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Biomedical subjects

P Fischer

Publications and source records attributed to P Fischer.

At least 37 records · Page 2Linked to original sources
PubMed2004

[Predictive factors of virological response to primary antiretroviral treatment].

OBJECTIVES: During 1999, first-line antiretroviral combinations for the treatment of HIV infections have diversified. The aim of our study was two-fold: define the factors associated with initial success and define the factors associated with virological rebound in patients in whom a primary antiretroviral therapy (ARV) had been initiated between 1999 and 2000. METHOD: We conducted a retrospective multicenter study regrouping 6 HIV clinics in the North-East of France. Data were Issued from the patients medical files. Primary success was defined as plasma HIV RNA viral load (VL<200 copies/ml within 6 Months of therapy and two consecutive VL<200 copies/ml. Virological rebound was defined as two consecutive VL>1000 copies/ml after primary success. Predictors of success were determined using multivariate logistic regression and SAS 8.2 software. RESULTS: Analysis concerned 123 patients, with 19% stage C when ARV was initiated. Their median CD4 and PVL values at baseline were 233/mm3 and 73,000 copies/ml respectively. The median duration of follow-up was of 20.7 Months [(mean (STD): 20.6 (6.7)]. Initial treatments were distributed as follows: 2 NRTI + 1NNRTI, n=66 (54%); 2 NRTI+1PI, n=44 (36%); 3 NRTI, n=13 (10%). Primary success was obtained in 100 (81,3%) patients. Among these, 6 (6%) developed secondary virologic failure. The absence of change in initial ARV treatment within first 4 Months, and good compliance to treatment were statistically associated with primary success in univariate (p values respectively: 0.004 and 0.04) and in multivariate analysis (p respectively: 0.009 and 0.03). The proportion of failure was higher in the patients with lower baseline CD4 levels lesser than 200/mm3 (p=0.09). CONCLUSION: In this cohort of patients, tolerance and compliance to the first regimen were associated to primary success. These results emphasize the role of compliance in primary success and reinforces need to work on compliance in such patients.

Adult↗
PubMed2004

Detection of filaria-specific IgG4 antibodies using Brugia Rapid test in individuals from an area highly endemic for Brugia timori.

The filarial parasite Brugia timori is of great public health importance in some islands of Eastern Indonesia. To establish a simple serological test for the identification and post-treatment monitoring of areas endemic for B. timori, a rapid immunochromatographic dipstick test (Brugia Rapid, BR) was evaluated on microfilaraemic and amicrofilaraemic individuals. This test is based on the detection of anti-filarial IgG4 antibodies that react with a recombinant Brugia malayi antigen (BmR1). In our study area on Alor island the prevalence of microfilaraemia was 26%. With the BR test, 100% of 196 sera from microfilaraemic persons and 76% of 563 sera from amicrofilaraemic persons, either symptomatic or asymptomatic, reacted positive. All 50 control sera from areas non-endemic for lymphatic filariasis gave negative BR test results. This study showed that the BR test can be also used to detect antibodies against B. timori. Due to the high prevalence of IgG4 antibodies as detected by the BR test (81%), no significant correlation with the prevalence of microfilaraemia could be detected within the endemic village. The BR test also shows great promise to be employed as a monitoring tool for B. timori in the framework of the Global Program to Eliminate Lymphatic Filariasis (GPELF).

Adolescent↗
PubMed2003

New electro-optic effect: sum-frequency generation from optically active liquids in the presence of a dc electric field.

We report the observation of sum-frequency signals that depend linearly on an applied electrostatic field and that change sign with the handedness of an optically active solute. This recently predicted chiral electro-optic effect exists in the electric-dipole approximation. The static electric field gives rise to an electric-field-induced sum-frequency signal (an achiral third-order process) that interferes with the chirality-specific sum-frequency at second order. The cross-terms linear in the electrostatic field constitute the effect and may be used to determine the absolute sign of second- and third-order nonlinear-optical susceptibilities in isotropic media.

