Outcomes of In-Patient admissions of children with intellectual and developmental disabilities to a specialized unit in Cape Town

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of MSc Child Health - Neurodevelopmental option. 2017.Children with intellectual and developmental disabilities are often hospitalized for management of challenging behaviour. A recent international trend is the development of specialized units for the containment, assessment and management of such challenging behaviours. A retrospective folder review was undertaken for children admitted to one such unit in Cape Town, South Africa, and the outcomes of these admissions were investigated. The results show that the majority of children admitted to this unit had poor socio-economic circumstances and limited access to community resources. They were admitted for either assessment or respite care. Of those admitted for assessment, improvements were recorded within all behavioural topographies, with the most improvement in destructive behaviours and the least improvement in stereotypy. Improvements were also recorded for basic skills. Neither the presence of autism spectrum disorder, nor pharmacologically controlled epilepsy, had an influence on outcomes. This is a first step towards establishing evidence-based treatment models for this population.LG201

Comparison of the composition and opsonic activities of imported and South African-manufactured intravenous and intramuscular immunoglobulin preparations

We compared the composition and opsonic activities for two common microbial pathogens (Staphylococcus aureus and Streptococcus pyogenes) of various imported intravenous (IV) (Sandoglobulin, Octagam and Gammagard) and intramuscular (IM) (Beriglobin and Globuman Berna) immunoglobulin (Ig) preparations with those of the corresponding locally manufactured products, Polygam (IV) and Intragam (IM). When tested at equivalent concentrations (1 g/1 00 ml) the total IgG and IgG subclass concentrations of the various IV and IM preparations were similar. All the test preparations (IV and IM) possessed similar opsonic activity for S. aureus and S. pyogenes. These findings demonstrate that, in respect of IgG content and protective biological activity, Intragam and Polygam, the locally manufactured IM and IV Ig preparations, respectively, compared extremely favourably with the corresponding imported products

Pharmacological control of neutrophil-mediated inflammation: Strategies targeting calcium handling by activated polymorphonuclear leukocytes

Unlike most other effector cells of the innate, as well as the adaptive immune systems, the neutrophil is a relatively undiscerning aggressor with scant regard for damage limitation. Although this highly combative, professional phagocyte has become increasingly implicated in the immunopathogenesis of many acute and chronic inflammatory disorders, of both infective and noninfective origin, effective pharmacological strategies to counter neutrophilaggression have remained elusive. Activation of neutrophils results in rapid mobilization of both stored and extracellular Ca2+, resulting in abrupt, usually transient increases in cytosolic Ca2+, which precede, and are a prerequisite for activation of the Ca2+-dependent pro-inflammatory activities of these cells. Mobilization of Ca2+ by, and restoration of Ca2+ homeostasis to activated neutrophils are multistep processes which present a number of potential targets, some well recognized and others noveland unconventional, for the pharmacological control of neutrophil-mediated inflammation. Uncovering these targets represents the primary focus of this review

Effect of smoking on acute phase reactants, stress hormone responses and vitamin C in pulmonary tuberculosis

