42 results on '"Spruyt M"'
Search Results
2. South African guidelines on the determination of death
- Author
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Thomson, D, Jouber, I, De Vasconcellos, K, Paruk, F, Mokogong, S, Mathivha, R, McCulloch, M, Morrow, B, Baker, D, Rossouw, B, Mdladla, N, Richards, G A, Welkovics, N, Levy, B, Coetzee, I, Spruyt, M, Ahmed, N, and Gopalan, D
- Abstract
Death is a medical occurrence that has social, legal, religious and cultural consequences requiring common clinical standards for its diagnosis and legal regulation. This document compiled by the Critical Care Society of Southern Africa outlines the core standards for determination of death in the hospital context. It aligns with the latest evidence-based research and international guidelines and is applicable to the South African context and legal system. The aim is to provide clear medical standards for healthcare providers to follow in the determination of death, thereby promoting safe practices and high-quality care through the use of uniform standards. Adherence to such guidelines will provide assurance to medical staff, patients, their families and the South African public that the determination of death is always undertaken with diligence, integrity, respect and compassion, and is in accordance with accepted medical standards and latest scientific evidence. The consensus guidelines were compiled using the AGREE II checklist with an 18-member expert panel participating in a three-round modified Delphi process. Checklists and advice sheets were created to assist with application of these guidelines in the clinical environment (https://criticalcare.org.za/resource/death-determination-checklists/). Key points • Brain death and circulatory death are the accepted terms for defining death in the hospital context.• Death determination is a clinical diagnosis which can be made with complete certainty provided that all preconditions are met.• The determination of death in children is held to the same standard as in adults but cannot be diagnosed in children
- Published
- 2023
3. South African guidelines on the determination of death
- Author
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Baker, D, Gopalan, D, Ahmed, N, Spruyt, M, Coetzee, I, Levy, B, Welkovics, N, Richards, G A, Mdladla, N, Rossouw, B, Thomson, D, Morrow, B, McCulloch, M, Mathivha, R, Mokogong, S, Paruk, F, De Vasconcellos, K, and Joubert, I
- Abstract
Death is a medical occurrence that has social, legal, religious and cultural consequences requiring common clinical standards for its diagnosis and legal regulation. This document compiled by the Critical Care Society of Southern Africa outlines the core standards for determination of death in the hospital context. It aligns with the latest evidence-based research and international guidelines and is applicable to the South African context and legal system. The aim is to provide clear medical standards for healthcare providers to follow in the determination of death, thereby promoting safe practices and high-quality care through the use of uniform standards. Adherence to such guidelines will provide assurance to medical staff, patients, their families and the South African public that the determination of death is always undertaken with diligence, integrity, respect and compassion, and is in accordance with accepted medical standards and latest scientific evidence. The consensus guidelines were compiled using the AGREE II checklist with an 18-member expert panel participating in a three-round modified Delphi process. Checklists and advice sheets were created to assist with application of these guidelines in the clinical environment (https://criticalcare.org.za/resource/death-determination-checklists/).Key points• Brain death and circulatory death are the accepted terms for defining death in the hospital context.• Death determination is a clinical diagnosis which can be made with complete certainty provided that all preconditions are met.• The determination of death in children is held to the same standard as in adults but cannot be diagnosed in children
- Published
- 2022
4. Iatrogenic blood loss in critical care: A prospective observational study conducted at Universitas Academic Hospital in the Free State Province, South Africa
- Author
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Adams, J C, primary, Barrett, C, additional, and Spruyt, M, additional
- Published
- 2022
- Full Text
- View/download PDF
5. Adapted tracer gas test for passive measurement of total air change rates using alternative tracer substance
- Author
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Paralovo, Sarah Lima, primary, Stranger, M., additional, Lazarov, B., additional, Spruyt, M., additional, and Laverge, J., additional
- Published
- 2021
- Full Text
- View/download PDF
6. Adapted tracer gas test for passive measurement of total air change rates using alternative tracer substance.
- Author
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Paralovo, Sarah Lima, Stranger, M., Lazarov, B., Spruyt, M., and Laverge, J.
- Subjects
ENVIRONMENTAL sampling ,GASES ,PERFLUOROCARBONS - Abstract
This paper describes the development of a new adaptation of the traditional tracer gas test (TGT) used for total air change rates (ACH) measurement. This adapted TGT, based on constant tracer injection, is intended for use in large-scale IAQ assessments and employs an alternative tracer gas that is more adequate than the currently employed SF
6 and perfluorocarbons, and that can be co-captured and co-analyzed with commonly assessed VOCs by commercial passive IAQ-sampling. As it is based on passive sampling, the proposed TGT yields long-term integrated ACH values, and is thus indicated only for studies focused on characterizations based on average estimations rather than on analyses requiring fine temporal resolution. By means of literature study and lab experiments, decane-D22 was selected as a suitable tracer substance. The selected tracer was shown not to adhere/absorb significantly to surfaces. A passive source of decane-D22 was selected and optimized in lab, providing stable and repeatable emission rates unaffected by varying RH and ACH. An exponential prediction curve was derived for determining the source emission rate from the average room temperature. Moreover, a range of adequate levels of liquid tracer inside the source is suggested. A successful field test application for validation of the new TGT is also described. [ABSTRACT FROM AUTHOR]- Published
- 2022
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7. Impact of depatuxizumab mafodotin on health-related quality of life and neurological functioning in the phase II EORTC 1410/INTELLANCE 2 trial for EGFR-amplified recurrent glioblastoma
- Author
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Clement, PM, Dirven, L, Eoli, M, Sepulveda-Sanchez, JM, Walenkamp, AM, Frenel, J S, Franceschi, E, Weller, M, Chinot, O, de Vos, FYF, Whenham, N, Sanghera, P, Looman, J, Kundu, MG, Peter de Geus, J, Nuyens, S, Spruyt, M, Gorlia, T, Coens, C, Golfinopoulos, V, Reijneveld, JC, van den Bent, Martin, Clement, PM, Dirven, L, Eoli, M, Sepulveda-Sanchez, JM, Walenkamp, AM, Frenel, J S, Franceschi, E, Weller, M, Chinot, O, de Vos, FYF, Whenham, N, Sanghera, P, Looman, J, Kundu, MG, Peter de Geus, J, Nuyens, S, Spruyt, M, Gorlia, T, Coens, C, Golfinopoulos, V, Reijneveld, JC, and van den Bent, Martin
- Abstract
Background: In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody–drug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFR-amplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular dose-limiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis. Patients and methods: Patients (n = 260) were randomised 1:1:1 to receive either Depatux-M 1.25 mg/kg or 1.0 mg/kg intravenously every 2 weeks with oral temozolomide (TMZ) 150 mg/m2, Depatux-M alone, or TMZ or oral lomustine (CCNU) 110 mg/m2 (TMZ/CCNU). HRQoL outcomes were recorded using the EORTC core Quality of Life QLQ-C30, and brain cancer-specific QLQ-BN20 questionnaires. Questionnaires were completed at baseline, weeks 8 and 16, and month 6, and changes from baseline to each time point were calculated. NDFS was defined as time to first deterioration in World Health Organisation performance status. Results: Compliance with HRQoL was 88.1% at baseline and decreased to 37.9% at month 6. Differences from baseline between Depatux-M arms and TMZ/CCNU in global health/QoL status throughout treatment did not reach clinical relevance (≥10 points). Self-reported visual disorders deteriorated to a clinically relevant extent with Depatux-M arms versus TMZ/CCNU at all timepoints (mean differences range: 24.6–35.1 points). Changes from baseline for other HRQoL scales and NDFS were generally similar between treatment arms. Conclusions: Depatux-M had no impact on HRQoL and NDFS in patients with EGFR-amplified recurrent glioblastoma, except for more visual disorders, an expected side-effect of the study drug. Clinical trial registration: NCT02343406.
