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G van der Spuy

Publications and source records attributed to G van der Spuy.

10 recordsLinked to original sources
PubMed2006

Spoligotype signatures in the Mycobacterium tuberculosis complex.

Evolution of the direct repeat region in Mycobacterium tuberculosis has created unique spoligotype signatures specifically associated with IS6110-defined strain families. Spoligotyping signatures may enable the analysis of the strain population structure in different settings and will enable the rapid identification of strain families that acquire drug resistance or escape protective immunity in drug and vaccine trials.

Bacterial Typing Techniques↗
PubMed2006

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↗
PubMed1999

DNA fingerprinting and molecular epidemiology of tuberculosis: use and interpretation in an epidemic setting.

Tuberculosis (TB) is still a major cause of morbidity and mortality. It is clear that control requires more than simple availability of antibiotics. In order to gain insight into the disease, DNA fingerprinting has been applied to the study of bacterial population structure. This technology has been used to quantitate various components of the disease in a high-incidence community, viz. recent transmission (RT) and reactivation (RA) and to monitor these over time as a tool to quantitate changes in the epidemic. In our high-incidence community, we find unexpectedly high strain diversity, lower than predicted RT, and that reactivation disease dominates. This technology can be used to examine and challenge traditional dogmas. Quantitative measure of RT varies over time, using a two-year sliding window for estimation as a useful period. The results show that the "epidemic" consists of subepidemics characterized by strain families that wax and wane in the community of TB patients. The technology is shown to be a useful and quantitative tool to assess disease status and can therefore be used to monitor intervention strategies and refine and monitor results of new control measures.

DNA Fingerprinting↗
PubMed1995

Transferrin C2 and Alzheimer's disease: another piece of the puzzle found?

A significant increase in the occurrence of the transferrin C2 genetic subtype has been found in patients with Alzheimer's disease. This variant has previously been linked to diseases thought to be associated with free radical damage. We hypothesize that Alzheimer's disease is caused by free radical damage to membranes of endocytic vesicles due to defective binding of iron and aluminium by Tf C2. The aluminium binds to the membranes, creating pores, while the iron reacts with H2O2 and superoxide radicals produced by activated microglia (brain phagocytes), to produce hydroxyl radicals (oxidative toxins), which attack the fatty acids in the membranes through these pores. In order to treat the disease successfully, it would be necessary to alleviate the multiple deficiencies caused by these toxins by constantly providing the cells with antioxidants and other essential nutrients. In addition, a drug that would stimulate the regrowth of neurons is needed.

Aluminum↗
PubMed1995

Gas exchange indices--how valid are they?

