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Biomedical subjects

C Junghans

Publications and source records attributed to C Junghans.

15 recordsLinked to original sources
PubMed2006

How effective are rapid access chest pain clinics? Prognosis of incident angina and non-cardiac chest pain in 8762 consecutive patients.

OBJECTIVE: To determine whether rapid access chest pain clinics are clinically effective by comparison of coronary event rates in patients diagnosed with angina with rates in patients diagnosed with non-cardiac chest pain and the general population. DESIGN: Multicentre cohort study of consecutive patients with chest pain attending the rapid access chest pain clinics (RACPCs) of six hospitals in England. PARTICIPANTS: 8762 patients diagnosed with either non-cardiac chest pain (n = 6396) or incident angina without prior myocardial infarction (n = 2366) at first cardiological assessment, followed up for a median of 2.57 (interquartile range 1.96-4.15) years. MAIN OUTCOME MEASURES: Primary end point--death due to coronary heart disease (International Classification of Diseases (ICD)10 I20-I25) or acute coronary syndrome (non-fatal myocardial infarction (ICD10 I21-I23), hospital admission with unstable angina (I24.0, I24.8, I24.9)). Secondary end points--all-cause mortality (ICD I20), cardiovascular death (ICD10 I00-I99), or non-fatal myocardial infarction or non-fatal stroke (I60-I69). RESULTS: The cumulative probability of the primary end point in patients diagnosed with angina was 16.52% (95% confidence interval (CI) 14.88% to 18.32%) after 3 years compared with 2.73% (95% CI 2.29% to 3.25%) in patients with non-cardiac chest pain. Coronary standardised mortality ratios for men and women with angina aged <65 years were 3.52 (95% CI 1.98 to 5.07) and 4.39 (95% CI 1.14 to 7.64). Of the 599 patients who had the primary end point, 194 (32.4%) had been diagnosed with non-cardiac chest pain. These patients were younger, less likely to have typical symptoms, more likely to be south Asian and more likely to have a normal resting electrocardiogram than patients with angina who had the primary end point. CONCLUSION: RACPCs are successful in identifying patients with incident angina who are at high coronary risk, but there is a need to reduce misdiagnosis and improve outcomes in patients diagnosed with non-cardiac chest pain who accounted for nearly one third of cardiac events during follow-up.

Angina Pectoris↗
PubMed2006

Rapid-access chest pain clinics and the traditional cardiology out-patient clinic.

BACKGROUND: The National Service Framework for coronary heart disease recommends rapid-access chest pain clinics (RACPCs) for cardiological assessment of new-onset chest pain within 2 weeks of referral. AIM: To measure the extent to which an RACPC successfully substituted for an out-patient cardiology clinic (OPCC) at a general hospital, in assessing new-onset chest pain referrals. METHODS: Prospective measurement of attendance and waiting times for consecutive patients at the RACPC and OPCC, and multivariate analysis of factors associated with referral for angiography. RESULTS: From September 2002 to August 2004, 1382 patients with chest pain attended the RACPC, and 228 patients, the OPCC. All RACPC patients were seen within 24 h of referral, except those referred on Friday afternoons, or the day before national holidays. The mean +/- SD waiting time for OPCC appointments was 97 +/- 43 days. Of 208 OPCC patients, 30 (14%) fulfilled the RACPC referral criterion of recent onset chest pain (<4 weeks duration) vs. 926/1382 (67%) RACPC patients. Thus the RACPC substituted for the OPCC in 926/956 (97%) new chest pain referrals. Patients from the OPCC were 3.82 (95%CI 1.85-7.90) more likely to be referred for a coronary angiogram. compared to those attending the RACPC. DISCUSSION: The RACPC has provided efficient and effective substitution for the OPCC in the assessment of new chest pain referrals according to pre-defined referral criteria. Broadening the referral criterion of the RACPC to patients with chest pain of >4 weeks duration would result in more referrals.

Ambulatory Care Facilities↗
PubMed2006

Cytokine and Ig-production by CG-containing sequences with phosphorodiester backbone and dumbbell-shape.

