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Biomedical subjects

M Sanders

Publications and source records attributed to M Sanders.

At least 19 recordsLinked to original sources
PubMed2006

Rifampicin mono-resistant Mycobacterium tuberculosis in Bujumbura, Burundi: results of a drug resistance survey.

SETTING: Bujumbura, Burundi. OBJECTIVES: To determine resistance levels of Mycobacterium tuberculosis (TB) to the main anti-tuberculosis drugs after 11 years of a DOTS programme using a WHO-recommended partially intermittent 6-month rifampicin (RMP) first-line regimen and fixed-dose drug combinations (FDCs). DESIGN: Drug susceptibility testing of systematic samples of M. tuberculosis isolated from newly registered sputum smear-positive cases in the capital during a 15-month period (2002-2003). RESULTS: Of 496 strains from new cases, 16.1% showed resistance to any drug, 6.3% to isoniazid (INH), 2.0% to RMP (1.4% multidrug-resistant TB [MDR-TB]), 13.3% to streptomycin and 1.6% to ethambutol. Among 69 strains from previously treated cases, the prevalence of resistance was 30%, 19%, 15% (12% MDR-TB strains), 25% and 6%, respectively. CONCLUSION: Levels of drug resistance in Bujumbura are higher than average for Africa, despite long-term use of the DOTS strategy with FDCs and a ban on sales of TB drugs. Most worrying is the appearance of MDR-TB and RMP-resistant, INH-susceptible strains in new cases. Although a survey cannot prove that high HIV prevalence, elevated levels of resistance to some other drugs and irregular intake allowed acquisition of drug resistance, the effectiveness and safety of 6-month regimens with (partially) intermittent RMP throughout under such conditions should be investigated.

Adolescent↗
PubMed2005

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

ATP-Binding Cassette Transporters↗
PubMed2005

Intracellular free radical production in synovial T lymphocytes from patients with rheumatoid arthritis.

OBJECTIVE: To investigate the cellular and molecular sources of oxidative stress in patients with rheumatoid arthritis (RA) through analysis of the production of reactive oxygen species (ROS) in synovium. METHODS: Cytochemical procedures based on the 3,3'-diaminobenzidine (DAB)-Mn2+ deposition technique were used on unfixed cryostat sections of synovium from RA patients and rheumatic disease controls. For immunophenotyping, sections were incubated, fixed, and stained with fluorescein isothiocyanate-labeled antibodies. Fluorescence-activated cell sorter analysis of the ROS-reactive dye 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate-di(acetoxymethyl ester) was used to measure intracellular ROS in T lymphocytes from peripheral blood and synovial fluid. To determine which enzymes produced ROS, different inhibitors were tested. RESULTS: Large quantities of DAB precipitated in the majority of RA synovial T lymphocytes, indicative of intracellular ROS production. These ROS-producing T lymphocytes were observed throughout the synovium. Polymerization of DAB was observed to a lesser extent in other forms of chronic arthritis, but was absent in osteoarthritis. DAB staining of cytospin preparations of purified RA synovial fluid T cells confirmed the presence of ROS-producing cells. One of the ROS involved appeared to be H2O2, since catalase suppressed intracellular ROS production. Superoxide dismutase, which uses superoxide as a substrate to form H2O2, diphenyleneiodonium (an inhibitor of NADPH oxidase), N(G)-monomethyl-L-arginine (an inhibitor of nitric oxide synthesis), nordihydroguaiaretic acid (an inhibitor of lipoxygenase), and rotenone (an inhibitor of mitochondrial ROS production) failed to suppress ROS production. CONCLUSION: Our findings show that chronic oxidative stress observed in synovial T lymphocytes is not secondary to exposure to environmental free radicals, but originates from intracellularly produced ROS. Additionally, our data suggest that one of the intracellularly generated ROS is H2O2, although the oxidase(s) involved in its generation remains to be determined.

Arthritis, Rheumatoid↗
PubMed2005

[Otolith function tests--a differentiated, quality-assured screening system].