Electromagnetic Fields↗
PubMed2003

An exploratory workplace study to investigate the perceived value of continuous low-level heatwrap therapy in manual workers.

BACKGROUND: Between 60 and 80% of the population in industrialized countries experience low back pain at some time in their lives. The physical demands of work, i.e. manual handling, lifting, bending, twisting, awkward postures and whole body vibration are associated with low back symptoms. This study was undertaken to investigate the benefits of a new form of continuous low-level heatwrap therapy available for the symptomatic relief of acute low back pain in the workplace. METHODS: The subjects were recruited to the study upon their visit to the occupational health doctor after being diagnosed with acute low back pain. RESULTS: The study results show that use of the heatwrap therapy significantly reduced pain intensity and impact of pain on everyday activities. The results of the study were further extrapolated to show potential cost reduction benefits of using this heatwrap therapy in the workplace.

Acute Disease↗
PubMed2003

Air pollution and mortality in The Netherlands: are the elderly more at risk?

The association between daily mortality and short-term variations in the ambient levels of ozone (O3), black smoke (BS), sulphur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and particulate matter was studied in The Netherlands. Daily total and cause-specific mortality counts (cardiovascular, chronic obstructive pulmonary disease (COPD) and pneumonia), air quality, temperature, relative humidity and influenza data were obtained from 1986-1994. The relationship between daily mortality and air pollution was modelled using Poisson regression analysis. All pollution mortality associations were adjusted for potential confounding due to long-term trends, seasonal trends, influenza epidemics, ambient temperature, ambient relative humidity, day of the week and holidays, using generalised additive models. Statistically significant associations were mostly found in the elderly, that is the age categories of 65-74 and > or = 75 yrs for the pollutants PM10 (particles with a 50%, cut-off aerodynamic diameter of 10 microm), BS, SO2, NO2 and CO. This may partly be due to a better precision of relative risk (RR) estimates for the larger numbers of deaths in these age groups. Significant associations for those < 65 yrs were found for O3 (total and COPD mortality), PM10 (pneumonia), NO2 (pneumonia) and CO (pneumonia). RR estimates for deaths between 45-65 yrs tended to be smaller than those in > 65 yrs, with the exception of ozone; for cardiovascular mortality the RR for PM10, O3 and CO were similar in these age groups. In conclusion, larger relative risks for air pollution were mostly found in the elderly except for ozone and for death-cause pneumonia which showed larger relative risk in younger age groups.

Aged↗
PubMed2002

Vienna Transdanube Aging "VITA": study design, recruitment strategies and level of participation.

The Vienna Transdanube Aging study "VITA" is a prospective, interdisciplinary cohort-study of all 75-years old inhabitants of the 21. and 22. district of Vienna (n = 1,745), which started in May 2000. The study design is described in this paper for the first time. The main scientific question of the study concerns the prediction of incident dementia in the elderly. The main statistical analysis will compare 8 predictors: episodic memory, verbal fluency, subjective memory complaints, depression, APOE-epsilon4, MAO-B activity in thrombocytes, MRT hippocampal atrophy, and MRT atrophy of the substantia innominata. The whole investigation comprises medical and psychosocial interviews, psychological tests, psychiatric and neurological scales, blood characteristic, genetic factors and cranial magnetic resonance imaging. Various variables will be compared with each other concerning sensitivity and specificity of prediction of cognitive decline. The dependent variable of the intended statistical analysis will be the individual's difference between Mini Mental State Examination scores at the two times of investigation. A high level of participation in geriatric epidemiological studies increases the general applicability of results but recruitment procedures must not ignore the individual's right to privacy and integrity. Using a liberal recruitment procedure as recommended by the local ethics commission the level of participation is between 36.7% and 44.3%.

Aged↗
PubMed2002

An internal control for the detection of Onchocerca volvulus DNA by PCR-ELISA and rapid detection of specific PCR products by DNA Detection Test Strips.

