Browsing by Author "Reuter, Helmuth"
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- ItemAdenosine deaminase activity - more than a diagnostic tool in tuberculous pericarditis(Clinics Cardiv Publishing, 2005-06) Reuter, Helmuth; Burgess, Lesley J.; Carstens, Machteld E.; Doubell, Anton F.Aim: To improve the understanding of factors that influence adenosine deaminase (ADA) activity in large pericardial effusions. Methods: A prospective study was carried out at Tygerberg Academic Hospital, South Africa. Patients underwent echocardiographically guided pericardiocentesis. ADA activity, as well as biochemistry, haematology, cytology, and in some cases, histology, were determined. Human immunodeficiency virus (HIV) status was assessed in all patients. Results: Two hundred and thirty-three patients presented to Tygerberg Hospital with large pericardial effusions requiring pericardiocentesis. Tuberculous pericarditis accounted for 162 effusions (69.5%). An ADA cut-off level of 40 U/l resulted in a test sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic efficiency of 84.0%, 80.0%, 91.0%, 66.0% and 83.0%, respectively. Pericardial exudates with an ADA activity ≥ 40 U/l were associated with increased total leukocyte and neutro - phil counts. Patients with tuberculous pericarditis and ADA ≥ 40 U/l also had increased lymphocyte counts. Pericardial ADA activity < 30 U/l was associated with severe depletion of CD4 cell counts in HIV-positive patients. ADA levels were higher in cases with histological evidence of granulomatous inflammation than in cases with serofibrinous pericarditis. Conclusions: An ADA cut-off level of 40 U/l results in best diagnostic test results. ADA production appears to be influenced by factors associated with the antituberculous immune response.
- ItemBenefit v. risk when using chloroquine in patients with severe COVID-19 disease(Health & Medical Publishing Group, 2020-04-02) Decloedt, Eric H.; Allwood, Brian W.; Parker, Arifa; Koegelenberg, Coenraad F. N.; Blockman, Marc; Taljaard, Jantjie; Reuter, HelmuthENGLISH ABSTRACT: Chloroquine (CQ) is widely advocated as treatment for coronavirus disease 2019 (COVID-19), including the president of the USA publicly supporting the use of hydroxychloroquine (HCQ) as a ‘game-changer’ on the social media platform Twitter. CQ and HCQ are structurally similar, with HCQ having an N-hydroxyl-ethyl side-chain in place of the N-diethyl group. Currently only CQ is being marketed in South Africa. We encourage the development of curative directed therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using appropriate designed trials and regulatory oversight, and caution against the indiscriminate use of CQ or HCQ. Careful patient selection is essential, including assessing prognosis, anticipated benefit and potential harms prior to initiating CQ/HCQ therapy.
- ItemExperience with adjunctive corticosteriods in managing tuberculous pericarditis(Clinics Cardiv Publishing, 2006-10) Reuter, Helmuth; Burgess, Lesley J.; Louw, Vernon J.; Doubell, Anton F.Objectives: To compare the efficacy of intrapericardial corticosteroid therapy to either oral corticosteroid therapy or intrapericardial placebo in addition to closed pericardiocentesis and anti-tuberculous therapy in patients with tuberculous pericarditis. Methods: Patients with large pericardial effusions requiring pericardiocentesis were included. A short-course anti-tuberculous regimen was initiated and patients were randomised to one of three treatment groups: 200 mg intrapericardial triamcinolone hexacetonide; oral prednisone plus intrapericardial placebo; or 5 ml intrapericardial 0.9% saline (placebo). Patients were followed up for at least one year. Results: Fifty-seven patients were included in the study; 21 tested HIV positive (36.8%). Forty (70.0%) had microbiological and/or histological evidence of tuberculosis, and 17 (30.0%) had a diagnosis based on clinical and laboratory data. All patients responded well to initial pericardiocentesis. However, nine patients (16.0%) were lost to follow up. The hospitalisation duration for the steroid groups was shorter than for the placebo group. This difference was not significant. Complications were similar for all arms. Conclusions: Intrapericardial and systemic corticosteroids were well tolerated but did not improve the clinical outcome. The standard six-month regimen was effective regardless of HIV infection. The potential benefits from adjunctive corticosteroids in the management of effusive tuberculous pericarditis could not be demonstrated in this three-year study.
