Publications by authors named "Karen Cilliers"

11 Publications

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Mycobacterium tuberculosis-stimulated whole blood culture to detect host biosignatures for tuberculosis treatment response.

Tuberculosis (Edinb) 2021 Apr 10;128:102082. Epub 2021 Apr 10.

DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Host markers to monitor the response to tuberculosis (TB) therapy hold some promise. We evaluated the changes in concentration of Mycobacterium tuberculosis (M.tb)-induced soluble biomarkers during early treatment for predicting short- and long-term treatment outcomes. Whole blood samples from 30 cured and 12 relapsed TB patients from diagnosis, week 1, 2, and 4 of treatment were cultured in the presence of live M.tb for seven days and patients followed up for 24 weeks after the end of treatment. 57 markers were measured in unstimulated and antigen-stimulated culture supernatants using Luminex assays. Top performing multi-variable models at diagnosis using unstimulated values predicted outcome at 24 months after treatment completion with a sensitivity of 75.0% (95% CI, 42.8-94.5%) and specificity of 72.4% (95% CI, 52.8-87.3%) in leave-one-out cross validation. Month two treatment responder classification was correctly predicted with a sensitivity of 79.2% (95% CI, 57.8-92.9%) and specificity of 92.3% (95% CI, 64.0-99.8%). This study provides evidence of the early M.tb-specific treatment response in TB patients but shows that the observed unstimulated marker models are not outperformed by stimulated marker models. Performance of unstimulated predictive host marker signatures is promising and requires validation in larger studies.
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http://dx.doi.org/10.1016/j.tube.2021.102082DOI Listing
April 2021

Trace element alterations in Alzheimer's disease: A review.

Authors:
Karen Cilliers

Clin Anat 2021 Feb 13. Epub 2021 Feb 13.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa.

Dyshomeostasis of trace elements have been implicated in the progression of Alzheimer's disease (AD), which is characterized by amyloid-β (Aβ) plaques. Trace elements are particularly associated with the Aβ plaques. Metal-protein attenuating compounds have been developed to inhibit metals from binding to Aβ proteins, which result in Aβ termination, in the hope of improving cognitive functioning. However, there are still some contradicting reports. This review aims to first establish which trace elements are increased or decreased in the brains of Alzheimer's patients, and secondly, to review the effectiveness of clinical trials with metal-protein attenuating compounds for AD. Studies have consistently reported unchanged or increased iron, contradicting reports for zinc, decreased copper, unchanged or decreased manganese, inconsistent results for calcium, and magnesium seems to be unaffected. However, varied results have been reported for all trace elements. Clinical trials using metal-protein attenuating compounds to treat AD have also reported varied results. Copper chelators have repeatedly been used in clinical trials, even though few studies report increased brain copper levels in AD patients. Homeostasis of copper levels is important since copper has a vital role in several enzymes, such as cytochrome c, Cu/Zn superoxide dismutase and ceruloplasmin. Dyshomeostasis of copper levels can lead to increased oxidative stress and neuronal loss. Future studies should assess a variety of trace element levels in moderately and severely affected AD patients since there are contradicting reports. This review thus provides some insight into trace element alterations in the brains of individuals with AD.
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http://dx.doi.org/10.1002/ca.23727DOI Listing
February 2021

Effect of human immunodeficiency virus on the brain: A review.

Anat Rec (Hoboken) 2020 Nov 24. Epub 2020 Nov 24.

Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg, Western Cape, South Africa.

Thirty million people are infected with human immunodeficiency virus (HIV) worldwide, and HIV-associated neurocognitive disorder (HAND) is one of the most common comorbidities of HIV. However, the effect of HIV on the brain has not been fully investigated. This article aimed to review the changes to the brain due to HIV in terms of atrophy, diffusion changes, and hyperintensities. Studies have observed significant atrophy in subcortical gray matter, as well as in cortical white and gray matter. Moreover, the ventricles enlarge, and the sulci widen. Although HIV causes changes to the white and gray matter of the brain, few diffusion tensor imaging studies have investigated the changes to gray matter integrity. White and gray matter hyperintensities have frequently been observed in HIV-positive individuals, with the subcortical gray matter (caudate nucleus and putamen) and periventricular white matter frequently affected. In conclusion, subcortical gray matter is the first brain region to be affected and is affected most severely. Additionally, this review highlights the gaps in the literature, since the effect of HIV on the brain is not fully known. Future studies should continue to investigate the effect of HIV on the brain in different stages of the disease, and alternate therapies should be developed since highly active antiretroviral therapy is currently ineffective at treating HAND.
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http://dx.doi.org/10.1002/ar.24573DOI Listing
November 2020

Multi-element Analysis of Brain Regions from South African Cadavers.