We developed a polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA) for the detection of Onchocerca volvulus DNA. To standardize the PCR and to avoid false-negative results, an internal control DNA was co-amplified by the same set of primers. We differentiated the wild-type PCR product of the O-150 DNA sequence from the internal control by specific DNA probes. Detection of biotinylated PCR products by DNA probes was performed by ELISA to quantify the PCR product or by DNA Detection Test Strips as a rapid field technique. The methods were evaluated on skin biopsies from individuals living in an area endemic for O. volvulus in Uganda, but with low microfilaria densities because of ivermectin treatment. Microfilaria density was assessed by a single skin snip and a second skin snip was examined by PCR. Among 69 samples from microfilaria carriers, 47 (68%) were positive by ELISA and 55 (80%) by test strip detection of PCR products. When 39 samples of microfilaria-negative individuals from the same area were tested, 10 (27%) were positive by ELISA and 12 (31%) by test strips. None of the 19 samples obtained from persons living in an area not endemic for O. volvulus but endemic for Mansonella streptocerca was positive in either test. Although the ELISA is theoretically more sensitive than the test strips for the detection of PCR products, examination of field samples revealed that the test strip method had a higher operational sensitivity and was more convenient to perform. Thus, the DNA Detection Test Strips are a rapid and low-tech tool for identification of PCR products in laboratories of countries endemic for onchocerciasis.

Animals↗
PubMed2002

[Depressive pseudodementia].

Elderly depressive patients complaining about cognitive symptoms are at particular risk of being labelled as demented. It is well documented that depressive disorders frequently cause mild cognitive deficits which manifest in psychometric procedures. A wide spectrum of potentially reversible cognitive deficits related to a depressive syndrome are summarized under the term of "Depressive Pseudodementia (DPD)". Most depressive patients who are referred to "DPD" suffer from cognitive dysfunctions outside the range of dementia. The clinical interface between depression and dementia is complex. There is some evidence that depression may be a risk factor for the expression of Alzheimer's disease in later life and that depression may occur as a prodrome for Alzheimer dementia. Moreover, depression often complicates the course of dementing disorders. However, there is no evidence that depressive disorders cause dementia without coexisting depressive symptoms. It is essential to search for depressive symptoms even after cognitive symptoms have been found.

Aged↗
PubMed2002

PCR-based detection and identification of the filarial parasite Brugia timori from Alor Island, Indonesia.

Brugia timori is widely distributed on Alor Island, Indonesia, where it causes a high degree of morbidity. The HhaI tandem repeat of B. timori was found to be identical to that of B. malayi, for which sensitive PCR-based assays have already been developed. Using one of these assays, a single microfilaria (mf) of B. timori, present in a spot of dry blood on filter paper, could be detected. The assay was equally sensitive in the detection of B. timori and B. malayi. When the collected mosquitoes were pooled according to species and tested with the assay, 39 (64%) of the 61 Anopheles barbirostris pools (containing a total of 642 mosquitoes) were positive. As none of the 33 Culex pools tested (which contained 624 mosquitoes) gave a positive result, and An. barbirostris is the only Anopheles species commonly caught on human bait in Alor, An. barbirostris is assumed to be the main and perhaps only local vector. Brugia timori could be differentiated from B. malayi by restriction-endonuclease digestion of the PCR-amplified mitochondrial cytochrome oxidase subunit 2. A few distinct nucleotide exchanges were also found in the second internal transcribed ribosomal spacer of the filariae, and in the 16S rDNA and FTSZ gene of their Wolbachia endobacteria. The results show that B. timori can be effectively detected using the PCR-based assay developed for B. malayi and can then be differentiated from B. malayi by other molecular markers. PCR-based techniques targeting the HhaI repeat can therefore be employed for monitoring B. timori in the framework of the Global Programme to Eliminate Lymphatic Filariasis.

Animals↗
PubMed2002

Development and standardization of a rapid, PCR-based method for the detection of Wuchereria bancrofti in mosquitoes, for xenomonitoring the human prevalence of bancroftian filariasis.