- ItemThe immunopathogenesis and treatment of tuberculous pericardial effusions in a population with a high prevalence of infection with the human immunodeficiency virus(Stellenbosch : University of Stellenbosch, 2005-12) Reuter, Helmuth; Doubell, Anton F.; Burgess, Lesley J.; University of Stellenbosch. Faculty of Health Sciences. Dept. of Medicine. Internal Medicine.Mycobacterium tuberculosis (M. tuberculosis) accounts for more adult deaths than any other infectious agents. The present study included 162 patients with tuberculous pericarditis; 50% of the tuberculous pericarditis patients studied were human immunodeficiency virus (HIV) positive, compared to only 4.2% of patients who presented with non-tuberculous pericardial effusions. A steady year-to-year rise in HIV prevalence was observed in this 6-year study. Although the prognosis of pericardial tuberculosis (TB) is excellent with appropriate medical treatment, untreated pericardial TB has a mortality of 80-85%. It is thus important to diagnose tuberculous pericarditis efficiently. Traditionally, the diagnosis of pericardial TB is established by positive mycobacterial culture and/or histological evidence of necrotising granulomatous inflammation of the pericardium. Our study confirmed the insensitivity of pericardial fluid culture and pericardial biopsy in the diagnosis of pericardial TB, and at the time of clinical decision-making, results were usually not available. To overcome these difficulties, we explored various alternative strategies and this resulted in two diagnostic tools, namely a diagnostic rule and a diagnostic algorithm or classification tree. By means of classification and regression tree analysis, we allocated a weighted diagnostic index to each of five independently predictive features (fever, night sweats, weight loss, serum globulin >40 g/L and peripheral blood leukocyte count <10x109/L). A total diagnostic index of 6 or more corresponded to 82-86% sensitivity and 76-87% specificity for a diagnosis of tuberculous pericarditis. When possible, pericardial fluid should be aspirated to determine adenosine deaminase (ADA) levels and pericardial differential leukocyte counts. Fluid should also be sent for Gram stain and culture. The proposed diagnostic classification tree utilises the independently predictive attributes of pericardial adenosine deaminase levels, pericardial fluid lymphocyte/neutrophil ratios, peripheral leukocyte counts and the HIV status. Applying this prediction model to our entire data set of 233 patients resulted in 96% sensitivity and 97% specificity for the correct diagnosis of tuberculous pericarditis. Generally, patients were critically ill at the time of enrolment; 90% of tuberculous pericarditis presented with echocardiographic features of cardiac tamponade. Echoguided percutaneous pericardiocentesis with an indwelling catheter and intermittent daily aspiration was highly effective and safe. It is likely that the combination of this drainage technique and the early initiation of anti-tuberculous chemotherapy contributed to the almost complete absence of constriction in the patients studied, and our data do not support the routine use of adjunctive corticosteroids in patients with tuberculous pericarditis. Tuberculous exudates result from a Th1 mediated immune response characterised by lymphocyte dominance, significantly elevated levels of gamma-interferon (IFN-γ) and undetectable levels of interleukin-4 (IL-4). IFN-γ levels were not influenced by HIV status in spite of the severely diminished pericardial CD4+ lymphocyte counts observed in this study. It is thus likely that in HIV positive patients IFN-γ production is partly maintained by activated CD8+ T cells, which were significantly elevated in HIV positive patients compared to HIV negative tuberculous pericarditis patients. This finding underlines the importance of IFN-γ in the human immune response against M. tuberculosis. We also demonstrated that the presence of ADA in pericardial fluids reflects the activity of the cellular immune response. Both IFN-γ and ADA can be utilised as sensitive and specific diagnostic tools for pericardial TB.