INTRODUCTION: More than 30% of all otogenic vestibular disorders are related to isolated macular dysfunction. Videooculographic examination techniques for the otolith-ocular reflex, e. g. by means of eccentric rotation tests, are not widely used in clinical routine as these put a considerable strain on technical and staff resources. Thus, there is a considerable risk of "false negative" classification of vertigo disorders being labelled as "non-otogenic". By means of vestibular-evoked myogenic potentials (VEMPs) and caloric irrigation in prone and supine position, several examination techniques for a side-related investigation of macula-induced vestibulo-ocular reflexes are available. The objective of this study is to compare and evaluate these techniques as screening tests. METHODS: In 32 patients with vestibular disorders we performed investigations for VEMPs, eccentric rotation tests, as well as caloric irrigation for macular reaction in prone and supine position. In addition, we performed other audiologic and vestibular function tests which were complemented by the clinical course in order to differentiate each case between otogenic and non-otogenic vertigo with or without macular affection. RESULTS: The technical feasibility as well as patients' acceptance for VEMP testing is better than for eccentric rotation tests. The sensitivity index for VEMPs (89%) as well as for caloric irrigation in prone and supine position for macular examination (71%) is satisfactory. However, the specificity of VEMPs is inferior (53%) to eccentric rotation (100%). DISCUSSION: Both the examination for VEMPs as well as caloric macular testing in prone and supine position carry features which make them feasible for screening, even though these two procedures test for two different parts of the otolith system. However, to confirm a diagnosis and to set up a therapeutic concept for macular function disorders, eccentric rotation should be added.

Caloric Tests↗
PubMed2005

Comparison of anatomical tibial plateau angle versus observer measurement from lateral radiographs in dogs.

This study was conducted to compare the anatomical tibial plateau angle (TPA) with that measured by observers from a lateral radiograph of the limb, the hypothesis being that there would not be any statistically significant differences between the observer measured TPA and the true anatomical TPA. Twelve pelvic limbs from skeletally mature greyhound cadavers, without any clinical or radiographic evidence of stifle pathology, were used in this study. The radiographs were taken of each limb in a lateral position with the primary beam centered over the tibial eminences and collimated to include the stifle and tarso-crural joints. For subsequent radiographs, Kirschner wires were inserted to enable identification of the tibial plateau. The TPA was then measured, by three observers, from the plain radiographs and by one observer from the marked radiographs. The mean observer TPA was 24.4 degrees (range 17-30 degrees) and the mean anatomical TPA was 23.8 degrees (range 15-31 degrees). The mean and median discrepancy between the anatomical TPA and the observer TPA was negative and very small (- 0.64 degrees and 0 degrees). The magnitude of the discrepancy between individual measurements made by the observers tended to overestimate small angles and underestimate the large ones, and this trend is statistically significant. These results suggest that the measurements made by observers accurately represent the anatomical slope of the tibial plateau. Therefore, observer TPA is suitable for the planning and assessment of TPLO procedures. However, as the anatomical TPA moves away from a median angle (23.25 degrees) the magnitude of error in the measurement increases.

Animals↗
PubMed2004

Genome sequence of the enterobacterial phytopathogen Erwinia carotovora subsp. atroseptica and characterization of virulence factors.

The bacterial family Enterobacteriaceae is notable for its well studied human pathogens, including Salmonella, Yersinia, Shigella, and Escherichia spp. However, it also contains several plant pathogens. We report the genome sequence of a plant pathogenic enterobacterium, Erwinia carotovora subsp. atroseptica (Eca) strain SCRI1043, the causative agent of soft rot and blackleg potato diseases. Approximately 33% of Eca genes are not shared with sequenced enterobacterial human pathogens, including some predicted to facilitate unexpected metabolic traits, such as nitrogen fixation and opine catabolism. This proportion of genes also contains an overrepresentation of pathogenicity determinants, including possible horizontally acquired gene clusters for putative type IV secretion and polyketide phytotoxin synthesis. To investigate whether these gene clusters play a role in the disease process, an arrayed set of insertional mutants was generated, and mutations were identified. Plant bioassays showed that these mutants were significantly reduced in virulence, demonstrating both the presence of novel pathogenicity determinants in Eca, and the impact of functional genomics in expanding our understanding of phytopathogenicity in the Enterobacteriaceae.

