60 results on '"M. Grobbelaar"'
Search Results
2. EMERGENCE OF BEDAQUILINE RESISTANCE AFTER COMPLETION OF BEDAQUILINE-BASED DRUGRESISTANT TB TREATMENT: A CASE STUDY FROM SOUTH AFRICA
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M. de Vos, S. Ley, B. Derendinger, A. Dippenaar, M. Grobbelaar, A. Reuter, J. Daniels, S. Burns, G. Theron, J. Posey, R. Warren, and H. Cox
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Infectious and parasitic diseases ,RC109-216 - Published
- 2018
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3. Verskyningsvorme van estetisisme en dekadensie in Sy kom met die sekelmaan en Kaapse rekwisiete
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M. Grobbelaar
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African languages and literature ,PL8000-8844 - Abstract
Manifestations of aestheticism and decadence in Sy kom met die sekelmaan and Kaapse rekwisiete This article offers a new perspective on the novels of two well-known Afrikaans authors, namely Hettie Smit's Sy kom met die sekelmaan (1937) and Wilma Stockenstrom's Kaapse rekwisiete (1987). Both literary works are read within the framework of late nineteenth-century Western European and British aestheticism and decadence. Characteristic elements of aesthetic and decadent literature, such as an emphasis on artificiality - especially the tendency towards the fictionalization of reality narcissism, sexual perversity, and the utilization of a flowery style are identified in both novels. Stockenstrum 's novel can, however, also be read from a feminist point of view, as is already indicated by the fact that everything is seen through the eyes d f a female character, and by the negative projection of male characters and heterosexual relationships. Lefebvre's Jungian-based search for the Self is a further indication of the feminist character of this novel, as the psychological views of Jung with his accent on identity and individualisation form a myth in its own way in feminist literature.
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- 1995
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4. Afskeid en vertrek as dekadente roman
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M. Grobbelaar and H. Roos
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African languages and literature ,PL8000-8844 - Abstract
Most of the arguments advanced in negative critical reviews of Karel Schoeman’s latest novel Afskeid en vertrek lose their validity if this novel is evaluated as a decadent text. Firstly, the vagueness regarding the apparently contemporary South African state of war depicted in this novel is in accordance with the decadent vision of the world, which is characterized by a fundamental rejection of reality. In Afskeid en vertrek the negation of an intolerable world takes the form of solipsism, acting and masquerade in an artificial and aestheticised existence, deviation from conventional heterosexual relationships and especially an escape in language. Secondly, critical remarks on the absence of a dynamic development of plot can be invalidated on the grounds that the static character of the novel and the use of images or "static portraits which interrupt the flow of narrative by halting visions" (Nalbantian, 1983:123) are typical stylistic traits of decadent literature.
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- 1993
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5. ’n Interpretasie van Karel Schoeman se roman, ’n Ander land binne die raamwerk van die laat negentiendeeeuse estetisistiese en dekadente literêre tradisie
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M. Grobbelaar and H. Roos
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African languages and literature ,PL8000-8844 - Abstract
The first motivation for reading Karel Schoeman’s novel ’n Ander land within the framework of late nineteenth century Western European decadcnt literature is the strong resemblance between Schoeman's character Versluis and Des Esseintes, main character of the so-called Bible of Decadence, namely Joris- Karl Huysmans’ A Rebours (1884). Schoeman’s cultivated narrative style, his use of archaic Dutch and French words and the fact that this novel h as 'no story’, confirm the affinity of ’n Ander land with the decadent literary tradition as established by Huysmans’ plotless novel. The ultimate vision communicated in ’n Ander land is that death, like the landscape of Africa, is infinitely empty. The journey of the dying Versluis to Bloemfontein with its emphasis on intense heat and desolation and its affinities with Dante's Divina Commedia can be seen as a symbolic descent into hell, with the suggestion that Versluis will never reach paradise.
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- 1993
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6. Assessing sexual attitudes among adult men: A descriptive survey in Kenya
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D.M. Ndasi, K. Adusei-Asante, M. Grobbelaar, A.V.V. Ha, and V. Fannam Nunfam
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Obstetrics and Gynecology ,Psychology (miscellaneous) - Published
- 2022
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7. Female sex research with men in Kenya: Fieldwork challenges and reflections
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Victor Fannam Nunfam, D.M. Ndasi, M. Grobbelaar, and Kwadwo Adusei-Asante
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Scrutiny ,Resource (biology) ,Policy making ,media_common.quotation_subject ,Reproduction (economics) ,Obstetrics and Gynecology ,Female sex ,Gender studies ,Human sexuality ,Doing gender ,Perception ,Psychology (miscellaneous) ,Sociology ,media_common - Abstract
Summary The sexuality of women during fieldwork with men becomes constantly scrutinised, and sexualised, and the perceptions of others on our sexuality often impinge on sex research processes in patriarchal societies. This paper discusses challenges and conceptual reflections of gender interactions in sex research fieldwork by a woman with men aged 18–54 in Nairobi, Kenya. It also provides insights on practical safety strategies for women conducting sex research fieldwork. The paper draws on the researcher's field notes and reflections on experiences and interactions with gatekeepers and male participants to present brief accounts of challenges of gender interactions in sex research fieldwork. The impact of gender on the well-being of women doing gender interactions sex research during fieldwork in patriarchal societies is particularly salient. The scrutiny on women, women's sexual subjectivities and positioning of their sexuality by men occur more often than may occur with male researchers who research women. The reproduction of sex knowledge is a key aspect of ethical considerations and part of the ethical reproduction of knowledge, which needs to consider difficulties with gender interactions. Hence, this paper is a proposed resource for fieldwork and policy making in programmes that support the sexuality of men.
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- 2022
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8. Relative hypercoagulopathy of the SARS-CoV-2 Beta and Delta variants when compared to the less severe Omicron variants is related to TEG parameters, the extent of fibrin amyloid microclots, and the severity of clinical illness
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Lize M. Grobbelaar, Arneaux Kruger, Chantelle Venter, Este M. Burger, Gert J. Laubscher, Tongai G. Maponga, Maritha J. Kotze, Hau C. Kwaan, Joseph B. Miller, Daniel Fulkerson, Wei Huff, Eric Chang, Grant Wiarda, Connor M. Bunch, Mark M. Walsh, Syed Raza, Mahmud Zamlut, Hunter B. Moore, Ernest E. Moore, Matthew D. Neal, Douglas B. Kell, and Etheresia Pretorius
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Fluorescence microscopy ,Fibrin ,Coagulation ,SDG 3 - Good Health and Well-being ,SARS-CoV-2 ,Microclots ,Omicron ,Variants ,Humans ,COVID-19 ,Hematology ,Cardiology and Cardiovascular Medicine - Abstract
Earlier variants of SARS-CoV-2 have been associated with plasma hypercoagulability (as judged by thromboelastography) and an extensive formation of fibrin amyloid microclots, which are considered to contribute to the pathology of the coronavirus 2019 disease (COVID-19). The newer Omicron variants appear to be far more transmissible, but less virulent, even when taking immunity acquired from previous infections or vaccination into account. We here show that while the clotting parameters associated with Omicron variants are significantly raised over those of healthy, matched controls, they are only raised to levels significantly lower than those seen with more severe variants such as Beta and Delta. We also observed that individuals infected with Omicron variants manifested less extensive microclot formation in platelet poor plasma compared to those harbouring the more virulent variants. The measurement of clotting effects between the different variants acts as a kind of ‘internal control’ that demonstrates the relationship between the extent of coagulopathies and the virulence of the variant of interest. This adds to the evidence that microclots play an important role in determining the severity of symptoms observed in COVID-19.
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- 2022
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9. SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19
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Gert Jacobus Laubscher, Petrus Johannes Lourens, Lize M Grobbelaar, Chantelle Venter, Malebogo Ngoepe, Janami Steenkamp, Etheresia Pretorius, Maré Vlok, and Douglas B. Kell
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Male ,Immunology & Inflammation ,medicine.medical_treatment ,Biochemistry ,fluorescence microscopy ,Fluorescence microscope ,Platelet ,Trypsin ,Lung ,Diagnostics & Biomarkers ,Research Articles ,Fibrin(ogen) ,biology ,Molecular Interactions ,Chemistry ,Fibrinolysis ,spike protein, SARS-CoV-2 ,Complement C3 ,Microfluidic Analytical Techniques ,Middle Aged ,Lytic cycle ,Spike Glycoprotein, Coronavirus ,Female ,Prothrombin ,Adult ,Blood Platelets ,Amyloid ,Protein subunit ,Spike protein Sa ,Biophysics ,Microclot ,Fibrin ,Virology ,medicine ,Humans ,Clinical significance ,Molecular Biology ,Aged ,electron microscopy ,SARS-CoV-2 ,COVID-19 ,Fibrinogen ,Thrombosis ,Cell Biology ,Trypsinization ,Immunology ,biology.protein - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies. One of the most important pathologies, is hypercoagulation and microclots in the lungs of patients. Here we study the effect of isolated SARS-CoV-2 spike protein S1 subunit as potential inflammagen sui generis. Using scanning electron and fluorescence microscopy as well as mass spectrometry, we investigate the potential of this inflammagen to interact with platelets and fibrin(ogen) directly to cause blood hypercoagulation. Using platelet-poor plasma (PPP), we show that spike protein may interfere with blood flow. Mass spectrometry also showed that when spike protein S1 is added to healthy PPP, it results in structural changes to β and γ fibrin(ogen), complement 3, and prothrombin. These proteins were substantially resistant to trypsinization, in the presence of spike protein S1. Here we suggest that, in part, the presence of spike protein in circulation may contribute to the hypercoagulation in COVID-19 positive patients and may cause substantial impairment of fibrinolysis. Such lytic impairment may result in the persistent large microclots we have noted here and previously in plasma samples of COVID-19 patients. This observation may have important clinical relevance in the treatment of hypercoagulability in COVID-19 patients.