- Published
- 2021
8. South African Guidelines on the Determination of Death
- Author
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Thomson, D, primary, Joubert, I, additional, De Vasconsellos, K, additional, Paruk, F, additional, Mokogong, S, additional, Mathivha, R, additional, McCulloch, M, additional, Morrow, B, additional, Baker, D, additional, Roussouw, B, additional, Mdladla, N, additional, Richards, G A, additional, Levy, B, additional, Coetzee, I, additional, Spruyt, M, additional, Ahmed, N, additional, and Gopalan, D, additional
- Published
- 2021
- Full Text
- View/download PDF
9. INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma
- Author
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Bent, M.J. (Martin) van den, Eoli, M. (Marica), Sepulveda, J.M. (Juan Manuel), Smits, M. (Marion), Walenkamp, A.M.E. (Annemiek M.), Frenel, J.-S. (Jean-Sebastian), Franceschi, C. (Claudio), Clement, P.M.J. (Paul), Chinot, O., De Vos, F. (Filip), Whenham, N. (Nicolas), Sanghera, P. (Paul), Weller, M. (Michael), Dubbink, H.J. (Erik Jan), French, P.J. (Pim), Looman, J. (Jim), Dey, J. (Jyotirmoy), Krause, S. (Scott), Ansell, P. (Pete), Nuyens, S. (Sarah), Spruyt, M. (Maarten), Brilhante, J. (Joana), Coens, C. (Corneel), Gorlia, T.S. (Thierry), Golfinopoulos, V. (Vassilis), Bent, M.J. (Martin) van den, Eoli, M. (Marica), Sepulveda, J.M. (Juan Manuel), Smits, M. (Marion), Walenkamp, A.M.E. (Annemiek M.), Frenel, J.-S. (Jean-Sebastian), Franceschi, C. (Claudio), Clement, P.M.J. (Paul), Chinot, O., De Vos, F. (Filip), Whenham, N. (Nicolas), Sanghera, P. (Paul), Weller, M. (Michael), Dubbink, H.J. (Erik Jan), French, P.J. (Pim), Looman, J. (Jim), Dey, J. (Jyotirmoy), Krause, S. (Scott), Ansell, P. (Pete), Nuyens, S. (Sarah), Spruyt, M. (Maarten), Brilhante, J. (Joana), Coens, C. (Corneel), Gorlia, T.S. (Thierry), and Golfinopoulos, V. (Vassilis)
- Abstract
BACKGROUND: Depatuxizumab mafodotin (Depatux-M) is a tumor-specific antibody-drug conjugate consisting of an antibody (ABT-806) directed against activated epidermal growth factor receptor (EGFR) and the toxin monomethylauristatin-F. We investigated Depatux-M in combination with temozolomide or as a single agent in a randomized controlled phase II trial in recurrent EGFR amplified glioblastoma. METHODS: Eligible were patients with centrally confirmed EGFR amplified glioblastoma at first recurrence after chemo-irradiation with temozolomide. Patients were randomized to either Depatux-M 1.25 mg/kg every 2 weeks intravenously, or this treatment combined with temozolomide 150-200 mg/m2 day 1-5 every 4 weeks, or either lomustine or temozolomide. The primary endpoint of the study was overall survival. RESULTS: Two hundred sixty patients were randomized. In the primary efficacy analysis with 199 events (median follow-up 15.0 mo), the hazard ratio (HR) for the combination arm compared with the control arm was 0.71 (95% CI = 0.50, 1.02; P = 0.062). The efficacy of Depatux-M monotherapy was comparable to that of the control arm (HR = 1.04, 95% CI = 0.73, 1.48; P = 0.83). The most frequent toxicity in Depatux-M treated patients was a reversible corneal epitheliopathy, occurring as grades 3-4 adverse events in 25-30% of patients. In the long-term follow-up analysis with median follow-up of 28.7 months, the HR for the comparison of the combination arm versus the control arm was 0.66 (95% CI = 0.48, 0.93). CONCLUSION: This trial suggests a possible role for the use of Depatux-M in combination with temozolomide in EGFR amplified recurrent glioblastoma, especially in patients relapsing well after the end of first-line adjuvant temozolomide treatment. (NCT02343406).
- Published
- 2020
- Full Text
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10. INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma
- Author
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van den Bent, Martin, Eoli, M, Sepulveda, JM, Smits, Marion, Walenkamp, A, Frenel, J S, Franceschi, E, Clement, PM, Chinot, O, Vos, F, Whenham, N, Sanghera, P, Weller, M, Dubbink, Erik jan, French, Pim, Looman, J, Dey, D, Krause, S, Ansell, P, Nuyens, S, Spruyt, M, Brilhante, J, Coens, C, Gorlia, T, Golfinopoulos, V, van den Bent, Martin, Eoli, M, Sepulveda, JM, Smits, Marion, Walenkamp, A, Frenel, J S, Franceschi, E, Clement, PM, Chinot, O, Vos, F, Whenham, N, Sanghera, P, Weller, M, Dubbink, Erik jan, French, Pim, Looman, J, Dey, D, Krause, S, Ansell, P, Nuyens, S, Spruyt, M, Brilhante, J, Coens, C, Gorlia, T, and Golfinopoulos, V
- Published
- 2020
11. Real-time selected ion flow tube mass spectrometry to assess short- and long-term variability in oral and nasal breath
- Author
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Slingers, G, primary, Goossens, R, additional, Janssens, H, additional, Spruyt, M, additional, Goelen, E, additional, Vanden, Eede M, additional, Raes, M, additional, and Koppen, G, additional
- Published
- 2020
- Full Text
- View/download PDF
12. South African guidelines on the determination of death.
- Author
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Thomson, D., Joubert, I., De Vasconcellos, K., Paruk, F., Mokogong, S., Mathivha, R., McCulloch, M., Morrow, B., Baker, D., Rossouw, B., Mdladla, N., Richards, G. A., Welkovics, N., Levy, B., Coetzee, I., Spruyt, M., Ahmed, N., and Gopalan, D.
- Published
- 2021
- Full Text
- View/download PDF
13. Real-time selected ion flow tube mass spectrometry to assess short- and long-term variability in oral and nasal breath.