Base Sequence↗
PubMed2003

Systematic restaining of sputum smears for quality control is useful in Burundi.

SETTING: Routine tuberculosis control services in Burundi. OBJECTIVE: To determine whether systematic restaining of sputum smears for acid-fast bacilli (AFB) prior to rechecking quality assessment is necessary. DESIGN: Blinded rechecking of peripheral routine smears, including a second control of discordants, before and after restaining. RESULTS: Without restaining, 10/825 (1.2%) negative, and 59/189 (31.2%) positive results were declared false. After restaining, there were 34 (4.1%) false negatives and 13 (6.9%) false positives, both highly significant changes. Before restaining, quantification of positive smears was usually considered too high, while after restaining 41 out of 42 positives were found to have too low readings. CONCLUSIONS: Despite mild climatic conditions in Burundi, restaining all slides before rechecking revealed an unrecognised, widespread problem of false negatives, rather than false positives. This indicated the need for critical re-appraisal of the standard procedure using cold staining, rather than re-training, as would have been inferred from results without restaining. Systematic restaining of all slides prior to rechecking may be more widely needed in National Tuberculosis Programmes to cover all possible serious causes of error. Cold staining should be avoided in field programmes since its performance is easily affected by frequently encountered adverse factors.

Burundi↗
PubMed2002

Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.

Animals↗
PubMed2002

Toxicological studies in tropical ecosystems: an ecotoxicological risk assessment of pesticide runoff in South Florida estuarine ecosystems.

A multiyear study in the C-111 canal system and associated sites in Florida Bay was undertaken to determine the potential pesticide risk that exists in South Florida. After the examination of extensive pesticide concentration data in surface water, tissues, and semipermeable membrane devices (SPMDs), canal contamination seems to be derived from the extensive agricultural production that drains into the C-111 canal. The results of this study indicate that runoff from agricultural processes led to quantifiable pesticide residues in both canal and bay surface water, which occasionally exceeded current water quality criteria. The major pesticide of concern was endosulfan, which was detected at 100% of the sites sampled. Endosulfan exposure did not cause any acute effects in fish and crustaceans deployed in field bioassays. Chronic effects were observed in copepods, clams, and oysters but could not be attributed to endosulfan exposure. The decision to alter the C-111 canal flow and allow increased freshwater flow into the adjacent Everglades National Park may result in discharges of pesticides into the Everglades. Continued monitoring in this area is needed during this change in flow regime.

Agriculture↗
PubMed2002

Origin and distribution of polycyclic aromatic hydrocarbons in surficial sediments from the savannah river.

Surface sediments collected from the Savannah River, located in the southeastern state of Georgia, USA, in June-July 1994 were analyzed for individual polycyclic aromatic hydrocarbons (PAHs). Three subdivisions of the river were identified for the study: upstream from, adjacent to, and downstream from the city of Savannah. There was high spatial variability in the total PAH (SigmaPAH) concentrations that ranged from 29 to 5,375 ng/g with an average concentration of 1,216 +/- 1,161 (SD). Of the three subdivisions, the highest SigmaPAH concentrations were in the middle segment, which was adjacent to urban and industrial areas. To elucidate sources, molecular indices based on indices among phenanthrene versus anthracene and fluoranthene versus pyrene were used to determine pyrogenic and petrogenic sources, respectively. These indices have been used by other authors to differentiate sources. In most cases, PAHs in sediments nearest the city of Savannah were of high temperature and pyrogenic origin. These pyrogenic PAHs were highly associated with toxicity to benthic organisms. The two-ringed naphthalene and substituted naphthalenes, which are petroleum-related PAHs, were significantly higher in the lower section of the river relative to the subdivisions. This river segment receives inputs primarily from shipping and boating traffic. Perylene, which is indicative of nonanthropogenic terrestrial inputs of carbon, had the highest concentration among the individual PAHs measured. High perylene concentrations were found at stations located upstream and adjacent to forested terrain and where salinity level was low. To discriminate pattern differences and similarities of individual PAHs among samples, principal component analysis (PCA) was performed on the more hydrophobic and persistent nonalkylated PAHs. These differences and similarities were used to infer perylene origin. PCA was performed on 14 nonalkylated PAHs that was normalized to the sum of nonalkylated PAHs, using a correlation matrix. Generally, the PAHs were separated into group patterns according to chemical and physical properties associated with log K(OW), except perylene. Perylene, a five-ringed PAH, was distinctly separated from the other five-ringed PAHs. The sources for perylene are likely from biogenic, terrestrial precursors. The collected data show that pyrogenic PAHs were highly associated with biological effects on benthic organisms, based on bioassay results. Perylene, a nonanthropogenic PAH, was found throughout the river and constituted a large percentage of total PAHs in the upper river.