PCR has recently been studied as a promising tool for monitoring the progress of efforts to eliminate lymphatic filariasis. PCR can be used to test concurrently at least 30 pools, with as many as 40 mosquitoes in each pool, for the presence of filarial larvae. The SspI PCR assay for the detection of Wuchereria bancrofti DNA in pools of mosquitoes has been used since 1994 in a variety of laboratories worldwide. During that time, the original assay has been modified in these different laboratories and no standardized assay currently exists. In an effort to standardize and improve the assay, a meeting was held on 15-16 November 2001, at Emory University in Atlanta, with representatives from most of the laboratories currently using the assay. The first round of testing was designed to test the four most promising methods for DNA extraction from pools of mosquitoes. Two of the four methods stood out as clearly the best and these will be now optimised and evaluated in two further rounds of testing.

Animals↗
PubMed2002

Traffic-related air pollution and respiratory health during the first 2 yrs of life.

As part of an international collaborative study on the impact of Traffic-Related Air Pollution on Childhood Asthma (TRAPCA), the health effects associated with long-term exposure to particles with a 50% cut-off aerodynamic diameter of 2.5 microm (PM2.5), PM2.5 absorbance, and nitrogen dioxide (NO2) were analysed. The German part of the TRAPCA study used data from subpopulations of two ongoing birth cohort studies (German Infant Nutrition Intervention Programme (GINI) and Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA)) based in the city of Munich. Geographic information systems (GIS)-based exposure modelling was used to estimate traffic-related air pollutants at the birth addresses of 1,756 infants. Logistic regression was used to analyse possible health effects and potential confounding factors were adjusted for. The ranges in estimated exposures to PM2.5, PM2.5 absorbance, and NO2 were 11.9-21.9 microg m(-3), 1.38-4.39 x 10(-5) m(-1), and 19.5-66.9 microg x m3, respectively. Significant associations between these pollutants and cough without infection (odds ratio (OR) (95% confidence interval (CI)): 1.34 (1.11-1.61), 1.32 (1.10-1.59), and 1.40 (1.12-1.75), respectively) and dry cough at night (OR (95% CI): 1.31 (1.07-1.60), 1.27 (1.04-1.55), and 1.36 (1.07-1.74), respectively) in the first year of life were found. In the second year of life, these effects were attenuated. There was some indication of an association between traffic-related air pollution and symptoms of cough. Due to the very young age of the infants, it was too early to draw definitive conclusions from this for the development of asthma.

Air Pollution↗
PubMed2001

The effects of light therapy on mini-mental state examination scores in demented patients.

BACKGROUND: Preliminary evidence suggests that demented patients may experience beneficial effects of light therapy. The authors tested whether bright light therapy (BLT) is capable of improving cognitive functions in patients with Alzheimer-type dementia (AD) or vascular dementia (VD). METHODS: Twenty-three patients with AD or VD were randomly assigned to either evening BLT or dim light therapy (DLT). Effects of light therapy on cognitive functions were assessed before and after light therapy using Mini-Mental State Examination (MMSE) scores. Body temperature rhythm (BTR) was additionally recorded pre- and posttreatment. RESULTS: Irrespective of their diagnosis, patients treated with BLT (p =.0012) but not with DLT (p =.73) showed a statistically significant increase in MMSE total scores after light therapy. Evening BLT simultaneously induced a significant phase delay of 56 min on BTR (p =.025). CONCLUSION: Our preliminary results suggest that short-term evening BLT may exert beneficial effects on cognitive functioning in patients with dementia.

Aged↗
PubMed2001

A P450 BM-3 mutant hydroxylates alkanes, cycloalkanes, arenes and heteroarenes.

