Profile and management of acute coronary syndromes at primary- and secondary-level healthcare facilities in Cape Town.

BACKGROUND: Little is known about the clinical profile and management of patients with acute coronary syndromes (ACS) in the South African public sector. METHODS: We conducted a retrospective study of patients presenting with ACS to a secondary-level healthcare facility in Cape Town during a one-year period to study the clinical profile and management of these patients. RESULTS: Among the 214 patients in this cohort, 48 (27.5%) had ST-segment elevation myocardial infarction (STEMI), 43 (24.7%) had non-ST-segment elevation myocardial infarction and 83 (47.7%) unstable angina pectoris. We identified high rates of >12-hour delays in first medical contact after symptom onset (46%) and inaccurate ECG diagnosis of STEMI (29.2%), which were associated with low rates of thrombolysis (39.6%). High rates of non-adherence and ACS recurrence were also observed. CONCLUSION: To address the local challenges in ACS management highlighted in this study, we propose the development of a regional referral network prioritising access to expedited care and primary reperfusion interventions in ACS.

International normalised ratio control in a non-metropolitan setting in Western Cape Province, South Africa.

BACKGROUND: The quality of international normalised ratio (INR) control determines the effectiveness and safety of warfarin therapy. Data on INR control in non-metropolitan settings of South Africa (SA) are sparse. OBJECTIVES: To examine the time in therapeutic range (TTR) and its potential predictors in a sample of Garden Route District Municipality primary healthcare clinics (PHCs). METHODS: INR records from eight PHCs were reviewed. The TTR and percentage of patients with a TTR >65% were determined. A host of variables were analysed for association with TTR. RESULTS: The median (interquartile range (IQR)) age of the cohort (N=191) was 56 (44 - 69) years. The median (IQR) TTR was 37.2% (20.2 - 58.8); only 17.8% of patients had a TTR ≥65%. Compared with patients aged >50 years, those aged <50 had worse INR control (median (IQR) TTR 26.6% (16.1 - 53.0) v. 43.5% (23.5 - 60.1); p=0.01). Patients hospitalised for any reason during the study period had worse INR control than patients not hospitalised (median (IQR) TTR 26.2% (16.2 - 50.2) v. 42.9% (23.5 - 62.0); p=0.02). On multivariable regression analysis, participants on warfarin for atrial fibrillation/flutter had better INR control than those with other indications for warfarin (odds ratio 2.21; 95% confidence interval 1.02 - 4.77; p=0.04), but the control was still very poor. CONCLUSIONS: INR control, as determined by TTR and proportion of TTR ≥65%, in these non-metropolitan clinics was poor. Age and hospitalisation as a marker of illness predicted poor control. There was a difference in control between groups, depending on the indication for warfarin. Evidence-based measures to improve the quality of INR control in patients on warfarin therapy need to be instituted as a matter of urgency.

Prognostic value of NT-proBNP for myocardial recovery in peripartum cardiomyopathy (PPCM).

INTRODUCTION: Peripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure worldwide. Although a significant number of women recover their left ventricular (LV) function within 12 months, some remain with persistently reduced systolic function. METHODS: Knowledge gaps exist on predictors of myocardial recovery in PPCM. N-terminal pro-brain natriuretic peptide (NT-proBNP) is the only clinically established biomarker with diagnostic value in PPCM. We aimed to establish whether NT-proBNP could serve as a predictor of LV recovery in PPCM, as measured by LV end-diastolic volume (LVEDD) and LV ejection fraction (LVEF). RESULTS: This study of 35 women with PPCM (mean age 30.0 ± 5.9 years) had a median NT-proBNP of 834.7 pg/ml (IQR 571.2-1840.5) at baseline. Within the first year of follow-up, 51.4% of the cohort recovered their LV dimensions (LVEDD < 55 mm) and systolic function (LVEF > 50%). Women without LV recovery presented with higher NT-proBNP at baseline. Multivariable regression analyses demonstrated that NT-proBNP of ≥ 900 pg/ml at the time of diagnosis was predictive of failure to recover LVEDD (OR 0.22, 95% CI 0.05-0.95, P = 0.043) or LVEF (OR 0.20 [95% CI 0.04-0.89], p = 0.035) at follow-up. CONCLUSIONS: We have demonstrated that NT-proBNP has a prognostic value in predicting LV recovery of patients with PPCM. Patients with NT-proBNP of ≥ 900 pg/ml were less likely to show any improvement in LVEF or LVEDD. Our findings have implications for clinical practice as patients with higher NT-proBNP might require more aggressive therapy and more intensive follow-up. Point-of-care NT-proBNP for diagnosis and risk stratification warrants further investigation.