- ItemIncident tuberculosis disease in patients receiving biologic therapies in the Western Cape, South Africa from 2007 to 2018(BMC (part of Springer Nature), 2019) Du Toit, Tessa; Esterhuizen, Tonya M.; Tiffin, Nicki; Abulfathi, Ahmed A.; Reuter, Helmuth; Decloedt, Eric H.Background: South Africa has one of the highest tuberculosis incidence rates. Biologic disease-modifying antirheumatic drugs are associated with an increased risk of tuberculosis. The objective of this study was to describe the tuberculosis disease incidence rate among public sector patients receiving biologic therapies in the Western Cape Province. Methods: A retrospective, descriptive analysis was undertaken using routine health data collated by the Provincial Health Data Centre from January 2007 (first use of biologic therapy in the Western Cape) to September 2018. Results: We identified 609 patients treated with tumour necrosis factor-alpha (TNF-α) or non-TNF-α biologic therapies. Thirty-seven (37) patients developed tuberculosis after biologic therapy exposure, of whom the majority (78%) had an immune mediated inflammatory disease and the remainder (22%) a haematologic malignancy. The incidence rate of tuberculosis per 100,000 person-years was 2227 overall [95% confidence interval (CI): 1591, 3037]. Patients treated with TNF-α inhibitors and non-TNF-α inhibitors had estimated incidence rates of 2819 [95% CI: 1669, 4480] and 1825 [95% CI: 1131, 2797], respectively (p = 0.10). Conclusion: Patients exposed to both TNF-α and non-TNF-α biologic therapies may have a higher incidence of tuberculosis disease compared to the background risk of 681 cases per 100,000 per year in the Western Cape.
- ItemIvermectin for COVID-19 : promising but not yet conclusive(Health & Medical Publishing Group, 2021-03) Van Rensburg, Roland; Decloedt, Eric H.; Reuter, Helmuth; Parker, Arifa; Schrueder, Neshaad; Lahri, Sa'adIvermectin has been proposed as a potential definitive and prophylactic treatment for COVID-19. Ivermectin is an anthelmintic drug that is usually indicated for filarial and resistant scabies infections, but has been shown to have antiviral activity and anti-inflammatory activity in vitro.[2,3] Ivermectin has the potential to be a promising directed therapy in the drug armamentarium against COVID-19, as it has been shown to have in vitro activity against SARS-CoV-2. Several randomised controlled trials (RCTs) and observational studies have reported on the effectiveness and safety outcomes of ivermectin in COVID-19.[1,5] These data are very promising, showing large treatment effects and acceptable adverse effect profiles for ivermectin against COVID-19, especially when combined in metaanalyses.
- ItemThe management of tuberculous pericardial effusion : experience in 233 consecutive patients(Clinics Cardiv Publishing, 2007-02) Reuter, Helmuth; Burgess, Lesley J.; Louw, Vernon J.; Doubell, Anton F.Aim: We report on the 30-day and one-year outcome of consecutive effusive pericarditis patients, including those with tuberculous pericarditis, over a six-year-period. Methods and Results: Patients with large pericardial effusions requiring pericardiocentesis were included in the study after having given written informed consent. Clinical and radiological evaluations were followed by echo-guided pericardiocentesis, and extended daily intermittent drainage via an indwelling pigtail catheter. A standard short-course anti-tuberculous regimen was initiated. A total of 233 patients was included. One hundred and sixty-two patients had pericardial tuberculosis (TB), including 118 (73%) with microbiological and/ or histological evidence of TB and 44 (27%) diagnosed on clinical and supportive laboratory data. Over the six-year period, two patients developed fibrous constrictive pericarditis after receiving adjuvant corticosteroid therapy. The 30-day mortality (8.0%) was statistically higher for HIV-positive patients (corresponding mortality 9.9%) than for HIV-negative patients (6.2%; p=0.04). The oneyear all-cause mortality was 17.3%. It was also higher for HIV-positive (22.2%) than for HIV-negative patients (12.3%; p=0.03). Cardiac mortality was equal for HIVpositive and -negative patients. Conclusion: Tuberculous pericardial effusions responded well to closed pericardiocentesis and a six-month treatment of antituberculous chemotherapy. The former was effective and safe irrespective of HIV status.