P450 monooxygenases from microorganisms, similar to those of eukaryotic mitochondria, display a rather narrow substrate specificity. For native P450 BM-3, no other substrates than fatty acids or an indolyl-fatty acid derivative have been reported (Li, Q.S., Schwaneberg, U., Fischer, P., Schmid, R.D., 2000. Directed evolution of the fatty-acid hydroxylase P450BM-3 into an indole-hydroxylating catalyst. Chem. Eur. J. 6 (9), 1531-1536). Engineering the substrate specificity of Bacillus megaterium cytochrome P-450 BM3: hydroxylation of alkyl trimethylammonium compounds. Biochem. J. 327, 537-544). We thus were quite surprised to observe, in the course of our investigations on the rational evolution of this enzyme towards mutants, capable of hydroxylating shorter-chain fatty acids, that a triple mutant P450 BM-3 (Phe87Val, Leu188-Gln, Ala74Gly, BM-3 mutant) could efficiently hydroxylate indole, leading to the formation of indigo and indirubin (Li, Q.S., Schwaneberg, U., Fischer, P., Schmid, R.D., 2000. Directed evolution of the fatty-acid hydroxylase P450BM-3 into an indole-hydroxylating catalyst. Chem. Eur. J. 6 (9), 1531-1536). Indole is not oxidized by the wild-type enzyme; it lacks the carboxylate group by which the proper fatty acid substrates are supposed to be bound at the active site of the native enzyme, via hydrogen bonds to the charged amino acid residues Arg47 and Tyr51. Our attempts to predict the putative binding mode of indole to P450 BM-3 or the triple mutant by molecular dynamics simulations did not provide any useful clue. Encouraged by the unexpected activity of the triple mutant towards indole, we investigated in a preliminary, but systematic manner several alkanes, alicyclic, aromatic, and heterocyclic compounds, all of which are unaffected by the native enzyme, for their potential as substrates. We here report that this triple mutant indeed is capable to hydroxylate a respectable range of other substrates, all of which bear little or no resemblance to the fatty acid substrates of the native enzyme.

Alkanes↗
PubMed2001

Magnetic domains in nanostructured media studied with M-TXM.

Combining X-ray magnetic circular dichroism (X-MCD) with a transmission X-ray microscope (TXM) allows to image element-specifically magnetic domain structures with 25nm lateral resolution. Both in-plane and out-of-plane systems can be studied in applied magnetic fields. Thus field-dependent parameters, as individual nucleation fields in magnetic nanostructures can be deduced and related to morphology. Images of thermomagnetically written bits in magneto-optical TbFeCo media proof the reliability of the writing process and the importance of an exact thermal design of the systems. Domains observed at corresponding Co L edges proof the chemical sensitivity of M-TXM and its potential to image few monolayer systems.

Journal Article↗
PubMed2001

A stress-responsive glyoxalase I from the parasitic nematode Onchocerca volvulus.

Glyoxal, methylglyoxal and other physiological alpha-oxoaldehydes are formed by the lipid peroxidation, glycation and degradation of glycolytic intermediates. They are detoxified enzymically by the glyoxalase system. To investigate the physiological function of glyoxalase I in parasitic organisms, the cDNA for glyoxalase I from the filarial nematode Onchocerca volvulus (designated Ov-GloI) has been cloned and characterized. The isolated cDNA contains an open reading frame of 579 bp encoding a protein with a calculated molecular mass of 21930 Da. Owing to the high degree of sequence identity (60%) with human glyoxalase I, for which the X-ray structure is available, it has been possible to build a three-dimensional model of Ov-GloI. The modelled core of Ov-GloI is conserved compared with the human glyoxalase I; however, there are critical differences in the residues lining the hydrophobic substrate-binding pocket of Ov-GloI. A 22 kDa protein was obtained by heterologous expression in Escherichia coli. A homogeneous enzyme preparation was obtained by affinity purification and functional characterization of the recombinant enzyme included the determination of kinetic constants for methylglyoxal and phenylglyoxal as well as inhibition studies. Gel filtration demonstrated a dimeric structure. To assess the role of Ov-GloI as a potential vaccine candidate or serodiagnostic tool, the serological reactivity of the recombinant Ov-GloI was analysed with sera from microfilaria carriers and specific IgG1 antibodies were detected. The effects of oxidative insult, namely plumbagin and xanthine/xanthine oxidase, on the gene transcript level of Ov-GloI were investigated. By using a semi-quantitative PCR ELISA it was shown that Ov-GloI is expressed at elevated levels under conditions of oxidative stress.

