-Q463), P8 (aa E469-G483), P13 (aa Q519-T533) and P16 (aa S549-K563). The positions of FK5 and FK2 derived peptides, representing epitopes, are either identical or overlapping or adjacent, as determined by amino acid sequence alignment. Antisera obtained against several longer peptides showed virus neutralising capacity, indicating neutralising epitopes in these peptides.

Evaluation of the efficacy of 2',3'-dideoxycytidine against adenovirus infection in a mouse pneumonia model.

The antiviral activity of 2',3'-dideoxycytidine (ddC) has been investigated in a mouse pneumonia model. Consolidation of lung, histopathological changes, DNA synthesis as well as levels of TNFalpha were assayed. In this in vivo model, the oral administration of ddC twice daily over 4 days, displayed an inhibitory effect. The drug significantly reduced histopathologic responses. Analysis indicated that under treatment pulmonary lesions were less severe than those of untreated controls. These data confirm the in vitro activity of ddC against adenovirus. Thus, ddC represents a potential therapeutic approach for inhibiting adenovirus infection and may offer promise as an anti-adenovirus agent for immunocompromised patients in whom serious adenovirus infection may prove fatal.

Inhibition of adenovirus DNA polymerase by modified nucleoside triphosphate analogs correlate with their antiviral effects on cellular level.

Adenovirus (Ad) infection results in significant morbidity and mortality in both immunocompetent and immunosuppressed hosts. There is currently no licensed chemotherapy effective in dealing with this virus infection. In this study the anti-adenoviral activity of a group of modified nucleoside analogs was investigated. The most efficient 3-fluorosubstituted nucleoside triphosphate inhibitors of Ad DNA polymerase were 3'-fluorothymidine triphosphate (IC50 0.63 microM), 2',3'-dideoxy-3'-fluoroguanosine triphosphate (IC50 0.71 microM) and 2',3'-dideoxy-3'-fluorouridine triphosphate (IC50 2.96 microM). The most efficient 2',3'-dideoxynucleoside triphosphates were 2',3'-dideoxycytidine triphosphate (ddCTP; IC50 1.0 microM), 2',3'-dideoxyadenosine triphosphate (IC50 1.6 microM) and 2',3'-dideoxythymidine triphosphate (IC50 1.82 microM). Kinetic studies indicate competitive inhibition of adenovirus DNA polymerase by ddCTP. These data confirm results previously obtained at the cellular level using a focus reduction assay involving Ad2-infected FL cells. Whereas the D-enantiomers 3'-fluorothymidine and 2',3'-dideoxycytidine are potent inhibitors of adenoviral replication, the corresponding L-enantiomers exhibited no inhibitory activity.

Hantavirus Dobrava infection with pulmonary manifestation.

Dobrava virus infection was diagnosed serologically by enzyme-linked immunosorbent and immunofluorescence assays. To determine which hantavirus serotype was involved, sera were analyzed by a focus reduction neutralization test. The clinical data indicated that only pulmonary manifestation was present. Our data support the presence of Dobrava virus infection outside the Balkan region. In conclusion, a previously healthy adult with unexplained pulmonary perfusion failure should be investigated for hantavirus infection.

Receptor binding sites and antigenic epitopes on the fiber knob of human adenovirus serotype 3.

The adenovirus fiber knob causes the first step in the interaction of adenovirus with cell membrane receptors. To obtain information on the receptor binding site(s), the interaction of labeled cell membrane proteins to synthetic peptides covering the adenovirus type 3 (Ad3) fiber knob was studied. Peptide P6 (amino acids [aa] 187 to 200), to a lesser extent P14 (aa 281 to 294), and probably P11 (aa 244 to 256) interacted specifically with cell membrane proteins, indicating that these peptides present cell receptor binding sites. Peptides P6, P11, and P14 span the D, G, and I beta-strands of the R-sheet, respectively. The other reactive peptides, P2 (aa 142 to 156), P3 (aa 153 to 167), and P16 (aa 300 to 319), probably do not present real receptor binding sites. The binding to these six peptides was inhibited by Ad3 virion and was independent of divalent cations. We have also screened the antigenic epitopes on the knob with recombinant Ad3 fiber, recombinant Ad3 fiber knob, and Ad3 virion-specific antisera by enzyme-linked immunosorbent assay. The main antigenic epitopes were presented by P3, P6, P12 (aa 254 to 269), P14, and especially the C-terminal P16. Peptides P14 and P16 of the Ad3 fiber knob were able to inhibit Ad3 infection of cells.

Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection.

An invading pathogen must be held in check by the innate immune system until a specific immune response can be mounted. In the case of Gram-negative bacteria, the principal stimulator of the innate immune system is lipopolysaccharide (LPS), a component of the bacterial outer membrane. In vitro, LPS is bound by lipopolysaccharide-binding protein (LBP) and transferred to CD14--the LPS receptor on the macrophage surface--or to high-density lipoprotein (HDL) particles. Transfer to CD14 triggers an inflammatory response which is crucial for keeping an infection under control. Here we investigate how LBP functions in vivo by using LBP-deficient mice. Surprisingly, we find that LBP is not required in vivo for the clearance of LPS from the circulation, but is essential for the rapid induction of an inflammatory response by small amounts of LPS or Gram-negative bacteria and for survival of an intraperitoneal Salmonella infection.