BACKGROUND: Immunostimulatory oligodeoxynucleotides (CpG-ODN) usually contain phosphorothioate (PS) backbones for nucleotide protection, which may result in some nonspecific side-effects like prolongation of coagulation time. OBJECTIVE: The aim of the present study was to investigate the immunomodulatory potential of DNA molecules without PS backbones. Thus, we designed phosphorodiester (PO) molecules with a dumbbell-like covalently-closed structure (dSLIM-30L1). METHODS: We analyzed their effects on peripheral blood mononuclear cells (PBMC) from spontaneous high and low immunoglobulin (Ig)E producer (allergic and nonallergic donors) in comparison with linear CpG-ODN (lin-30L1) with PS backbones, using enzyme-linked immunosorbent assay and flow cytometry. RESULTS: We observed a decrease of spontaneous IgE levels in PBMC from high IgE producer of approximately 27% with both dSLIM-30L1 and lin-30L1. In addition, both molecules enhanced the production of IgA, IgM and IgG1/IgG2, but with a slightly different pattern. Both molecules stimulated the secretion of the T(H)1-like cytokines interleukin (IL)-2, interferon-gamma and IL-12p40 and the pro-inflammatory cytokine IL-6. The immunomodulatory potential of dSLIM-30L1 and lin-30L1 was also effective in PBMC from nonallergic donors, as was confirmed for IL-2, IL-12p40, IgG1/IgG2 and IgM. CONCLUSION: Our data show an inhibition of IgE production but also enhancement of the inflammatory cytokine response in PBMC from allergic and nonallergic donors by covalently-closed PO-based dSLIM-30L1 with a pattern similar to that of linear PS-based lin-30L1, while avoiding PS-modifications and thus PS-mediated side-effects. Whether such molecules are useful for the treatment of allergic diseases will need further clarification by appropriate in vivo studies.

Adult↗
PubMed2004

DNA immunisation with minimalistic expression constructs.

The low efficacy obtained in large animals makes plasmid-based DNA vaccines commercially unviable. Another concern is the presence of antibiotic resistance markers on virtually all conventional plasmids. Here we describe the use of minimalistic, immunogenically defined gene expression (MIDGE) vectors for DNA vaccination. MIDGE are linear, covalently-closed vectors containing all the essential information for gene expression and none of the non-essential and potentially dangerous plasmid backbone sequences. MIDGE vectors can also be chemically modified on both ends at defined positions allowing targeting of the DNA to specific cell types or cellular compartments. Immunisation of mice with simple and end-modified MIDGE vectors showed that they are efficacious tools to generate and/or manipulate antigen-specific immune responses.

Animals↗
PubMed2002

DNA vaccination with linear minimalistic (MIDGE) vectors confers protection against Leishmania major infection in mice.

Immunization protocols based on priming with plasmid DNA and boosting with recombinants of vaccinia virus (rVV) encoding the same antigen offer great promise for the prevention and treatment of many parasitic and viral infections for which conventional vaccination has little or no effect. To overcome some of the potential problems associated to the use of plasmids, we have developed minimalistic, immunogenically defined, gene expression (MIDGE((R))) vectors. These linear vectors contain only the minimum sequence required for gene expression and can be chemically modified to increase the immune response. Here, we demonstrate that MIDGE vectors coding for the LACK antigen confer a highly effective protection against Leishmania infection in susceptible Balb/c mice. Protection is achieved at lower doses of vector compared to conventional plasmids. This efficacy could be greatly improved by the addition of a nuclear localization signal (NLS) peptide to the end of the MIDGE vector. In fact, immunization with two doses of NLS-modified MIDGE conferred similar or even better protection than that achieved by priming with plasmid DNA followed by boosting with rVV. These results demonstrate that MIDGE vectors are a good alternative to plasmid and rVV for immunization.

Animals↗
PubMed2001

A novel minimal-size vector (MIDGE) improves transgene expression in colon carcinoma cells and avoids transfection of undesired DNA.

Viral and plasmid vectors may cause unwanted immunological side effects resulting from the expression of nontherapeutic genes contained in their sequence. Furthermore, replication-defective viral vectors carry the potential risk of recombination with wild-type viruses or activation of oncogenes. A new vector type for minimalistic, immunologically defined gene expression (MIDGE) may overcome these problems. MIDGE is a minimal-size gene transfer unit containing the expression cassette, including promoter, gene, and RNA-stabilizing sequence, flanked by two short hairpin oligonucleotide sequences. The resulting vector is a small, linear, covalently closed, dumbbell-shaped molecule. DNA not encoding the desired gene is reduced to a minimum. Here, we transfected colon carcinoma cell lines using cationic lipid, cationic polymer, and electroporation with several MIDGE vectors and corresponding plasmids containing transgenes encoding enhanced green fluorescent protein (eGFP) and human interleukin-2 (hIL-2). Transfection efficiency as measured qualitatively and quantitatively with eGFP was found to be comparable for both vector types. However, hIL-2 secretion and eGFP expression were approximately two- to fourfold higher in most cells transfected with these transgenes using MIDGE vectors compared to the plasmid control. This report demonstrates the advantages of this new vector type and its prospects for ex vivo gene therapy studies.

