[Current strategies in the treatment of ventricular tachycardia by catheter ablation : A review]. / Aktuelles Management der Therapie ventrikulärer Tachykardien durch Katheterablation : Eine Übersicht.

The treatment of ventricular tachycardia has recently undergone relevant changes as certain interventional treatment options, such as radiofrequency catheter ablation, have gained in importance. Numerous current publications have demonstrated the advantages of catheter ablation compared to conventional therapy with antiarrhythmic drugs in terms of effectiveness and morbidity. Improving the ablation technique and identifying those patient collectives who are most likely to benefit from ablation are still the objectives of current research. The treatment of ventricular tachycardia in the setting of different cardiac and non-cardiac conditions can be challenging and requires understanding of the current procedures and the recommendations for catheter ablation of ventricular tachycardia. This review succinctly summarizes the current research in this evolving field of interventional cardiology.

Amplification of advanced modulation formats with a semiconductor optical amplifier cascade.

The convergence of optical metro networks and access networks extends the area of network coverage, and therefore requires the use of optical amplifiers. For this purpose, semiconductor optical amplifiers (SOA) would be attractive, because they are broadband, can be centered between 1250 nm and 1600 nm, and because they are cheap in production and operation. We show that signals encoded with advanced modulation formats such as BPSK, QPSK, 8PSK, and 16QAM can be amplified by a cascade of at least four SOAs. This enables high-capacity paths with a capacity in the order of Tbit/s for converged metro-access networks.

Linear semiconductor optical amplifiers for amplification of advanced modulation formats.

The capability of semiconductor optical amplifiers (SOA) to amplify advanced optical modulation format signals is investigated. The input power dynamic range is studied and especially the impact of the SOA alpha factor is addressed. Our results show that the advantage of a lower alpha-factor SOA decreases for higher-order modulation formats. Experiments at 20 GBd BPSK, QPSK and 16QAM with two SOAs with different alpha factors are performed. Simulations for various modulation formats support the experimental findings.

[Changes in quality of life of glaucoma patients over a period of 8 years]. / Veränderungen der Lebensqualität von Glaukompatienten über einen Zeitraum von 8 Jahren.

PURPOSE: The quality of life (QoL) of glaucoma patients is affected by many factors. In particular, patient activity is compromised by the chronicity of the disease. In this study, we evaluated the change in QoL and its impact on activities over a period of 8 years. METHODS: A total of 43 patients with glaucomatous optic nerve damage were enrolled in this retrospective longitudinal observational study. Changes in intraocular pressure (IOP), best-corrected visual acuity (BCVA) and visual field (VF) parameters, number of IOP-lowering eye drops and IOP-lowering surgery were assessed over a period of 8 years. Assessment of QoL was obtained by patient-reported visual functioning using the Rasch-calibrated glaucoma activity limitation 9 (GAL-9) questionnaire at baseline and after 8 years. RESULTS: The BCVA of the better eye changed from 0.16 ± 0.22 to 0.21 ± 0.14 logMAR, whereas there was a change from 0.27 ± 0.25 to 1.39 ± 1.1 logMAR in the worse eye. The VF parameter mean deviation (MD) of the better eye changed from -2.39 ± 4.55 dB to -4.83 ± 5.09 dB, while it altered significantly from -8.86 ± 5.86 dB to -12.05 ± 8.07 dB in the worse eye. Values of GAL­9 changed from -2.39 ± 2.14 to -1.38 ± 2.78 (in the Rasch analysis, more negative values account for a better QoL), according to a sum score change from 79.17 ± 19.63 to 69.22 ± 27.95. This change showed a highly significant correlation with the MD at follow-up, especially with the worse eye (r = 0.43). The impact of the MD at follow-up on QoL could also be well predicted in a regression model. CONCLUSION: The QoL of glaucoma patients decreased significantly over time. Changes in the VF, particularly of the worse eye, have a great impact on reported functioning. Careful treatment, especially of the eye with greater glaucomatous damage, is mandatory.

Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression.

An HIV-1-seropositive volunteer was infused with an expanded autologous cytotoxic T lymphocyte (CTL) clone directed against the HIV-1 nef protein. This clone was adoptively transferred to determine whether supplementing CTL activity could reduce viral load or improve clinical course. Unexpectedly, infusion was followed by a decline in circulating CD4+ T cells and a rise in viral load. Some of the HIV isolates obtained from the plasma or CD4+ cells of the patient were lacking the nef epitope. These results suggest that active CTL selection of viral variants could contribute to the pathogenesis of AIDS and that clinical progression can occur despite high levels of circulating HIV-1-specific CTLs.