Animals↗
PubMed2002

Improving diagnostic procedure and treatment in patients with non-epileptic seizures (NES).

The purpose of this study was to examine the incidence of patients with NES vs. NES and concomitant epilepsy in an epilepsy centre and to present a diagnostic algorithm. We collected and reviewed the data of 322 patients consecutively referred to the adult ward of our epilepsy centre in 1 year. The results of our study reveal that 44 (14%) of all patients referred had NES. Of these, nine proved to have concomitant epilepsy. Of 44 patients with NES, 20 were treated with AED on admission. In 14 cases this unnecessary antiepileptic drug treatment was stopped. In six remaining patients with NES and concomitant epilepsy, the total number of AEDs could be reduced until discharge. The maximum duration of AED treatment among patients with NES only, had been longer than 360 months (median 72 months). Much has been written about whether the diagnosis of psychogenic non-epileptic events is overused. According to our experience however, the fact that many patients with so-called 'pharmacoresistant epilepsy', suspected NES or other diagnoses are referred to a centre of excellence much too late, proves to be the key problem in diagnosis and treatment of NES. We conclude that early admission of so-called 'pharmacoresistant epilepsy' to an epilepsy centre, establishing a standard work-up and clarifying the medical terminology will improve diagnosis and lead to adequate therapy of NES as well as prevent unnecessary drug treatment.

Adolescent↗
PubMed2001

The Vfl1 Protein in Chlamydomonas localizes in a rotationally asymmetric pattern at the distal ends of the basal bodies.

In the unicellular alga Chlamydomonas, two anterior flagella are positioned with 180 degrees rotational symmetry, such that the flagella beat with the effective strokes in opposite directions (Hoops, H.J., and G.B. Witman. 1983. J. Cell Biol. 97:902-908). The vfl1 mutation results in variable numbers and positioning of flagella and basal bodies (Adams, G.M.W., R.L. Wright, and J.W. Jarvik. 1985. J. Cell Biol. 100:955-964). Using a tagged allele, we cloned the VFL1 gene that encodes a protein of 128 kD with five leucine-rich repeat sequences near the NH(2) terminus and a large alpha-helical-coiled coil domain at the COOH terminus. An epitope-tagged gene construct rescued the mutant phenotype and expressed a tagged protein (Vfl1p) that copurified with basal body flagellar apparatuses. Immunofluorescence experiments showed that Vfl1p localized with basal bodies and probasal bodies. Immunogold labeling localized Vfl1p inside the lumen of the basal body at the distal end. Distribution of gold particles was rotationally asymmetric, with most particles located near the doublet microtubules that face the opposite basal body. The mutant phenotype, together with the localization results, suggest that Vfl1p plays a role in establishing the correct rotational orientation of basal bodies. Vfl1p is the first reported molecular marker of the rotational asymmetry inherent to basal bodies.

Algal Proteins↗
PubMed2001

Threshold doses for nicotine discrimination in smokers and non-smokers.