OBJECTIVE: This study examined the arterial-alveolar oxygen tension difference (AaDO2), arterial oxygen tension to inspired oxygen fraction ratio (PaO2/FiO2) and alveolar to arterial oxygen tension ratio (PAO2/PaO2) with regard to: (i) their correlation with the calculated pulmonary shunt in critically ill patients; and (ii) the influence of the inspired oxygen fraction on these indices before, during and after general anaesthesia. DESIGN: This study comprised two sections: (i) retrospective analyses of blood gas data retrieved from the intensive care computerised database; and (ii) analyses of arterial blood gases before, during and after abdominal and orthopaedic surgery in patients subjected to various inspired fractions of oxygen. SETTING: The study was conducted at an academic hospital. PATIENTS: The first section of the study was a retrospective analysis of blood gases retrieved from a computerised database from the surgical and respiratory intensive care units. Blood gases which indicated hypoxaemia (arterial haemoglobin saturation less than 90%) were collected from patients who suffered from adult respiratory distress syndrome. The calculated pulmonary shunt was correlated with the AaDO2, PaO2/FiO2 and PAO2/PaO2. In the second section of this study, 15 patients of American Society of Anesthesiologists status 1, scheduled to undergo peripheral orthopaedic and intra-abdominal surgery, were exposed to various concentrations of inspired oxygen before, during and after general anaesthesia. At the end of a 15-minute period of exposure to a particular level of inspired oxygen (which was varied at random), arterial blood gases were analysed. A correlation was attempted between the inspired oxygen fraction and the various indices of pulmonary gas exchange. INTERVENTION: Patients were subjected to the various inspired fractions of oxygen before, during and after general anaesthesia. A radial artery cannula, inserted under local anaesthesia, allowed the researchers to collect arterial blood gas analysis. RESULTS: The correlation between the calculated pulmonary shunt and indices of gas exchange showed r = 0.35 for the AaDO2, r = 0.08 for the PaO2/FiO2 and r = 0.40 for the PAO2/PaO2. Stepwise variable selection demonstrated that the FiO2, PaCO2, PAO2 and shunt were the main components of the final models. The inspired oxygen fraction had an effect on the indices of gas exchange inasmuch as they all varied directly with the change in inspired oxygen concentration. Furthermore, the slope of this relationship was less steep during anaesthesia than in the case of values obtained before and after anaesthesia. CONCLUSIONS: The so-called non-invasive indices of pulmonary gas exchange do not correlate well with the calculated pulmonary shunt, which is regarded as the gold standard that reflects the various components of gas exchange. We speculate that the poor performance of these indices can be explained by the fact that they do not take into account the mixed venous saturation and, except for the alveolar to arterial oxygen tension ratio, ignore the effects of alveolar ventilation. The effect of the inspired oxygen fraction on these ratios makes them difficult to interpret if similar inspired oxygen fractions are not used. The effect of the FiO2 on these indices could possibly be explained by the denitrogenation and collapse of alveoli with low ventilation perfusion ratios. The change in the slope of the FiO2 and the indices that was demonstrated during anaesthesia could possibly be explained by the expected change in the mixed venous saturation that occurs during anaesthesia.

Adult↗
PubMed1994

Effect of amygdaloid kindling on rat striatal dopamine D1- and D2-receptors.

The effect of kindling on dopaminergic (DA) neurotransmission was assessed by measuring dopamine D1- and D2-receptor binding in the dorsal and ventral striatum of rats either 2 hours (short-term) or 3-4 weeks (long-term) after the last kindled seizure. Kindling did not have any significant long-term effect on DA D2-receptor Kd or Bmax values in the dorsal or ventral striatum or on DA D1-receptor parameters in the dorsal striatum. The short-term effect of kindled seizures was to abolish the asymmetry in DA D2-receptor density observed in the dorsal striatum of control rats. DA D1-receptor density was also increased in the dorsal striatum contralateral to the kindled amygdala of short-term rats. The short-term effects support the notion that limbic seizures can modify the lateral imbalance of DA activity in the striatum.

Amphetamine↗
PubMed1992

Effect of amygdaloid kindling on [3H]dopamine and [14C]acetylcholine release from rat prefrontal cortex and striatal slices.

The involvement of the dopaminergic (DA) systems in the control of limbic kindled seizures is ill defined. The effects of kindling on DA activity may have been overlooked in the past, because of its subtle unilateral occurrence and/or the variance of the endogenous imbalance of DA activity in normal animals. In the present study rats were screened for their endogenous DA imbalance using amphetamine-induced rotational behaviour. Electrical or sham kindling was applied in the hemisphere with the higher endogenous DA activity. Sections of the bilateral prefrontal cortex and dorsal and ventral striatum were dissected either 2 hours or 21 days after the final seizure and the electrically stimulated release of [3H]DA and [14C]acetylcholine (ACh) determined. Release was also measured in the presence of quinpirole or sulpiride to assess the activity of pre- and postsynaptic DA D2-receptors. Long-term effects of kindling consisted of facilitation of ACh release in the ventral striatum contralateral to the kindled amygdala and bilateral depression of DA release in the prefrontal cortex. Kindling therefore produced area specific changes in neurotransmitter systems giving rise to increased pro-convulsive cholinergic activity in the ventral striatum and decreased anti-convulsive dopaminergic activity in the prefrontal cortex.

Acetylcholine↗