Introduction et objectifs: Les préparations coliques sont utilisées pour nettoyer le côlon avant de subir une coloscopie. Il existe plusieurs types de préparations coliques; celles-ci contiennent du polyéthylène glycol (PEG), du phosphate de sodium (NaP), du picosulfate (PICOS) ou une solution orale contenant du sulfate (OSS). L'administration en doses fractionnées est recommandées par plusieurs études randomisées mais une étude approfondie de la littérature n'a pas encore été effectuée. Notre objectifs est de déterminer l’efficacité des doses fractionnées comparativement à d’autres régimes posologiques, ainsi que le produit optimal et le volume le plus efficace. Méthode: Nous avons procédé à une recension systématique de la littérature publiée entre janvier 1980 et mars 2014, à partir des bases de données MEDLINE, Embase, Scopus, CENTRAL et ISI Web of Knowledge. Une méta-analyse a été effectuée en incluant les études randomisées qui comparent des doses fractionnées à des doses administrées uniquement la veille de l’examen (non fractionnées). Ont été exclues les études portant sur une population pédiatrique ainsi que celles portant sur des patients hospitalisés ou atteints d’une affection intestinale inflammatoire. L’issue primaire consistait à déterminer la propreté du côlon. Les issues secondaires sont les effets indésirables,les issues procédurales, la volonté des patients à répéter la préparation colique et le temps requis pour reprendre leurs activités normales. Résultats: Quarante-sept études randomisées répondant aux critères d’inclusion ont été répertoriées (n = 13 487 patients). La propreté du côlon était signficativement supérieure avec les doses fractionnées [rapport de cotes (RC) = 2,51; intervalle de confiance à 95 % (IC) = (1,86-3,39)]. Le côlon était significativement plus propre avec les doses fractionnées de PEG [RC=2,60 (1,46-4,63)] de même qu’avec le NaP [RC=9,34 (2,12-41,11)] et le PICOS [RC=3,54 (1,95-6,45)] comparativement aux doses non fractionnées du même produit. La solution de 3 L ou plus de PEG en doses fractionnées a démontré une propreté supérieure à celle du PEG en doses fractionnées de faible volume [RC=1,89 (1,01-3,46)], mais seulement dans les analyses par intention de traitement. La volonté de répéter la préparation colique était supérieur chez les patients ayant reçu des doses fractionnées comparé aux doses non fractionnées [RC=1,90 (1,05-3,46)]; de même, que ceux ayant reçu <3 L de PEG en doses fractionnées comparativement à ceux qui ont PEG ≥ 3L en doses fractionnées [RC=4,95 (2,21-11,10)]. Les différences n’étaient pas significatives pour les autres issues. Conclusion: Les doses fractionnées augmentent le degré de propreté du côlon, en plus d’être le mode d’administration que les patients préfèrent, comparativement aux doses non fractionnées. D’autres études sont nécessaires afin d’évaluer L'OSS et les volumes réduits de PEG. / Abstract : Background & Aims Bowel preparations are used before a colonoscopy to clean the bowel. There are different regimens of preparing the colon for colonoscopy, including polyethylene glycol (PEG), sodium phosphate (NaP), picosulfate (PICO), or oral sulfate solutions (OSS). Split-dose are recommended in several randomized trials but a thorough literature review has not yet been performed. Our aim was to determine the efficacy of split-dose vs other colon preparation regimens, the optimal products for use, and the most effective preparation volumes. Methods We performed systematic searches of MEDLINE, EMBASE, Scopus, CENTRAL, and ISI Web of Knowledge databases, from January 1980 to March 2014. A meta-analysis was done by including all randomized trials that assessed split-dose regimens vs day before colonoscopy preparation. We excluded studies that included pediatric or hospitalized patients, or patients with inflammatory bowel disease. The primary outcome was efficacy of bowel cleansing. Secondary outcomes included side effects, outcomes of procedures, patients’ willingness to repeat the procedure, and the amount of time required for patients to resume daily activities. Results We identified 47 trials that fulfilled our inclusion criteria (n=13,487 patients). Split-dose preparations provided significantly better colon cleansing than all day-before preparations (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.86–3.39), as well as day-before preparations with PEG (OR, 2.60; 95% CI, 1.46–4.63), sodium phosphate (OR, 9.34; 95% CI, 2.12–41.11), or picosulfate (OR, 3.54; 95% CI, 1.95–6.45). PEG split-dose preparations of 3L or more yielded greater bowel cleanliness than lower-volume split-dose regimens (OR, 1.89; 95% CI, 1.01–3.46), but only in intention-to-treat analysis. A higher proportion of patients were willing to repeat split-dose vs day-prior cleansing (OR, 1.90; 95% CI, 1.05–3.46) and low-volume split-dose preparations vs high-volume split-dose preparation (OR, 4.95; 95% CI, 2.21–11.10). There were no differences between preparations in other secondary outcome measures. Conclusion Based on meta-analysis, split-dose regimens increase quality of colon cleansing and are preferred by patients, compared with day-before preparations. Additional research is required to further evaluate oral sulfate solution-based and PEG low-volume regimens.