Factors Associated with Self-Reported Dysphagia in Older Adults Receiving Meal Support.

OBJECTIVES: Dysphagia is common in older adults. However, there are no current estimates of dysphagia in community-dwelling older adults those receiving meal support. It is unknown whether dysphagia is associated with other measures of physical function (activities of daily living [ADL] ability or nutrition status). The study purposes were to determine the prevalence of self-reported dysphagia and to identify factors associated with self-reported dysphagia in community-dwelling older adults receiving meal support. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: 476 community-dwelling older adults (78.5±0.51 years) across five Elder Nutrition Program meal services in Wisconsin participated in the study. MEASUREMENTS: Data were collected through administration of validated ADL and nutrition questionnaires (nutritional status, functional status with ADLs, chewing ability, dental conditions, and prior diagnoses of dysphagia, pneumonia, and dementia). For self-reported dysphagia, the validated 10-item eating assessment tool (EAT-10) was used. RESULTS: The prevalence of self-reported dysphagia (EAT-10 score of ≥ 3) was 20.4%. Multivariate logistic regression results indicated that poor nutritional status (OR=3.1, p=0.04), difficulty chewing (OR=2.2, p=0.03), prior dysphagia diagnosis (OR=34.8, p<0.001), prior pneumonia diagnosis (OR=2.1, p=0.04), and meal service site (OR=2.68, p=0.02) were associated with self-reported dysphagia. CONCLUSION: Approximately one in five community-dwelling older adults receiving meal support had self-reported dysphagia. Increased risk for poor nutrition, reduced chewing ability, prior dysphagia and pneumonia diagnosis, and meal service site were identified as factors associated with dysphagia on the EAT-10. Results highlight the need for further studies across more sites to identify dysphagia risk indicators in community-dwelling older adults receiving meal support state-wide.

B-cell activation by lipopolysaccharide. Distinct pathways for induction of mitosis and antibody production.

The role played by macrophages in two effects of lipopolysaccharide (LPS) on the immune system of the mouse-substitution for helper T cells and induction of B-cell mitosis-has been investigated. C3H/HeJ mice are unresponsive and do not produce (as other strains do) antibody to 2,4,6-trinitrophenol (TNP) conjugated with autologous mouse erythrocytes (MRBC-TNP) in the presence of LPS. We found that C3H/HeJ spleen cells produce antibody to MRBC-TNP when (a) LPS and macrophages from LPS-responsive C3HeB/FeJ mice or (b) tumor necrosis serum ([TNS] induced by LPS in responsive mice) are added. The mitotic response was not restored. The findings suggest that adjuvanticity and mitogenicity represent distinct pathways of B-cell activation by LPS, subject to different regulatory mechanisms.

High human T cell lymphotropic virus type 1 (HTLV-1)-specific precursor cytotoxic T lymphocyte frequencies in patients with HTLV-1-associated neurological disease.

The frequencies of human T cell lymphotropic virus type 1 (HTLV-1)-specific CD8+ precursor cytotoxic T lymphocytes (pCTL) were quantitated from lymphocytes obtained from the peripheral blood and cerebrospinal fluid (CSF) of infected individuals with and without HTLV-1-associated neurological disease. An estimate of the pCTL was obtained by separating CD8+ cells, plating these cells in limiting dilution, and testing wells for HTLV-1 specific lysis. Targets consisted of autologous lymphoblastoid cell lines (LCL) infected with vaccinia constructs expressing HTLV-1 gene products or LCL pulsed with HTLV-1 synthetic peptides. In patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the frequency of HTLV-1 p40X-specific pCTL was at least 40-280-fold higher than in asymptomatic HTLV-1-infected individuals. All HAM/TSP patients (five of five) predominantly recognized HTLV-1 products encoded within the pX region. Lower pCTL to env were demonstrated in three patients, and only one of five HAM/TSP patients had pCTL to gag. A synthetic peptide corresponding to the tax region of HTLV-1 (peptide 11-19, amino acid sequence LLFGYPVYV) was recognized in association with human histocompatibility leukocyte antigen (HLA)-A2 in two HLA-A2 HAM/TSP patients with a high CD8+ pCTL frequency of 1/325 and 1/265, respectively. A second immunodominant region of HTLV-1 tax (peptide 90-55, amino acid sequence VPYKRIEEL) was identified to be restricted by HLA-B14 in two HLA-B14 HAM/TSP patients with a CD8+ pCTL frequency of 1/640 and 1/1,125, respectively. Lymphocytes from the CSF of a patient with HAM/TSP also showed a pCTL frequency against p40X of similar magnitude to that demonstrated from peripheral blood lymphocytes (PBL). The HLA-A2-mediated CSF pCTL activity to the immunodominant tax-specific peptide 11-19 was also comparable to pCTL from PBL. These results indicate that an extremely high pCTL frequency to HTLV-1 tax-encoded peptides may be related to pathogenesis of myeloneuropathy associated with HTLV-1.