- ItemNon-allopathic adjuvant management of osteoarthritis by alkalinisation of the diet(AOSIS Publishing, 2015) Van Velden, David P.; Reuter, Helmuth; Kidd, Martin; Muller, F. OttoBackground: Osteoarthritis (OA) is a chronic condition. Nonsteroidal anti-inflammatory drugs recommended for treatment have serious adverse effects. A compelling body of anecdotal evidence alerted the authors to the therapeutic potential of dietary supplementation with Multiforce® (MF) Alkaline Powder for relief of OA symptoms. Aim: The aim of the study was to test the hypothesis that dietary supplementation with MF relieves clinical signs and symptoms of OA of the hands. Setting: The study was done at the MEDSAC hospital in Somerset West, Western Cape, South Africa. Methods: The research was conducted in two stages. An open interventional study (n = 40) confirmed the notion that MF 7.5 g twice daily is likely to be an effective alternative or adjunct for relief of symptoms of OA of the hands. The main study was conducted with 100 eligible, consenting volunteers (aged 47–89 years) according to a randomised, placebo-controlled, crossover design. Study duration was 56 days, 28 days per regimen; crossover to alternate regimens took place on day 28. Results: Compared to placebo, MF intake over 28 days was associated with significant reductions ( p < 0.005) in pain, tenderness and stiffness of interphalangeal and metacarpophalangeal joints of the hand. Confirmation of systemic alkalinisation by MF, which is rich in organic anions in the form of citrate salts, was reflected by a significant and sustained increase in urine pH. Conclusion: A dietary supplement, Multiforce® Alkaline Powder, containing citrate salts which are converted into bicarbonate in vivo, was efficacious and safe as sole therapeutic intervention, significantly attenuating OA-associated signs and symptoms of the hands.
- ItemAn overview of the biological disease modifying drugs available for arthritic conditions in South Africa(Taylor & Francis, 2016) Harmse, Leonie; Reuter, HelmuthENGLISH ABSTRACT: The past decade has seen a major change in the treatment options and strategies for rheumatoid arthritis (RA) and the other immune-mediated arthritic diseases. The disease modifying antirheumatic drugs (DMARDs) are now used in early stages of the disease in order to preserve joint architecture. There are two groups of DMARDs, the small molecules, like methotrexate, and the biological DMARDs, which are frequently referred to as “magic bullets” since they target specific cytokines and immune cells associated with arthritic conditions. They are monoclonal antibodies or fusion proteins designed to bind and inactivate immune targets. Tumour necrosis factor-alpha (TNF-α) plays an important role in the pathogenesis of rheumatoid disorders and is the target of four biological DMARDs, etanercept, infliximab, golimumab and adalimumab. The other biological DMARDs include abatacept, rituximab and tocilizumab and these prevent T-cell costimulation, cause the depletion of mature CD20 positive B cells or prevent the activation of the interleukin-6 receptor molecule, respectively. Ustekinumab, a monoclonal antibody against IL12/IL23 is effective in psoriatic arthritis. Biological agents are indicated when patients do not respond adequately to the traditional DMARDs. Numerous clinical trials have shown that the biological agents reduce joint inflammation and erosive damage, especially when used in combination with methotrexate. Apart from their prohibitive cost, the biological agents are not without potentially serious adverse effects with infections being the main concern. The TNF-α inhibitors increase the risk for tuberculosis and other opportunistic infections, whereas the non-TNF-α immune inhibitors increase the risk for opportunistic viral, fungal and bacterial infections. This review provides an overview of the biological agents currently available in South Africa.
- ItemPentastomiasis (armillifer armillatus infestation)(Health and Medical Publishing Group (HMPG), 2007-10) Du Plessis, Vicci; Birnie, Andrew J.; Eloff, Ivor; Reuter, Helmuth; Andronikou, SavvasPentastomiasis, also known as ‘tongue worm’ infestation or porocephalosis, is a parasitic zoonosis endemic to western and central Africa. In 1847, Pruner described the first human infection by a pentastomid in Cairo. The definitive hosts are snakes and other reptiles, while the intermediate hosts are carnivorous mammals and, rarely, humans. Most cases of human pentastomiasis are caused by two species of pentastomids, both of which have characteristics of arthropods and annelids, viz. Armillifer armillatus and Linguatula serrata.