Cerebral blood flow dynamics is an essential component for preserving cerebral integrity. Cerebral blood flow abnormalities are often seen in patients with central nervous system pathologies such as epilepsy, migraine, Alzheimer's Disease, vascular dementia, stroke, and even HIV/AIDS. There is increasing clinical and experimental evidence implicating cerebral hypoperfusion during ageing. The determination of cerebral perfusion has therefore become an important objective in physiological, pathological, pharmacological, and clinical investigations. The knowledge of regional cerebral blood flow further provides useful diagnostic information and/or data for a better understanding of the complex clinical presentations in patients with neurological and psychiatric disorders. Several cerebrovasoactive drugs have found application in the clinical setting of cerebrovascular diseases such as migraine and dementia. Due to the similarities between humans and non-human primates with respect to their brains, both structurally and behaviourally, numerous studies have been conducted and several non-human primate models have been developed for physiological, pathological, pharmacological, and clinical studies, amongst others in Parkinson's disease and diabetes. The relatively large size of the Cape baboon Papio Ursinus with a weight of 27-30 kg for a large male, makes this primate especially suitable for in vivo brain studies using radiotracers and Single Photon Emission Computed Tomography (SPECT). The main aim of the current study was therefore to develop a suitable radiotracer (99m Tc-hexamethylpropylene amine oxime (HMPAO) or 99m Tc_ethyl_cysteinatedimer (ECD) or 123l-iodoamphetamine (IMP)) for adapted in vivo cerebral blood flow measurements in a non-human primate (Papio ursinus) as an investigative model. The model was to be validated and applied in various drug studies for the evaluation of pharmacological interventions. The study design made use of split-dose methodology, whereby the radiopharmaceutical (radiotracer) was administered twice during each study. The first administration was injected soon after the induction of the anaesthesia, and was followed by the first SPECT data acquisition. The second administration of the radioligand, a double dose of radioactivity with respect to the first radioligand injection, was done at a specific time during the study, which took into account the pharmacodynamics of the drug. A second SPECT data acquisition followed subsequently. The drugs that were included in the study were acetazolamide, a carbonic acid anhydrase inhibitor (often used in nuclear medicine to determine cerebral reserve); sumaptriptan, a 5-HT (serotonin) agonist used for treatment of migraine; sodium valproate (an anti-epileptic drug); nimodipine, a calcium channel blocker and nitro-glycerine, a vasodilator used for angina. Arterial blood pressures were recorded from a catheter in the femoral artery and heart rates were concurrently monitored. The split-dose method was successfully applied to develop a non-human primate cerebral blood flow model under anaesthesia. The model showed differences in cerebral perfusion of the different anaesthesia regimes. These anaesthesia data sets were suitable as control/baseline results for drug intervention studies. Acetazolamide evaluation through the split-dose method in the baboon confirmed the sensitivity of the model by presenting comparable perfusion. This result compared to those already familiar prompted the model to be applied in pharmacological intervention studies. Subsequent results of these investigations showed increases in perfusion for single drug nimodipine treatment (25%). However, nimodipine attenuated the increases in perfusion when administered in combination with acetazolamide. Sumatriptan was able to decrease and normalise the increased perfusion after long duration anaesthesia. Decreased cerebral blood flow was observed for combinations of nimodipine with sodium valproate suggesting drug-drug interaction with important clinical implications. Similar decreases were found also for sumatriptan and nitro-glycerine when administered in combination with nimodipine. Studies with the various tracers (99m Tc_HMPAO or 99m Tc_ECD or 123l_IMP) showed clear differences in the perfusion data, confirming variation in the biochemical performance of the tracers. These differences, if not taken into consideration, caution for inappropriate clinical conclusions and subsequent erroneous therapeutic decisions. Improvement of radiotracer efficacy was subsequently attempted through application of the cyclodextrine complexation approach. Although cyciodextrine technology did not markedly improve the brain disposition of the 99m Tc-ECD, protection of the tracer against degradation was demonstrated. This study encouraged further exploration of this method for protection of the tracer against chemical and metabolic degradation. The current study was aimed to develop and effectively apply a non-human primate model with nuclear medicine technology for cerebral blood flow determinations after pharmacological interventions. This was achieved through the split-dose method and dedicated computer programming, which yielded a successful model with the non-human primate under anaesthesia. The model was validated with the application of acetazolamide to confirm familiar cerebrovascular reserve results, indicating that the model is sensitive to CBF changes. The model was also effectively applied in several pharmacological intervention studies, whereby cerebropharmacodynamics of selected drugs were investigated and established. This unique model of a non-human primate, Papio ursinus for cerebral blood flow determinations has served pharmacological research successfully during the past 12 years and could do so in the future, with scope to investigate new frontiers with improved technologies. / Thesis (Ph.D. (Pharmacology))--North-West University, Potchefstroom Campus, 2004.