Biol Trace Elem Res 2021 Feb 2;199(2):425-441. Epub 2020 May 2.

Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg, Western Cape, South Africa.

Trace elements are vital for a variety of functions in the brain. However, an imbalance can result in oxidative stress. It is important to ascertain the normal levels in different brain regions, as such information is still lacking. Therefore, this study aimed to provide baseline trace element concentrations from a South African population, as well as determine trace element differences between sex and brain regions. Samples from the caudate nucleus, putamen, globus pallidus and hippocampus were analysed using inductively coupled plasma mass spectrometry. Aluminium, antimony, arsenic, barium, boron, cadmium, calcium, chromium, cobalt, copper, iron, lead, magnesium, manganese, mercury, molybdenum, nickel, phosphorus, potassium, selenium, silicon, sodium, strontium, vanadium and zinc were assessed. A multiple median regression model was used to determine differences between sex and regions. Twenty-nine male and 13 female cadavers from a Western Cape, South African population were included (mean age 35 years, range 19 to 45). Trace element levels were comparable to those of other populations, although magnesium was considerably lower. While there were no sex differences, significant anatomical regional differences existed; the caudate nucleus and hippocampus were the most similar, and the globus pallidus and hippocampus the most different. In conclusion, this is the first article to report the trace element concentrations of brain regions from a South African population. Low magnesium levels in the brain may be linked to a dietary deficiency, and migraines, depression and epilepsy have been linked to low magnesium levels. Future research should be directed to increase the dietary intake of magnesium.
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http://dx.doi.org/10.1007/s12011-020-02158-zDOI Listing
February 2021

Effect of Human Immunodeficiency Virus on Trace Elements in the Brain.

Biol Trace Elem Res 2021 Jan 1;199(1):41-52. Epub 2020 Apr 1.

Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg, Western Cape, South Africa.

Comorbidities of human immunodeficiency virus (HIV) include HIV-associated neurocognitive disorder (HAND). Changes in the brain due to HIV include atrophy, hyperintensities, and diffusion changes. However, no research has focused on trace elements concentration changes in the brain due to HIV, as seen in other neurodegenerative diseases. Therefore, the aim of this study was to determine the concentration of several trace elements in the brains of individuals with and without HIV infection. Prior to formalin embalming, blood was drawn and tested in triplicate with Determine HIV-1/2 rapid tests and confirmed with a SD HIV Device 1/2 3.0 rapid HIV Kit. After embalming, tissue was sampled from the caudate nucleus and analyzed using inductively coupled plasma mass spectrometry. A Kruskal-Wallis test was used to determine statistically significant differences between the two groups (p < 0.05). Fifteen HIV-positive and 14 HIV-negative male cadavers were included (mean age 44, range 22 to 61). Cadmium was marginally decreased, possibly due to malnutrition or utilization by the HIV nucleocapsid. Nickel was marginally increased, perhaps due to a reduced capability to remove metals from the body. In conclusion, this article provides the first information on trace element levels in the brains from HIV-infected individuals and postulates that cadmium and nickel may play a role in the pathophysiology of HAND. This information can contribute to finding a treatment for HAND, other than the use of antiretroviral drugs. Future studies should asses the levels of cadmium and nickel in a larger cohort of HIV-infected individuals.
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http://dx.doi.org/10.1007/s12011-020-02129-4DOI Listing
January 2021

Trace Element Concentration Changes in Brain Tumors: A Review.

Anat Rec (Hoboken) 2020 05 6;303(5):1293-1299. Epub 2019 Oct 6.

Division of Clinical Anatomy, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Western Cape, South Africa.

