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M Bosman

Publications and source records attributed to M Bosman.

12 recordsLinked to original sources

Mapping chemical and bonding information using multivariate analysis of electron energy-loss spectrum images.

Electron energy-loss spectroscopy (EELS) in the transmission electron microscope (TEM) is used to obtain high-resolution information on the composition and the type of chemical bonding of materials. Spectrum imaging, where a full EEL spectrum is acquired and stored at each pixel in the image, gives an exact correlation of spatial and spectral features. However, determining and extracting the important spectral components from the large amount of information contained in a spectrum image (SI) can be difficult. This paper demonstrates that principal component analysis of EEL SIs can be used to extract chemically relevant components. With weighted or two-way scaled principal component analysis, both compositional and bonding information can be extracted. Mapping of the chemical variations in a partially reduced titanium dioxide sample and the orientation-dependent bonding in boron nitride and carbon nanotubes are given as examples.

Journal Article↗

Ethambutol resistance testing by mutation detection.

OBJECTIVE: To identify chromosomal mutations that confer resistance to ethambutol (EMB) in Mycobacterium tuberculosis. DESIGN: Drug-resistant (n = 235) and drug-susceptible (n = 117) M. tuberculosis isolates collected from the Western Cape in South Africa were subjected to embB gene analysis and the results were compared to phenotypic EMB testing. RESULTS: Genotypic analysis identified mutations at codon 306 of the embB gene in 20% (47/235) of the resistant isolates in comparison to only 1.7% (4/235) of those that were phenotypically resistant to EMB by the agar diffusion method. No gene mutations were detected in susceptible isolates. Phenotypic retesting in BACTEC demonstrated that the 47 genotypically resistant isolates were phenotypically resistant to EMB. This implies that 91.4% (43/47) of EMB resistance had been phenotypically missed by routine laboratory procedures. EMB resistance was closely linked to multidrug resistance (MDR); 87.2% (41/47) of the EMB-resistant isolates were resistant to both isoniazid and rifampicin. A newly developed one-step amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method correctly detected the EMB-resistant genotype. CONCLUSION: Implementation of more accurate diagnosis of EMB resistance may enhance patient management in South Africa, as standardised treatment of MDR-TB with second-line drugs is currently dependent on the outcome of the EMB resistance test.

Antitubercular Agents↗

Frequency and implications of pyrazinamide resistance in managing previously treated tuberculosis patients.

OBJECTIVE: To determine the extent of pyrazinamide (PZA) resistance in isolates from previously treated patients from the Western Cape, South Africa. DESIGN: Drug-resistant isolates, isolates resistant to one or more drugs other than PZA (PZA resistance is not routinely determined) (n = 127), and drug-susceptible (n = 47) clinical isolates of Mycobacterium tuberculosis from previously treated patients from the Western Cape were phenotypically (BACTEC MGIT 960) and genotypically (pncA gene sequencing) analysed for PZA resistance. RESULTS: MGIT analysis found that 68 of the 127 drug-resistant isolates were PZA-resistant. Nearly all (63/68) PZA-resistant isolates had diverse nucleotide changes scattered throughout the pncA gene, and five PZA-resistant isolates had no pncA mutations. Of the 47 phenotypically susceptible isolates, 46 were susceptible to PZA, while one isolate was PZA-monoresistant (OR = 53.0, 95% CI = 7.1-396.5). A pncA polymorphism (Thr114Met) that did not confer PZA resistance was also identified. PZA resistance was strongly associated with multidrug-resistant tuberculosis (MDR-TB). CONCLUSION: An alarmingly high proportion of South African drug-resistant M. tuberculosis isolates are PZA-resistant, indicating that PZA should not be relied upon in managing patients with MDR-TB in the Western Cape. A method for the rapid detection of PZA resistance would be beneficial in managing patients with suspected drug resistance.

Antitubercular Agents↗

Establishment and development of the National Tuberculosis Control Programme in Vietnam.

OBJECTIVE: To describe the establishment and development of the National Tuberculosis Control Programme (NTP) of Vietnam. METHODS: Data were obtained from the surveillance system established by the new NTP in 1986 and based on the principles now described as the WHO DOTS strategy. RESULTS: The proportion of districts covered by the NTP increased from 40% in 1986 to almost 100% in 2000. The proportion of communes applying NTP guidelines increased from 18% in 1986 to 99.8% in 2000. The total number of tuberculosis cases notified increased from 8737 in 1986 to 89 792 in 2000. Most of these are new smear-positive cases. Based on WHO estimations of the incidence rate, the proportion of new smear-positive cases detected and put on short-course treatment has been over 70% since 1996. Reported cure rates with short-course chemotherapy are consistently over 85%. CONCLUSIONS: DOTS is feasible in a low-income, high-burden country. The main reasons for success were political commitment, a well-functioning health network, integration of tuberculosis control into the general health service at district level, a continuous supply of drugs and effective external support. Major challenges are long-term financial support, expansion to remote areas and vulnerable groups, definition of the role of the private sector, and future developments of the HIV epidemic and multidrug resistance.

Humans↗

Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis.