- ItemThe population pharmacokinetics of meropenem in adult patients with rifampicin-sensitive pulmonary tuberculosis(Frontiers Media S.A., 2021-06) Abulfathi, Ahmed A.; De Jager, Veronique; Van Brakel, Elana; Reuter, Helmuth; Gupte, Nikhil; Vanker, Naadira; Barnes, Grace L.; Nuermberger, Eric; Dorman, Susan E.; Diacon, Andreas H.; Dooley, Kelly E.; Svensson, Elin M.Background: Meropenem is being investigated for repurposing as an anti-tuberculosis drug. This study aimed to develop a meropenem population pharmacokinetics model in patients with pulmonary tuberculosis and identify covariates explaining inter-individual variability. Methods: Patients were randomized to one of four treatment groups: meropenem 2 g three times daily plus oral rifampicin 20 mg/kg once daily, meropenem 2 g three times daily, meropenem 1 g three times daily, and meropenem 3 g once daily. Meropenem was administered by intravenous infusion over 0.5-1 h. All patients also received oral amoxicillin/clavulanate together with each meropenem dose, and treatments continued daily for 14 days. Intensive plasma pharmacokinetics sampling over 8 h was conducted on the 14th day of the study. Nonlinear mixed-effects modeling was used for data analysis. The best model was chosen based on likelihood metrics, goodness-of-fit plots, and parsimony. Covariates were tested stepwise. Results: A total of 404 concentration measurements from 49 patients were included in the analysis. A two-compartment model parameterized with clearance (CL), inter-compartmental clearance (Q), and central (V1) and peripheral (V2) volumes of distribution fitted the data well. Typical values of CL, Q, V1, and V2 were 11.8 L/h, 3.26 L/h, 14.2 L, and 3.12 L, respectively. The relative standard errors of the parameter estimates ranged from 3.8 to 35.4%. The covariate relations included in the final model were creatinine clearance on CL and allometric scaling with body weight on all disposition parameters. An effect of age on CL as previously reported could not be identified. Conclusion: A two-compartment model described meropenem population pharmacokinetics in patients with pulmonary tuberculosis well. Covariates found to improve model fit were creatinine clearance and body weight but not rifampicin treatment. The final model will be used for an integrated pharmacokinetics/pharmacodynamics analysis linking meropenem exposure to early bactericidal activity.
- ItemPsychopathology and coping in recently diagnosed HIV/AIDS patients : the role of gender(Health & Medical Publishing Group, 2003) Olley, Benjamin O.; Gxamza, Faniswa; Seedat, Soraya; Theron, Hugo; Taljaard, Jantjie; Reid, Emile; Reuter, Helmuth; Stein, Dan J.ENGLISH SUMMARY : Background: Although there is growing literature on the psychological responses to and the psychopathology associated with HIV/AIDS, few investigations have focused on the role of gender. This study compared psychiatric morbidity, coping responses, and disability in male and female outpatients recently diagnosed with HIV/AIDS. Method. One hundred and forty-nine patients (44 male, 105 female) with HIV/AIDS (mean ± standard deviation (SD) months since diagnosis 5.8 ± 4.1) attending an infectious diseases clinic at Tygerberg Hospital, Cape Town, were evaluated. Subjects were assessed using the MINI International Neuropsychiatric Interview (MINI), the Carver Brief COPE, and the Sheehan Disability Scale. In addition, negative life events and risk behaviours were evaluated. Results. Fifty-six per cent of patients were diagnosed with a psychiatric disorder, most commonly major depression (34.9%), dysthymic disorder (21.5%), post-traumatic stress disorder (14.8%), and alcohol dependence (10.1%). There were no significant gender differences in the prevalence of mood disorders in the sample. Men, however, were more likely than women to meet diagnostic criteria for alcohol abuse or dependence, and to engage in certain risky sexual behaviours. Women were more likely to suffer from post-traumatic stress disorder, and to use coping strategies of planning and religion to deal with the illness. There were no significant gender differences in disability. Conclusion. Psychiatric disorders are common in recently diagnosed HIV/AIDS patients in South Africa. Clinicians should be aware of the high prevalence of mood disorders in both men and women, and of gender-different responses such as increased alcohol and substance use and more risky sexual behaviour in men.