Anchor sequence-dependent endogenous processing of human immunodeficiency virus 1 envelope glycoprotein gp160 for CD4+ T cell recognition.

Human CD4+ T cell clones and cell lines were shown to lyse recombinant vaccinia virus-infected cells that synthesize the HIV-1 envelope glycoprotein gp160. The processing of endogenously synthesized gp160 for recognition by CD4+ T cells required that the protein, after synthesis on the rough endoplasmic reticulum and during subsequent cellular transport, remain attached to the luminal/extracellular membrane face by a hydrophobic anchor sequence.

Vaccination of rhesus monkeys with synthetic peptide in a fusogenic proteoliposome elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes.

An effective vaccine against the human immunodeficiency virus should be capable of eliciting both an antibody and a cytotoxic T lymphocyte (CTL) response. However, when viral proteins and peptides are formulated with traditional immunological adjuvants and inoculated via a route acceptable for use in humans, they have not been successful at eliciting virus-specific, major histocompatibility complex (MHC) class I-restricted CTL. We have designed a novel viral subunit vaccine by encapsulating a previously defined synthetic peptide CTL epitope of the simian immunodeficiency virus (SIV) gag protein within a proteoliposome capable of attaching to and fusing with plasma membranes. Upon fusing, the encapsulated contents of this proteoliposome can enter the MHC class I processing pathway through the cytoplasm. In this report, we show that after a single intramuscular vaccination, rhesus monkeys develop a CD8+ cell-mediated, MHC class I-restricted CTL response that recognizes the synthetic peptide immunogen. The induced CTL also demonstrate antiviral immunity by recognizing SIV gag protein endogenously processed by target cells infected with SIV/vaccinia recombinant virus. These results demonstrate that virus-specific, MHC class I-restricted, CD8+ CTL can be elicited by a safe, nonreplicating viral subunit vaccine in a primate model for acquired immune deficiency syndrome. Moreover, the proteoliposome vaccine formation described can include multiple synthetic peptide epitopes, and, thus, offers a simple means of generating antiviral cell-mediated immunity in a genetically heterogeneous population.

Protective humoral response against pneumococcal infection in mice elicited by recombinant bacille Calmette-Guérin vaccines expressing pneumococcal surface protein A.

Pneumococcal surface protein A (PspA), a cell-surface protein present on all strains of pneumococci, has been shown to elicit protective antibody responses in mice in the absence of capsular polysaccharide. Whereas PspA is polymorphic, considerable cross-reactivity and cross-protection have been demonstrated among PspA proteins of pneumococci exhibiting different capsular and PspA serotypes. A gene segment encoding the nonrepetitive variable NH2-terminal portion of PspA has been cloned into three distinct recombinant Bacille Calmette-Guérin (rBCG) vectors, allowing for expression of PspA as a cytoplasmic or secreted protein, or a chimeric exported membrane-associated lipoprotein. All rBCG-PspA strains elicited comparable anti-PspA ELISA titers, ranging from 10(4) to 10(5) (reciprocal titers) in both BALB/c and C3H/HeJ mice. However, protective responses were observed only in animals immunized with the rBCG-PspA vaccines expressing PspA as a secreted protein or chimeric exported lipoprotein. In addition, anti-PspA immune sera elicited by the rBCG vaccines passively protected X-linked immunodeficient mice from lethal challenge with the highly virulent, encapsulated WU2 strain of Streptococcus pneumoniae and two additional virulent strains exhibiting heterologous PspA and capsular serotypes. These studies confirm previous PspA immunization studies showing cross-protection against heterologous serotypes of S. pneumoniae and demonstrate a potential for rBCG-based PspA vaccines to elicit protective humoral responses against pneumococcal disease in humans.

Biological and biochemical characterization of a cloned Leu-3- cell surviving infection with the acquired immune deficiency syndrome retrovirus.

