Optimising Asthma Care

The dawn of the new millennium held much promise for medicine – especially for chronic disorders such as hypertension, diabetes mellitus and asthma. Major clinical trials had been published, new therapies developed and the unraveling of pathogenetic mechanisms had opened our minds to a molecular network tantamount to a medical revolution. The next quantum leap that doctors had to make was to embrace this knowledge and transform medical practice: instead of having patients managed sub-optimally such that they remained diseased but rather to optimise treatment to render them “normal"? - through near complete cessation of the pathological processes such that patients are completely asymptomatic and occult target organ damage nullified. This quantum step was not taken. Why? The chronic disorders mentioned above have one thing in common- they're largely invisible. When, you observe a patient, you can't “see"? these diseases. Because of this, they're treated inadequately and patients remain symptomatic with impairment of lifestyle and on-going disease progression. South African Family Practice Vol. 49 (5) 2007: pp.

Pulmonary scar carcinoma in South Africa

Background. The association between lung scarring and the subsequent development of cancer remains controversial. South Africa has one of the highest incidences of tuberculosis in the world, and resultant scarring may predispose to malignancy. The country also carries a very high burden of smoking and smoking-related diseases that may be synergistic in malignant transformation.Objective. To assess the frequency of pulmonary scarring in patients with lung cancer.Methods. All patients with confirmed lung cancer and a staging computed tomography (CT) scan of the chest were included in this 2-year retrospective study. Pulmonary scarring was categorised according to location as present in: (i) the same lobe as the primary tumour, (ii) a different lobe of the same lung, or (iii) the contralateral lung; or (iv) as diffuse. Post-obstructive bronchiectasis and other changes secondary to cancer were considered not to represent scarring.Results. We identified 435 cases of primary lung cancer. In total, 95 patients (21.8%) had CT evidence of pulmonary scarring. Eighty-three of 85 patients (97.6%) had focal scarring in the same lobe as the primary tumour. Of these, 37 (43.5%) also had scarring involving a different lobe of the same lung, whereas only one (1.2%; p<0.001) had scarring isolated to a different lobe of the same lung. Moreover, 21 patients (24.7%) also had scarring of the opposite lung, but only one patient (1.2%; p<0.001) had scarring isolated to the contralateral lung. Ten patients had diffuse scarring, caused by bronchiectasis (n=5), idiopathic pulmonary fibrosis (n=4) and silicosis (n=1).Conclusion. At least one in five patients with lung cancer had scarring, which was significantly more likely to be present in the same lobe as the tumour, suggesting a predisposition to malignancy

Tricyclic antidepressant overdose necessitating ICU admission

Tricyclic antidepressant (TCA) overdose necessitating intensive care unit (ICU) admission remains a significant problem in the Western Cape. In this retrospective study, we reviewed the course of life-threatening TCA overdose in our centre to identify potential prognostic indicators. TCA levels >1 000 ng/ml were associated with QT and QRS prolongation and convulsions. However, no single parameter predicted non-survival. The overall mortalityof TCA overdose was very low. Our findings should encourage clinicians to offer medical care including ICU admission, if necessary, to patients with TCA overdose

Paediatric Bacterial urinary tract infections in the South African context

Thesis (MMed)--Stellenbosch University, 2017.ENGLISH ABSTRACT: Please refer to full text for abstractAFRIKAANSE OPSOMMING: Raadpleeg teks vir opsommin

Functional Evaluation in Respiratory Disorders

Geneeskunde en GesondheidswetenskappeInterne GeneeskundePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

Glucocorticosteroid receptor characteristics of peripheral blood mononuclear cells in oral steroid dependent asthma : utilization of an in vitro model of steroid resistant asthma to investigate mechanisms of resistance and functional consequences of altered receptor affinity.

Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2007.Background: Although glucocorticoids are the most effective treatment for asthma, some patients show a poor response. In such patients with steroid resistant asthma, this has been ascribed to altered glucocorticoid receptor (GR) ligand-binding affinity induced by IL-2 combined with IL-4 or IL-13 alone- all of which can also modulate glucocorticoid function in vitro. Objective: We sought to assess the ligand-binding affinity in a distinct group of oral steroid-dependent asthmatic subjects and examine the mechanisms by which IL-2 and IL-4 (or IL-13) modify the ligand-binding affinity of the GR. Methods: Using dexamethasone-binding assays, we examined PBMCs ex vivo from healthy subjects, subjects with controlled asthma, and oral steroiddependent subjects with severe asthma. In addition, IL-2 and IL-4 were used to alter GR affinity in vitro. We used mediators or inhibitors of signal transduction to investigate the mechanisms of resistance. We also determined cytokine production of PBMC's by means of ELISA. Results: GR ligand-binding affinity was significantly reduced in the nucleus but not in the cytoplasm of oral steroid-dependent asthmatic subjects compared with that seen in steroid-sensitive and healthy subjects (dissociation constant, 41.37 ± 17.83 vs. 25.36 ± 2.63 nmol/L vs. 9.40 ± 4.01 nmol/L, respectively [p<.05 for both in comparison to normals] ). This difference in ligand-binding affinity could be mimicked by IL-2 and IL-4 co-treatment and was blocked by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. PBMC's rendered resistant in vitro demonstrated lower IL-10 and increased GM-CSF production following LPS or PMA & PHA stimulation compared to cells with normal GR affinity. Resistant cells also showed reduced dexamethasone repression of LPSstimulated IL-10 release. These effects were also reversed by SB203580. Inhibition of the ERK MAPK pathway by PD098059 (10 mol/L), phosphoinositol 3 kinase by wortmannin (5 nmol/L) or treatment with IL-10 (10 ng/mL) failed to modulate the effect of IL-2 and IL-4 on receptor affinity. Ro318220 (10 nmol/L), a specific protein kinase C inhibitor and theophylline, similarly, had no effect on affinity. Conclusion: GR ligand binding affinity is tiered; compared to normal subjects; steroid responsive asthmatics have a mild reduction in ligand binding whereas oral steroid dependent asthmatics have greater reductions. When mononuclear cells are rendered resistant in vitro, cytokine production (low IL-10 and high GM-CSF) favours a pro-inflammatory state. Our data do not support the ERK MAPK, phosphoinositol 3 kinase, protein kinase C pathways in steroid resistance. Treatment with IL-10 and theophylline also failed to modulate the effect of IL-2 and IL-4 on receptor affinity. However, P38 MAPK inhibitors may have potential in reversing glucocorticoid insensitivity and re-establishing the beneficial effects of glucocorticoids in patients with severe asthma