- Author
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Slingers, G, Goossens, R, Janssens, H, Spruyt, M, Goelen, E, Vanden, Eede M, Raes, M, and Koppen, G
- Subjects
MASS spectrometry ,DIMETHYL sulfide ,BENZENE compounds ,ACETONE ,ACETALDEHYDE ,TUBES - Abstract
Breath-based non-invasive diagnostics have the potential to provide valuable information about a person's health status. However, they are not yet widely used in clinical practice due to multiple factors causing variability and the lack of standardized procedures. This study focuses on the comparison of oral and nasal breathing, and on the variability of volatile metabolites over the short and long term. Selected ion flow tube mass spectrometry (SIFT-MS) was used for online analysis of selected volatile metabolites in oral and nasal breath of 10 healthy individuals five times in one day (short-term) and six times spread over three weeks (long-term), resulting in nearly 100 breath samplings. Intra-class correlation coefficients (ICCs) were used to assess short- and long-term biological variability. Additionally, the composition of ambient air was analyzed at different samplings. The selected volatiles common in exhaled breath were propanol, 2,3-butanedione, acetaldehyde, acetone, ammonia, dimethyl sulfide, isoprene, pentane, and propanal. Additionally, environmental compounds benzene and styrene were analyzed as well. Volatile metabolite concentrations in ambient air were not correlated with those in exhaled breath and were significantly lower than in breath samples. All volatiles showed significant correlation between oral and nasal breath. Five were significantly higher in oral breath compared to nasal breath, while for acetone, propanal, dimethyl sulfide, and ammonia, concentrations were similar in both matrices. Variability depended on the volatile metabolite. Most physiologically relevant volatiles (acetone, isoprene, propanol, acetaldehyde) showed good to very good biological reproducibility (ICC > 0.61) mainly in oral breath and over a short-term period of one day. Both breathing routes showed relatively similar patterns; however, bigger differences were expected. Therefore, since sampling from the mouth is practically more easy, the latter might be preferred. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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14. Compliance With A Three Month Telecoaching Program To Enhance Physical Activity In Patients With Chronic Obstructive Pulmonary Disease
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Loeckx, M., Louvaris, Z., Tanner, R. J., Yerramasu, C., Buesching, G., Frei, A., Oosterom, H., Spruyt, M., Jong, de, Corina, Gimeno-Santos, E., Perez, C., Rabinovich, R., Vogiatzis, I., Puhan, M. A., Polkey, M. I., Aymerich, J. Garcia, Troosters, T., Demeyer, H., and Groningen Research Institute for Asthma and COPD (GRIAC)
- Published
- 2015
15. Starch safety in resuscitation
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Hodgson, R E, Richards, G A, Lundgren, A C, Spruyt, M G L, Pretorius, J P, Mathiva, L R, Dickerson, R, and Gopalan, P D
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biological phenomena, cell phenomena, and immunity ,reproductive and urinary physiology - Published
- 2013
16. De ‘sterke punten’-benadering werkt. Onderzoek naar effecten van aandacht voor talent
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van Woerkom, M., Stienstra, M., Tjepkema, S., Spruyt, M., and Department of Human Resource Studies
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ComputingMilieux_LEGALASPECTSOFCOMPUTING - Published
- 2011
17. Umberto Eco’s The Mysterious Flame of Queen Loana: A conduit for culture, consciousness and cognition
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Spruyt, M
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postmodernist literature, graphic novel, culture, archetypes - Abstract
Eco’s novel describes the popular culture of the Italian fascist period, by deconstructing signs, symbols and signals from a particular period in the lives of both the author and his protagonist. In this sense, the novel can be regarded as a crossover between two genres, the literary and historical. However, the mixture of art and text as a medium for storytelling, or for making references to the human condition, places it in the genre of the graphic novel. This article explores the novel on three levels. A surface reading establishes it as an historical construct, which prioritizes unofficial memory and popular culture. On a deeper level, however, the protagonist’s search into his past can be regarded, in a Jungian sense, as an archetypal journey of discovery. On a third level the ancestral home, Solara, can be regarded as a metaphor for, on the one hand, the collective unconscious, where recurring symbols and motifs act as transformational metaphors and often serve as links between states and levels of consciousness and, on the other hand, for the human brain. Keywords: postmodernist literature, graphic novel, culture, archetypes
- Published
- 2010
18. Critical care admission of South African (SA) surgical patients: Results of the SA Surgical Outcomes Study.
- Author
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Skinner, D. L., de Vasconcellos, K., Wise, R., Esterhuizen, T. M., Fourie, C., Mahomed, A. Goolam, Gopalan, P. D., Joubert, I., Kluyts, H., Mathivha, L. R., Mrara, B., Pretorius, J. P., Richards, G., Smith, O., Spruyt, M. G. L., Pearse, R. M., Madiba, T. E., and Biccard, B. M.
- Published
- 2017
- Full Text
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19. Therapeutic drug monitoring for continuous infusion of vancomycin in critically ill patients
- Author
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Van den Heever, T., Spruyt, M. G. L., Van den Heever, T., and Spruyt, M. G. L.
- Abstract
English: Introduction Studies on therapeutic drug monitoring for continuous infusion of vancomycin in critically ill patients are scant. It has been proven that therapeutic levels of 15 – 20 mg/L is effective in treating severe gram positive infections and if kept in this range the amount of drug entering in and out of the tissue are equal. A loading dose of 15mg/kg should be administered irrespective of the renal function. The maintenance infusion in non renal impaired patients should be 30mg/kg and adjusted on a daily basis according levels. This study was over a short period of time and no nephrotoxicity was detected. Methods A prospective analytical study of 10 consecutive patients meeting the inclusion criteria, admitted to the Multidisciplinary Intensive Care Unit at Universitas Hospital was applied. Results were summarised by means of standard deviations or percentiles (numerical variables), frequencies and percentages (categorical variables). The distribution volume was used to calculate the estimated dosage of vancomycin to be given in order to achieve a therapeutic plasma concentration, in the case of vancomycin 15 – 20 mg/L. A loading does of 15mg/kg in 200ml 5% dextrose water over a 2 hour period was administered. Immediately after the loading dose a constant infusion of 30mg/kg in 200ml 5% dextrose water was started at a rate of 8ml/hr ivi. Results Of the thirteen patients only ten met the inclusion criteria. After the loading dose the mean concentration was 34,9 mg/L. The mean concentration after the first, second and third time interval was between 15 – 20 mg/L. The mean time to reach therapeutic levels of 15 – 20 mg/L was 21 hours. A mean