Background: Chronic inflammation, possibly exacerbated by cigarette smoking, is considered to be the primary cause of pulmonary damage in patients with tuberculosis (TB). However, the mechanisms which underpin these harmful inflammatory responses, have not been well documented.Objectives: The current study was undertaken to determine possible associations between systemic biomarkers of inflammation (acute phase reactants, stress hormones, leukocyte vitamin C) and smoking status in patients (n=71, 20 smokers) with newly-diagnosed pulmonary TB presenting at a tertiary hospital, Johannesburg, South Africa.Methods: Plasma concentrations of C-reactive protein (CRP), ferritin, cortisol, epinephrine, norepinephrine, dopamine and leukocyte vitamin C were measured using a combination of immunonephelometric, radioimmunoassay, immunochromatographic and spectrophotometric procedures. Demographic, clinical and laboratory data was captured and analysed by parametric and non-parametric analyses where appropriate.Results: Smokers were predominantly males (P<0.0001), of older age (P<0.0003) with a significantly lower body mass index (P<0.03). Plasma levels of CRP, ferritin and dopamine were higher in the group of smokers in the setting of lower levels of epinephrine, and leukocyte vitamin C, with CRP and vitamin C attaining statistical significance (P<0.04 and P<0.02 respectively). Those of cortisol and norepinephrine were comparable to those of non-smokers, as were radiographic changes and clinical indices of disease activity.Conclusion: Cigarette smoking is associated with an exaggerated systemic inflammatory response in pulmonary TB in the setting of decreased concentrations of leukocyte vitamin C. Although no significant associations with radiographic changes and most clinical indices of disease activity were evident on presentation, these pro-inflammatory interactions may have prognostic significance.Keywords: Catecholamines, C-reactive protein, ferritin, Mycobacterium tuberculosis, leukocyte vitamin

Harmful interactions of non-essential heavy metals with cells of the innate immune system

In trace amounts, some heavy metals are essential for optimum health, while exposure to others, which are non-essential, presents the potential hazard of acute or chronic organ toxicity. Cadmium, mercury, lead, vanadium, platinum and palladium are commonly encountered, non-essential heavy metals which mediate their toxic activities by various mechanisms. All have the potential to interact with extracellular and intracellular protein sulfhydryls, rendering them not only potentially allergenic, but also predisposing to oxidative stress, while displacement of essential elements from their protein carriers may result in deficiency disorders. In addition, several of these metals, especially cadmium, palladium, platinum, and vanadium interact pro-oxidatively with the phagocytic cells of the innate immune system, potentiating the reactivity and toxicity of phagocyte-derived reactive oxygen species. This review is focused on the pro-oxidative/pro-inflammatory interactions of non-essential heavy metals with the cells of the innate immune system, a somewhat under-appreciated mechanism of metal induced toxicity.This article was originally published in a special issue, Heavy Metal Toxicity handled by Editor(s). Dr. Noreen Khan-Mayberry, National Aeronautics & Space Administration at Lyndon B. Johnson Space Center in Houston, USAhttp://http://www.omicsonline.org/jcthome.phpam201

Protein kinase C promotes restoration of calcium homeostasis to platelet activating factor-stimulated human neutrophils by inhibition of phospholipase C

<p>Abstract</p> <p>Background</p> <p>The role of protein kinase C (PKC) in regulating the activity of phospholipase C (PLC) in neutrophils activated with the chemoattractant, platelet-activating factor (PAF, 20 and 200 nM), was probed in the current study using the selective PKC inhibitors, GF10903X (0.5 - 1 μM) and staurosporine (400 nM).</p> <p>Methods</p> <p>Alterations in cytosolic Ca²⁺, Ca²⁺influx, inositol triphosphate (IP₃), and leukotriene B₄production were measured using spectrofluorimetric, radiometric and competitive binding radioreceptor and immunoassay procedures, respectively.</p> <p>Results</p> <p>Activation of the cells with PAF was accompanied by an abrupt increase in cytosolic Ca²⁺followed by a gradual decline towards basal levels. Pretreatment of neutrophils with the PKC inhibitors significantly increased IP₃production with associated enhanced Ca²⁺release from storage vesicles, prolongation of the peak cytosolic Ca²⁺transients, delayed clearance and exaggerated reuptake of the cation, and markedly increased synthesis of LTB₄. The alterations in Ca²⁺fluxes observed with the PKC inhibitors were significantly attenuated by U73122, a PLC inhibitor, as well as by cyclic AMP-mediated upregulation of the Ca²⁺-resequestering endomembrane ATPase.</p> <p>Taken together, these observations are compatible with a mechanism whereby PKC negatively modulates the activity of PLC, with consequent suppression of IP₃production and down-regulation of Ca²⁺mediated pro-inflammatory responses of PAF-activated neutrophils.</p> <p>Conclusion</p> <p>Although generally considered to initiate and/or amplify intracellular signalling cascades which activate and sustain the pro-inflammatory activities of neutrophils and other cell types, the findings of the current study have identified a potentially important physiological, anti-inflammatory function for PKC, at least in neutrophils.</p