The changing landscape of infective endocarditis in South Africa.

BACKGROUND: Little is known about the current clinical profile and outcomes of patients with infective endocarditis (IE) in South Africa (SA). OBJECTIVES: To provide a contemporary and descriptive overview of IE in a representative SA tertiary centre. METHODS: We conducted a retrospective review of the records of patients admitted to Groote Schuur Hospital, Cape Town, between 2009 and 2016 fulfilling universal criteria for definite or possible IE, in search of demographic, clinical, microbiological, echocardiographic, treatment and outcome information. RESULTS: A total of 105 patients fulfilled the modified Duke criteria for IE. The median age of the cohort was 39 years (interquartile range (IQR) 29 - 51), with a male preponderance (61.9%). The majority of the patients (72.4%) had left-sided native valve endocarditis, 14.3% had right-sided disease, and 13.3% had prosthetic valve endocarditis. A third of the cohort had rheumatic heart disease. Although 41.1% of patients with left-sided disease had negative blood cultures, the three most common organisms cultured in this subgroup were Staphylococcus aureus (18.9%), Streptococcus spp. (16.7%) and Enterococcus spp. (6.7%). Participants with right-sided endocarditis were younger (29 years, IQR 27 - 37) and were mainly intravenous drug users (73.3%), and the majority cultured positive for S. aureus (73.3%) with frequent septic pulmonary complications (40.0%). The overall in-hospital mortality was 16.2%, with no deaths in the group with right-sided endocarditis. Predictors of death in our patients were heart failure (odds ratio (OR) 8.16, 95% confidence interval (CI) 1.77 - 37.70; p=0.007) and age >45 years (OR 4.73, 95% CI 1.11 - 20.14; p=0.036). Valve surgery was associated with a reduction in mortality (OR 0.09, 95% CI 0.02 - 0.43; p=0.001). CONCLUSIONS: IE remains an important clinical problem in a typical teaching tertiary care centre in SA. In this setting, it continues to affect mainly young people with post-inflammatory valve disease and congenital heart disease. The in-hospital mortality associated with IE remains high. Intravenous drug-associated endocarditis caused by S. aureus is an important IE subset, comprising ~10% of all cases, which was not reported 15 years ago, and culture-negative endocarditis remains highly prevalent. Heart failure in IE carries a significant risk of death and needs a more intensive level of care in hospital. Finally, cardiac surgery was associated with reduced mortality, with the largest impact in patients with heart failure.

The prognostic significance of the 12-lead ECG in peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure, which appears in previously healthy women towards the end of pregnancy or within five months following delivery. Although the ECG is widely used in clinical practice, its prognostic value has not been established in PPCM. METHODS: We analysed 12-lead ECGs of patients with PPCM, taken at index presentation and follow-up visits at 6 and 12 months. Poor outcome was determined by the composite endpoint of death, readmission, NYHA functional class III/IV or left ventricular ejection fraction (LVEF) of ≤35% at follow-up. RESULTS: This cohort of 66 patients had a median age of 28.59 (IQR 25.43-32.19). The median LVEF at presentation (33%, IQR 25-40) improved significantly at follow-up (LVEF 49%, IQR 38-55, P < 0.001 at 6 months; 52% IQR 38-57, P = 0.001 at 12 months). Poor outcome occurred in 27.91% at 6 months and 41.18% at 1 year. Whereas sinus tachycardia at baseline was an independent predictor of poor outcome at 12 months (OR 6.56, 95% CI 1.17-20.41, P = 0.030), sinus arrhythmia was associated with event free survival (log rank P = 0.013). T wave inversion was associated with an LVEF ≤35% at presentation (P = 0.038), but did not predict poor outcome. A prolonged QTc interval at presentation (found in almost half of the cohort) was an independent predictor of poor outcome at 6 months (OR 6.34, 95% CI 1.06-37.80, P = 0.043). CONCLUSION(S): A prolonged QTc and sinus tachycardia at baseline were independent predictors of poor outcome in PPCM at 6 months and 1 year respectively.