elimination constant of 0.150 was shown to be the most effective in obtaining therapeutic levels whilst on a constant vancomycin infusion. If the elimination constant was more than 0.150 then the maintenance dosage had to be reduced and vice versa. The mean total Vancomycin administered to reach therapeutic levels w, Afrikaans: Inleiding Daar is huidiglik wynig studies gepubliseer oor die monitoring van ‘n deurlopende infuus van vancomycin. Hierdie studie bewys dat terapeutiese vlakke van 15 – 20 mg/L effektief is in die behandeling van gram positiewe infeksies. Gelykvlak in die weefsel word bereik as terapeutiese vlakke van 15 – 20 mg/L bereik word. ‘n Ladings dosering van 15 mg/kg word aanbeveel ongeag die nierfunksie. Vir pasïente met geen nierfunskie inkorting nie word ‘n instandhoudings dosering van 30 mg/kg aanbeveel. Hierdie studie is oor ‘n kort tydperk uitgevoer en geen nefrotoksisiteit is waargeneem nie. Metodes ‘n Prospektiewe analitiese studie met 10 pasïente wat aan die insluitingskriteria voldoen het, is in die studie ingelsuit. Die studie is gedoen in die Multidissiplinere Intensiewe Sorg Eenheid te Universitas hospitaal. Resultate was opgesom met behulp van standaard deviasies of persentiele (numeriese veranderlikes), frekwensies en persentasies (kategoriese veranderlikes). Die distribusie volume was gebruik om die instandhoudings dosering van vancomycin aan te pas, in orde om ‘n terapeutiese plasma vlak van 15 – 20 mg/L te verkry. Die ladingsdosereing wat gebruik is, is 15 mg/kg opgelos in 200ml 5% Dextrose water. Die ladingsdosering is oor ‘n tydperk van twee ure toegedien. Onmiddelik na die ladingsdosering is die instandhoudings infuus van 30 mg/kg in 200ml 5% dextrose water teen 8 ml per uur begin. Resultate Van die dertien pasïente het slegs tien aan die insluitingskriteria voldoen. Na die ladingsdosering was die gemiddelde vlak 34,9 mg/L. Die gemiddelde konsentrasie na die eerste, tweede en derde tydsinterval was tussen 15 – 20 mg/L. Die gemiddelde tydsduur om ‘n terapeutiese vlak van 15 – 20 mg/L te bereik was 21 uur. Die gemene elliminasie konstante van 0.150 was bewys om die mees effektiefste te wees in orde om terapeutiese vlakke te bereik. As die elliminasie konstante meer as 0.150 was dan moes die instandhoudings dosering verminder word, en vice versa
- Published
- 2011
20. Airflow distribution with manual hyperinflation as assessed through gamma camera imaging: a crossover randomised trial
- Author
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van Aswegen, H., primary, van Aswegen, A., additional, Raan, H. Du, additional, Toit, R. Du, additional, Spruyt, M., additional, Nel, R., additional, and Maleka, M., additional
- Published
- 2013
- Full Text
- View/download PDF
21. PM and NO2 at urban sites with different traffic exposure: curb site measurements in Flemish cities
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Van Poppel, M., primary, De Dekker, E., additional, Int Panis, L., additional, Bleux, N., additional, Spruyt, M., additional, and Berghmans, P., additional
- Published
- 2007
- Full Text
- View/download PDF
22. The Predictive Value of Diagnostic Sonography for the Effectiveness of Conservative Treatment of Tennis Elbow
- Author
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Struijs, P. A. A., primary, Spruyt, M., additional, Assendelft, W. J. J., additional, and van Dijk, C. N., additional
- Published
- 2005
- Full Text
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23. The place of cataloguing and classification in the curricula of South African universities
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Spruyt, M L and Kesting, J G
- Subjects
Cataloging ,Classification ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) - Abstract
Bibliography: pages 361-372., The aim of this study is to determine the place of cataloguing and classification in the library and information science curricula of South African universities today, and to determine whether, in compiling the syllabus comprising bibliographic description and subject analysis, new developments and changes are being taken into consideration. With this in mind, attention has been given to the following: (a) Developments in general have been reconstructed by means of a review of the history of cataloguing and classification, from ancient to present times; (b) a review of the comprehensive development of education for librarianship overseas and in South Africa; and (c) an investigation of the present position of bibliographic description and subject analysis in the curricula of library and information science of South African universities.
- Published
- 1980
24. Postoperative internal iliac artery embolisation as salvage therapy for bleeding in an HIV-positive patient with giant cell tumour of bone.
- Author
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Heever, T. van den, Barrett, C. L., Webb, M. J., Spruyt, M. G. L., and Louw, C. J.
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HEMORRHAGE treatment ,TREATMENT of surgical complications ,SURGICAL blood loss ,ACUTE kidney failure ,BLOOD transfusion ,BONE tumors ,GIANT cell tumors ,ILIAC artery ,OVARIES ,RESUSCITATION ,RETROPERITONEUM ,HIV seroconversion ,RADIOEMBOLIZATION ,SALVAGE therapy ,THERAPEUTICS ,TUMORS - Abstract
Giant cell tumour o f bone (GCTB) is a highly vascular tumour, sporadically complicated by massive bleeding during surgery. We report a rare case of GCTB in an HIV-positive patient who suffered massive blood loss intra-and postoperatively.The patient was a 46-year-old HIV-positive female with symptoms and signs of a pelvic mass, and ultrasound evidence of an ovarian mass. Surgery was performed, and a highly vascular retroperitoneal mass originating from her sacrum was identified. Massive blood loss occurred, which required aggressive resuscitation and transfusion of blood products. Damage control surgery was performed, and bleeding was ultimately only controlled postoperatively using bilateral internal iliac artery radiological embolisation. The patient suffered acute kidney injury, which was multifactorial in aetiology, which recovered within 6 days. She was discharged from ICU in a stable condition 7 days postoperatively. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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25. Starch safety in resuscitation.
- Author
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Hodgson, R. E., Richards, G. A., Lundgren, A. C., Spruyt, M. G. L., Pretorius, J. P., Mathiva, L. R., Dickerson, R., and Gopalan, P. D.
- Published
- 2013
- Full Text
- View/download PDF
26. Annotatie artikelen 393-419 W.I.B.92 en 146-175 K.B.W.I.B.92
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Delanote, Mark, Spruyt, M. De Jonckheere En A., and Fiscaal Recht
- Subjects
niet van toepassing - Abstract
niet van toepassing
- Published
- 2006
27. Corrigendum to INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma.
- Author
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van den Bent M, Eoli M, Sepulveda JM, Smits M, Walenkamp A, Frenel JS, Franceschi E, Clement PM, Chinot O, de Vos F, Whenham N, Sanghera P, Weller M, Dubbink HJ, French P, Looman J, Dey J, Krause S, Ansell P, Nuyens S, Spruyt M, Brilhante J, Coens C, Gorlia T, and Golfinopoulos V
- Published
- 2021
- Full Text
- View/download PDF
28. Impact of depatuxizumab mafodotin on health-related quality of life and neurological functioning in the phase II EORTC 1410/INTELLANCE 2 trial for EGFR-amplified recurrent glioblastoma.