Practical approach to diagnosis and management of primary immunodeficiency diseases

The occurrence of primary immunodeficiency diseases (PIDs) is low compared to that of immune-mediated disorders of autoimmune or atopic origin. However, progress in basic and clinical immunology over the past 3–4 decades has facilitated not only improved detection of PIDs, but has also created an awareness of an expanding spectrum of these conditions. Given that those who suffer from the most severe types of PID experience life-threatening microbial and viral infections usually from an early age, prompt recognition and definitive diagnosis enable implementation of appropriate prophylaxis and therapy, and, most importantly, corrective, immunorestoration using allogeneic haematopoietic stem cell transplantation. The purpose of the current review is therefore to alert family physicians to the presentation and types of PID that they may encounter in clinical practice, as well as to immunological screening procedures that can be undertaken to confirm or exclude the existence of the most common types of PID. This is followed by a consideration of prophylactic and therapeutic options and, finally, by a brief overview of gene therapy and gene-editing strategies that may offer alternatives to, or eventually replace, stem cell therapy.http://www.safpj.co.za/index.php/safpjhttp://www.tandfonline.com/loi/ojfp20am2019Immunolog

Acute phase proteins and stress hormone responses in patients with newly diagnosed active pulmonary tuberculosis

INTRODUCTION : Despite the high burden of disease, there have been surprisingly few studies of the acute phase and plasma catecholamine/cortisol stress hormone responses in patients with active pulmonary tuberculosis. We wished to document acute phase reactant and stress hormone responses in patients with newly diagnosed, active pulmonary tuberculosis and to compare these responses to those of a group of surgical/medical cases with conditions other than tuberculosis. METHODS : This was a prospective study of consecutive patients with newly diagnosed pulmonary tuberculosis, admitted to a tertiary hospital in Johannesburg, South Africa, documenting demographic, clinical, routine laboratory, acute phase protein and stress hormone responses relative to those of the control group. RESULTS : TB patients had a higher body temperature and pulse rate, as well as a platelet counts, ferritin, CRP and dopamine levels, with a tendency to higher cortisol levels compared to the control group. Conversely, they had a lower BMI, haemoglobin, leucocyte count, MCV and epinephrine levels than the control group. CONCLUSIONS : Patients with active pulmonary tuberculosis were documented to mount an acute stress response which was more intense than that of a control group of patients with surgical/medical conditions other than tuberculosis.National Research Foundation of South Africahttp://link.springer.com/journal/4082016-02-28hb201

Montelukast: More than a Cysteinyl Leukotriene Receptor Antagonist?

The prototype cysteinyl leukotriene receptor antagonist, montelukast, is generally considered to have a niche application in the therapy of exercise- and aspirin-induced asthma. It is also used as add-on therapy in patients whose asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the combination of a long-acting β(2)-agonist and an inhaled corticosteroid. Recently, however, montelukast has been reported to possess secondary anti-inflammatory properties, apparently unrelated to conventional antagonism of cysteinyl leukotriene receptors. These novel activities enable montelukast to target eosinophils, monocytes, and, in particular, the corticosteroid-insensitive neutrophil, suggesting that this agent may have a broader spectrum of anti-inflammatory activities than originally thought. If so, montelukast is potentially useful in the chemotherapy of intermittent asthma, chronic obstructive pulmonary disease, cystic fibrosis, and viral bronchiolitis, which, to a large extent, involve airway epithelial cell/neutrophil interactions. The primary objective of this mini-review is to present evidence for the cysteinyl leukotrien–independent mechanisms of action of montelukast and their potential clinical relevance