PubMed Health⌕ Search

Biomedical subjects

C Lange

Publications and source records attributed to C Lange.

At least 19 recordsLinked to original sources
PubMed2007

Sequencing and analysis of the biosynthetic gene cluster of the lipopeptide antibiotic Friulimicin in Actinoplanes friuliensis.

Actinoplanes friuliensis produces the lipopeptide antibiotic friulimicin, which is a cyclic peptide with one exocyclic amino acid linked to a branched-chain fatty acid acyl residue. The structural relationship to daptomycin and the excellent antibacterial performance of friulimicin make the antibiotic an attractive drug candidate. The complete friulimicin biosynthetic gene cluster of 24 open reading frames from A. friuliensis was sequenced and analyzed. In addition to genes for regulation, self-resistance, and transport, the cluster contains genes encoding peptide synthetases, proteins involved in the synthesis and linkage of the fatty acid component of the antibiotic, and proteins involved in the synthesis of the nonproteinogenic amino acids pipecolinic acid, methylaspartic acid, and 2,3-diaminobutyric acid. By using heterologous gene expression in Escherichia coli, we provide biochemical evidence for the stereoselective synthesis of L-pipecolinic acid by the deduced protein of the lysine cyclodeaminase gene pip. Furthermore, we show the involvement of the dabA and dabB genes in the biosynthesis of 2,3-diaminobutyric acid by gene inactivation and subsequent feeding experiments.

Aminobutyrates↗
PubMed2007

A study of how socioeconomic status moderates the relationship between SNPs encompassing BDNF and ADHD symptom counts in ADHD families.

Recent animal research suggests that brain-derived neurotrophic factor (BDNF), may mediate response to different environmental stimuli. In this paper, we evaluated the possible role of BDNF as a moderator of attention deficit hyperactivity disorder (ADHD) in the context of different socioeconomic classes. We genotyped ten single nucleotide polymorphisms (SNPs) in and around BDNF in 229 families and evaluate whether there are SNP-by-socioeconomic status (SES) interactions for attention deficit hyperactivity. We developed three quantitative phenotypes for ADHD from nine inattentive and nine hyperactive-impulsive symptoms that were used in SNP-by-SES interaction analyses using a new methodology implemented in the computer program PBAT. Findings were adjusted for multiple comparisons using the false discovery rate. We found multiple significant SNP-by-SES interactions using the inattentive symptom count. This study suggests that different SES classes may modify the effect of the functional variant(s) in and around BDNF to have an impact on the number of ADHD symptom counts that are observed. The two exons within BDNF represent potential functional variants that may be causing the observed associations.

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

Application of advanced Monte Carlo Methods in numerical dosimetry.

Many tasks in different sectors of dosimetry are very complex and highly sensitive to changes in the radiation field. Often, only the simulation of radiation transport is capable of describing the radiation field completely. Down to sub-cellular dimensions the energy deposition by cascades of secondary electrons is the main pathway for damage induction in matter. A large number of interactions take place until such electrons are slowed down to thermal energies. Also for some problems of photon transport a large number of photon histories need to be processed. Thus the efficient non-analogue Monte Carlo program, AMOS, has been developed for photon and electron transport. Various applications and benchmarks are presented showing its ability. For radiotherapy purposes the radiation field of a brachytherapy source is calculated according to the American Association of Physicists in Medicine Task Group Report 43 (AAPM/TG43). As additional examples, results for the detector efficiency of a high-purity germanium (HPGe) detector and a dose estimation for an X-ray shielding for radiation protection are shown.

Algorithms↗
PubMed2006

Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons.