- Author
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Clement PMJ, Dirven L, Eoli M, Sepulveda-Sanchez JM, Walenkamp AME, Frenel JS, Franceschi E, Weller M, Chinot O, De Vos FYFL, Whenham N, Sanghera P, Looman J, Kundu MG, Peter de Geus J, Nuyens S, Spruyt M, Gorlia T, Coens C, Golfinopoulos V, Reijneveld JC, and van den Bent MJ
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized adverse effects, Antineoplastic Agents, Immunological adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Brain Neoplasms diagnosis, Brain Neoplasms genetics, Brain Neoplasms mortality, ErbB Receptors antagonists & inhibitors, ErbB Receptors genetics, Europe, Female, Functional Status, Glioblastoma diagnosis, Glioblastoma genetics, Glioblastoma mortality, Humans, Male, Middle Aged, Neurologic Examination, Progression-Free Survival, Surveys and Questionnaires, Time Factors, Vision Disorders chemically induced, Vision Disorders physiopathology, Vision, Ocular drug effects, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Brain Neoplasms drug therapy, Gene Amplification, Glioblastoma drug therapy, Neoplasm Recurrence, Local, Quality of Life
- Abstract
Background: In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody-drug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFR-amplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular dose-limiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis., Patients and Methods: Patients (n = 260) were randomised 1:1:1 to receive either Depatux-M 1.25 mg/kg or 1.0 mg/kg intravenously every 2 weeks with oral temozolomide (TMZ) 150 mg/m
2 , Depatux-M alone, or TMZ or oral lomustine (CCNU) 110 mg/m2 (TMZ/CCNU). HRQoL outcomes were recorded using the EORTC core Quality of Life QLQ-C30, and brain cancer-specific QLQ-BN20 questionnaires. Questionnaires were completed at baseline, weeks 8 and 16, and month 6, and changes from baseline to each time point were calculated. NDFS was defined as time to first deterioration in World Health Organisation performance status., Results: Compliance with HRQoL was 88.1% at baseline and decreased to 37.9% at month 6. Differences from baseline between Depatux-M arms and TMZ/CCNU in global health/QoL status throughout treatment did not reach clinical relevance (≥10 points). Self-reported visual disorders deteriorated to a clinically relevant extent with Depatux-M arms versus TMZ/CCNU at all timepoints (mean differences range: 24.6-35.1 points). Changes from baseline for other HRQoL scales and NDFS were generally similar between treatment arms., Conclusions: Depatux-M had no impact on HRQoL and NDFS in patients with EGFR-amplified recurrent glioblastoma, except for more visual disorders, an expected side-effect of the study drug., Clinical Trial Registration: NCT02343406., Competing Interests: Conflict of interest statement Linda Dirven, Sarah Nuyens, Maarten Spruyt, Thierry Gorlia, Corneel Coens and Jaap C. Reijneveld have nothing to disclose. Paul M. J. Clement received study budget funds from AstraZeneca; was an advisory board member for AbbVie, AstraZeneca, BMS, Daiichi-Sankyo, Leo Pharma, Merck Serono, MSD and Vifor Pharma. Marica Eoli received consulting fees from AbbVie. Juan M. Sepulveda-Sanchez reports personal fees and non-financial support from AbbVie; a grant from Pfizer as principal investigator; personal fees and non-financial support from Celgene; non-financial support from Ipsen; and personal fees from Astellas. Annemiek M. E. Walenkamp received research grants from IPSEN and Novartis; was an advisory board member for IPSEN, Karyopharm, Novartis and Polyphor; and received study budget funds from AbbVie, BMS, Genzyme, Karyopharm Therapeutics and Roche. Jean Sebastien Frenel has received consulting fees from AstraZeneca, BIOCAD, Lilly, Novartis, Pfizer and Roche. Enrico Franceschi was an advisory board member for Celgene and Karyopharm. Michael Weller has received research grants from AbbVie, Adastra, Merck, Sharp & Dohme (MSD), Merck (EMD) and Novocure; and honoraria for lectures or advisory board participation or consulting from AbbVie, Basilea, Bristol Myers Squibb (BMS), Celgene, Medac, Merck, Sharp & Dohme (MSD), Merck (EMD), Nerviano Medical Sciences, Novartis, Orbus, Philogen, Roche and Tocagen. Olivier Chinot reports personal fees and non-financial support from Abbvie, during the conduct of the study; personal fees from immatics, non-financial support from BMS, non-financial support from Servier, grants, personal fees and non-financial support from Roche, outside the submitted work. Filip Y. F. L. De Vos received research grants from Novartis. Nicholas Whenham has received consulting fees from Bayer and Janssen. Paul Sanghera was an advisory board member for AbbVie and Roche. Jim Looman, Madan G. Kundu and Jan Peter de Geus are AbbVie employees and may own stock. Vassilis Golfinopoulos received research funding from AbbVie during the conduct of the study. Martin J. van den Bent received consulting fees from AbbVie, Agios, Bayer, Boston Pharmaceuticals, Carthera, Genenta, Karyopharm and Nerviano., (Copyright © 2021 Elsevier Ltd. All rights reserved.)- Published
- 2021
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29. Real-time versus thermal desorption selected ion flow tube mass spectrometry for quantification of breath volatiles.
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Slingers G, Vanden Eede M, Lindekens J, Spruyt M, Goelen E, Raes M, and Koppen G
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Young Adult, Breath Tests methods, Mass Spectrometry methods, Volatile Organic Compounds chemistry
- Abstract
Rationale: Selected ion flow tube mass spectrometry (SIFT-MS) is versatile, rapidly provides result output and determines a wide range of volatiles, making it suitable for biomedical applications. When direct sampling into the SIFT-MS instrument is impractical, combining thermal desorption (TD) and SIFT-MS might offer a solution as it allows sample storage on sorbent tubes for later analysis. This work compares off-line TD SIFT-MS and real-time SIFT-MS for the quantification of selected breath volatiles., Methods: Ten healthy non-smoking individuals provided 60 breath samples per method. For off-line analysis, breath was collected onto sorbent tubes via a breath sampler provided with filtered inspiratory air. After TD, samples were re-collected in Tedlar bags which were then connected to the SIFT-MS instrument. For real-time analysis, breath was sampled directly into the instrument. In both cases the analytical method included a total of 155 product ions, and 14 selected volatiles were quantified. The agreement between the methods was assessed using Pearson correlation coefficients and Bland-Altman plots., Results: Overall, correlations between real-time and off-line analysis were moderate to very strong (r = 0.43-0.92) depending on the volatile of interest, except for 2,3-butanedione and styrene. The difference between real-time and off-line measured breath concentrations (average bias) ranged between -14.57 and 20.48 ppbv. For acetone and isoprene, it was 251.53 and 31.9 ppbv, respectively., Conclusions: Real-time SIFT-MS and off-line TD SIFT-MS for quantification of selected breath volatiles did not show optimal agreement. Analyzing a multitude of analytes in breath via direct exhalation into a SIFT-MS instrument for real-time analysis is challenging. On the other hand, off-line analysis using a breath collection device also has its issues such as possible sample losses due to selective absorption depending on the sorbent used or during desorption and transfer to the instrument. Despite these drawbacks, both methods were moderately well correlated., (© 2020 John Wiley & Sons Ltd.)
- Published
- 2021
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30. South African guidelines on the determination of death.
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Thomson D, Joubert I, De Vasconcellos K, Paruk F, Mokogong S, Mathiva R, McCulloch M, Morrow B, Baker D, Rossouw B, Mdladla N, Richards GA, Welkovics N, Levy B, Coetzee I, Spruyt M, Ahmed N, and Gopalan D
- Abstract
Death is a medical occurrence that has social, legal, religious and cultural consequences requiring common clinical standards for its diagnosis and legal regulation. This document compiled by the Critical Care Society of Southern Africa outlines the core standards for determination of death in the hospital context. It aligns with the latest evidence-based research and international guidelines and is applicable to the South African context and legal system. The aim is to provide clear medical standards for healthcare providers to follow in the determination of death, thereby promoting safe practices and high-quality care through the use of uniform standards. Adherence to such guidelines will provide assurance to medical staff, patients, their families and the South African public that the determination of death is always undertaken with diligence, integrity, respect and compassion, and is in accordance with accepted medical standards and latest scientific evidence. The consensus guidelines were compiled using the AGREE II checklist with an 18-member expert panel participating in a three-round modified Delphi process. Checklists and advice sheets were created to assist with application of these guidelines in the clinical environment (https://criticalcare.org.za/resource/death-determination-checklists/). Key points • Brain death and circulatory death are the accepted terms for defining death in the hospital context. • Death determination is a clinical diagnosis which can be made with complete certainty provided that all preconditions are met. • The determination of death in children is held to the same standard as in adults but cannot be diagnosed in children <36 weeks' corrected gestation. • Brain-death testing while on extra-corporeal membrane oxygenation is outlined. • Recommendations are given on handling family requests for accommodation and on consideration of the potential for organ donation. • The use of a checklist combined with a rigorous testing process, comprehensive documentation and adequate counselling of the family are core tenets of death determination. This is a standard of practice to which all clinicians should adhere in end-of-life care.
- Published
- 2021
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31. INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma.