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- 2021
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10. SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: Implications for microclot formation in COVID-19
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Petrus Johannes Lourens, Gert Jacobus Laubscher, Lize M Grobbelaar, Malebogo Ngoepe, Etheresia Pretorius, Maré Vlok, Chantelle Venter, Janami Steenkamp, and Douglas B. Kell
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biology ,Chemistry ,medicine.medical_treatment ,Protein subunit ,Fibrin ,Trypsinization ,Lytic cycle ,Fibrinolysis ,Immunology ,medicine ,Fluorescence microscope ,biology.protein ,Platelet ,Platelet-poor plasma - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies. One of the most important pathologies, is hypercoagulation and microclots in the lungs of patients. Here we study the effect of isolated SARS-CoV-2 spike protein S1 subunit as potential inflammagensui generis. Using scanning electron and fluorescence microscopy as well as mass spectrometry, we investigate the potential of this inflammagen to interact with platelets and fibrin(ogen) directly to cause blood hypercoagulation. Using platelet poor plasma (PPP), we show that spike protein may interfere with blood flow. Mass spectrometry also showed that when spike protein S1 is added to healthy PPP, it results in structural changes to β and γ fibrin(ogen), complement 3, and prothrombin. These proteins were substantially resistant to trypsinization, in the presence of spike protein S1. Here we suggest that, in part, the presence of spike protein in circulation may contribute to the hypercoagulation in COVID-19 positive patients and may cause substantial impairment of fibrinolysis. Such lytic impairment may result in the persistent large microclots we have noted here and previously in plasma samples of COVID-19 patients. This observation may have important clinical relevance in the treatment of hypercoagulability in COVID-19 patients.
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- 2021
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11. Measurement of air and ground vibrations produced by explosions situated on the Earth's surface
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M. Grobbelaar, R. Durrheim, and T. Molea
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Surface (mathematics) ,Metals and Alloys ,PPV ,prediction ,Geophysics ,Geotechnical Engineering and Engineering Geology ,surface explosions ,demolition ,Situated ,Materials Chemistry ,Ground vibrations ,Geology ,Earth (classical element) ,secondary shock wave - Abstract
SYNOPSIS Most equations used to predict the ground motion produced by explosions were developed using confined blasts that were detonated for breaking rock in mining or tunnelling. Ground motion is usually recorded by geophones or seismometers. The air blast produced by open-pit blasts and explosions on the surface can pose a significant risk, thus microphones and pressure gauges are often also used to monitor the effects of the explosion. The aim of this study is to determine whether the predictive equations developed for confined explosions can be used to predict the effects from explosions on the surface, with appropriate adjustments to the various coefficients. Three predictive equations developed for buried explosions were tested. The study shows that the US Bureau of Mines peak particle velocity (PPV) predictive equation is the most reliable. In addition, a predictive equation that uses the secondary atmospheric shock wave phenomenon also produced good results, and uses the scaled delay time parameter, which is easier to measure. These equations may be utilized for demolition sites, where old and potentially unstable explosives and obsolete equipment are destroyed on the surface, and for assisting in forensic seismology to determine the details of an unexpected and unknown explosion. Keywords: surface explosions, prediction, demolition, PPV, secondary shock wave.
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- 2020
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12. Heart rate variability as a predictor of hypotension following spinal for elective caesarean section: a prospective observational study
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D. G. Bishop, M. Grobbelaar, R.N. Rodseth, and Carel Cairns
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Adult ,medicine.medical_treatment ,Blood Pressure ,Logistic regression ,Anesthesia, Spinal ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Heart Rate ,Predictive Value of Tests ,Pregnancy ,030202 anesthesiology ,Heart rate ,Anesthesia, Obstetrical ,Humans ,Medicine ,Heart rate variability ,Caesarean section ,Prospective Studies ,030212 general & internal medicine ,Cesarean Section ,business.industry ,Infant, Newborn ,Prognosis ,Anesthesiology and Pain Medicine ,Anesthesia ,Electrocardiography, Ambulatory ,Female ,Observational study ,Hypotension ,Elective caesarean section ,business ,Complication ,Body mass index - Abstract
Post-spinal hypotension remains a common and clinically-important problem during caesarean section, and accurate pre-operative prediction of this complication might enhance clinical management. We conducted a prospective, single-centre, observational study of heart rate variability in 102 patients undergoing elective caesarean section in a South African regional hospital. We performed Holter recording for ≥ 5 min in the hour preceding spinal anaesthesia. The low-frequency/high-frequency ratio component of heart rate variability was compared, using a logistic regression model, with baseline heart rate and body mass index (BMI) as a predictor of hypotension (defined as systolic arterial pressure < 90 mmHg) occurring from the time of spinal insertion until 15 min after delivery of the baby. We also assessed clinically relevant cut-point estimations for low-frequency/high-frequency ratio. Low-frequency/high-frequency ratio predicted hypotension (p = 0.046; OR 1.478, 95%CI 1.008-1.014), with an optimal cut-point estimation of 2.0; this threshold predicted hypotension better than previously determined thresholds (p = 0.003; c-statistic 0.645). Baseline heart rate (p = 0.20; OR 1.022, 95%CI 0.988-1.057) and BMI (p = 0.60; OR 1.017, 95%CI 0.954-1.085) did not predict hypotension. Heart rate variability analysis is a potentially useful clinical tool for the prediction of hypotension. Future studies should consider a low-frequency/high-frequency ratio threshold of 2.0 for prospective validation.
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- 2017
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13. Heart Rate Variability as a Predictor of Hypotension Following Spinal for Elective Caesarean Section: A Prospective Observational Study
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R.N. Rodseth, M. Grobbelaar, Carel Cairns, and D. G. Bishop
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,030208 emergency & critical care medicine ,030204 cardiovascular system & hematology ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Heart rate ,medicine ,Cardiology ,Heart rate variability ,Observational study ,Caesarean section ,Elective caesarean section ,Complication ,business ,Body mass index - Abstract
Post-spinal hypotension remains a common and clinically-important problem during caesarean section, and accurate pre-operative prediction of this complication might enhance clinical management. We conducted a prospective, single-centre, observational study of heart rate variability in 102 patients undergoing elective caesarean section in a South African regional hospital. We performed Holter recording for ≥ 5 min in the hour preceding spinal anaesthesia. The low-frequency/high-frequency ratio component of heart rate variability was compared, using a logistic regression model, with baseline heart rate and body mass index (BMI) as a predictor of hypotension (defined as systolic arterial pressure < 90 mmHg) occurring from the time of spinal insertion until 15 min after delivery of the baby. We also assessed clinically relevant cut-point estimations for low-frequency/high-frequency ratio. Low-frequency/high-frequency ratio predicted hypotension (p = 0.046; OR 1.478, 95%CI 1.008-1.014), with an optimal cut-point estimation of 2.0; this threshold predicted hypotension better than previously determined thresholds (p = 0.003; c-statistic 0.645). Baseline heart rate (p = 0.20; OR 1.022, 95%CI 0.988-1.057) and BMI (p = 0.60; OR 1.017, 95%CI 0.954-1.085) did not predict hypotension. Heart rate variability analysis is a potentially useful clinical tool for the prediction of hypotension. Future studies should consider a low-frequency/high-frequency ratio threshold of 2.0 for prospective validation.
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- 2018
- Full Text
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14. South African Paediatric Surgical Outcomes Study: a 14-day prospective, observational cohort study of paediatric surgical patients
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A. Torborg, L. Cronje, J. Thomas, H. Meyer, A. Bhettay, J. Diedericks, C. Cilliers, H. Kluyts, B. Mrara, M. Kalipa, R. Rodseth, B. Biccard, K. Allopi, U. Singh, P. Diyelela-Ndwandwa, N. Nongqo, B. Ravid, P. Anamourlis, G. Coetzee, M. Dlamini, C. Foster, P. Mogane, D. Nel, A. Oosthuizen, L. Redford, R. Murray, C. Basson, J. Joubert, N. Tshifularo, T. Els, J. Orrock, M. Muthambi, T. Matebesi, G. Tshukudu, D. Maela, N. Allorto, J. Bertie, D. Bishop, K. Chetty, M. Grobbelaar, R. Wise, I. von Steiger, P. Nundlal, E. Garoufalias, G. Westcott, J. Davids, C. Rajah, C. Cairns, Y. Mzoneli, K. Bhagwan, E. Cloete, M. Jaworska, E. Semenya, O. Porrill, R. Mungar, P. Seonandan, N. Perumal, C. Alphonsus, M. Bosman, A. De Castro, L. Drummond, M. Du Bruyn, P. Govender, T. Hardcastle, Z. Hlangu, P. Jeena, M. Mbuyisa, T. Naidu, J. Sewlall, J. Taylor, K. Timakia, W. Van der Walt, T. Biyase, Z. Khumalo, B. Kusel, I. Mukama, M. Ramburuth, S. Singaram, M. Mbeki, H. Schutte, P. Anderson, B. Dorasamy, P. Kint, S. Goga, L. Cronjé, N. Dube, S. Jithoo, L. Naidoo, L. Naidu, T. Reddy, Y. Saman, D. Rungan, K. Naidoo, K. Kabambi, N. Mgoqo, M. Mofoka, A. Usenbo, C. Chiu, N. Machere, D. Maiwald, G. Davies, T. Serdyn, P. Gokal, N. Dhanjee, M. Wege, S. Govender, S. Tarr, M. Moodley, M. Balkisson, A. Maharaj, S. Ngcobo, N. Rorke, S. Sikhakhane, M. Khumalo, T. Ramsamy, K. Kabongo, W. Kuhn, R. Matos-Puig, R. Naidoo, A. Thotharam, A. Chohan, S. Adam, I. Appel, A. Burke, C. de Vos, S. Gautam, E. Joubert, R. Rautenbach, D. Roytowski, A. Szpytko, E. Brits, B. Diedericks, G. Naude, J. van Niekerk, and Z. Fullerton
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Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Population ,Infections ,Cohort Studies ,03 medical and health sciences ,South Africa ,0302 clinical medicine ,Postoperative Complications ,030202 anesthesiology ,Risk Factors ,Medicine ,Humans ,Hospital Mortality ,Prospective Studies ,Prospective cohort study ,education ,Child ,education.field_of_study ,business.industry ,Mortality rate ,Incidence (epidemiology) ,Incidence ,Infant, Newborn ,Infant ,Perioperative ,Length of Stay ,Clinical trial ,Anesthesiology and Pain Medicine ,Treatment Outcome ,Child, Preschool ,General Surgery ,Female ,Outcomes research ,business ,Cohort study - Abstract
Children comprise a large proportion of the population in sub-Saharan Africa. The burden of paediatric surgical disease exceeds available resources in Africa, potentially increasing morbidity and mortality. There are few prospective paediatric perioperative outcomes studies, especially in low- and middle-income countries (LMICs).We conducted a 14-day multicentre, prospective, observational cohort study of paediatric patients (aged16 yrs) undergoing surgery in 43 government-funded hospitals in South Africa. The primary outcome was the incidence of in-hospital postoperative complications.We recruited 2024 patients at 43 hospitals. The overall incidence of postoperative complications was 9.7% [95% confidence interval (CI): 8.4-11.0]. The most common postoperative complications were infective (7.3%; 95% CI: 6.2-8.4%). In-hospital mortality rate was 1.1% (95% CI: 0.6-1.5), of which nine of the deaths (41%) were in ASA physical status 1 and 2 patients. The preoperative risk factors independently associated with postoperative complications were ASA physcial status, urgency of surgery, severity of surgery, and an infective indication for surgery.The risk factors, frequency, and type of complications after paediatric surgery differ between LMICs and high-income countries. The in-hospital mortality is 10 times greater than in high-income countries. These findings should be used to develop strategies to improve paediatric surgical outcomes in LMICs, and support the need for larger prospective, observational paediatric surgical outcomes research in LMICs.NCT03367832.