The changing landscape of infective endocarditis in South Africa

Background. Little is known about the current clinical profile and outcomes of patients with infective endocarditis (IE) in South Africa (SA). Objectives. To provide a contemporary and descriptive overview of IE in a representative SA tertiary centre. Methods. We conducted a retrospective review of the records of patients admitted to Groote Schuur Hospital, Cape Town, between 2009 and 2016 fulfilling universal criteria for definite or possible IE, in search of demographic, clinical, microbiological, echocardiographic, treatment and outcome information. Results. A total of 105 patients fulfilled the modified Duke criteria for IE. The median age of the cohort was 39 years (interquartile range (IQR) 29 - 51), with a male preponderance (61.9%). The majority of the patients (72.4%) had left-sided native valve endocarditis, 14.3% had right-sided disease, and 13.3% had prosthetic valve endocarditis. A third of the cohort had rheumatic heart disease. Although 41.1% of patients with left-sided disease had negative blood cultures, the three most common organisms cultured in this subgroup were Staphylococcus aureus (18.9%), Streptococcus spp. (16.7%) and Enterococcus spp. (6.7%). Participants with right-sided endocarditis were younger (29 years, IQR 27 - 37) and were mainly intravenous drug users (73.3%), and the majority cultured positive for S. aureus (73.3%) with frequent septic pulmonary complications (40.0%). The overall in-hospital mortality was 16.2%, with no deaths in the group with right-sided endocarditis. Predictors of death in our patients were heart failure (odds ratio (OR) 8.16, 95% confidence interval (CI) 1.77 - 37.70; p=0.007) and age >45 years (OR 4.73, 95% CI 1.11 - 20.14; p=0.036). Valve surgery was associated with a reduction in mortality (OR 0.09, 95% CI 0.02 - 0.43; p=0.001). Conclusions. IE remains an important clinical problem in a typical teaching tertiary care centre in SA. In this setting, it continues to affect mainly young people with post-inflammatory valve disease and congenital heart disease. The in-hospital mortality associated with IE remains high. Intravenous drug-associated endocarditis caused by S. aureus is an important IE subset, comprising ~10% of all cases, which was not reported 15 years ago, and culture-negative endocarditis remains highly prevalent. Heart failure in IE carries a significant risk of death and needs a more intensive level of care in hospital. Finally, cardiac surgery was associated with reduced mortality, with the largest impact in patients with heart failure

Concussion knowledge and attitudes among amateur South African rugby players

Background: The South African Rugby Union's BokSmart programme currently educates coaches and referees on concussion. Rugby players are often more familiar with their teammates than the coach or referee. Therefore they are well-positioned to play a pivotal role in rugby safety if they have adequate knowledge to identify subtle signs and abnormal behaviour displayed by a concussed teammate. However, no programme focuses on concussion education among South African rugby players and there is a dearth of literature on concussion education programmes among rugby players which could lead to safer return to play (RTP) habits.Objectives: To evaluate South African rugby players' concussion knowledge and attitudes/behaviours regarding RTP following a concussion.Methods: A descriptive, cross-sectional study was used. Participants (n=294) were divided into junior amateur high school (JAHS) (n=216) and senior amateur club (SAC) (n=78) players. The modified RoCKAS-ST questionnaire was used to evaluate their concussion knowledge index (CKI) and concussion attitudes/behaviours index (CAI) regarding RTP.Results: On average, 62% (JAHS) and 60% (SAC) of the CKI questions were answered correctly. JAHS participants correctly identified 66% of concussion symptoms, similarly to the SAC participants (63%), rendering similar (p=0.37) overall CKI scores when comparing the two groups. The CAI questions yielded similar (p=0.98) results between the groups, reporting safe responses in 66% (JAHS) and 67% (SAC) of the items.Discussion and conclusion: Junior and senior South African amateur rugby players lacked approximately one-third of essential concussion knowledge, which may lead to a display of unsafe attitudes/ behaviours to concussion and RTP. Further research is warranted to inform educational programmes on concussion among rugby players