Amino Acid Sequence↗
PubMed2001

Acupuncture for idiopathic headache.

BACKGROUND: Acupuncture is widely used for the treatment of headache, but its effectiveness is controversial. OBJECTIVES: To determine whether acupuncture is: - more effective than no treatment - more effective than 'sham' (placebo) acupuncture - as effective as other interventions used to treat idiopathic (primary) headaches. SEARCH STRATEGY: Electronic searches were performed in MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and the database of the Cochrane Field for Complementary Medicine. We also contacted researchers in the field and checked the bibliographies of all articles obtained. SELECTION CRITERIA: Randomized or quasi-randomized clinical trials comparing acupuncture with any type of control intervention for the treatment of idiopathic (primary) headaches were included. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, methods, and results was extracted by at least two independent reviewers using a pre-tested standard form. Results on headache frequency and intensity were summarized descriptively. Responder rate ratios (responder rate in treatment group/responder rate in control group) were calculated as a crude indicator of results for sham-acupuncture-controlled trials. Quantitative meta-analysis was not possible due to trial heterogeneity and insufficient reporting. MAIN RESULTS: Twenty-six trials including a total of 1151 patients (median, 37; range, 10-150) met the inclusion criteria. Sixteen trials were conducted among patients with migraine, six among patients with tension-type headache, and four among patients with various types of headaches. The majority of trials had methodological and/or reporting shortcomings. In eight of the 16 trials comparing true and sham (placebo) acupuncture in migraine and tension-type headache patients, true acupuncture was reported to be significantly superior; in four trials there was a trend in favor of true acupuncture; and in two trials there was no difference between the two interventions. (Two trials were uninterpretable.) The 10 trials comparing acupuncture with other forms of treatment yielded contradictory results. REVIEWER'S CONCLUSIONS: Overall, the existing evidence supports the value of acupuncture for the treatment of idiopathic headaches. However, the quality and amount of evidence are not fully convincing. There is an urgent need for well-planned, large-scale studies to assess the effectiveness and cost-effectiveness of acupuncture under real-life conditions.

Acupuncture Therapy↗
PubMed2001

The B cell superantigen-like interaction of intravenous immunoglobin (IVIG) with Fab fragments of V(H) 3-23 and 3-30/3-30.5 germline gene origin cloned from a patient with Kawasaki disease is enhanced after IVIG therapy.

The etiology of Kawasaki disease (KD) is still unknown. Therefore, the diagnosis relies on clinical criteria only. Although a specific therapy for KD is not available, coronary complications can be significantly reduced with the help of intravenous immunoglobulin (IVIG) therapy. It is not clear how IVIG interacts with the immune system. Previously, we selected a large number of IgG and IgM Fab fragments specifically reacting with IVIG molecules by phage display and antiidiotypic panning from three patients with autoimmune thrombocytopenia, a patient with lupus, and a healthy individual. Sequencing revealed that the favored V(H) germline gene segments of these IVIG-bound Fabs were 3-23 or 3-30/3-30.5, the most frequently rearranged V(H) genes among human B cells. The binding pattern suggested a B cell superantigen-like, specific interaction of an IVIG subset with B cells that present B cell receptors derived from these two germline genes. The aim of the current study was to investigate whether treatment with IVIG influences this restricted interaction. Therefore we cloned and selected Fab fragments from a patient with KD before and after IVIG therapy. A favored selection of antibodies derived from both the 3-23 and the 3-30/3-30.5 germline gene segments as before was observed. Importantly, the reactivity with IVIG was significantly higher for clones from the library prepared after the IVIG treatment, providing the first in vivo functional evidence that a subset of IVIG may selectively activate B cells of this germline origin. This mechanism may add to the therapeutic effect of IVIG in the treatment of KD.

B-Lymphocytes↗