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- 2018
15. EMERGENCE OF BEDAQUILINE RESISTANCE AFTER COMPLETION OF BEDAQUILINE-BASED DRUGRESISTANT TB TREATMENT: A CASE STUDY FROM SOUTH AFRICA
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Helen Cox, Johnny Daniels, James E. Posey, Grant Theron, Brigitta Derendinger, Serej D. Ley, Scott Burns, Anja Reuter, Rob Warren, M. Grobbelaar, Anzaan Dippenaar, and M. de Vos
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medicine.medical_specialty ,business.industry ,Immunology ,Infectious and parasitic diseases ,RC109-216 ,chemistry.chemical_compound ,Infectious Diseases ,chemistry ,Internal medicine ,Immunology and Allergy ,Medicine ,Bedaquiline ,business ,Tb treatment - Published
- 2018
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16. Platform session
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G. Feigl, W. Rosmarin, B. Weninger, R. Likar, P. V. Hoogland, R. J. M. Groen, W. Vorster, M. Grobbelaar, C. J. F. Muller, D. F. du Toit, B. Moriggl, M. Greher, A. Klauser, U. Eichenberger, J. M. Prades, A. Timoshenko, M. Faye, C. H. Martin, M. Baroncini, H. Baiz, A. Ben Henda, C. Fontaine, G. Baksa, M. Toth, L. Patonay, A. Gonçalves-Ferreira, C. Gonçalves, L. Neto, T. Fonseca, H. Gaspar, J. Rino, M. Fernandes, P. Fernandes, H. Cardoso, B. Miranda, J. Rego, A. Hamel, P. Guillouche, O. Hamel, M. Garçon, S. Lager, Y. Blin, O. Armstrong, R. Robert, J. M. Rogez, J. Le Borgne, G. Kahilogulları, A. Comert, A. F. Esmer, E. Tuccar, I. Tekdemir, M. Ozdemir, A. B. Odabasi, A. Elhan, M. K. Anand, P. R. Singh, M. Verma, C. J. Raibagkar, H. J. Kim, H. H. Kwak, K. S. Hu, J. P. Francke, V. Macchi, A. Porzionato, A. Parenti, P. Metalli, G. F. Zanon, R. De Caro, A. Bernardes, J. Dionísio, P. Messias, J. Patrício, N. Apaydin, A. Uz, O. Evirgen, K. S. Shim, H. D. Park, K. H. Youn, M. Cajozzo, T. Bartolotta, F. Cappello, A. Sunseri, M. Romeo, G. Altieri, G. Modica, G. La Barbera, G. La Marca, F. Valentino, B. Valentino, A. Martino, G. Dees, W. A. Kleintjes, R. Williams, B. Herpe, J. Leborgne, S. Lagier, A. Cordova, R. Pirrello, F. Moschella, M. V. Mahajan, U. B. Bhat, S. V. Abhayankar, M. V. Ambiye, D. K. Kachlík, J. S. Stingl, B. S. Sosna, P. F. Fára, A. L. Lametschwandtner, B. M. Minnich, Z. S. Straka, M. Ifrim, C. Feng Ifrim, M. Botea, R. Latorre, F. Sun, R. Henry, V. Crisóstomo, F. Gil Cano, J. Usón, F. Mtez-Gomaríz, S. Climent, V. Hurmusiadis, S. Barrick, J. Barrow, N. Clifford, F. Morgan, R. Wilson, L. Wiseman, O. A. Fogg, M. Loukas, R. A. Tedman, N. Capaccioli, L. Capaccioli, A. Mannini, G. Guazzi, M. Mangoni, F. Paternostro, P. Terrosi Vagnoli, M. Gulisano, S. Pacini, B. Grignon, R. Jankowski, D. Hennion, X. Zhu, J. Roland, G. Mutiu, V. Tessitore, M. L. Uzzo, G. Bonaventura, G. Milio, G. F. Spatola, T. Ilkan, T. Selcuk, A. M. Mustafa, C. H. Hamdi, T. C. Emel, U. Faruk, G. Bulent, V. Báča, A. Doubková, D. Kachlík, J. Stingl, C. Saylam, Ö. Kitiş, H. Üçerler, E. Manisahı, A. S. Gönül, G. H. R. Dashti, M. Nematbaksh, M. Mardani, J. Hami, M. Rezaian, B. Radmehr, M. Akbari, M. R. Paryani, H. Gilanpour, C. Zamfir, M. Zamfir, C. Lupusoru, C. Raileanu, R. Lupusoru, P. Bordei, D. Iliescu, E. Şapte, S. Adam, C. Baker, C. Sergi, F. Barberini, M. Ripani, V. Di Nitto, A. Zani, F. Magnosi, R. Heyn, G. Familiari, U. Elgin, D. Demiryurek, N. Berker, B. Ilhan, T. Simsek, A. Batman, A. Bayramoglu, Q. A. Fogg, A. Bartczak, M. Kamionek, M. Kiedrowski, M. Fudalej, T. Wagner, W. Artibani, C. Tiengo, G. Taglialavoro, F. Mazzoleni, R. Scapinelli, E. Ardizzone, V. Cannella, D. Peri, R. Pirrone, and G. Peri
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Multimedia ,business.industry ,Medicine ,Radiology, Nuclear Medicine and imaging ,Surgery ,Session (computer science) ,Anatomy ,business ,computer.software_genre ,computer ,Pathology and Forensic Medicine - Published
- 2005
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17. Cefaclor, an alternative to third generation cephalosporins for the treatment of gonococcal urethritis in the developing world?
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E. Van Dyck, Marie Laga, Y Dangor, T M Grobbelaar, R. C. Ballard, and F Crabbé
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Male ,Sexually transmitted disease ,medicine.medical_specialty ,medicine.drug_class ,Urology ,Bacterial diseases ,Gonorrhea ,Antibiotics ,Administration, Oral ,Microbial Sensitivity Tests ,Dermatology ,medicine.disease_cause ,Africa, Southern ,Agar dilution ,South Africa ,Drug sensitivity testing ,Internal medicine ,polycyclic compounds ,medicine ,Humans ,Urethritis ,Cefaclor ,Antibacterial agent ,Probenecid ,business.industry ,Uricosuric Agents ,medicine.disease ,Neisseria gonorrhoeae ,Cephalosporins ,Surgery ,Treatment Outcome ,Infectious Diseases ,Drug resistance ,Drug Therapy, Combination ,business ,Research Article ,medicine.drug - Abstract
OBJECTIVE: To reassess the in vivo and in vitro efficacy of cefaclor for the treatment of uncomplicated gonococcal infection. DESIGN: Open clinical trail conducted in South Africa among consecutive male patients with symptoms and signs of uncomplicated urethritis and laboratory evidence of gonorrhoea. METHODS: Patients were treated with 3 g of cefaclor plus 1 g probenecid as a single dose. Urethral specimens were cultured for Neisseria gonorrhoeae at the initial visit and at follow up. Patients were considered cured if follow up cultures were negative. Treatment was considered to have failed in the patients infected with identical gonococcal strains at the initial and at the control visit. Those with evidence of infection at the follow up visit were administered 400 mg of ofloxacin and doxycycline 100 mg twice daily for 7 days. Minimal inhibitory concentrations (MICs) of cefaclor were determined by an agar dilution technique on the gonococcal isolates from the study subjects. The results were compared with those of isolates from three other African countries. RESULTS: Of 155 patients evaluated, 151 were cured (97%). Thirty per cent of the patients complained of adverse effects, mainly gastrointestinal. Even though MICs for the isolates from the three other African countries were significantly higher than those for the isolates from the study, none was considered resistant to cefaclor in vitro. MICs were markedly influenced by the type of test medium used. CONCLUSION: The trial demonstrated the efficacy of a single oral dose of cefaclor with probenecid for the treatment of uncomplicated gonococcal urethritis in South Africa. Its potential as an alternative therapy to third generation cephalosporins deserves to be further investigated.