Leu-3- cells that survive infection with the acquired immune deficiency syndrome (AIDS) retrovirus can be induced with IUdR to express infectious virus. A cellular clone (8E5), isolated by limiting dilution of a mass culture of survivor cells, was found to contain a single, integrated provirus that was constitutively expressed. Although IUdR treatment of 8E5 cells failed to induce infectious virus, cocultivation with Leu-3+ cells generated the characteristic syncytia associated with acute AIDS retrovirus infection. The single integrated copy of proviral DNA directs the synthesis of all major viral structural proteins except p64, as monitored by immunoblotting. The relationship of the 8E5 clone to viral latency and persistence is discussed.

Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine.

The current vaccine against tuberculosis, Mycobacterium bovis strain bacille Calmette-Guerin (BCG), offers potential advantages as a live, innately immunogenic vaccine vehicle for the expression and delivery of protective recombinant antigens (Stover, C.K., V.F. de la Cruz, T.R. Fuerst, J.E. Burlein, L.A. Benson, L.T. Bennett, G.P. Bansal, J.F. Young, M.H. Lee, G.F. Hatfull et al. 1991. Nature [Lond]. 351:456; Jacobs, W.R., Jr., S.B. Snapper, L. Lugosi and B.R. Bloom. 1990. Curr. Top. Microbiol. Immunol. 155:153; Jacobs, W.R., M. Tuckman, and B.R. Bloom. 1987. Nature [Lond.]. 327:532); but as an attenuated intracellular bacterium residing in macrophages, BCG would seem to be best suited for eliciting cellular responses and not humoral responses. Since bacterial lipoproteins are often among the most immunogenic of bacterial antigens, we tested whether BCG expression of a target antigen as a membrane-associated lipoprotein could enhance the potential for a recombinant BCG vaccine to elicit high-titered protective antibody responses to target antigens. Immunization of mice with recombinant BCG vaccines expressing the outer surface protein A (OspA) antigen of Borrelia burgdorferi as a membrane-associated lipoprotein resulted in protective antibody responses that were 100-1,000-fold higher than responses elicited by immunization with recombinant BCG expressing OspA cytoplasmically or as a secreted fusion protein. Furthermore, these improved antibody responses were observed in heterogeneous mouse strains that vary in their immune responsiveness to OspA and sensitivity to BCG growth. Thus, expression of protective antigens as chimeric membrane-associated lipoproteins on recombinant BCG may result in the generation of new candidate vaccines against Lyme borreliosis and other human or veterinary diseases where humoral immunity is the protective response.

[Maturation of the autonomic nervous system: differences in heart rate variability at different gestational weeks]. / Reifung des Autonomen Nervensystems: Unterschiede in der Herzfrequenzvariabilität in unterschiedlichen Gestationswochen.

AIMS: Heart rate variability (HRV) reveals information on the functional state of the autonomic nervous system (ANS). This study was initiated to assess the physiological and maturational development of the ANS by comparing HRV data of a large number healthy foetus of different gestational ages from the 24(th) to the 42(nd) week. METHODS: Cardiotocogram (CTG) recordings of HRV of 172 healthy foetus (24-42 weeks' gestation) were performed to establish normative data. Frequency domain HRV parameters were computed in three frequency bands. RESULTS: The gestational ages of the foetuses correlate with HRV. Lower gestational age in weeks showed lower frequency domain parameters than higher gestational age in weeks. The most significant differences were discerned for HRV parameters reflecting sympathetic activity in LF (low frequency) and VLF (very low frequency), due to the adrenergic system. CONCLUSIONS: Maturation of the ANS is accompanied by increasing HRV with a pronounced increase of sympathetic activity. These changes are measurable by CTG recordings with a computer algorithm which can calculate short-term variability on the basis of CTG data. Problems of the CTG signal, as shown before, were the parameters of the time domain, which could only be well detected by ECG or foetal magnetocardiography (FMCG).

Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination.

Virtually all uropathogenic strains of Escherichia coli, the primary cause of cystitis, assemble adhesive surface organelles called type 1 pili that contain the FimH adhesin. Sera from animals vaccinated with candidate FimH vaccines inhibited uropathogenic E. coli from binding to human bladder cells in vitro. Immunization with FimH reduced in vivo colonization of the bladder mucosa by more than 99 percent in a murine cystitis model, and immunoglobulin G to FimH was detected in urinary samples from protected mice. Furthermore, passive systemic administration of immune sera to FimH also resulted in reduced bladder colonization by uropathogenic E. coli. This approach may represent a means of preventing recurrent and acute infections of the urogenital mucosa.

Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy.