Ethionamide (ETA) is an important component of second-line therapy for the treatment of multidrug-resistant tuberculosis. Synthesis of radiolabeled ETA and an examination of drug metabolites formed by whole cells of Mycobacterium tuberculosis (MTb) have allowed us to demonstrate that ETA is activated by S-oxidation before interacting with its cellular target. ETA is metabolized by MTb to a 4-pyridylmethanol product remarkably similar in structure to that formed by the activation of isoniazid by the catalase-peroxidase KatG. We have demonstrated that overproduction of Rv3855 (EtaR), a putative regulatory protein from MTb, confers ETA resistance whereas overproduction of an adjacent, clustered monooxygenase (Rv3854c, EtaA) confers ETA hypersensitivity. Production of EtaA appears to be negatively regulated by EtaR and correlates directly with [(14)C]ETA metabolism, suggesting that EtaA is the activating enzyme responsible for thioamide oxidation and subsequent toxicity. Coding sequence mutations in EtaA were found in 11 of 11 multidrug-resistant MTb patient isolates from Cape Town, South Africa. These isolates showed broad cross-resistance to thiocarbonyl containing drugs including ETA, thiacetazone, and thiocarlide.

Amino Acid Substitution↗

Transdermal nicotine: single dose effects on mood, EEG, performance, and event-related potentials.

A 21-mg dose of nicotine was administered transdermally to 16 overnight smoking-deprived smokers in a double-blind, placebo-controlled design. Mood ratings, electroencephalography (EEG), behavioral performance and event-related potential (ERP: P300) indices of attention and information processing speed were assessed before and 4 h after placebo/nicotine treatment. Although nicotine, relative to placebo, failed to alter mood, it increased absolute and relative power indices of EEG arousal, shortened reaction times, and increased P300 amplitudes. The results are discussed in relation to nicotine's actions on cholinergic transmission and its role in smoking behavior.

Administration, Cutaneous↗

Tuberculosis and the HIV epidemic: increasing annual risk of tuberculous infection in Kenya, 1986-1996.

OBJECTIVES: The purpose of this study was to assess the impact of the increased incidence of tuberculosis (TB) due to HIV infection on the risk of TB infection in schoolchildren. METHODS: Tuberculin surveys were carried out in randomly selected primary schools in 12 districts in Kenya during 1986 through 1990 and 1994 through 1996. Districts were grouped according to the year in which TB notification rates started to increase. HIV prevalence in TB patients and changes in TB infection prevalence were compared between districts. RESULTS: Tuberculous infection prevalence rates increased strongly in districts where TB notification rates had increased before 1994 (odds ratio = 3.1, 95% confidence interval = 2.3, 4.1) but did not increase in districts where notification rates had increased more recently or not at all. HIV prevalence rates in TB patients were 50% in districts with an early increase in notification rates and 28% in the other study districts. CONCLUSIONS: Countries with an increasing prevalence of HIV infection will need additional resources for TB control, not only for current patients but also for the patients in additional cases arising from the increased risk of TB infection.

AIDS-Related Opportunistic Infections↗

Postexercise protein-carbohydrate and carbohydrate supplements increase muscle glycogen in men and women.

We have previously demonstrated that women did not increase intramuscular glycogen in response to an increased percent of dietary carbohydrate (CHO) (from 60 to 75% of energy intake) (M. A. Tarnopolsky, S. A. Atkinson, S. M. Phillips, and J. D. MacDougall. J. Appl. Physiol. 78: 1360-1368, 1995). CHO and CHO-protein (Pro) supplementation postexercise can potentiate glycogen resynthesis compared with placebo (K. M. Zawadzki, B. B. Yaspelkis, and J. L. Ivy. J. Appl. Physiol. 72: 1854-1859, 1992). We studied the effect of isoenergetic CHO and CHO-Pro-Fat supplements on muscle glycogen resynthesis in the first 4 h after endurance exercise (90 min at 65% peak O2 consumption) in trained endurance athletes (men, n = 8; women, tested in midfollicular phase, n = 8). Each subject completed three sequential trials separated by 3 wk; a supplement was provided immediately and 1-h postexercise: 1) CHO (0.75 g/kg) + Pro (0.1 g/kg) + Fat (0.02 g/kg), 2) CHO (1 g/kg), and 3) placebo (Pl; artificial sweetener). Subjects were given prepackaged, isoenergetic, isonitrogenous diets, individualized to their habitual diet, for the day before and during the exercise trial. During exercise, women oxidized more lipid than did men (P < 0.05). Both of the supplement trials resulted in greater postexercise glucose and insulin compared with Pl (P < 0.01), with no gender differences. Similarly, both of these trials resulted in increased glycogen resynthesis (37.2 vs. 24. 6 mmol . kg dry muscle-1 . h-1, CHO vs. CHO-Pro-Fat, respectively) compared with Pl (7.5 mmol . kg dry muscle-1 . h-1; P < 0.001) with no gender differences. We conclude that postexercise CHO and CHO-Pro-Fat nutritional supplements can increase glycogen resynthesis to a greater extent than Pl for both men and women.

Adult↗