- Published
- 1997
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18. Afskeid en vertrek as dekadente roman
- Author
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H. Roos and M. Grobbelaar
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Literature ,Linguistics and Language ,Vision ,Literature and Literary Theory ,business.industry ,media_common.quotation_subject ,Vagueness ,Solipsism ,Art ,Language and Linguistics ,Portrait ,Negation ,Karel ,Narrative ,Plot (narrative) ,business ,computer ,media_common ,computer.programming_language - Abstract
Most of the arguments advanced in negative critical reviews of Karel Schoeman’s latest novel Afskeid en vertrek lose their validity if this novel is evaluated as a decadent text. Firstly, the vagueness regarding the apparently contemporary South African state of war depicted in this novel is in accordance with the decadent vision of the world, which is characterized by a fundamental rejection of reality. In Afskeid en vertrek the negation of an intolerable world takes the form of solipsism, acting and masquerade in an artificial and aestheticised existence, deviation from conventional heterosexual relationships and especially an escape in language. Secondly, critical remarks on the absence of a dynamic development of plot can be invalidated on the grounds that the static character of the novel and the use of images or "static portraits which interrupt the flow of narrative by halting visions" (Nalbantian, 1983:123) are typical stylistic traits of decadent literature.
- Published
- 1993
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19. ’n Interpretasie van Karel Schoeman se roman, ’n Ander land binne die raamwerk van die laat negentiendeeeuse estetisistiese en dekadente literêre tradisie
- Author
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H. Roos and M. Grobbelaar
- Subjects
Linguistics and Language ,Literature and Literary Theory ,media_common.quotation_subject ,Narrative style ,lcsh:PL8000-8844 ,Character (symbol) ,Art ,Language and Linguistics ,lcsh:African languages and literature ,Politics ,Karel ,Paradise ,computer ,Humanities ,computer.programming_language ,Decadence ,media_common - Abstract
The first motivation for reading Karel Schoeman’s novel ’n Ander land within the framework of late nineteenth century Western European decadcnt literature is the strong resemblance between Schoeman's character Versluis and Des Esseintes, main character of the so-called Bible of Decadence, namely Joris- Karl Huysmans’ A Rebours (1884). Schoeman’s cultivated narrative style, his use of archaic Dutch and French words and the fact that this novel h as 'no story’, confirm the affinity of ’n Ander land with the decadent literary tradition as established by Huysmans’ plotless novel. The ultimate vision communicated in ’n Ander land is that death, like the landscape of Africa, is infinitely empty. The journey of the dying Versluis to Bloemfontein with its emphasis on intense heat and desolation and its affinities with Dante's Divina Commedia can be seen as a symbolic descent into hell, with the suggestion that Versluis will never reach paradise.
- Published
- 1993
20. Is airway diameter measured accurately on routine axial CT scans? Comparison with true axial diameter using MPR in children with airway compression owing to pulmonary TB
- Author
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Savvas Andronikou and M Grobbelaar
- Subjects
lcsh:Medical physics. Medical radiology. Nuclear medicine ,medicine.medical_specialty ,lcsh:R895-920 ,Bronchoscopy ,Medicine ,Tuberculosis ,Radiology, Nuclear Medicine and imaging ,Multiplanar Reconstruction ,Children ,Lung ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Axial CT ,business.industry ,Soft tissue ,Multiplanar reconstruction ,respiratory system ,medicine.disease ,respiratory tract diseases ,Stenosis ,Airway ,medicine.anatomical_structure ,Airway compression ,Radiology ,business ,Pulmonary tb - Abstract
Airway compression is a common complication of TB lymphadenopathy in children, and the diagnostic workup of patients with suspected tracheal or bronchial stenoses includes bronchoscopy and CT (computed tomography).2 This process affords the opportunity to study aspects of CT relating to airway stenosis. Axial CT scans produce excellent resolution in the horizontal plane, but the extent of airway disease may be underestimated if only axial images are obtained. An advantage of using multidetector CT (MDCT) is the use of multiplanar reconstruction (MPR) to align the image along the longitudinal axis of the airway. There is also uncertainty if window settings affect the measurement of the airway diameter. We wished to determine if there was a significant difference between the measurements of compressed airway diameter in the axial plane compared with measurements of diameter using MPR for determining longitudinal axis of the airway; and to evaluate how measurements on lung window settings compare with soft tissue window settings.
- Published
- 2010
21. Chylothorax as a complication of pulmonary tuberculosis in children
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Salomine Theron, M Grobbelaar, Reena George, A Mapukata, Savvas Andronikou, and Pierre Goussard
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Male ,medicine.medical_specialty ,Tuberculosis ,Chyle ,Chylothorax/*etiology/*radiography ,Chylothorax ,Tuberculous meningitis ,Thoracic duct ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Tuberculosis, Pulmonary ,Tomography, X-Ray Computed ,business.industry ,Cisterna chyli ,Infant ,medicine.disease ,Tuberculous lymphadenitis ,Surgery ,Tuberculosis, Pulmonary/*complications/radiography ,medicine.anatomical_structure ,Lymphatic system ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Radiology ,business - Abstract
Chylothorax is a rare clinical entity characterized by a milky white aspirate with increased triglyceride levels. The commonest aetiology is malignancy and trauma. Pulmonary tuberculosis is an extremely rare cause of chylothorax. Two children with chylothorax and pulmonary tuberculosis are described. One child had bilateral and the other unilateral chylous effusions. Extensive mediastinal and hilar lymphadenopathy was demonstrated. Diseased lymph nodes may infiltrate other intrathoracic structures such as the thoracic duct, and they can also obstruct the cisterna chyli and thoracic duct. A possible explanation for the development of a chylothorax in our patients is obstruction of the thoracic duct by tuberculous lymphadenopathy with subsequent increase in pressure in the surrounding lymphatic system and leaking of chyle into the pleural space. Pediatr Radiol
- Published
- 2007
22. Pulmonary Kaposi sarcoma in six children
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A Mapukata, Nicky Wieselthaler, Murray Hayes, Reena George, Pierre Goussard, Savvas Andronikou, Salomine Theron, M Grobbelaar, Alan Davidson, and Jaco du Plessis
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Male ,medicine.medical_specialty ,Lung Neoplasms ,Radiography ,Ascites ,medicine ,Axillary Lymphadenopathy ,Humans ,Radiology, Nuclear Medicine and imaging ,Child ,Sarcoma, Kaposi ,Neuroradiology ,Bilateral hilar lymphadenopathy ,business.industry ,Infant ,Retrospective cohort study ,medicine.disease ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Radiography, Thoracic ,Radiology ,Sarcoma ,medicine.symptom ,business ,Tomography, X-Ray Computed ,Zones of the lung - Abstract
Pulmonary involvement in Kaposi sarcoma is rare in children and can be difficult to distinguish from other pathology. To describe the radiological findings in paediatric pulmonary Kaposi sarcoma. Sequential chest radiographs of six children and CT scans of four of these children were evaluated retrospectively. Their ages ranged from 18 months to 10 years; four were male and two were female. All six children were HIV-positive. The observers were two radiologists. Chest radiographs revealed air-space (100%) and reticular (83%) opacification in the mid- and lower lung zones; pleural effusions were present in 83% of the children. All the children showed progressive air-space opacification on follow-up radiography. CT demonstrated bilateral air-space opacification in a perihilar distribution in all the children; reticular opacification was seen in 75%. All the children had mediastinal and axillary lymphadenopathy; 75% had bilateral hilar lymphadenopathy. In both adults and children, chest radiography demonstrates perihilar and lower zone involvement. Pleural effusions are more common on radiographs in children. Air-space disease and lymphadenopathy are much more common on CT in children than adults.
- Published
- 2007
23. Modern imaging of renal tuberculosis in children
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M Grobbelaar, Savvas Andronikou, L Jee, Stephen Fasulakis, A Mapukata, and Mignon McCulloch
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Diagnostic Imaging ,Male ,medicine.medical_specialty ,Tuberculosis ,Intravenous urography ,urologic and male genital diseases ,Imaging modalities ,Medical imaging ,Medicine ,Humans ,Tuberculosis, Renal ,Radiology, Nuclear Medicine and imaging ,Child ,Hydronephrosis ,Renal tuberculosis ,Retrospective Studies ,business.industry ,Tuberculosis, Renal/*diagnosis ,Ultrasound ,Retrospective cohort study ,medicine.disease ,Female ,Radiology ,business - Abstract
Renal tuberculosis is relatively uncommon in children. Imaging of renal tuberculosis in children differs from adults in that intravenous urography is rarely performed for urinary symptoms in childhood because of radiation dose considerations. Modern imaging modalities include cross-sectional techniques such as ultrasound, CT and MRI, which successfully show renal, calyceal, ureteric and bladder pathology of renal tuberculosis in children. Australas Radiol
- Published
- 2007
24. Localized basal meningeal enhancement in tuberculous meningitis
- Author
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Freda Steyn, Savvas Andronikou, A Mapukata, Jaco du Plessis, Salomine Theron, and M Grobbelaar
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Contrast enhancement ,Adolescent ,urologic and male genital diseases ,Tuberculous meningitis ,Basal (phylogenetics) ,Meninges ,X ray computed ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Cerebrospinal fluid culture ,Child ,Neuroradiology ,Retrospective Studies ,business.industry ,Infant, Newborn ,Infant ,medicine.disease ,Radiographic Image Enhancement ,medicine.anatomical_structure ,Tomography x ray computed ,Child, Preschool ,Tuberculosis, Meningeal ,Pediatrics, Perinatology and Child Health ,Female ,Radiology ,business ,Tomography, X-Ray Computed - Abstract
Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM).To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM.CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern.The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient.Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic.