BACKGROUND: BCG-vaccination can confound tuberculin skin test (TST) reactions in the diagnosis of latent tuberculosis infection. METHODS: We compared the TST with a Mycobacterium tuberculosis specific whole blood interferon-gamma assay (QuantiFERON-TB-Gold In Tube; QFT-G) during ongoing investigations among close contacts of sputum smear positive source cases in Hamburg, Germany. RESULTS: During a 6-month period, 309 contacts (mean age 28.5 +/- 10.5 years) from a total of 15 source cases underwent both TST and QFT-G testing. Of those, 157 (50.8%) had received BCG vaccination and 84 (27.2%) had migrated to Germany from a total of 25 different high prevalence countries (i.e. >20 cases/100,000). For the TST, the positive response rate was 44.3% (137/309), whilst only 31 (10%) showed a positive QFT-G result. The overall agreement between the TST and the QFT-G was low (kappa = 0.2, with 95% CI 0.14.-0.23), and positive TST reactions were closely associated with prior BCG vaccination (OR 24.7; 95% CI 11.7-52.5). In contrast, there was good agreement between TST and QFT-G in non-vaccinated persons (kappa = 0.58, with 95% CI 0.4-0.68), increasing to 0.68 (95% CI 0.46-0.81), if a 10-mm cut off for the TST was used instead of the standard 5 mm recommended in Germany. CONCLUSION: The QFT-G assay was unaffected by BCG vaccination status, unlike the TST. In close contacts who were BCG-vaccinated, the QFT-G assay appeared to be a more specific indicator of latent tuberculosis infection than the TST, and similarly sensitive in unvaccinated contacts. In BCG-vaccinated close contacts, measurement of IFN-gamma responses of lymphocytes stimulated with M. tuberculosis-specific antigen should be recommended as a basis for the decision on whether to perform subsequent chest X-ray examinations or to start treatment for latent tuberculosis infection.

Adult↗
PubMed2006

Practical way to assess metabolic syndrome using a continuous score obtained from principal components analysis.

AIMS/HYPOTHESIS: We devised a practical continuous score to assess the metabolic syndrome, and assessed whether this syndrome score predicts incident diabetes and cardiovascular disease. SUBJECTS AND METHODS: Among 5,024 participants of the Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) cohort, we defined a metabolic syndrome score by the first principal component (PC1), using only the correlations between continuous metabolic syndrome measures (glucose, waist circumference, triglycerides, and systolic blood pressure). This metabolic syndrome score was highly correlated with a similar score also including insulin and HDL cholesterol (r ( s )=0.94). Over 9 years of follow-up, incident diabetes and cardiovascular disease (CVD) were predicted by logistic regression using the simpler metabolic syndrome score. RESULTS: The means of the metabolic syndrome measures differed between men and women. Nevertheless, as the degree of variance explained and the PC1 coefficients were remarkably similar, we used a common metabolic syndrome score. The metabolic syndrome score explained 50% of the variance of the metabolic syndrome measures, and waist circumference had the highest correlation (0.59) with this score. Each standard deviation increase in the metabolic syndrome score was associated with a markedly increased age-adjusted risk of developing diabetes (odds ratios: men 3.4 [95% CI 2.6-4.4]; women 5.1 [3.6-7.2]) and with increased incident CVD of 1.7 (1.4-2.1) in men and 1.7 (1.0-2.7) in women. CONCLUSIONS/INTERPRETATION: Our results, which should be confirmed in other populations, suggest that it is possible to evaluate the risk of the metabolic syndrome in a pragmatic fashion with a continuous score, obtained from principal components analysis of the basic, continuous syndrome measures.

Adult↗
PubMed2006

Overview of the pharmacogenetics of asthma treatment.

Asthma affects approximately 300 million individuals worldwide. Medications comprise a substantial portion of asthma expenditures. Despite the availability of three primary therapeutic classes of medications, there are a significant number of nonresponders to therapy. Available data, as well as previous pharmacogenetic studies, suggest that genetics may contribute as much as 60-80% to the interindividual variability in treatment response. In this methodologic review, after providing a broad overview of the asthma pharmacogenetics literature to date, we describe the application of a novel family-based screening algorithm to the analysis of pharmacogenetic data and highlight our approach to identifying and verifying loci influencing asthma treatment response. This approach seeks to address issues related to multiple comparisons, statistical power, population stratification, and failure to replicate from which previous population-based or case-control pharmacogenetic association studies may suffer. Identification of such replicable loci is the next step towards the goal of 'individualized therapy' for asthma.

Adrenergic beta-Agonists↗
PubMed2006

Cost-optimisation of screening for latent tuberculosis in close contacts.