- ItemThe role of chest radiography in diagnosing patients with tuberculous pericarditis(Clinics Cardiv Publishing, 2005-04) Reuter, Helmuth; Burgess, Lesley J.; Doubell, Anton F.Aim: To describe the abnormalities on chest X-ray (CXR) in patients presenting with tuberculous pericardial effusions. Methods: One hundred and seventy patients presented to Tygerberg Hospital with large pericardial effusions (epi-pericardial separation > 10 mm). All patients had a diagnostic work-up, which included CXR, ECG, two-dimensional echocardiography and HIV serology. Echocardiography was followed by pericardiocentesis and drainage. Pericardial fluid was analysed for adenosine deaminase (ADA), Ziehl Neelsen (ZN) stain, bacterial and mycobacterial cultures. Sputum was sent for ZN stain and mycobacterial cultures. Tuberculous pericardial effusions were diagnosed according to predetermined criteria. Results: The diagnosis of tuberculous pericarditis was made in 53% (n = 90) of patients with pericardial effusions. Forty-one of the subjects (45.5%) were HIV positive. All patients had an enlarged cardiac silhouette and in the majority of cases, the cardiac shadow was globular with distinct margins. The cardiothoracic ratio (CTR) exceeded 0.55 in all patients. The amount of fluid drained correlated with the radiographic finding of cardiac enlargement. Conclusion: In developing countries where TB is very prevalent, CXR plays an important role in the identification of large pericardial effusions. Although sonography will still be required for a definite diagnosis, the results of this study show that CXR is a useful screening tool.
- ItemSpeckle tracking echocardiography in acute lupus myocarditis : comparison to conventional echocardiography(BioScientifica, 2017) Du Toit, Riette; Herbst, Phillip G.; Van Rensburg, Annari; Snyman, Hendrik W.; Reuter, Helmuth; Doubell, Anton F.Aims: Lupus myocarditis occurs in 5–10% of patients with systemic lupus erythematosus (SLE). No single feature is diagnostic of lupus myocarditis. Speckle tracking echocardiography (STE) can detect subclinical left ventricular dysfunction in SLE patients, with limited research on its utility in clinical lupus myocarditis. We report on STE in comparison to conventional echocardiography in patients with clinical lupus myocarditis. Methods and results: A retrospective study was done at a tertiary referral hospital in South Africa. SLE patients with lupus myocarditis were included and compared to healthy controls. Echocardiographic images were reanalyzed, including global longitudinal strain through STE. A poor echocardiographic outcome was defined as final left ventricular ejection fraction (LVEF) <40%. 28 SLE patients fulfilled the criteria. Global longitudinal strain correlated with global (LVEF: r = −0.808; P = 0.001) and regional (wall motion score: r = 0.715; P < 0.001) function. In patients presenting with a LVEF ≥50%, global longitudinal strain (P = 0.023), wall motion score (P = 0.005) and diastolic function (P = 0.004) were significantly impaired vs controls. Following treatment, LVEF (35–47% (P = 0.023)) and wall motion score (1.88–1.5 (P = 0.017)) improved but not global longitudinal strain. Initial LVEF (34%; P = 0.046) and global longitudinal strain (−9.5%; P = 0.095) were lower in patients with a final LVEF <40%. Conclusions: This is the first known report on STE in a series of patients with clinical lupus myocarditis. Global longitudinal strain correlated with regional and global left ventricular function. Global longitudinal strain, wall motion score and diastolic parameters may be more sensitive markers of lupus myocarditis in patients presenting with a preserved LVEF ≥50%. A poor initial LVEF and global longitudinal strain were associated with a persistent LVEF <40%. Echocardiography is a non-invasive tool with diagnostic and prognostic value in lupus myocarditis.
- ItemTuberculous pericarditis and HIV infection in Africa(Health and Medical Publishing Group (HMPG), 2008) Reuter, Helmuth[No abstract available]
- ItemAn unusual case of an unusual bug(Health and Medical Publishing Group (HMPG), 2005-08) Buckley, Philippa; Reuter, HelmuthMany doctors dislike patients presenting with psychiatric symptoms. This may lead to less careful examination and less precise laboratory testing. When routine examinations and tests are declared normal, the patients are medically cleared, and many diseases are missed. The patient is rapidly referred to a psychiatrist who may inappropriately treat for a non-existent psychiatric disorder. To avoid diagnostic disasters, it is essential to remember that psychiatric and behavioural symptoms are nonspecific. Other causes must be excluded before any psychiatric treatment begins.