Cations↗
PubMed2001

Priming of immune responses to hepatitis B surface antigen with minimal DNA expression constructs modified with a nuclear localization signal peptide.

Nuclear localization signal (NLS) peptides conjugated to DNA increase transfection efficiency in vitro. We tested in mice whether conjugation of NLS peptides to DNA vaccines enhances their immunogenicity after intramuscular injection or gene gun mediated intradermal delivery. We constructed the plasmid pMOK-HBsAY that contains a transcription unit encoding hepatitis B surface antigen (HBsAg) and bacterial sequences for amplification of plasmid DNA. From this plasmid we derived the minimal expression construct pMOK-HBsAY-MIDGE, a covalently closed linear DNA that contains only the HBsAg transcription unit. Both constructs stimulated similar (predominantly IgG1) antibody response to HBsAg after gene gun immunization. In contrast, pMOK-HBsAY plasmid DNA was more efficient than pMOK-HBsAY-MIDGE DNA in priming predominantly IgG2a antibody responses to HBsAg after intramuscular injection. Both constructs efficiently primed cytotoxic T lymphocyte responses after intramuscular immunization. When a NLS peptide was coupled to the pMOK-HBsAY-MIDGE DNA, HBsAg transfection efficiency in vitro and priming of antibody responses to HBsAg after intramuscular (but not gene gun mediated) injection was enhanced 10- to 15-fold. These data show: (a) MIDGE constructs can be used as DNA vaccines indicating that bacterial sequences are not essential cofactors; and (b) in intramuscular (but not gene gun mediated) delivery the immunogenicity of a MIDGE-based vaccine is enhanced by coupling NLS peptides to the vector DNA.

Animals↗
PubMed2000

Protection against FIV challenge infection by genetic vaccination using minimalistic DNA constructs for FIV env gene and feline IL-12 expression.

OBJECTIVE: To evaluate the efficacy of a genetic vaccination protocol based on minimalistic, immunogenic defined gene expression (MIDGE) vectors coding for domains of the feline immunodeficiency virus (FIV) env gene and feline IL-12. METHODS: Three groups of four cats each were immunized three times within 6 weeks by the ballistic transfer of gold particles coated with MIDGE vectors. Group 1 received non-coated gold beads, groups 2 and 3 MIDGE vectors expressing FIV surface plus part of the transmembrane protein. In addition, group 3 received feline IL-12 DNA. All cats were challenged by intraperitoneal injection of 25 TCID50 of infectious FIV Z2. The following criteria were monitored: clinical signs, antibodies to transmembrane protein, antibodies to whole FIV, haematological parameters and kinetics of CD4 and CD8 cells, FIV proviral load (determined by quantitative polymerase chain reaction; PCR) and cytotoxic T lymphocyte (CTL) activity (in selected cats). RESULTS: None of the cats developed a detectable antibody response during immunizations. Four weeks after challenge exposure, all cats in group 1 (control) and group 2 (FIV surface-transmembrane protein) had seroconverted and showed a high proviral load until week 19 (end of experiment). In contrast, only one of four cats in group 3 (surface-transmembrane protein and IL-12) showed antibodies; it was provirus positive at reduced virus load. Short-lived CTL activity was found in two cats in group 3. CONCLUSION: Genetic vaccination using a MIDGE-based construct for the expression of the surface-transmembrane protein domain of FIV env and feline IL-12 DNA led to protection against homologous virus challenge in three out of four vaccinated cats.

Animals↗
PubMed2000

Immunization of cats against feline immunodeficiency virus (FIV) infection by using minimalistic immunogenic defined gene expression vector vaccines expressing FIV gp140 alone or with feline interleukin-12 (IL-12), IL-16, or a CpG motif.