The aim of the present study was to perform cost-minimisation analysis of contact investigation from a public health perspective using the tuberculin skin test (TST) and a new blood assay, QuantiFERON-TB Gold (QFT-G). A decision-analysis model simulated the costs of investigating a cohort of adult close tuberculosis contacts by the public health service following the current German guidelines over a period of 2 yrs. The economic outcomes were compared with alternative screening strategies. These were: 1) QFT-G instead of TST; 2) TST followed by QFT-G; and 3) TST followed by QFT-G in vaccinated (bacille Calmette-Guérin (BCG)) subjects. In a base-case analysis, the costs of TST-based screening were 91.06 Euros (EUR).contact(-1), assuming a 1% tuberculosis-case-finding incidence. The least expensive strategy was TST screening plus subsequent QFT-G testing (52.05 EUR), resulting in a 43% cost reduction. Using QFT-G alone in BCG-vaccinated subjects who tested positive in the TST led to a 39% cost reduction. The savings using QFT-G alone instead of TST amounted to 29.77 EUR.contact(-1). The results depended on the acquisition costs assumed and the proportion of positive results in TST-based screening. Screening for tuberculosis by combining tuberculin skin testing and QuantiFERON-TB Gold markedly reduces public health costs compared with tuberculin skin test screening alone.

Antigens, Bacterial↗
PubMed2006

Avoiding the effect of BCG vaccination in detecting Mycobacterium tuberculosis infection with a blood test.

Bacille Calmette-Guérin (BCG) vaccination can confound tuberculin skin test (TST) reactions in the diagnosis of latent tuberculosis infection (LTBI). The TST was compared with a Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunospot (ELISPOT) assay during an outbreak of MTB infection at a police academy in Germany. Participants were grouped according to their risk of LTBI in close (n = 36) or occasional (n = 333) contacts to the index case. For the TST, the positive response rate was 53% (19 out of 36) among close and 16% (52 out of 333) among occasional contacts. In total, 56 TST-positive contacts (56 out of 71 = 78.9%) and 27 TST-negative controls (27 out of 298 = 9.1%) underwent ELISPOT testing. The odds ratio (OR) of a positive test result across the two groups was 29.2 (95% confidence interval (CI) 3.5-245.0) for the ELISPOT and 19.7 (95% CI 2.0-190.2) for the TST with a 5 mm cut-off. Of 369 contacts, 158 (42.8%) had previously received BCG vaccination. The overall agreement between the TST and the ELISPOT was low, and positive TST reactions were confounded by BCG vaccination (OR 4.8 (95% CI 1.3-18.0)). In contrast, use of a 10-mm induration cut-off for the TST among occasional contacts showed strong agreement between TST and ELISPOT in nonvaccinated persons. In bacille Calmette-Guérin-vaccinated individuals, the Mycobacterium tuberculosis-specific enzyme-linked immunospot assay is a better indicator for the risk of latent tuberculosis infection than the tuberculin skin test.

Adolescent↗
PubMed2006

[Anxiety and depression after loss of a lower limb].

A good number of psychosocial-, disease-, and disability-related variables influence the adaptation process after the loss of a lower limb. In this case psychological problems, as a result of a failed adaptation process, are common. Of the 75 patients examined who had an amputation of a lower extremity 27% showed increased depression and 25% increased anxiety scores; 18.3% showed higher than normal scores in both categories. Regression analysis showed that in addition to pain reception poor acceptance of the prosthesis is an important predictive factor for the development of psychological disorders and diseases like anxiety and depression. Therefore, measures for psychological diagnostics and care should be initiated soon after the amputation to prevent psychological abnormalities. Here interdisciplinary management and cooperation of the professions involved in the care of the patient are recommended.

Adolescent↗
PubMed2006

Continuous complete hematological and cytogenetic remission with molecular minimal residual disease 9 years after discontinuation of interferon-alpha in a patient with Philadelphia chromosome-positive chronic myeloid leukemia.