- Published
- 2006
25. Neurofibromatosis I (NF-I): features on MRI
- Author
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Reena George, Salomine Theron, M Grobbelaar, Savvas Andronikou, and A Mapukata
- Subjects
lcsh:Medical physics. Medical radiology. Nuclear medicine ,Pathology ,medicine.medical_specialty ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,lcsh:R895-920 ,Perforation (oil well) ,Cowden syndrome ,medicine.disease ,Inferior vena cava ,Intervertebral disk ,medicine.vein ,medicine ,Radiology, Nuclear Medicine and imaging ,Subcutaneous port ,business ,Myelography ,Chiari malformation ,Neuroradiology - Published
- 2006
26. Paragangliomas of the head and neck
- Author
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M Grobbelaar, Reena George, J.A.K. du Plessis, and Murray Hayes
- Subjects
lcsh:Medical physics. Medical radiology. Nuclear medicine ,medicine.medical_specialty ,Radiological and Ultrasound Technology ,business.industry ,lcsh:R895-920 ,Perforation (oil well) ,Mediastinum ,Inferior vena cava ,Intervertebral disk ,medicine.anatomical_structure ,medicine.vein ,medicine ,Radiology, Nuclear Medicine and imaging ,Subcutaneous port ,Radiology ,Craniofacial ,Head and neck ,business ,Neuroradiology - Published
- 2006
27. Morphology of the human internal vertebral venous plexus: A cadaver study after latex injection in the 21-25-week fetus
- Author
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O. Verhoof, G. van Solinge, P V J M Hoogland, Christo J. F. Muller, M. Grobbelaar, D. F. Du Toit, Rob J. M. Groen, and VU University medical center
- Subjects
Adult ,Male ,Thorax ,medicine.medical_specialty ,Histology ,vertebral venons system ,Gestational Age ,Veins ,Fetal Development ,Fetus ,Hematoma ,Lumbar ,spontaneous spinal epidural hematoma ,Cadaver ,Humans ,Medicine ,Aged ,Aged, 80 and over ,Internal vertebral venous plexus ,business.industry ,aging ,Gestational age ,General Medicine ,Anatomy ,Middle Aged ,Hematoma, Epidural, Spinal ,medicine.disease ,Spine ,Surgery ,Female ,Posterior internal vertebral venous plexus ,business ,SYSTEM - Abstract
The morphology of the anterior and posterior internal vertebral venous plexus (IVVP) in human fetuses between 21-25 weeks of gestational age is described. The results are compared to the findings of a previous morphological study of the IVVP in the aged. The morphological pattern of the anterior IVVP in the fetus is very similar with the anterior IVVP in the aged human. In contrast, the posterior IVVP in the fetus lacks the prominent transverse bridging veins that are present in the aged lower thoracic and the lumbar posterior IVVP. The background of these morphological differences is unclear. Maybe the thoracolumbar part of the posterior IVVP is subject to "developmental delay," or the observed differences in the aged may result from functional and age-related factors that trigger this part of the vertebral venous system during (erect) life. The observed age related morphological differences of the posterior IVVP support the concept of the venous origin of the spontaneous spinal epidural hematoma (SSEH).
- Published
- 2005
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28. The early experience of general practitioners using Green Prescription
- Author
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B, Gribben, F, Goodyear-Smith, M, Grobbelaar, D, O'Neill, and S, Walker
- Subjects
Adult ,Male ,Surveys and Questionnaires ,Humans ,Female ,Program Development ,Family Practice ,Exercise ,Health Education ,New Zealand ,Program Evaluation - Abstract
Sedentary lifestyle is a significant risk factor for increased morbidity and mortality in many medical conditions. A Hillary Commission initiative, Green Prescription is a written exercise prescription given by general practitioners (GPs) to sedentary patients to encourage physical activity. Our aim was to establish the extent to which GPs in the North Health region in 1997 issued with Green Prescription packages had used them, the circumstances under which they were used, and barriers to their use.433 GPs issued with packs were faxed a one-page questionnaire for immediate completion, with follow-up of non-responders.The response rate was 73%, with 65% of respondents having written Green Prescriptions. Their main reasons for use were patient need for more exercise and presence of high-risk medical conditions such as hypertension, cardiovascular disease, obesity and diabetes. Reasons for non-use were: GP already giving advice about physical activity; concern that Green Prescription was patronising and simplistic; compliance issues and time restraints. Some requested a computerised version.Non-responders may be non-users, hence we estimate that 48-65% of targeted GPs used Green Prescription. Barriers identified by GPs have assisted in Green Prescription development, which is now nationwide and assessed by independent researchers tri-annually.
- Published
- 2000
29. A useful ultrasound artifact and its application - the 'twinkling sign'
- Author
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Salomine Theron, M Grobbelaar, A Mapukata, Savvas Andronikou, H Lameen, and F. Steyn
- Subjects
lcsh:Medical physics. Medical radiology. Nuclear medicine ,Radiological and Ultrasound Technology ,business.industry ,lcsh:R895-920 ,Ultrasound ,Infusion catheter ,Metastatic tumor ,Inferior vena cava ,Intervertebral disk ,medicine.vein ,medicine ,Blood oxygenation ,Radiology, Nuclear Medicine and imaging ,Subcutaneous port ,Computer vision ,Artificial intelligence ,business ,Twinkling - Published
- 2006
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- View/download PDF
30. Morphology of the human internal vertebral venous plexus: A cadaver study after latex injection in the 21–25‐week fetus.
- Author
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R.J.M. Groen, M. Grobbelaar, C.J.F. Muller, G. van Solinge, O. Verhoof, D.F. du Toit, and P.V.J.M. Hoogland
- Published
- 2005
- Full Text
- View/download PDF
31. Obstetric spinal hypotension: Preoperative risk factors and the development of a preliminary risk score â€' the PRAM score
- Author
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D Bishop, R Rodseth, C Cairns, and M Grobbelaar
- Subjects
Medicine ,Medicine (General) ,R5-920 - Abstract
Background. Obstetric spinal hypotension is a common and important problem during caesarean delivery. Identifying patients at risk for hypotension may guide clinical decision-making and allow timeous referral.Objective. Using preoperative risk factors, to develop a simple scoring system to predict systolic hypotension.Methods. This prospective, single-centre, observational study of patients undergoing elective or urgent caesarean delivery assessed body mass index, baseline heart rate, baseline mean arterial pressure (MAP), maternal age, urgency of surgery (elective v. non-elective) and preoperative haemoglobin concentration as predictors of spinal hypotension (systolic blood pressure 90 bpm, age >25 years, MAP
- Published
- 2017
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32. Neurofibromatosis I (NF-I): features on MRI
- Author
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M Grobbelaar, R George, S H Theron, A Mapukata, and S Andronikou
- Subjects
Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Published
- 2006
- Full Text
- View/download PDF
33. A useful ultrasound artifact and its application - the 'twinkling sign'
- Author
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H Lameen, S Theron, F Steyn, M Grobbelaar, A Mapukata, and S Andronikou
- Subjects
Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Published
- 2006
- Full Text
- View/download PDF
34. Paragangliomas of the head and neck
- Author
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R George, M Grobbelaar, J du Plessis, and M Hayes
- Subjects
Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Published
- 2006
- Full Text
- View/download PDF
35. Droplet based whole genome amplification for sequencing minute amounts of purified Mycobacterium tuberculosis DNA.
- Author
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Dippenaar A, Ismail N, Heupink TH, Grobbelaar M, Loubser J, Van Rie A, and Warren RM
- Subjects
- Humans, Nucleic Acid Amplification Techniques methods, Nanopore Sequencing methods, High-Throughput Nucleotide Sequencing methods, Tuberculosis microbiology, Tuberculosis diagnosis, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis isolation & purification, DNA, Bacterial genetics, DNA, Bacterial isolation & purification, Whole Genome Sequencing methods, Genome, Bacterial
- Abstract
Implementation of whole genome sequencing (WGS) for patient care is hindered by limited Mycobacterium tuberculosis (Mtb) in clinical specimens and slow Mtb growth. We evaluated droplet multiple displacement amplification (dMDA) for amplification of minute amounts of Mtb DNA to enable WGS as an alternative to other Mtb enrichment methods. Purified genomic Mtb-DNA (0.1, 0.5, 1, and 5 pg) was encapsulated and amplified using the Samplix Xdrop-instrument and sequenced alongside a control sample using standard Illumina protocols followed by MAGMA-analysis. The control and 5 pg input dMDA samples underwent nanopore sequencing followed by Nanoseq and TB-profiler analysis. dMDA generated 105-2400 ng DNA from the 0.1-5 pg input DNA, respectively. Followed by Illumina WGS, dMDA raised mean sequencing depth from 7 × for 0.1 pg input DNA to ≥ 60 × for 5 pg input and the control sample. Bioinformatic analysis revealed a high number of false positive and false negative variants when amplifying ≤ 0.5 pg input DNA. Nanopore sequencing of the 5 pg dMDA sample presented excellent coverage depth, breadth, and accurate strain characterization, albeit elevated false positive and false negative variants compared to Illumina-sequenced dMDA sample with identical Mtb DNA input. dMDA coupled with Illumina WGS for samples with ≥ 5 pg purified Mtb DNA, equating to approximately 1000 copies of the Mtb genome, offers precision for drug resistance, phylogeny, and transmission insights., (© 2024. The Author(s).)