Cerebral blood flow dynamics is an essential component for preserving cerebral integrity. Cerebral blood flow abnormalities are often seen in patients with central nervous system pathologies such as epilepsy, migraine, Alzheimer's Disease, vascular dementia, stroke, and even HIV/AIDS. There is increasing clinical and experimental evidence implicating cerebral hypoperfusion during ageing. The determination of cerebral perfusion has therefore become an important objective in physiological, pathological, pharmacological, and clinical investigations. The knowledge of regional cerebral blood flow further provides useful diagnostic information and/or data for a better understanding of the complex clinical presentations in patients with neurological and psychiatric disorders. Several cerebrovasoactive drugs have found application in the clinical setting of cerebrovascular diseases such as migraine and dementia. Due to the similarities between humans and non-human primates with respect to their brains, both structurally and behaviourally, numerous studies have been conducted and several non-human primate models have been developed for physiological, pathological, pharmacological, and clinical studies, amongst others in Parkinson's disease and diabetes. The relatively large size of the Cape baboon Papio Ursinus with a weight of 27-30 kg for a large male, makes this primate especially suitable for in vivo brain studies using radiotracers and Single Photon Emission Computed Tomography (SPECT). The main aim of the current study was therefore to develop a suitable radiotracer (99m Tc-hexamethylpropylene amine oxime (HMPAO) or 99m Tc_ethyl_cysteinatedimer (ECD) or 123l-iodoamphetamine (IMP)) for adapted in vivo cerebral blood flow measurements in a non-human primate (Papio ursinus) as an investigative model. The model was to be validated and applied in various drug studies for the evaluation of pharmacological interventions. The study design made use of split-dose methodology, whereby the radiopharmaceutical (radiotracer) was administered twice during each study. The first administration was injected soon after the induction of the anaesthesia, and was followed by the first SPECT data acquisition. The second administration of the radioligand, a double dose of radioactivity with respect to the first radioligand injection, was done at a specific time during the study, which took into account the pharmacodynamics of the drug. A second SPECT data acquisition followed subsequently. The drugs that were included in the study were acetazolamide, a carbonic acid anhydrase inhibitor (often used in nuclear medicine to determine cerebral reserve); sumaptriptan, a 5-HT (serotonin) agonist used for treatment of migraine; sodium valproate (an anti-epileptic drug); nimodipine, a calcium channel blocker and nitro-glycerine, a vasodilator used for angina. Arterial blood pressures were recorded from a catheter in the femoral artery and heart rates were concurrently monitored. The split-dose method was successfully applied to develop a non-human primate cerebral blood flow model under anaesthesia. The model showed differences in cerebral perfusion of the different anaesthesia regimes. These anaesthesia data sets were suitable as control/baseline results for drug intervention studies. Acetazolamide evaluation through the split-dose method in the baboon confirmed the sensitivity of the model by presenting comparable perfusion. This result compared to those already familiar prompted the model to be applied in pharmacological intervention studies. Subsequent results of these investigations showed increases in perfusion for single drug nimodipine treatment (25%). However, nimodipine attenuated the increases in perfusion when administered in combination with acetazolamide. Sumatriptan was able to decrease and normalise the increased perfusion after long duration anaesthesia. Decreased cerebral blood flow was observed for combinations of nimodipine with sodium valproate suggesting drug-drug interaction with important clinical implications. Similar decreases were found also for sumatriptan and nitro-glycerine when administered in combination with nimodipine. Studies with the various tracers (99m Tc_HMPAO or 99m Tc_ECD or 123l_IMP) showed clear differences in the perfusion data, confirming variation in the biochemical performance of the tracers. These differences, if not taken into consideration, caution for inappropriate clinical conclusions and subsequent erroneous therapeutic decisions. Improvement of radiotracer efficacy was subsequently attempted through application of the cyclodextrine complexation approach. Although cyciodextrine technology did not markedly improve the brain disposition of the 99m Tc-ECD, protection of the tracer against degradation was demonstrated. This study encouraged further exploration of this method for protection of the tracer against chemical and metabolic degradation. The current study was aimed to develop and effectively apply a non-human primate model with nuclear medicine technology for cerebral blood flow determinations after pharmacological interventions. This was achieved through the split-dose method and dedicated computer programming, which yielded a successful model with the non-human primate under anaesthesia. The model was validated with the application of acetazolamide to confirm familiar cerebrovascular reserve results, indicating that the model is sensitive to CBF changes. The model was also effectively applied in several pharmacological intervention studies, whereby cerebropharmacodynamics of selected drugs were investigated and established. This unique model of a non-human primate, Papio ursinus for cerebral blood flow determinations has served pharmacological research successfully during the past 12 years and could do so in the future, with scope to investigate new frontiers with improved technologies. / Thesis (Ph.D. (Pharmacology))--North-West University, Potchefstroom Campus, 2004.