Predictors of treatment success in smoking cessation with varenicline combined with nicotine replacement therapy v. varenicline alone

Background. Identification of the predictors of treatment success in smoking cessation may help healthcare workers to improve the effectiveness of attempts at quitting.Objective. To identify the predictors of success in a randomised controlled trial comparing varenicline alone or in combination with nicotine replacement therapy (NRT).Methods. A post-hoc analysis of the data of 435 subjects who participated in a 24-week, multicentre trial in South Africa was performed. Logistic regression was used to analyse the effect of age, sex, age at smoking initiation, daily cigarette consumption, nicotine  dependence, and reinforcement assessment on abstinence rates at 12 and 24 weeks. Point prevalence and continuous abstinence rates were self-reported and confirmed biochemically with exhaled carbon monoxide readings.Results. The significant predictors of continuous abstinence at 12 and 24 weeks on multivariate analysis were lower daily cigarette consumption (odds ratio (OR) 1.86, 95% confidence interval (CI) 1.21 - 2.87, p=0.005 and OR 1.83, 95% CI 1.12 - 2.98, p=0.02, respectively) and older age (OR 1.52, 95% CI 1.00 - 2.31, p=0.049 and OR 1.79, 95% CI 1.13 - 2.84, p=0.01, respectively). There was no difference in the predictors of success in the univariate analysis, except that older age predicted point prevalence abstinence at 12 weeks (OR 1.47, 95% CI 1.00 - 2.15, p=0.049). The findings were inconclusive for an association between abstinence and lower nicotine dependence, older age at smokinginitiation and positive reinforcement.Conclusion. Older age and lower daily cigarette consumption are associated with a higher likelihood of abstinence in patients using varenicline, regardless of the addition of NRT

Effect of accelerators and stabilizers on the formation and characteristics of electroless Ni–P deposits

The effect of thiourea, succinic acid and lead acetate on the formation and characteristics of electroless Ni–P deposits obtained from an acidic hypophosphite reduced electroless nickel bath is addressed in this paper. The rate of deposition of electroless Ni–P coating is found to be a function of concentration of these additives. Thiourea accelerates the rate of deposition up to 0.8 ppm and started to inhibit at a concentration of 1 ppm. Similarly, succinic acid increases the plating rate up to 12 g l−1 and exhibit an inhibiting effect at higher concentrations of the order of 15 g l−1. Addition of lead acetate inhibits the rate of deposition even at a concentration of 0.5 ppm and the extent of inhibition is increased when the concentration is higher than 1 ppm. Addition of these additives also caused a change in phosphorus content of the deposits; lead acetate (1 ppm) tends to increase the phosphorus content whereas thiourea (0.8 ppm) and succinic acid (12 g l−1) tends to decrease the phosphorus content. The X-ray diffraction patterns of electroless Ni–P coatings obtained in the absence of additives and in presence of 1 ppm of lead acetate exhibit a single broad peak centered at 44.5◦ 2θ, indicating the amorphous nature of these coatings. The peak broadening suggests a greater tendency to form amorphous structure when lead acetate is used as the additive. In contrast, for electroless Ni–P coatings obtained from thiourea and succinic acid containing baths, besides the reflection from Ni (1 1 1) plane, a weak reflection from Ni (2 0 0) plane is also observed. The X-ray diffraction patterns of electroless Ni–P coatings after annealing at 400 ◦C for 1 h exhibit the formation of fcc nickel and bct nickel phosphide (Ni3P) phases in all the cases with Ni3P (2 3 1) as the most intense reflection. Electroless Ni–P coatings obtained in presence of thiourea and succinic acid exhibit a nodular feature with a typical cauliflower like structure. The size of the nodules is relatively less in the latter case. In contrast, the electroless Ni–P coating obtained in the absence of additives and in presence of 1 ppm of lead acetate is relatively smooth. However, the deposit obtained in the absence of additives reveals the presence of fine particulates, attributed to the precipitation of Ni3P phases in the absence of stabilizers. The DSC traces of electroless Ni–P coatings exhibit a single well-defined exothermic peak in the temperature range studied in all the cases, which could be attributed to the precipitation of metallic nickel phase and formation of nickel phosphide (Ni3P) phase. The variation in the peak temperature and the energy evolved during the phase transition is due to the slight variation in the phosphorus content caused by the addition of thiourea, succinic acid and lead acetate. The study recommends that the choice of accelerators and stabilizers should be made only after a careful study