- Author
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Van Den Bent M, Eoli M, Sepulveda JM, Smits M, Walenkamp A, Frenel JS, Franceschi E, Clement PM, Chinot O, De Vos F, Whenham N, Sanghera P, Weller M, Dubbink HJ, French P, Looman J, Dey J, Krause S, Ansell P, Nuyens S, Spruyt M, Brilhante J, Coens C, Gorlia T, and Golfinopoulos V
- Subjects
- Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Alkylating therapeutic use, ErbB Receptors genetics, Humans, Lomustine therapeutic use, Temozolomide therapeutic use, Brain Neoplasms drug therapy, Glioblastoma drug therapy
- Abstract
Background: Depatuxizumab mafodotin (Depatux-M) is a tumor-specific antibody-drug conjugate consisting of an antibody (ABT-806) directed against activated epidermal growth factor receptor (EGFR) and the toxin monomethylauristatin-F. We investigated Depatux-M in combination with temozolomide or as a single agent in a randomized controlled phase II trial in recurrent EGFR amplified glioblastoma., Methods: Eligible were patients with centrally confirmed EGFR amplified glioblastoma at first recurrence after chemo-irradiation with temozolomide. Patients were randomized to either Depatux-M 1.25 mg/kg every 2 weeks intravenously, or this treatment combined with temozolomide 150-200 mg/m2 day 1-5 every 4 weeks, or either lomustine or temozolomide. The primary endpoint of the study was overall survival., Results: Two hundred sixty patients were randomized. In the primary efficacy analysis with 199 events (median follow-up 15.0 mo), the hazard ratio (HR) for the combination arm compared with the control arm was 0.71 (95% CI = 0.50, 1.02; P = 0.062). The efficacy of Depatux-M monotherapy was comparable to that of the control arm (HR = 1.04, 95% CI = 0.73, 1.48; P = 0.83). The most frequent toxicity in Depatux-M treated patients was a reversible corneal epitheliopathy, occurring as grades 3-4 adverse events in 25-30% of patients. In the long-term follow-up analysis with median follow-up of 28.7 months, the HR for the comparison of the combination arm versus the control arm was 0.66 (95% CI = 0.48, 0.93)., Conclusion: This trial suggests a possible role for the use of Depatux-M in combination with temozolomide in EGFR amplified recurrent glioblastoma, especially in patients relapsing well after the end of first-line adjuvant temozolomide treatment. (NCT02343406)., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
- Published
- 2020
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32. Methodological rigor lacking in an analysis of acute myeloid leukemia incidence and geographic distribution in Canada.
- Author
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Ranade S, Palleschi C, Hirji MM, Spruyt M, and MacIntyre E
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- Cities, Humans, Incidence, Ontario, Leukemia, Myeloid, Acute
- Published
- 2020
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33. Four-oil intravenous lipid emulsion effect on plasma fatty acid composition, inflammatory markers and clinical outcomes in acutely ill patients: A randomised control trial (Foil fact).
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Donoghue V, Schleicher GK, Spruyt MGL, Malan L, Nel DG, Calder PC, and Blaauw R
- Subjects
- Aged, Biomarkers blood, Dietary Fats, Unsaturated, Double-Blind Method, Female, Fish Oils, Humans, Male, Middle Aged, Parenteral Nutrition, Treatment Outcome, Triglycerides, Critical Care methods, Critical Illness epidemiology, Critical Illness therapy, Fat Emulsions, Intravenous administration & dosage, Fat Emulsions, Intravenous therapeutic use, Fatty Acids blood
- Abstract
Background and Aims: Data in critically ill patients on the effect of intravenous lipid emulsions (LEs), containing omega-3 polyunsaturated fatty acids (PUFAs), in parenteral nutrition (PN) are scarce and conflicting. This study compared the effects of a four-oil LE (30% soybean oil, 30% medium-chain triglycerides, 25% olive oil and 15% fish oil (FO)) (SMOFlipid®) to those of a 100% soybean oil-based LE in critically ill adult intensive care unit (ICU) patients., Methods: In this double-blind, randomised study, patients (n = 75) predicted to need PN for more than 5 days were randomised to receive either a four-oil LE (Study Group (SG)) or a 100% soybean oil LE (Control Group (CG)). Isocaloric, isonitrogenous PN was administered continuously for 5 days. FO was provided at a dose of 0.09-0.22 g/kg body weight. Measurements included biochemical parameters and sequential organ failure assessment (SOFA) score daily and plasma total phospholipid fatty acids (FAs) and cytokine levels on days 1, 3, 6. Days on mechanical ventilation, length of stay and mortality were also recorded. ANOVA was used to compare response variables between the two groups over the time and Pearson correlation was used to measure relationships between continuous variables., Results: 68 patients completed the study (n = 35 SG, n = 33 CG), with male predominance (66% SG, 56% CG). Average age was 60.8 ± 13.9 years (SG) versus 55.7 ± 14.8 (CG) (p = 0.143). The majority were surgical admissions (85% SG versus 91% CG) followed by medical. Plasma phospholipid oleic acid (p = 0.022) and alpha-linolenic acid (p<0.0005) increased in both groups. In the SG, plasma phospholipid EPA and DHA increased (both p<0.001), whereas the omega-6:omega-3 PUFA (n-6:n-3 PUFA) ratio decreased (p < 0.001). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin decreased in both treatment groups. Considering only the change from day 1 to day 6 there was a bigger decrease in AST, ALT and bilirubin levels in the SG. Concentrations of TNF-α decreased from day 1 to day 6 in the SG, whereas they increased in the CG, but the change was not statistically significant (p = 0.112). A significant negative correlation was found between EPA provision on day 3 and the SOFA score (r = -0.4047, p = 0.018). Days on mechanical ventilation (1.24 ± 0.83 days in SG versus 0.88 ± 1.63 days in CG, p = 0.385) and ICU LOS (9.5 ± 7.09 days in SG versus 10.7 ± 7.6 days in CG, p = 0.490) were not different between groups., Conclusion: PN containing a four-oil LE increased plasma EPA and DHA, decreased n-6:n-3 PUFA ratio, and was safe and well tolerated. The negative relationship between day 3 EPA and SOFA score seems promising, but EPA intake and effects may have been diluted by enteral nutrition which was started in more than half of patients on day 4. There was no significant difference in terms of other biochemical measurements, SOFA score, length of ICU stay and mortality. More research is needed in this patient population, particularly regarding dose, duration and timing of FO and the effects on clinical outcomes., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2019
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34. Influence of suspended particles on the emission of organophosphate flame retardant from insulation boards.
- Author
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Lazarov B, Swinnen R, Poelmans D, Spruyt M, Goelen E, Covaci A, and Stranger M
- Subjects
- Vehicle Emissions, Flame Retardants analysis, Organophosphates analysis
- Abstract
The influence of the presence of the so-called seed particles on the emission rate of Tris (1-chloroisopropyl) phosphate (TCIPP) from polyisocyanurate (PIR) insulation boards was investigated in this study. Two Field and Laboratory Emission Test cells (FLEC) were placed on the surface of the same PIR board and respectively supplied with clean air (reference FLEC) and air containing laboratory-generated soot particles (test FLEC). The behavior of the area-specific emission rates (SER A ) over a time period of 10 days was studied by measuring the total (gas + particles) concentrations of TCIPP at the exhaust of each FLEC. The estimated SER A of TCIPP from the PIR board at the quasi-static equilibrium were found to be 0.82 μg m(-2) h(-1) in the absence of seed particles, while the addition of soot particles led to SER A of 2.16 μg m(-2) h(-1). This indicates an increase of the SER A of TCIPP from the PIR board with a factor of 3 in the presence of soot particles. The TCIPP partition coefficient to soot particles at the quasi-static equilibrium was 0.022 ± 0.012 m(3) μg(-1). In the next step, the influence of real-life particles on TCIPP emission rates was investigated by supplying the test FLEC with air from a professional kitchen where mainly frying and baking activities took place. Similar to the reference FLEC outcomes, SER A was also found to increase in this real-life experiment over a time period of 20 days by a factor 3 in the presence of particles generated during cooking activities. The median value of estimated particle-gas coefficient for this test was 0.062 ± 0.037 m(3) μg(-1).