- Published
- 2024
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- View/download PDF
36. Microfluidic Capture of Mycobacterium tuberculosis from Clinical Samples for Culture-Free Whole-Genome Sequencing.
- Author
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Ismail N, Dippenaar A, Morgan G, Grobbelaar M, Wells F, Caffry J, Morais C, Gizynski K, McGurk D, Boada E, Murton H, Warren RM, and Van Rie A
- Subjects
- Humans, Microfluidics, Microbial Sensitivity Tests, Whole Genome Sequencing, Antitubercular Agents pharmacology, Mycobacterium tuberculosis genetics, Tuberculosis microbiology
- Abstract
Mycobacterium tuberculosis whole-genome sequencing (WGS) is a powerful tool as it can provide data on population diversity, drug resistance, disease transmission, and mixed infections. Successful WGS is still reliant on high concentrations of DNA obtained through M. tuberculosis culture. Microfluidics technology plays a valuable role in single-cell research but has not yet been assessed as a bacterial enrichment strategy for culture-free WGS of M. tuberculosis. In a proof-of-principle study, we evaluated the use of Capture-XT, a microfluidic lab-on-chip cleanup and pathogen concentration platform to enrich M. tuberculosis bacilli from clinical sputum specimens for downstream DNA extraction and WGS. Three of the four (75%) samples processed by the microfluidics application passed the library preparation quality control, compared to only one of the four (25%) samples not enriched by the microfluidics M. tuberculosis capture application. WGS data were of sufficient quality, with mapping depth of ≥25× and 9 to 27% of reads mapping to the reference genome. These results suggest that microfluidics-based M. tuberculosis cell capture might be a promising method for M. tuberculosis enrichment in clinical sputum samples, which could facilitate culture-free M. tuberculosis WGS. IMPORTANCE Diagnosis of tuberculosis is effective using molecular methods; however, a comprehensive characterization of the resistance profile of Mycobacterium tuberculosis often requires culturing and phenotypic drug susceptibility testing or culturing followed by whole-genome sequencing (WGS). The phenotypic route can take anywhere from 1 to >3 months to result, by which point the patient may have acquired additional drug resistance. The WGS route is a very attractive option; however, culturing is the rate-limiting step. In this original article, we provide proof-of-principle evidence that microfluidics-based cell capture can be used on high-bacillary-load clinical samples for culture-free WGS., Competing Interests: The authors declare a conflict of interest. GM-employed by QuantuMDx Ltd JC-employed by QuantuMDx Ltd CM-employed by QuantuMDx Ltd KG-previously employed by QuantuMDx Ltd DM-employed by QuantuMDx Ltd EB-employed by QuantuMDx Ltd HM-previously employed by QuantuMDx Ltd
- Published
- 2023
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37. Evaluation of Nanopore sequencing for Mycobacterium tuberculosis drug susceptibility testing and outbreak investigation: a genomic analysis.
- Author
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Hall MB, Rabodoarivelo MS, Koch A, Dippenaar A, George S, Grobbelaar M, Warren R, Walker TM, Cox H, Gagneux S, Crook D, Peto T, Rakotosamimanana N, Grandjean Lapierre S, and Iqbal Z
- Subjects
- Humans, Microbial Sensitivity Tests, Sequence Analysis, DNA, Genomics, Disease Outbreaks, Mycobacterium tuberculosis genetics, Nanopore Sequencing, Tuberculosis diagnosis, Tuberculosis drug therapy, Tuberculosis epidemiology
- Abstract
Background: Mycobacterium tuberculosis whole-genome sequencing (WGS) has been widely used for genotypic drug susceptibility testing (DST) and outbreak investigation. For both applications, Illumina technology is used by most public health laboratories; however, Nanopore technology developed by Oxford Nanopore Technologies has not been thoroughly evaluated. The aim of this study was to determine whether Nanopore sequencing data can provide equivalent information to Illumina for transmission clustering and genotypic DST for M tuberculosis., Methods: In this genomic analysis, we analysed 151 M tuberculosis isolates from Madagascar, South Africa, and England, which were collected between 2011 and 2018, using phenotypic DST and matched Illumina and Nanopore data. Illumina sequencing was done with the MiSeq, HiSeq 2500, or NextSeq500 platforms and Nanopore sequencing was done on the MinION or GridION platforms. Using highly reliable PacBio sequencing assemblies and pairwise distance correlation between Nanopore and Illumina data, we optimise Nanopore variant filters for detecting single-nucleotide polymorphisms (SNPs; using BCFtools software). We then used those SNPs to compare transmission clusters identified by Nanopore with the currently used UK Health Security Agency Illumina pipeline (COMPASS). We compared Illumina and Nanopore WGS-based DST predictions using the Mykrobe software and mutation catalogue., Findings: The Nanopore BCFtools pipeline identified SNPs with a median precision of 99·3% (IQR 99·1-99·6) and recall of 90·2% (88·1-94·2) compared with a precision of 99·6% (99·4-99·7) and recall of 91·9% (87·6-98·6) using the Illumina COMPASS pipeline. Using a threshold of 12 SNPs for putative transmission clusters, Illumina identified 98 isolates as unrelated and 53 as belonging to 19 distinct clusters (size range 2-7). Nanopore reproduced 15 out of 19 clusters perfectly; two clusters were merged into one cluster, one cluster had a single sample missing, and one cluster had an additional sample adjoined. Illumina-based clusters were also closely replicated using a five SNP threshold and clustering accuracy was maintained using mixed Illumina and Nanopore datasets. Genotyping resistance variants with Nanopore was highly concordant with Illumina, having zero discordant SNPs across more than 3000 SNPs and four insertions or deletions (indels), across 60 000 indels., Interpretation: Illumina and Nanopore technologies can be used independently or together by public health laboratories performing M tuberculosis genotypic DST and outbreak investigations. As a result, clinical and public health institutions making decisions on which sequencing technology to adopt for tuberculosis can base the choice on cost (which varies by country), batching, and turnaround time., Funding: Academy for Medical Sciences, Oxford Wellcome Institutional Strategic Support Fund, and the Swiss South Africa Joint Research Award (Swiss National Science Foundation and South African National Research Foundation)., Competing Interests: Declaration of interests ZI, SGL, and NR had travel and accommodation costs reimbursed when speaking at an Oxford Nanopore Technology (ONT) conference in 2017. SGL and NR previously received consumables from ONT when establishing Nanopore sequencing capacity in Madagascar. ONT matched the contributions from the Longitude Prize Discovery Award to ZI and TMW in 2017 to provide consumables for sequencing in Viet Nam and India. All other authors declare no competing interests. ONT did not provide funding (direct or in kind) for this project, and had no input or knowledge of the design, data analysis, or paper writing. Funders had no input into the design, data analysis, or paper writing of this project., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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38. Nanopore Sequencing for Mycobacterium tuberculosis: a Critical Review of the Literature, New Developments, and Future Opportunities.
- Author
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Dippenaar A, Goossens SN, Grobbelaar M, Oostvogels S, Cuypers B, Laukens K, Meehan CJ, Warren RM, and van Rie A
- Subjects
- High-Throughput Nucleotide Sequencing methods, Humans, Sequence Analysis, DNA, Software, Mycobacterium tuberculosis genetics, Nanopore Sequencing
- Abstract
The next-generation, short-read sequencing technologies that generate comprehensive, whole-genome data with single nucleotide resolution have already advanced tuberculosis diagnosis, treatment, surveillance, and source investigation. Their high costs, tedious and lengthy processes, and large equipment remain major hurdles for research use in high tuberculosis burden countries and implementation into routine care. The portable next-generation sequencing devices developed by Oxford Nanopore Technologies (ONT) are attractive alternatives due to their long-read sequence capability, compact low-cost hardware, and continued improvements in accuracy and throughput. A systematic review of the published literature demonstrated limited uptake of ONT sequencing in tuberculosis research and clinical care. Of the 12 eligible articles presenting ONT sequencing data on at least one Mycobacterium tuberculosis sample, four addressed software development for long-read ONT sequencing data with potential applications for M. tuberculosis. Only eight studies presented results of ONT sequencing of M. tuberculosis, of which five performed whole-genome and three did targeted sequencing. Based on these findings, we summarize the standard processes, reflect on the current limitations of ONT sequencing technology, and the research needed to overcome the main hurdles. The low capital cost, portable nature and continued improvement in the performance of ONT sequencing make it an attractive option for sequencing for research and clinical care, but limited data are available on its application in the tuberculosis field. Important research investment is needed to unleash the full potential of ONT sequencing for tuberculosis research and care.
- Published
- 2022
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39. Optimizing liquefaction and decontamination of sputum for DNA extraction from Mycobacterium tuberculosis.
- Author
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Dippenaar A, Ismail N, Grobbelaar M, Oostvogels S, de Vos M, Streicher EM, Heupink TH, van Rie A, and Warren RM
- Subjects
- Humans, Bacteriological Techniques methods, Sensitivity and Specificity, Tuberculosis diagnosis, Decontamination methods, Decontamination standards, Decontamination statistics & numerical data, Mycobacterium tuberculosis isolation & purification, Mycobacterium tuberculosis metabolism, Specimen Handling methods, Specimen Handling standards, Sputum microbiology
- Abstract
Whole genome sequencing (WGS) can investigate the entire Mycobacterium tuberculosis (Mtb) genome but currently requires large amounts of mycobacterial DNA, necessitating culture. Culture-free Mtb WGS could revolutionize the clinical use of WGS but is hampered by the high viscosity, low mycobacterial load, and high contamination with bacterial and human DNA in sputum samples. To improve the sputum liquefaction and decontamination step prior to DNA extraction, we assessed the efficiency of Myco-TB, MycoPrep, and Sputolysin with/without TiKa-Kic in liquefying and decontaminating sputum and aimed to evaluate the effect of these approaches on mycobacterial viability, and Mtb DNA quality and quantity. Experiments using spiked sputum samples showed that Myco-TB and BD MycoPrep with standard (15 min) or increased (30 min) incubation time, but not reduced (7,5 min) incubation time performed well in liquefying and decontaminating sputum. No difference in DNA quality or quantity, contamination, or the amount of human DNA present was observed. In comparison, Sputolysin with/without TiKa-Kic was less effective for liquefaction and decontamination of sputum. PCR amplification of the human GAPDH gene after sputum treatment, showed the presence of human DNA in all samples, regardless of sputum treatment. Focused efforts are needed to deplete contaminating DNA for culture-free Mtb WGS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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40. In silico repurposing of a Novobiocin derivative for activity against latency associated Mycobacterium tuberculosis drug target nicotinate-nucleotide adenylyl transferase (Rv2421c).