RATIONALE: Tobacco use during initial experimentation often involves modest nicotine exposure, escalating to larger doses and more frequent exposure with the onset of tobacco dependence. Threshold doses for nicotine discrimination therefore may differ between naive and experienced tobacco users. OBJECTIVES: We determined the lowest (threshold) dose of nasal spray nicotine that smokers and non-smokers could reliably discriminate from placebo spray. METHODS: Male and female smokers (n=18) and non-smokers (n=17) were initially trained to discriminate 20 microg/kg from placebo before proceeding to threshold determination sessions, which involved discrimination of progressively lower doses below 20 microg/kg ("descending order" subgroup) or higher doses above 1 microg/kg ("ascending order" subgroup). Threshold was determined by the lowest dose reliably discriminated from placebo (correct on > or =80% of testing trials) and by failure to discriminate the next lowest dose. RESULTS: Threshold doses for nicotine discrimination were low and not different between smokers and non-smokers (median thresholds of 3 versus 2 microg/kg and approximate blood levels of 2.6 versus 1.6 ng/ml, respectively). Thresholds were similar between descending and ascending order subgroups. Several subjective responses differentiated threshold dose from the dose just below threshold, particularly in non-smokers. CONCLUSIONS: Threshold doses for nasal spray nicotine discrimination in humans are low, well below the typical nicotine delivery of most cigarette brands, and may not change after long-term smoking exposure.

Administration, Intranasal↗
PubMed2001

Quitting cigarette smoking produces minimal loss of chronic tolerance to nicotine.

RATIONALE: Long-term exposure to nicotine is associated with chronic tolerance to its acute effects, adaptation that may lead to tobacco dependence. The time course for loss of this tolerance after cessation of exposure is not known in humans but could relate to risk of smoking relapse. OBJECTIVES: We examined changes in responses to nicotine as a function of days, weeks, or years of smoking cessation in formerly dependent smokers to determine at what point sensitivity to nicotine is reinstated (i.e., loss of tolerance). METHODS: Acute subjective, cardiovascular, performance, and reinforcing (self-administration) effects of nicotine nasal spray (0-20 microg/kg) were assessed prospectively in men and women smokers before and then day-by-day (study 1) or 3 weeks (study 2) after stopping smoking. A smoking resumption period (study 1) and a group of non-quitting smokers (study 2) were included to control for the passage of time. These effects were also compared cross-sectionally between those who had quit for 1-4 years and those who had for 6-19 years in a separate sample of long-time ex-smokers to determine whether lengthier abstinence causes greater loss of tolerance (study 3). RESULTS: No clear loss of tolerance was observed on any measure in studies 1 or 2, suggesting that chronic tolerance is fully maintained for at least weeks after quitting smoking. Sensitivity to nicotine's effects was also not different as a function of years quit in study 3. CONCLUSIONS: Chronic tolerance to nicotine is not lost within several weeks of quitting smoking and may not change even after years of abstinence from tobacco use.

Administration, Intranasal↗
PubMed2001

Dissociation of nicotine tolerance from tobacco dependence in humans.

Chronic functional tolerance to nicotine generally is believed to be associated with processes responsible for tobacco dependence. The dose-related effects of nicotine (0-20 microg/kg by nasal spray) on subjective, cardiovascular, and performance responses were compared among four groups varying in current or past dependence: dependent smokers (21 cigarettes per day for 20 years; n = 45), nondependent smokers (three cigarettes per day for 14 years; n = 12), former dependent smokers (mean of 7 years quit after smoking 25 cigarettes per day for 19 years; n = 17), and life-long nonsmokers (n = 19). Chronic tolerance was determined by a shift to the right, or flattening, of the dose-response curve relative to the curve for nonsmokers. Responses were corrected for plasma nicotine concentration to rule out dispositional tolerance. Chronic tolerance was observed for most subjective responses, but little or none for cardiovascular and performance effects. Tolerance was substantial and virtually identical between dependent and nondependent smokers, whereas tolerance of former smokers was intermediate between nonsmokers and dependent smokers. Identical chronic tolerance between dependent and nondependent smokers indicates that tolerance is not a linear function of smoking exposure and does not require presence of dependence. Thus, the wide variability in daily smoking rate among smokers cannot be attributed to differences in tolerance and must involve other processes of adaptation to nicotine. The modest reversal of tolerance in long-time former smokers suggests that such tolerance reversal is either limited or extremely slow after extended abstinence, despite loss of dependence. These results suggest there is no close link between nicotine tolerance and dependence and question the utility of tolerance as one of the criteria for defining dependence.

Adult↗