Health; Well-Being and Wellness: an Anthropological Eco-Systemic Approach

More than two decades ago; Fritjof Capra commended - and indeed advocated - a paradigm shift in health science and care. In his book The Turning Point (1982) he talks of a major shift from the preoccupation with micro-organisms to a careful study of the `host organism and its environment'; of `significant attempts to develop a unified approach to the mind/body system' in Western medicine; of `a new holistic paradigm' (as opposed to `the old biomedical paradigm') regarding the problem of health and healing; of `a holistic and humanistic approach to primary care'; and of `a holistic therapy' as opposed to `the traditional biochemical practice of associating a physical disease with a specific physical cause'. Our concern in this article is with the paradigm shift advocated by Capra in this book and the progress that has since been made

Microbial populations associated with commercial bread production.

The microbial ecology of a commercial bread production line was assessed by plate counts and characterization of microbial populations of raw materials, dough, equipment surfaces, air inside the bakery and baked bread. Aerobic plate counts for raw materials were higher than mould counts. Dough samples had high aerobic plate counts, but low mould counts. Mould counts on pre-baking equipment surfaces were lower than those on post-baking equipment surfaces, while aerobic plate counts on equipment surfaces varied. Counts of bacteria and moulds on bread increased during storage at 30 degrees C and moulds predominated over bacteria on air settle plates. Of the 316 bacterial isolates, 50% were Bacillus and 31.6% Micrococcus. Of the 97 mould isolates, 37.1% were Penicillium, 18.6% Aspergillus and 13.4% Cladosporium. Bacillus, Aspergillus and Penicillium were isolated predominantly from baked bread.

The tyrosinase-positive oculocutaneous albinism gene shows locus homogeneity on chromosome 15q11-q13 and evidence of multiple mutations in southern African negroids.

Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotypes are concordant within families, suggesting that there may be more than one mutation at the ty-pos OCA locus. Linkage studies carried out in 41 families have shown linkage between markers in the Prader-Willi/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13 and ty-pos OCA. Analysis showed no obligatory crossovers between the alleles at the D15S12 locus and ty-pos OCA, suggesting that the D15S12 locus is very close to or part of the disease locus, which is postulated to be the human homologue, P, of the mouse pink-eyed dilution gene, p. Unlike caucasoid "ty-pos OCA" individuals, negroid ty-pos OCA individuals do not show any evidence of locus heterogeneity. Studies of allelic association between the polymorphic alleles detected at the D15S12 locus and ephelus status suggest that there was a single major mutation giving rise to ty-pos OCA without ephelides. There may, however, be two major mutations causing ty-pos OCA with ephelides, one associated with D15S12 allele 1 and the other associated with D15S12 allele 2. The two loci, GABRA5 and D15S24, flanking D15S12, are both hypervariable, and many different haplotypes were observed with the alleles at the three loci on both ty-pos OCA-associated chromosomes and "normal" chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

The CEPH consortium linkage map of human chromosome 15q.

The CEPH consortium map of chromosome 15q is presented. The map contains 41 loci defined by genotypes generated from CEPH family DNAs with 45 different probe and restriction enzyme combinations contributed by 10 laboratories. A total of 29 loci have been placed on the map with likelihood support of at least 1000:1. The map extends from 15q13 to 15q25-qter. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 127, 190, and 158 cM, respectively. The largest interval is 21 cM and is between D15S37 and D15S74. The on-average locus spacing is 5.6 cM and the mean genetic distance between the 21 uniquely placed loci is 8 cM.

A steady-state kinetic analysis of the reaction between arginine esterase E-I from Bitis gabonica venom and synthetic arginine substrates and the influence of pH, temperature and solvent deuterium isotope.

1. Using synthetic arginines as substrates, steady-state kinetic studies showed a deviation from Michaelis-Menten kinetics for esterase E-I purified from the venom of Bitis gabonica. Graphical analysis indicated a rate equation of at least a degree of 3:3. 2. pH variation of the kinetic parameters indicated the involvement of groups with pK values of approximately 7 and approximately 9 which had to be in the ionic form for activity. 3. Solvent isotope studies suggested transition states where proton transfer or reorganization was the rate-limiting step of proteolytic catalysis. A single protogenic site was postulated. 4. Temperature effects on the enzymic reaction showed a significant reduction in entropy loss upon formation of the transition state with both esters and extended tail polypeptide-anilides in comparison with the activation entropy for benzoyl-L-arginine p-nitroanilide.