Trace elements have been implicated in cancer, since the levels differ between cancerous and noncancerous tissue, different cancer types, and different malignancy grades. However, few studies have been conducted on trace element concentrations in brain tumors. Thus, this study aims to review the available literature on trace element changes related to brain tumors, and to identify gaps in the literature. A literature search was done on Google Scholar and PubMed from their start date to January 2018, using terms related to trace element concentration and brain tumors. All brain tumor types were included, and articles could be published in any year. From this search, only 11 articles on this topic could be found. Tumors had significantly higher concentrations of arsenic, thorium, lanthanum, lutetium, cerium, and gadolinium compared to control brain samples. Compared to adjacent tissue, tumor tissue indicated increased magnesium, decreased copper, and contradicting results for zinc. Furthermore, the higher the malignancy grade, the lower the calcium, cadmium, iron, phosphorus and sulfur concentration, and the higher the mercury, manganese, lead, and zinc concentrations. In conclusion, altered trace element levels differ amongst different tumor types, as well as malignancy grades. Consequently, it is impossible to compare data from these studies, and available data are still considerably inconclusive. Ideally, future studies should have a sufficient samples size, compare different tumor types, and compare tumors with adjacent healthy tissue as well as with samples from unaffected matched brains. Anat Rec, 303:1293-1299, 2020. © 2019 American Association for Anatomy.
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http://dx.doi.org/10.1002/ar.24254DOI Listing
May 2020

Human immunodeficiency virus in cadavers: A review.

Clin Anat 2019 May 21;32(4):603-610. Epub 2019 Mar 21.

Division of Clinical Anatomy, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Western Cape, South Africa.

Millions of people are infected with human immunodeficiency virus (HIV); however, limited research focuses on post-mortem HIV detection. Post-mortem HIV testing is vital because medical records are not always available, and the HIV status can be unknown. The aims of this study were to review the available literature and determine the most efficient HIV test for post-mortem samples, the optimal tissue or bodily fluid to be tested, and the duration that HIV remains reliably detectable. A literature search was conducted using PubMed and Google Scholar. Terms were related to HIV (HIV detection, HIV testing, HIV prevalence) and deceased individuals (post-mortem, cadaver, deceased, organ donor). Inclusion criteria included English studies, or articles with at least an English abstract, while review articles were excluded. From this literature search, 43 studies were applicable. These studies most commonly used enzyme-linked immunosorbent assay and Western blot as screening and confirmation tests, respectively. As for the optimal tissue or bodily fluid, serum remained the golden standard, while testing skin seemed promising. HIV remains detectable in the body up to 58 days after death, although few studies tested samples after 48 h. Knowledge of the HIV status can be beneficial in the case of accidental exposure and can create a range of possible research opportunities on the effects of HIV in different organ systems. This review outlined several gaps in the current literature and future studies should investigate these gaps because this information can be relevant to numerous professions. Clin. Anat. 32:603-610, 2019. © 2019 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ca.23358DOI Listing
May 2019

Variation and Anomalies of the Posterior Cerebral Artery: Review and Pilot Study.

Turk Neurosurg 2019 ;29(1):1-8

Stellenbosch University, Department of Anatomy and Histology, Cape Town, South Africa.

Variations and anomalies of the posterior cerebral artery (PCA) have several clinical implications, including assisting in understanding the clinical signs of a stroke. Anomalies have been described previously; however, few reports mention the origins, absence, duplication and triplication of the cortical branches. Furthermore, the PCA branching pattern has not been adequately described. The aim of this study was to describe the anatomy and anomalies of the PCA. Results of a pilot study were additionally included. The quantity, origin, diameter and length of the PCA cortical branches were described in this review, as well as the branching pattern and the anomalies. Accordingly, the pilot study reported on these aspects. In the pilot study it was evident that the description of the branching pattern is not the "normal" pattern, since it was only observed in one case. This pattern was re-evaluated and three groups were described; monofurcation, bifurcation and trifurcation. Furthermore, one case of a fenestration was observed. Aneurysms tend to form at branching points, thus knowledge of the branching pattern can aid in detection of ruptured and unruptured aneurysms in this region. This review outlined several gaps in the literature, and a pilot study was included to fill some of these gaps. Future research should especially focus on the branching pattern of the PCA. Possible sex, age and population differences may also exist.
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http://dx.doi.org/10.5137/1019-5149.JTN.21443-17.2DOI Listing
February 2019

The anatomical variation of the circulus arteriosus cerebri in a cadaver cohort representing the population dynamics of the Western Cape.

Br J Neurosurg 2018 Feb 5;32(1):61-67. Epub 2017 Sep 5.

a Anatomy & Histology, Faculty of Medicine and Health Sciences , Stellenbosch University , Cape Town , South Africa.