One of the common neurological complications in patients with the acquired immune deficiency syndrome (AIDS) is a subacute encephalopathy with progressive dementia. By using the techniques of cocultivation for virus isolation, in situ hybridization, immunocytochemistry, and transmission electron microscopy, the identity of an important cell type that supports replication of the AIDS retrovirus in brain tissue was determined in two affected individuals. These cells were mononucleated and multinucleated macrophages that actively synthesized viral RNA and produced progeny virions in the brains of the patients. Infected brain macrophages may serve as a reservoir for virus and as a vehicle for viral dissemination in the infected host.

Ultrasound-guided vascular access in critical illness.

Over the past two decades, ultrasound (US) has become widely accepted to guide safe and accurate insertion of vascular devices in critically ill patients. We emphasize central venous catheter insertion, given its broad application in critically ill patients, but also review the use of US for accessing peripheral veins, arteries, the medullary canal, and vessels for institution of extracorporeal life support. To ensure procedural safety and high cannulation success rates we recommend using a systematic protocolized approach for US-guided vascular access in elective clinical situations. A standardized approach minimizes variability in clinical practice, provides a framework for education and training, facilitates implementation, and enables quality analysis. This review will address the state of US-guided vascular access, including current practice and future directions.

Prenatal Exposure to Famine and Risk for Development of Psychopathology in Adulthood: A Meta-Analysis.

Prenatal famine, resulting in intrauterine malnutrition, impacts offspring psychopathology later in adulthood. In addition, the specific impact of intrauterine malnutrition of different psychopathology differs by the timing of the exposure. Using a meta-analysis, the current study assessed the specific risk of developing affective, psychotic, and personality disorders. Studies were identified using PubMed and PsycINFO. Studies met the following criteria for inclusion in the analysis: availability in peer-reviewed English journals, use of human subjects, prenatal exposure to famine, and psychopathology in adulthood defined by diagnostic criteria as an outcome. Fixed effect relative risks (RRs) were calculated for affective, psychotic, and personality domains. Furthermore, timing of exposure was assessed as an effect modifier in our analysis, defined by the index trimester at the height of famine. Our meta-analysis found that adults exposed in utero during the 1st trimester were at a significant increased risk of psychotic disorders (RR=1.46, 95% CI=1.08, 1.97, p=0.014), and personality disorders (RR=2.31, 95% CI=1.36, 3.92, p=0.002). Those exposed during the 2nd trimester were at a significant increased risk of affective disorders (RR=1.45, 95% CI=1.22, 1.72, p<0.0001), and psychotic disorders (RR=1.46, 95% CI=1.13, 1.89, p=0.004). Similarly, those exposed in the 3rd trimester were at a significant increased risk of affective disorders (RR=1.33, 95% CI=1.13, 1.57, p=0.0001), and psychotic disorders RR=1.47, 95% CI=1.10, 1.97, p=0.010). Our findings suggest that there is differential risk across the different domains of psychopathology by trimester of exposures. This meta-analysis underscores the need for further investigation into the mechanisms underlying prenatal maternal nutrition and offspring psychopathology where magnitude of elevated risk differs by the exposure timing during pregnancy.

Diagnostic yield of active case finding for tuberculosis at human immunodeficiency virus testing in Haiti.

SETTING: The Groupe Haïtien d'étude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) Centres, Port-au-Prince, Haiti, facilitate "test and treat" strategies by screening all patients for tuberculosis (TB) at human immunodeficiency virus (HIV) testing.OBJECTIVE: 1) To determine the proportion of patients with chronic cough at HIV testing diagnosed with TB, stratified by HIV test results; and 2) to evaluate the additional diagnostic yield of Xpert® MTB/RIF vs. sputum microscopy.DESIGN: We conducted a retrospective cohort analysis including all adults tested for HIV at GHESKIO from August 2014 to July 2015.RESULTS: Of 29 233 adult patients tested for HIV, 2953 (10%) were diagnosed as HIV-positive. Chronic cough lasting ≥2 weeks was reported by 1116 (38%) HIV-positive patients; 984 (88%) were tested and 265 (27%) were diagnosed with TB. Chronic cough was reported by 5985 (23%) HIV-negative patients; 5654 (94%) were tested and 1179 (21%) were diagnosed with TB. Of all bacteriologically confirmed cases, 27% were smear-negative and Xpert-positive. Among all TB patients, 81% were HIV-negative.CONCLUSIONS: Screening for TB at HIV testing was high-yield, among both HIV-infected and HIV-negative individuals. Testing for both diseases should be conducted among patients who present with chronic cough at HIV testing.