Inactivation of arginine esterase E-I of Bitis gabonica venom by irreversible inhibitors including a water-soluble carbodiimide, a chloromethyl ketone and isatoic anhydride.

1. Esterase E-I from Bitis gabonica was inactivated with irreversible inhibitors which included studies with a water-soluble carbodiimide, an affinity labelling peptide and a mechanism-based inactivator. 2. The reaction with 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide was biphasic and the dominant part followed saturation kinetics. At pH 5.5 a rate constant of 0.4 min-1 for inactive enzyme formation was calculated and a dissociation constant (Ki) of 0.2 M for the enzyme-inhibitor complex. 3. Inactivation with D-Phe-Pro-Arg-chloromethyl ketone indicated a two-step mechanism, for which the reaction parameters at pH 8.0 were determined. The Ki value was 0.2 microM and the inactivation rate was 2.5 min-1. 4. With isatoic anhydride pseudo-first-order kinetics was observed. At pH 8.0 a rate constant of 0.9 min-1 and a Ki of 2.0 mM were obtained. The inactivation of the enzyme was found to be governed by a group in the enzyme showing a pK value of 7.3.

Crystallization and preliminary diffraction analysis of caudoxin and notexin; two monomeric phospholipase A2 neurotoxins.

Two monomeric neurotoxic phospholipases A2 have been crystallized and their diffraction properties characterized. Crystals of caudoxin (from the venom of Bitis caudalis) and notexin (from the venom of Notechis scutatus scutatus) were grown at neutral pH, in the absence of calcium ion, and diffract to a resolution of 2.3 and 1.6 A, respectively.

Deviation from Michaelis-Menten kinetics for esterase E-II from the venom of Bitis gabonica, using synthetic arginine amides as substrates.

Steady state kinetic studies on the reaction between esterase E-II from the venom of Bitis gabonica and the fluorogenic substrates, N-alpha-benzoyl-L-phenylalanyl-L-valyl-L-arginine-4-methylcoumaryl-7-amide and N-alpha-benzoyl-L-arginine-4-methylcoumaryl-7-amide were found to deviate from Michaelis-Menten kinetics. Analysis of algebraic graphs and application of non-linear regression allowed an empirical rate law to be selected. The results revealed a rate equation of at least third degree at pH values above 7.0 and of 2:2 degree in the pH range 6-7. The data were interpreted in terms of a molecular model involving an enzyme with one catalytic site and several auxiliary or regulatory sites which, through cooperative effects, may either activate or inhibit the enzyme. Substrate activation is observed at low substrate values and might follow from an obligatory order of binding involving two of the sites, the modifier substrate molecule binding before the substrate molecule undergoing transformation to products. Inhibitory sites apparently become available only at alkaline pH. The inhibition is only noted at high substrate concentrations and is of the partial type.

Isolation and amino acid sequence of caudoxin, a presynaptic acting toxic phospholipase A2 from the venom of the horned puff adder (Bitis caudalis).

A presynaptic acting toxic phospholipase A2, designated caudoxin, was purified from the venom of Bitis caudalis by a combination of gel filtration and ion-exchange chromatography. The specificity of the enzyme was shown to be of the A2 type. The enzyme contains 121 amino acid residues in a single chain and is cross-linked by seven disulfide bridges. Application of cyanogen bromide cleavage and digestion with trypsin and chymotrypsin yielded peptides providing the necessary overlaps to complete derivation of the sequence. Structural features of caudoxin in relation to other toxic and non-toxic phospholipases A2 are discussed.

Configuration assignments of the amino acid residues and the presence of N-methyldehydroalanine in toxins from the blue-green alga, Microcystis aeruginosa.

The configuration assignment of the alpha-carbon atom of amino acid residues in four toxin variants from Microcystis aeruginosa have been made by stereospecific enzymic transformations. The relative conformation assignment of the beta-carbon atom of beta-CH3-aspartic acid could be made by comparison of the electrophoretic mobility with literature values reported for the authentic compound. The presence of an N-methyldehydroalanine residue, which, due to elimination of methylamine under hydrolytic conditions, previously escaped detection by conventional means, has been confirmed by identification of N-methylalanine in the hydrolysate after reduction of toxin with sodium borohydride.