The literature revealed a connection between the variations of the Circulus arteriosus cerebri (CAC) and cerebrovascular disease, ischemia, stroke, aneurysms and atherosclerosis. The diameters of the vessels forming the CAC have been classified into 22 types by previous authors. The aim of this study was to assess the variation of the CAC (diameter, length and anomalies) in a cadaver cohort representing the population of the Western Cape. Thirty-nine subjects (female n = 11, male n = 28) who had died of causes unrelated to brain trauma, were obtained from Stellenbosch University. Additionally, a pilot study was done on 20 specimens. The CAC were removed and fixed for three weeks in 10% buffered formaldehyde. Digital images were taken and the vessels were measured using Adobe Creative Suite 5: Extended edition (Photoshop). The normal diameter (type 1) was observed in 41% of specimens and type 4 (hypoplastic posterior communicating artery) was observed in 23.1%. One case (bilateral hypoplastic posterior communicating arteries and a hypoplastic right posterior cerebral artery) was classified as "other", since it could not be classified into the 22 types. Additional variations included duplication (17.9%) and one point fusion (15.4%) of the anterior communicating artery. Studies have shown that about half of a healthy population have a typical CAC (normal diameter and no anomalies). In the present study the prevalence of a typical CAC was only 15.4%. Studies can only be compared if the same definitions for variations are used. The knowledge of these variations is important in endarterectomy, stenting head and neck surgery and angiography.
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http://dx.doi.org/10.1080/02688697.2017.1374348DOI Listing
February 2018

Anatomy of the Middle Cerebral Artery: Cortical Branches, Branching Pattern and Anomalies.

Turk Neurosurg 2017 ;27(5):671-681

Stellenbosch University, Department of Anatomy and Histology, Cape Town, South Africa.

The middle cerebral artery (MCA) covers a large part of the cerebral hemispheres and is therefore exposed during surgical intervention in this area. Aspects of cerebral branches tend to vary, different branching patterns can be described, and several anomalies can be observed. Knowledge of these variations and anomalies is important and can be helpful to neurosurgeons and clinicians. The aim of this manuscript was to review the available literature on the cortical branches, branching pattern and anomalies of the MCA, to identify the gaps in the literature, and to fill these gaps by including the results of a pilot study. Twenty hemispheres were perfused with colored silicone and the MCA was dissected. For the cortical branches, the diameter, length, presence, duplication and origins were noted. Most commonly duplicated was the anterior parietal artery in 30.0%, and most commonly absent was the common temporal artery in 65.0%. A detailed description on the origins is given. Criteria were described for the bifurcation subtypes and medial bifurcation (50.0%) was most commonly observed. No anomalies were observed. Aspects previously neglected of the MCA cortical branches were reported in the pilot study. The branching subtypes were identified and criteria are given. Illustrations of the different branching subtypes and anomalies are provided. Certain aspects of the MCA anatomy have been neglected, and future studies should give adequate descriptions of the MCA cortical branches, MCA branching pattern, and any anomalies observed.
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http://dx.doi.org/10.5137/1019-5149.JTN.18127-16.1DOI Listing
March 2018

Review of the Anatomy of the Distal Anterior Cerebral Artery and Its Anomalies.

Turk Neurosurg 2016 ;26(5):653-61

Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Anatomy and Histology, Cape Town, Western Cape, South Africa.

The anterior cerebral artery (ACA) varies considerably and this complicates the description of the normal anatomy. The segmentation of the ACA is mostly agreed on by different authors, although the relationship of the pericallosal and callosomarginal arteries (CmA) is not agreed upon. The two basic configurations of the ACA are determined by the presence or absence of the CmA. The diameter, length and origin of the cortical branches have been measured and described by various authors and display great variability. Common anomalies of the ACA include the azygos, bihemispheric, and median anterior cerebral arteries. A pilot study was done on 19 hemispheres to assess the variation of the branches of the ACA. The most common variations included absence and duplication. The inferior internal parietal artery and the CmA were most commonly absent and the paracentral lobule artery was the most frequently duplicated (36.8%). The inferior internal parietal artery originated from the posterior cerebral artery in 40.0% and this was the most unusual origin observed. It is important to be aware of the possibility of variations since these variations can have serious clinical implications. The knowledge of these variations can be helpful to clinicians and neurosurgeons. The aim of this article is to review the anatomy and variations of the anterior cerebral artery, as described in the literature. This was also compared to the results from a pilot study.
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http://dx.doi.org/10.5137/1019-5149.JTN.14294-15.1DOI Listing
April 2017