- Author
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Cloete R, Shahbaaz M, Grobbelaar M, Sampson SL, and Christoffels A
- Subjects
- Inhibitory Concentration 50, Computer Simulation, Aminocoumarins chemistry, Aminocoumarins pharmacology, Quantitative Structure-Activity Relationship, Molecular Dynamics Simulation, Protein Conformation, Novobiocin analogs & derivatives, Novobiocin pharmacology, Antitubercular Agents chemistry, Antitubercular Agents pharmacology, Mycobacterium tuberculosis drug effects, Nicotinamide-Nucleotide Adenylyltransferase antagonists & inhibitors, Nicotinamide-Nucleotide Adenylyltransferase chemistry
- Abstract
Nicotinamide-nucleotide adenylyl transferase (Rv2421c) was selected as a potential drug target, because it has been shown, in vitro, to be essential for Mycobacterium tuberculosis growth. It is conserved between mycobacterium species, is up-regulated during dormancy, has a known 3D crystal structure and has no known human homologs. A model of Rv2421c in complex with nicotinic acid adenine dinucleotide and magnesium ion was constructed and subject tovirtual ligand screening against the Prestwick Chemical Library and the ZINC database, which yielded 155 potential hit molecules. Of the 155 compounds identified five were pursued further using an IC50 based 3D-QSAR study. The 3D-QSAR model validated the inhibition properties of the five compounds based on R2 value of 0.895 and Q2 value of 0.944 compared to known inhibitors of Rv2421c. Higher binding affinities was observed for the novel ZINC13544129 and two FDA approved compounds (Novobiocin sodium salt, Sulfasalazine). Similarly, the total interaction energy was found to be the highest for Cromolyn disodium system (-418.88 kJ/mol) followed by Novobiocin (-379.19 kJ/mol) and Sulfasalazine with (-330.13 kJ/mol) compared to substrate DND having (-185.52 kJ/mol). Subsequent in vitro testing of the five compounds identified Novobiocin sodium salt with activity against Mycobacterium tuberculosis at 50 μM, 25μM and weakly at 10μM concentrations. Novobiocin salt interacts with a MG ion and active site residues His20, Thr86, Gly107 and Leu164 similar to substrate DND of Mycobacterium tuberculosis Rv2421c. Additional in silico structural analysis of known Novobiocin sodium salt derivatives against Rv2421c suggest Coumermycin as a promising alternative for the treatment of Mycobacterium tuberculosis based on large number of hydrogen bond interactions with Rv2421c similar in comparison to Novobiocin salt and substrate DND., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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41. Development of a Clinical Prediction Model for In-hospital Mortality from the South African Cohort of the African Surgical Outcomes Study.
- Author
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Kluyts HL, Conradie W, Cloete E, Spijkerman S, Smith O, Alli A, Koto MZ, Montwedi OD, Govender K, Cronjé L, Grobbelaar M, Omoshoro-Jones JA, Rorke NF, Anderson P, Torborg A, Alphonsus C, Alexandris P, Mallier Peter A, Singh U, Diedericks J, Mrara B, Reed A, Davies GL, Davids JG, Van Zyl HA, Govindasamy V, Rodseth R, Matos-Puig R, Bhat KAP, Naidoo N, Roos J, Jaworska M, Steyn A, Dippenaar JM, Pearse RM, Madiba T, and Biccard BM
- Subjects
- Adult, Clinical Decision Rules, Delivery of Health Care statistics & numerical data, Female, Healthcare Disparities statistics & numerical data, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Assessment, Risk Factors, South Africa epidemiology, Surgical Procedures, Operative adverse effects, Treatment Outcome, Delivery of Health Care standards, Hospital Mortality, Models, Statistical, Surgical Procedures, Operative mortality
- Abstract
Background: Data on the factors that influence mortality after surgery in South Africa are scarce, and neither these data nor data on risk-adjusted in-hospital mortality after surgery are routinely collected. Predictors related to the context or setting of surgical care delivery may also provide insight into variation in practice. Variation must be addressed when planning for improvement of risk-adjusted outcomes. Our objective was to identify the factors predicting in-hospital mortality after surgery in South Africa from available data., Methods: A multivariable logistic regression model was developed to identify predictors of 30-day in-hospital mortality in surgical patients in South Africa. Data from the South African contribution to the African Surgical Outcomes Study were used and included 3800 cases from 51 hospitals. A forward stepwise regression technique was then employed to select for possible predictors prior to model specification. Model performance was evaluated by assessing calibration and discrimination. The South African Surgical Outcomes Study cohort was used to validate the model., Results: Variables found to predict 30-day in-hospital mortality were age, American Society of Anesthesiologists Physical Status category, urgent or emergent surgery, major surgery, and gastrointestinal-, head and neck-, thoracic- and neurosurgery. The area under the receiver operating curve or c-statistic was 0.859 (95% confidence interval: 0.827-0.892) for the full model. Calibration, as assessed using a calibration plot, was acceptable. Performance was similar in the validation cohort as compared to the derivation cohort., Conclusion: The prediction model did not include factors that can explain how the context of care influences post-operative mortality in South Africa. It does, however, provide a basis for reporting risk-adjusted perioperative mortality rate in the future, and identifies the types of surgery to be prioritised in quality improvement projects at a local or national level.
- Published
- 2021
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42. Evolution of rifampicin treatment for tuberculosis.
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Grobbelaar M, Louw GE, Sampson SL, van Helden PD, Donald PR, and Warren RM
- Subjects
- Dose-Response Relationship, Drug, Drug Resistance, Bacterial drug effects, Humans, Rifampin pharmacology, World Health Organization, Rifampin administration & dosage, Tuberculosis drug therapy
- Abstract
Rifampicin was discovered in 1965 and remains one of the most important drugs in tuberculosis treatment that is valued for its sterilizing activity and ability to shorten treatment. Antimicrobial activity of rifampicin was initially proved in vitro; subsequently numerous in vivo studies showed the bactericidal properties and dose-dependent effect of rifampicin. Rifampicin was first during the late 1960s to treat patients suffering from chronic drug-resistant pulmonary TB. Decades later, rifampicin continues to be studied with particular emphasis on whether higher doses could shorten the duration of treatment without increasing relapse or having adverse effects. Lesion-specific drug penetration and pharmacokinetics of rifampicin are improving our understanding of effective concentration while potentially refining drug regimen designs. Another prospective aspect of high-dose rifampicin is its potential use in treating discrepant mutation thereby eliminating the need for MDR treatment. To date, several clinical trials have shown the safety, efficacy, and tolerability of high-dose rifampicin. Currently, high-dose rifampicin has been used successfully in a routine clinical setting for the treatment of high-risk patients. However, the WHO and other relevant policy makers have not committed to implementing a controlled rollout thereof. This review describes the course that rifampicin has travelled to the present-day exploration of high-dose rifampicin treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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43. Structure based identification of novel inhibitors against ATP synthase of Mycobacterium tuberculosis: A combined in silico and in vitro study.
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Shahbaaz M, Cloete R, Grobbelaar M, Sampson S, and Christoffels A
- Subjects
- Drug Design, Enzyme Inhibitors metabolism, Mitochondrial Proton-Translocating ATPases chemistry, Mitochondrial Proton-Translocating ATPases metabolism, Molecular Docking Simulation, Molecular Dynamics Simulation, Protein Conformation, Computer Simulation, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Mitochondrial Proton-Translocating ATPases antagonists & inhibitors, Mycobacterium tuberculosis enzymology
- Abstract
The shortcomings of conventional tuberculosis treatments resulting from the development of drug resistance in Mycobacterium tuberculosis drive a need for the formulation of novel therapeutic agents. The diarylquinoline class of drugs such as bedaquiline was recently approved for the treatment of multidrug-resistant strains of tuberculosis, primarily targeting c and ε subunits of the ATP synthases. Yet resistance to bedaquiline has already been reported. Therefore, Rv1311 was used as the target for the identification of possible inhibitors against the M. tuberculosis. The structure of Rv1311 was predicted and common feature pharmacophore models were generated which facilitated the identification of potential inhibitors in the ZINC database. The activities of the selected molecules were compared with known inhibitors of the ATP synthase using quantitative structure-activity relationship. The ZINC classified inhibitors showed comparable predicted activities with that of known inhibitors. Furthermore, the inhibitory behavior of the studied drug molecules was experimentally determined using in vitro techniques and showed the minimum inhibitory concentration as low as 25 μM. The resulted outcomes provide a deeper insight into the structural basis of Rv1311 inhibitions and can facilitate the process of drug design against tuberculosis., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
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44. Bedaquiline Microheteroresistance after Cessation of Tuberculosis Treatment.
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de Vos M, Ley SD, Wiggins KB, Derendinger B, Dippenaar A, Grobbelaar M, Reuter A, Dolby T, Burns S, Schito M, Engelthaler DM, Metcalfe J, Theron G, van Rie A, Posey J, Warren R, and Cox H
- Subjects
- Aged, Drug Therapy, Combination, Humans, Male, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis isolation & purification, Whole Genome Sequencing, Antitubercular Agents therapeutic use, Diarylquinolines therapeutic use, Drug Resistance, Mycobacterium tuberculosis genetics, Tuberculosis, Multidrug-Resistant drug therapy
- Published
- 2019
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45. Lumbar Cerebrospinal Fluid Evolution in Childhood Tuberculous Meningitis.