- Published
- 2016
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35. Air sampling of flame retardants based on the use of mixed-bed sorption tubes--a validation study.
- Author
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Lazarov B, Swinnen R, Spruyt M, Maes F, Van Campenhout K, Goelen E, Covaci A, and Stranger M
- Subjects
- Gas Chromatography-Mass Spectrometry, Halogenated Diphenyl Ethers analysis, Limit of Detection, Organophosphates analysis, Reproducibility of Results, Air Pollutants analysis, Environmental Monitoring methods, Flame Retardants analysis
- Abstract
An analytical methodology using automatic thermal desorption and gas chromatography mass spectrometry analysis was optimized and validated for simultaneous determination of a set of components from three different flame retardant chemical classes: polybrominated diphenyl ethers (PBDEs) (PBDE-28, PBDE-47, PBDE-66, PBDE-85, PBDE-99, PBDE-100), organophosphate flame retardants (PFRs) (tributyl phosphate, tripropyl phosphate, tris(2-chloroethyl)phosphate-, tris(1,3-dichloro-2-propyl) phosphate, tris(2-ethylhexyl) phosphate, triphenyl phosphate, tris(2-chloro-1-methylethyl) phosphate and tricresylphosphate), and "novel" brominated flame retardants (NBFRs) (pentabromotoluene, 2,3,4,5,6-pentabromoethylbenzene, (2,3-dibromopropyl) (2,4,6-tribromophenyl) ether, hexabromobenzene, and 2-ethylhexyl 2,3,4,5-tetrabromobenzoate) in air. The methodology is based on low volume active air sampling of gaseous and particulate air fractions on mixed-bed (polydimethylsiloxane (PDMS)/Tenax TA) sorption tubes. The optimized method provides recoveries >88%; a limit of detection in the range of 6-25 pg m(-3) for PBDEs, 6-171 pg m(-3) for PFRs, and 7-41 pg m(-3) for NBFRs; a linearity greater than 0.996; and a repeatability of less than 10% for all studied compounds. The optimized method was compared with a standard method using active air sampling on XAD-2 sorbent material, followed by liquid extraction. On the one hand, the PDMS/Tenax TA method shows comparable results at longer sampling time conditions (e.g., indoor air sampling, personal air sampling). On the other hand, at shorter sampling time conditions (e.g., sampling from emission test chambers), the optimized method detects up to three times higher concentrations and identifies more flame retardant compounds compared to the standard method based on XAD-2 loading.
- Published
- 2015
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36. Starch safety in resuscitation.
- Author
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Hodgson RE, Richards GA, Lundgren AC, Spruyt MG, Pretorious JP, Mathiva LR, Dickerson R, and Gopalan PD
- Subjects
- Humans, Fluid Therapy methods, Hydroxyethyl Starch Derivatives therapeutic use, Plasma Substitutes therapeutic use, Resuscitation methods
- Published
- 2013
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37. The predictive value of diagnostic sonography for the effectiveness of conservative treatment of tennis elbow.
- Author
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Struijs PA, Spruyt M, Assendelft WJ, and van Dijk CN
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Pain Measurement, Predictive Value of Tests, Prognosis, Treatment Outcome, Ultrasonography, Braces, Physical Therapy Modalities, Tennis Elbow diagnostic imaging, Tennis Elbow therapy
- Abstract
Objective: Tennis elbow is a common complaint. Several treatment strategies have been described, but an optimal strategy has not been identified. Sonographic imaging as a predictive factor has never been studied. The aim of our study was to determine the value of sonographic findings in predicting response to conservative therapy for tennis elbow. This was done in a randomized controlled trial in which the effectiveness of a brace only, physical therapy only, and a combination of both were compared., Subjects and Methods: Patients with tennis elbow complaints were randomized. Sonography was performed before randomization in 57 patients. Outcome measures at 6 weeks' follow-up were success rate and decrease in pain (scale, 0-100). Data were analyzed using an intention-to-treat analysis., Results: In only 75% of the imaged patients, sonographic abnormalities were identified and the clinical diagnosis could thus be confirmed. The following entities were identified: hypo- and hyperechogenicity, swelling, calcification, bursitis, enthesopathy, and tendinosis. The positive predictive value of sonography for the different entities varied between 0.78 and 0.82, and the negative predictive value ranged between 0.23 and 0.71. Predictive value was studied by subgroups of sonographic findings: hypoechoic, swelling present, enthesopathy, any entity present, and no entity present. We found no significant differences among the subgroups for either success rate (range, 40-54%) or mean decrease in pain (range, 16-28 percentage points)., Conclusion: No predictive value of sonography for the detection of abnormalities was identified in this study. Its diagnostic capability showed limited value. However, limitations in this study necessitate drawing definitive conclusions with care.
- Published
- 2005
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38. Activation of heterotrimeric G-protein signaling by a ras-related protein. Implications for signal integration.
- Author
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Cismowski MJ, Ma C, Ribas C, Xie X, Spruyt M, Lizano JS, Lanier SM, and Duzic E
- Subjects
- Amino Acid Sequence, DNA, Complementary, GTP-Binding Protein alpha Subunit, Gi2, GTP-Binding Protein alpha Subunits, GTP-Binding Proteins genetics, Guanosine Triphosphate metabolism, Heterotrimeric GTP-Binding Proteins genetics, Humans, Hydrolysis, Molecular Sequence Data, Protein Binding, Proto-Oncogene Proteins genetics, Saccharomyces cerevisiae, Sequence Homology, Amino Acid, Signal Transduction, ras Proteins genetics, GTP-Binding Protein alpha Subunits, Gi-Go, GTP-Binding Proteins metabolism, Guanine Nucleotide Exchange Factors metabolism, Heterotrimeric GTP-Binding Proteins metabolism, Proto-Oncogene Proteins metabolism, ras Proteins metabolism
- Abstract
Utilizing a functional screen in the yeast Saccharomyces cerevisiae we identified mammalian proteins that activate heterotrimeric G-protein signaling pathways in a receptor-independent fashion. One of the identified activators, termed AGS1 (for activator of G-protein signaling), is a human Ras-related G-protein that defines a distinct subgroup of the Ras superfamily. Expression of AGS1 in yeast and in mammalian cells results in specific activation of Galpha(i)/Galpha(o) heterotrimeric signaling pathways. In addition, the in vivo and in vitro properties of AGS1 are consistent with it functioning as a direct guanine nucleotide exchange factor for Galpha(i)/Galpha(o). AGS1 thus presents a unique mechanism for signal integration via heterotrimeric G-protein signaling pathways.
- Published
- 2000
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39. Characterization of endogenous APP processing in a cell-free system.