Four groups of cats, each containing four animals, were immunized at 0, 3, and 6 weeks with minimalistic immunogenic defined gene expression vector (MIDGE) vaccines containing the gene(s) for feline immunodeficiency virus (FIV) gp140, FIV gp140 and feline interleukin-12 (IL-12), FIV gp140 and feline IL-16, or FIV gp140 and a CpG motif. MIDGEs were coated onto gold beads and injected intradermally with a gene gun. A fifth group of four cats were immunized in an identical manner but with blank gold beads. All cats were challenge exposed to virulent FIV 4 weeks following the final immunization, and the course of infection was monitored. The two groups of cats immunized with the FIV gp140 gene alone or with blank gold particles became highly viremic and seroconverted as early as 4 weeks after infection. In contrast, three of four cats immunized with FIV gp140 in combination with feline IL-12 failed to become viremic or seropositive, as has been shown elsewhere (F. S. Boretti, C. M. Leutenegger, C. Mislin, et al., AIDS 14:1749-1757, 2000). Here we show the effect of IL-12 when used as an adjuvant on the viral RNA and DNA load and on the cytokine profile. In addition, the two groups of cats immunized either with gp140 and IL-16 or with gp140 and the CpG had greatly reduced viremia. Protection correlated weakly with cytotoxic T-lymphocyte activity and increased cytokine transcription of IL-12, gamma interferon, and IL-10 by peripheral blood mononuclear cells in the postchallenge period. This study extends the data on IL-12 and provides new results on CpG motifs and IL-16 used as adjuvants in the FIV cat model.

Animals↗
PubMed1999

Uniform risk of clinical progression despite differences in utilization of highly active antiretroviral therapy: Swiss HIV Cohort Study.

OBJECTIVE: To compare the initiation of highly active antiretroviral therapy (HAART) in HIV-infected patients according to sex, route of HIV acquisition and education, and to assess the impact of differences in utilization on the probability of progression to AIDS. DESIGN AND SETTING: Swiss HIV Cohort Study, a national prospective multi-centre study. PARTICIPANTS: A total of 3342 patients, including 1007 (30%) women. HIV was acquired through injection drug use in 1155 (35%) cases and through sex between men in 1172 (35%). Twenty-eight per cent (957) of participants had attained only the minimum level of schooling. At baseline, the median CD4 cell count was 269x10(6)/l cells, median HIV-1 RNA was 4.3 log10 copies/ml and 2917 (87%) were free of AIDS. METHODS: Kaplan-Meier life tables and Cox proportional hazards regression. RESULTS: During 7007 person-years of follow-up 2285 (69%) patients started HAART and 318 (10%) developed a new AIDS event. In multivariable analysis controlling for CD4 cell count, viral load and disease stage at baseline, the probability of starting HAART was lower in injection drug users compared with men who have sex with men, hazard ratio 0.63 (95% confidence intervals 0.56-0.70) and in patients with minimum schooling compared with those with vocational training, hazard ratio 0.82 (0.75-0.91). The risk of progression to AIDS was similar among men and women, patients with a history of injecting drug use, and patients with lower educational attainment in both univariable and multivariable analysis. CONCLUSION: HIV-infected injecting drug users and those with lower levels of educational attainment start HAART later than other patient groups. The deferred initiation of therapy in these patients does not, however, appear to translate into an increased risk of clinical disease progression. This observation has important implications for treatment policy and the design of future clinical trials.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Approaches to the genetics of cardiovascular disease through genetic field work.

Successful molecular genetic studies of complex disease require exact, careful phenotypization, which is more difficult than that performed for monogenic diseases. We have developed a family-oriented field working approach, which relies on index patients, their primary care physicians, and a minimum number of field working staff. The patients are responsible for recruiting their family members. Packets containing an explanatory pamphlet, an informed consent statement, a questionnaire, and blood cuvettes are provided. Data are transferred from questionnaire and from the laboratory into a computer program that facilitates construction of the family tree. We have applied this genetic field working approach primarily to patients with lipid disorders. Coupling results from genetic field working with modern DNA diagnostic tests such as the oligonucleotide ligation assay, has enabled us to effectively identify patients with familial hypercholesterolemia in the German population. We are now extending genetic field working to hypertension. Hypertension is much more difficult to study, because the phenotype is more difficult to discern and document. Both complex diseases have the disadvantage that the parents of the index patients are likely to already be dead. Nevertheless, we concentrate on the recruitment of large pedigrees, sibling pairs with parents whenever possible, and trios consisting of index patient and both parents or index patient, parent and sibling. With these constellations we can conduct association studies, linkage analysis, and novel combinations of both approaches.

Automation↗
PubMedDate not supplied

[Multiple sensitization to topically used corticosteroids].

Sensitivity to single corticosteroids is well known. Polyvalent sensitization towards several different steroids has been described rarely. Contact allergy due to diflucortolone-21-valerate has not been described previously as far as we know. In our case the patient was allergic to three corticosteroids.

Administration, Topical↗