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Grobbelaar M, van Toorn R, and Solomons R
- Subjects
- Analysis of Variance, Child, Child, Preschool, Female, Glucose cerebrospinal fluid, Humans, Infant, Lymphocytes pathology, Male, Neutrophils pathology, Severity of Illness Index, Time Factors, Cerebrospinal Fluid metabolism, Tuberculosis, Meningeal cerebrospinal fluid, Tuberculosis, Meningeal diagnosis
- Abstract
As early diagnosis of childhood tuberculous meningitis cannot rely on mycobacterial confirmation, clinical, cerebrospinal fluid and neuroimaging features are essential. We aimed to describe the evolution of serially analyzed lumbar cerebrospinal fluid parameters. We performed a retrospective observational study including children <13 years with suspected tuberculous meningitis at Tygerberg Hospital, Cape Town, South Africa. Cerebrospinal fluid parameters at admission and weeks 1, 2, and 3 were analyzed. Of 318 children with suspected tuberculous meningitis, 53 (17%) had "definite" tuberculous meningitis and 265 (83%) "probable" tuberculous meningitis. Longitudinal clustering revealed 3 distinct profiles, with 1 group atypically demonstrating initial increase in lymphocyte count, neutrophil count, and protein concentration. The decreasing cerebrospinal fluid glucose trend remained uniform among all groups. A gradual decline in cerebrospinal fluid lymphocyte, neutrophil and protein count, and rise in cerebrospinal fluid glucose concentration is expected; however, normal variability exists.
- Published
- 2018
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46. In Response.
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Bishop D, Cairns C, Grobbelaar M, and Rodseth R
- Subjects
- Cesarean Section, Female, Humans, Hypotension, Pregnancy, Anesthesia, Spinal, Phenylephrine
- Published
- 2018
- Full Text
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47. Obstetric spinal hypotension: Preoperative risk factors and the development of a preliminary risk score - the PRAM score.
- Author
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Bishop DG, Cairns C, Grobbelaar M, and Rodseth RN
- Abstract
Background: Obstetric spinal hypotension is a common and important problem during caesarean delivery. Identifying patients at risk for hypotension may guide clinical decision-making and allow timeous referral., Objective: Using preoperative risk factors, to develop a simple scoring system to predict systolic hypotension., Methods: This prospective, single-centre, observational study of patients undergoing elective or urgent caesarean delivery assessed body mass index, baseline heart rate, baseline mean arterial pressure (MAP), maternal age, urgency of surgery (elective v. non-elective) and preoperative haemoglobin concentration as predictors of spinal hypotension (systolic blood pressure <90 mmHg). We used empirical cut-point estimations in a logistic regression model to develop a scoring system for prediction of hypotension., Results: From 504 eligible patients, preoperative heart rate (odds ratio (OR) 1.02, 95% confidence interval (CI) 1.00 - 1.03; p=0.012), preoperative MAP (OR 0.97, 95% CI 0.95 - 0.98; p<0.001) and maternal age (OR 1.05, 95% CI 1.02 - 1.08; p=0.002) were found to be predictors of hypotension. We derived a preliminary scoring system (pulse rate >90 bpm, age >25 years, MAP <90 mmHg - the PRAM score) for the prediction of systolic hypotension following obstetric spinal anaesthesia. Patients with three factors had a 53% chance of developing hypotension, compared with the overall incidence of 30%. The PRAM score showed good discrimination, with a c-statistic of 0.626 (95% CI 0.576 - 0.676) and good calibration., Conclusions: Preoperative heart rate, preoperative MAP and maternal age were predictive of hypotension in elective and emergency caesarean delivery. The PRAM score shows promise as a simple, practical means to identify these patients preoperatively, but requires prospective validation.
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- 2017
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48. Prophylactic Phenylephrine Infusions to Reduce Severe Spinal Anesthesia Hypotension During Cesarean Delivery in a Resource-Constrained Environment.
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Bishop DG, Cairns C, Grobbelaar M, and Rodseth RN
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- Adult, Cesarean Section adverse effects, Female, Humans, Hypotension epidemiology, Infusions, Intravenous, Postoperative Complications drug therapy, Postoperative Complications epidemiology, Pregnancy, Prospective Studies, South Africa epidemiology, Vasoconstrictor Agents administration & dosage, Young Adult, Anesthesia, Obstetrical methods, Anesthesia, Spinal methods, Cesarean Section methods, Health Resources, Hypotension drug therapy, Phenylephrine administration & dosage
- Abstract
Phenylephrine infusions are considered as standard management for obstetric spinal hypotension, but there remains reluctance to implement them in resource-limited contexts. This prospective, alternating intervention study of patients undergoing elective or urgent cesarean delivery under spinal anesthesia compared a vasopressor bolus strategy to fixed-rate, low-dose prophylactic phenylephrine infusion with supplemental boluses. The primary outcome was the incidence of severe hypotension (mean arterial pressure <70% baseline or systolic blood pressure <80 mm Hg). Fewer patients receiving prophylactic phenylephrine infusions had severe hypotension (47.4% [n = 120/253] vs 62.1% [n = 157/253], P = .001, estimated relative risk 0.84, 95% confidence interval, 0.69-1.02), with no significant difference in the rate of hypertension (15% [n = 39/253] vs 11% [n = 27/253], P = .11, estimated relative risk 1.39, confidence interval 0.87-2.20). Guidelines for resource-constrained settings should consider a fixed, low-dose phenylephrine infusion in combination with rescue vasopressor bolus therapy.
- Published
- 2017
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49. Heart rate variability as a predictor of hypotension following spinal for elective caesarean section: a prospective observational study.
- Author
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Bishop DG, Cairns C, Grobbelaar M, and Rodseth RN
- Subjects
- Adult, Blood Pressure drug effects, Body Mass Index, Electrocardiography, Ambulatory, Female, Humans, Infant, Newborn, Predictive Value of Tests, Pregnancy, Prognosis, Prospective Studies, Anesthesia, Obstetrical adverse effects, Anesthesia, Spinal adverse effects, Cesarean Section methods, Heart Rate drug effects, Hypotension diagnosis, Hypotension etiology
- Abstract
Post-spinal hypotension remains a common and clinically-important problem during caesarean section, and accurate pre-operative prediction of this complication might enhance clinical management. We conducted a prospective, single-centre, observational study of heart rate variability in 102 patients undergoing elective caesarean section in a South African regional hospital. We performed Holter recording for ≥ 5 min in the hour preceding spinal anaesthesia. The low-frequency/high-frequency ratio component of heart rate variability was compared, using a logistic regression model, with baseline heart rate and body mass index (BMI) as a predictor of hypotension (defined as systolic arterial pressure < 90 mmHg) occurring from the time of spinal insertion until 15 min after delivery of the baby. We also assessed clinically relevant cut-point estimations for low-frequency/high-frequency ratio. Low-frequency/high-frequency ratio predicted hypotension (p = 0.046; OR 1.478, 95%CI 1.008-1.014), with an optimal cut-point estimation of 2.0; this threshold predicted hypotension better than previously determined thresholds (p = 0.003; c-statistic 0.645). Baseline heart rate (p = 0.20; OR 1.022, 95%CI 0.988-1.057) and BMI (p = 0.60; OR 1.017, 95%CI 0.954-1.085) did not predict hypotension. Heart rate variability analysis is a potentially useful clinical tool for the prediction of hypotension. Future studies should consider a low-frequency/high-frequency ratio threshold of 2.0 for prospective validation., (© 2017 The Association of Anaesthetists of Great Britain and Ireland.)
- Published
- 2017
- Full Text
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50. Rifampicin reduces susceptibility to ofloxacin in rifampicin-resistant Mycobacterium tuberculosis through efflux.
- Author
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Louw GE, Warren RM, Gey van Pittius NC, Leon R, Jimenez A, Hernandez-Pando R, McEvoy CR, Grobbelaar M, Murray M, van Helden PD, and Victor TC
- Subjects
- Adrenergic Uptake Inhibitors pharmacology, Animals, Bacterial Proteins drug effects, Bacterial Proteins genetics, Calcium Channel Blockers pharmacology, Cell Culture Techniques, DNA-Directed RNA Polymerases, Disease Models, Animal, Mice, Mice, Inbred BALB C, Microbial Sensitivity Tests, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis genetics, Reserpine pharmacology, Reverse Transcriptase Polymerase Chain Reaction, Tuberculosis, Multidrug-Resistant genetics, Verapamil pharmacology, Anti-Bacterial Agents pharmacology, Antibiotics, Antitubercular pharmacology, Ofloxacin pharmacology, Rifampin pharmacology, Tuberculosis, Multidrug-Resistant drug therapy
- Abstract
Rationale: Central dogma suggests that rifampicin resistance in Mycobacterium tuberculosis develops solely through rpoB gene mutations., Objective: To determine whether rifampicin induces efflux pumps activation in rifampicin resistant M. tuberculosis strains thereby defining rifampicin resistance levels and reducing ofloxacin susceptibility., Methods: Rifampicin and/or ofloxacin minimum inhibitory concentrations (MICs) were determined in rifampicin resistant strains by culture in BACTEC 12B medium. Verapamil and reserpine were included to determine their effect on rifampicin and ofloxacin susceptibility. RT-qPCR was applied to assess expression of efflux pump/transporter genes after rifampicin exposure. To determine whether verapamil could restore susceptibility to first-line drugs, BALB/c mice were infected with a MDR-TB strain and treated with first-line drugs with/without verapamil., Measurements and Main Findings: Rifampicin MICs varied independently of rpoB mutation and genetic background. Addition reserpine and verapamil significantly restored rifampicin susceptibility (p = 0.0000). RT-qPCR demonstrated that rifampicin induced differential expression of efflux/transporter genes in MDR-TB isolates. Incubation of rifampicin mono-resistant strains in rifampicin (2 μg/ml) for 7 days induced ofloxacin resistance (MIC > 2 μg/ml) in strains with an rpoB531 mutation. Ofloxacin susceptibility was restored by exposure to efflux pump inhibitors. Studies in BALB/c mice showed that verapamil in combination with first-line drugs significantly reduced pulmonary CFUs after 1 and 2 months treatment (p < 0.05)., Conclusion: Exposure of rifampicin resistant M. tuberculosis strains to rifampicin can potentially compromise the efficacy of the second-line treatment regimens containing ofloxacin, thereby emphasising the need for rapid diagnostics to guide treatment. Efflux pump inhibitors have the potential to improve the efficacy of anti-tuberculosis drug treatment.
- Published
- 2011
- Full Text
- View/download PDF
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