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Brown AM, Potempska A, Tummolo D, Spruyt MA, Jacobsen JS, and Sonnenberg-Reines J
- Abstract
We have developed a simple in vitro assay using tissue homogenates that allows detection and characterization of several endogenous proteolytic activities which convert Alzheimer's amyloid precursor protein (APP) to the smaller, carboxy-terminal fragments, postulated to be intermediates in the formation of β-amyloid peptide (Aβ). Incubation at 37°C results in the degradation of transmembrane APP and formation of a mixture of carboxy-terminal containing peptides with mass values of 9-12 kDa. Epitope mapping and electrophoretic comparison with a truncated APP standard showed one of these peptides to contain the entire Aβ sequence. Analysis of pH dependence shows that formation of this carboxy-terminal product as well as another fragment, that is the likely product of 'secretase' activity, requires acidic pH. This suggests that cleavage of full-length APP to secreted forms may take place in an acidic intracellular compartment.
- Published
- 1998
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40. Evaluation of cathepsins D and G and EC 3.4.24.15 as candidate beta-secretase proteases using peptide and amyloid precursor protein substrates.
- Author
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Brown AM, Tummolo DM, Spruyt MA, Jacobsen JS, and Sonnenberg-Reines J
- Subjects
- Amino Acid Sequence, Amyloid Precursor Protein Secretases, Amyloid beta-Protein Precursor chemistry, Animals, Aspartic Acid metabolism, Brain Chemistry, Cathepsin G, Endopeptidases isolation & purification, Evaluation Studies as Topic, Hydrolysis, Methionine metabolism, Molecular Sequence Data, Peptides metabolism, Protein Conformation, Rabbits, Serine Endopeptidases, Substrate Specificity, Amyloid beta-Protein Precursor metabolism, Cathepsin D metabolism, Cathepsins metabolism, Endopeptidases metabolism, Metalloendopeptidases metabolism
- Abstract
No single protease has emerged that possesses all the expected properties for beta-secretase, including brain localization, appropriate peptide cleavage specificity, and the ability to cleave amyloid precursor protein exactly at the amino-terminus of beta-amyloid peptide. We have isolated and purified a brain-derived activity that cleaves the synthetic peptide substrate SEVKMDAEF between methionine and aspartate residues, as required to generate the amino-terminus of beta-amyloid peptide. Its molecular size of 55-60 kDa and inhibitory profile indicate that we have purified the metalloprotease EC 3.4.24.15. We have compared the sequence specificity of EC 3.4.24.15, cathepsin D, and cathepsin G for their ability to cleave the model peptide SEVKMDAEF or related peptides that contain substitutions reported to modulate beta-amyloid peptide production. We have also tested the ability of these enzymes to form carboxyl-terminal fragments from full-length, membrane-embedded amyloid precursor protein substrate or amyloid precursor protein that contains the Swedish KM --> NL mutation. The correct cleavage was tested with an antibody specific for the free amino-terminus of beta-amyloid peptide. Our results exclude EC 3.4.24.15 as a candidate beta-secretase. Although cathepsin G cleaves the model peptide correctly, it displays poor ability to cleave the Swedish KM --> NL peptide and does not generate carboxy-terminal fragments that are immunoreactive with amino-terminal-specific antiserum. Cathepsin D does not cleave the model peptide or show specificity for wild-type amyloid precursor protein; however, it cleaves the Swedish "NL peptide" and "NL precursor" substrates appropriately. Our results suggest that cathepsin D could act as beta-secretase in the Swedish type of familial Alzheimer's disease and demonstrate the importance of using full-length substrate to verify the sequence specificity of candidate proteases.
- Published
- 1996
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41. The release of Alzheimer's disease beta amyloid peptide is reduced by phorbol treatment.
- Author
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Jacobsen JS, Spruyt MA, Brown AM, Sahasrabudhe SR, Blume AJ, Vitek MP, Muenkel HA, and Sonnenberg-Reines J
- Subjects
- Amino Acid Sequence, Amyloid beta-Peptides isolation & purification, Animals, Cell Line, Chlorocebus aethiops, Cloning, Molecular, Humans, Kidney, Molecular Sequence Data, Mutagenesis, Site-Directed, Peptide Fragments isolation & purification, Peptide Fragments metabolism, Sequence Deletion, Tumor Cells, Cultured, Amyloid beta-Peptides biosynthesis, Phorbol 12,13-Dibutyrate pharmacology
- Abstract
Amyloid precursor protein (APP) is cleaved predominantly within the beta amyloid peptide (BAP) domain to release a non-amyloidogenic amino-terminal PN2 fragment. Treatment of cells with phorbol dibutyrate, an agent which activates protein kinase C, has been shown to increase the release of an amino-terminal fragment. A panel of mutant APP reporter constructs was expressed in which each of the potential phosphorylation sites located within the cytoplasmic domain of APP was replaced with alanine residues. Phorbol response patterns were unchanged for each of these mutants, suggesting that induced cleavage occurs independently of APP substrate phosphorylation. We find that phorbol (a) increases the release of a PN2 fragment that is consistent with the normal secretase activity, (b) decreases the release of a shorter amino-terminal APP fragment that is cleaved near the amino terminus of BAP, and (c) decreases the release of BAP which was identified based on electrophoretic mobility, epitope mapping, and radio-sequencing. These data demonstrate that pharmacological treatment can reduce the formation of BAP and suggests that protein kinase C activators could be developed as therapeutic agents to block BAP formation.
- Published
- 1994
42. Release of amino-terminal fragments from amyloid precursor protein reporter and mutated derivatives in cultured cells.
- Author
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Sahasrabudhe SR, Spruyt MA, Muenkel HA, Blume AJ, Vitek MP, and Jacobsen JS
- Subjects
- Amino Acid Sequence, Amyloid Precursor Protein Secretases, Amyloid beta-Protein Precursor genetics, Amyloid beta-Protein Precursor isolation & purification, Animals, Aspartic Acid Endopeptidases, CHO Cells, Cell Line, Cell Membrane metabolism, Cloning, Molecular, Cricetinae, Enkephalin, Methionine genetics, Epitopes analysis, Humans, Kinetics, Molecular Sequence Data, Molecular Weight, Oligopeptides immunology, Peptide Mapping, Plasmids, Restriction Mapping, Substance P genetics, Transfection, Tumor Cells, Cultured, Amyloid beta-Protein Precursor metabolism, Endopeptidases metabolism, Mutation, Protein Processing, Post-Translational
- Abstract
Abnormal proteolytic processing of amyloid precursor protein (APP) is thought to be central to the formation and deposition of beta amyloid peptide in Alzheimer's disease. A putative "secretase" activity normally releases an amino-terminal APP fragment by cleaving APP at residues within the beta amyloid peptide thereby precluding amyloidogenesis. In order to better understand the requirements for APP cleavage by secretase, we have expressed a modified cDNA construct representing the 751-amino acid isoform of APP (APP-REP) and mutated APP-REP proteins in cultured cells. Here, we show that: (a) APP-REP is predominantly associated with membranes; (b) intracellular turnover and processing of APP-REP is similar to that reported for the intact APP protein; (c) secretion appears unaltered by introduction of the glutamate to glutamine mutation found in the APP gene of patients suffering from hereditary cerebral hemorrhage with amyloidosis of Dutch origin; (d) a mutation in which the 18 juxtamembranous amino acids encompassing the secretase site are deleted also allows release of an amino-terminal fragment into the conditioned medium; and (e) kinetics of cleavage of APP-REP and its mutated derivatives are similar. These results indicate that the secretory cleavage of the extracellular amino-terminal fragments of APP-REP can occur in the presence of different novel juxtamembranous amino acid sequences.
- Published
- 1992
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