Interferon-alpha has been used as standard therapy for patients with Philadelphia-positive chronic myeloid leukemia (CML) for more than 20 years. Recently randomized trials have shown a superiority of the tyrosine kinase inhibitor imatinib in respect to its efficacy to induce complete hematological and cytogenetic remissions and more importantly in overall survival. Although follow-up is much shorter for imatinib than for interferon-alpha, this data changed the treatment algorithms in this disease. At the end of the era of interferon-alpha as a single-drug first-line treatment for most patients we present a case report which exemplifies a rare but exciting property of interferon-alpha in CML: the induction of complete hematological and cytogenetic remissions which can persist over years after discontinuation of the drug. Hence, the enrollment of CML patients in clinical trials which explore a combination treatment of imatinib and interferon-alpha is warranted.

Aged↗
PubMed2005

[The health of unemployed women and men. First results of the Telephone Health Survey 2003].

Unemployment has material and psychosocial consequences that can also have an adverse effect on health. According to the Telephone Health Survey 2003, unemployed women and men suffer more frequently from many diseases and complaints. Their assessment of their own state of health is also more negative, and they say more often that their quality of life is restricted by their health. In the case of men, health problems are especially common among the long-term unemployed (>1 year), whereas women can suffer equally (or even more) serious effects on their health as a result of short-term unemployment. On the other hand, the analysis clearly indicates that poor health heightens a person's risk of becoming unemployed. However, no conclusive statement can be made on the direction of causality between unemployment and health, since this requires more longitudinal data.

Adolescent↗
PubMed2005

Fatal outcome of a hyperinfection syndrome despite successful eradication of Strongyloides with subcutaneous ivermectin.

We report the case of a 77-year-old man who developed a Strongyloides hyperinfection syndrome following immunosuppressive therapy more than 60 years after he moved away from an area endemic for Strongyloides stercoralis. Successful eradication of the nematode was achieved with an off label subcutaneous formulation of ivermectin. However, the patient subsequently died from acute respiratory distress syndrome (ARDS). Despite a high wormload in the stool and sputum of the patient and delayed infection control measures in the hospital, testing of the medical staff revealed a very low risk of Strongyloides transmission among healthcare workers.

Aged↗
PubMed2005

Results of endovascular repair of inflammatory abdominal aortic aneurysms. A report from the EUROSTAR database.

OBJECTIVES: To investigate the results following endovascular treatment of patients with inflammatory abdominal aortic aneurysms (IAAA). DESIGN: Retrospective study based on the EUROSTAR registry. MATERIAL AND METHODS: Patients included in the EUROSTAR registry with IAAA (n=52, 1.4%) were compared to those having aneurysms without aortic fibrosis (n=3613, 98.6%). The mean follow-up period in patients with IAAA was 23 months (range 1-60). In 11 of the patients detailed information on the effect of endovascular repair and perianeurysmal fibrosis and ureteral entrapment was obtained by a dedicated questionnaire. RESULTS: Twelve patients (23%) with IAAA had preoperative impairment of renal function and five had known hydronephrosis. Variables that were significantly associated with IAAA included younger age (p<.0001, mean difference 5.9, CI 3.7-7.9) and lower pulmonary risks score (OR 0.38, CI 0.19-0.74). At completion of the endovascular procedure, device stenosis was more frequently observed in patients with IAAA (OR 18.1, CI 3.52-93.0). There were no differences with regard to the rates of mortality, rupture or conversion in patients with IAAA and controls. In the majority, the aneurysm size regressed irrespective of nature of aneurysm. Of the 11 patients with a detailed assessment three had deterioration of renal function and three still had ureteral entrapment during follow-up. CONCLUSION: Despite persistence of perianeurysmal inflammation in a proportion of patients operative and midterm results of endovascular repair were comparable in the patients with inflammatory and standard AAA.

Adult↗
PubMed2005

[Labeling of mesenchymal stem cells with different superparamagnetic particles of iron oxide and detectability with MRI at 3T].

PURPOSE: In vitro evaluation of labeling efficiency of human mesenchymal stem cells (hMSCs) with different types of superparamagnetic iron oxide nanoparticles as well as detection and quantification by MRI at 3T. MATERIAL AND METHODS: hMSCs were incubated for 24 hours with 5 ultrasmall superparamagnetic particles of iron oxide (USPIO) contrast agents (1 : 30 - 1 : 30,000) of different size, coating and core compound: Endorem, Resovist, citric acid coated magnetite cores of 3 nm (CMF3), 7 nm (CMF7) and 12 nm (CoF, core: cobalt ferrite). Iron uptake, intracellular retention, detection and quantification were evaluated with MRI up to 5 weeks after incubation by cytological analysis (Prussian blue), atomic absorption spectrometry and MR relaxometry measurements. RESULTS: An effective labeling of hMSCs was achieved using Resovist, CMF3 and CMF7 with mean iron concentrations of 5.1/1.8, 1.9/1.4 and 1.5/1.0 pg/cell (dilutions 1:30 [933, 2100, 2800 microg Fe/ml]/1 : 300 [93, 210, 280 microg Fe/ml]) compared with 0.58/0.34 and 0.43/0.30 pg/cell (Endorem, CoF, dilution 1 : 30 [400, 4200 microg Fe/ml]/1 : 300 [40, 420 microg Fe/ml] unlabelled control cells: 0.01 pg/cell). Particle uptake correlated with the concentration of USPIO in the incubation medium. Detection of 5 x 10 (4) labelled cells/ml with MRI was possible up to 5 weeks after incubation (Resovist, CMF7 and CMF3). MR relaxometry measurements showed a strong correlation between cellular iron load and R2* (1/T2*), r > 0.78. No changes in cell viability or toxic effects were found. CONCLUSION: Efficiency of labeling hMSCs with USPIOs depends on coating, size and core compound of used particles. Carboxydextran-coated, clinically approved SPIO (Resovist, 50 nm) or ultrasmall citrate-coated particles (< 10 nm) result in an improved cellular uptake. In principle, the long intracellular retention of particles offers the possibility of cell tracking and migration monitoring in MRI.

Cells, Cultured↗
PubMed2005

Ruptured abdominal aortic aneurysm secondary to tuberculous spondylitis.

A 69-year-old man was admitted with low back pain and signs of nerve root compression. A computed tomography (CT) scan showed abscess formation in the left psoas region, spondylodiscitis L3-L4 and a ruptured abdominal aortic aneurysm. The aortic aneurysm was replaced with a bifurcated vascular graft. One week later, laminectomy at the L4-level was done. In a small abscess, Mycobacterium bovis was found. The condition was considered to be a mycobacterial spondylitis secondary to BCG instillations of the urinary bladder for carcinoma. The patient received antituberculous medication for 9 months. Subsequently bone transplantation and internal fixation of the spine became necessary. Three years after surgery he is in good condition and there are no signs of graft infection on CT. Spondylitis and mycotic aortic aneurysm should be kept in mind in patients who have been treated for carcinoma of the bladder with BCG instillations.

Aged↗
PubMed2004

Omega-pyridiniumalkylethers of steroidal phenols: new compounds with potent antibacterial and antiproliferative activities.

Novel omega-pyridiniumalkylethers of two steroidal phenols were synthesized as compounds with potential antimicrobial activity. 3-Hydroxy-estra-1,3,5(10)-triene-17-one and 1-hydroxy-4-methyl-estra-1,3,5(10)-triene-17-one were reacted with omega,omega'-dibromoalkanes to omega-bromoalkoxy-estra-1,3,5(10)-trienes followed by reaction with pyridine to obtain the desired steroidal omega-pyridiniumalkoxy compounds as bromides. Their antimicrobial activity against strains of multiresistant Staphylococcus aureus (MRSA), a vancomycin resistant Enterococcus faecalis and fast growing mycobacteria depends clearly on the length of the alkyl chain. A strong broadband activity has been found for the compounds with eight or 10 C-atoms; in some cases better than ciprofloxacin or cetylpyridinium salts. In addition, the antiproliferative and cytotoxic activity depends on the chain length, too. The differentiation between antibacterial and cytotoxic activity is better for the steroid hybrid molecules than the cetylpyridinium salts. These new compounds can serve as lead compounds for further optimization.

Anti-Bacterial Agents↗