Thesis (M. Phil.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

BACKGROUND: In a 2006 WHO report, diarrheal diseases ranked second among conditions afflicting children. Pediatric acute diarrhea, although most often the result of a gastrointestinal infection, can also occur as a result of antibiotic exposure. This is often referred to as antibiotic-associated diarrhea (AAD). Previous research suggests that probiotics may be effective in the treatment or prevention of various types of PAD. METHODS: The first study involved a systematic review and meta-analysis of RCTs involving probiotics as an adjunct to antibiotics for preventing AAD in children. The second study was a systematic review of definitions and primary outcome measures employed in RCTs of PAD. The third study used a modified Delphi consensus procedure to develop a new instrument for evaluating the severity of PAD. The study involved steering committee discussions (phase 1) and two electronic surveys (phase 2 and 3) of leading experts in measurement and clinical gastroenterology. RESULTS: The per protocol meta-analysis of ten RCTs significantly favored probiotics to prevent the incidence of diarrhea (NNT = 10). However, this effect did not withstand ITT analysis and among included trials there was considerable inconsistency regarding definitions for the reviews primary outcome measure, the incidence of diarrhea. Study two identified 121 RCTs that reported 62 unique definitions of diarrhea, 64 unique definitions of diarrhea resolution and 62 unique primary outcome measures. Thirty-one trials used grading systems to support outcome evaluation. However, none of the trials (or their citations) reported evidence of their validation. In study three experts agreed on the inclusion of five attributes containing 13 items. Attributes proposed for the IPADDS include: Diarrhea Frequency and Duration, Vomiting Frequency and Duration, Fever, Restrictions in Normal Daily Activities and Dehydration. CONCLUSION: It is premature to draw a valid conclusion about the efficacy of probiotics for pediatric AAD. Definitions of diarrhea and primary outcome measures in RCTs of PAD are heterogeneous and lack evidence of validity. The third study represents content validity evidence for IPADDS. A numerical scoring system needs to be added and further empirical evidence of reliability and validity are required. / Experimental Medicine

Alpha-tocopherol, the most abundant form of vitamin E in man, is transported in the circulation by plasma lipoproteins. It plays important roles, not only in preventing lipid peroxidation, but also in modulating several cell functions such as cell signaling and gene expression. While chylomicrons transport dietary alpha-tocopherol after intestinal absorption, LDL and HDL are the major carriers of alpha-tocopherol in fasting plasma and largely contribute to its delivery to cells and tissues. Exchanges of alpha-tocopherol occur between plasma lipoproteins. In addition, alpha-tocopherol transfers have also been observed, in both directions, between plasma lipoproteins and artificial chylomicrons such as intravenous lipid emulsion particles used in parenteral nutrition. In acute conditions, intravenous supply of vitamin E via lipid emulsions, which bypasses the intestinal tract, may offer some advantages over oral administration to rapidly increase alpha-tocopherol plasma concentration. However, many questions remain unanswered regarding kinetics and factors facilitating vitamin E exchanges between lipid emulsions and plasma lipoproteins. The first part of this work aimed at characterizing alpha-tocopherol transfers between alpha-tocopherol rich emulsion particles and plasma lipoproteins as well as the potential for plasma proteins to modulate such transfers. An in vitro model of incubation was used in which emulsion triglyceride concentration was relatively low and lipoprotein levels comparable to those commonly found in the circulation. Results indicate a high capacity for LDL and HDL to acquire extra-amounts of alpha-tocopherol by rapid mass transfers from alpha-tocopherol-rich emulsion particles. Data further shows that, at a fixed alpha-tocopherol concentration provided by emulsion particles, the limiting factor for alpha-tocopherol enrichment is not the capacity of plasma lipoproteins to accommodate extra-amounts of alpha-tocopherol but the facilitating effect of plasma proteins on alpha-tocopherol transfer, the duration of the incubation and possibly the competition between different acceptor particles. Two lipid transfer proteins, PLTP and CETP, appear to largely mediate facilitation of alpha-tocopherol transfer; however, other plasma proteins may be involved. Data further shows that alpha-tocopherol enriched LDL and HDL can readily transfer newly acquired alpha-tocopherol to cells, without any regulation by plasma proteins. Short-term prophylactic vitamin E supplementation has been suggested to be beneficial in some patients in acute conditions who present reduced plasma vitamin E concentrations in association with important changes in plasma lipids and severe oxidative stress. However, it was not clear whether low plasma vitamin E concentration in critically ill patients is related to changes in the composition of plasma lipoproteins or to a decrease in the number of alpha-tocopherol carriers. In the second part of this work, two clinical studies were conducted to analyze changes of lipoprotein concentration and composition in relation to inflammatory reaction and oxidative stress in selected subgroups of critically ill patients, namely patients undergoing cardiac surgery with different procedures. Important changes in LDL and HDL lipid content were observed, some of which contrast with previous observations made in critically ill septic patients. The reduced plasma level of alpha-tocopherol measured after cardiac surgery is entirely due to a reduced number of circulating LDL and HDL particles. Data suggests that such reduced number in alpha-tocopherol carriers post-surgery may impede the delivery of alpha-tocopherol to cells in conditions of increased requirements due to oxidative stress. Avoidance of extracorporeal circulation during cardiac surgery does not reduce inflammation-related changes in plasma lipids but largely prevents oxidative stress. This data on changes occurring in plasma lipoproteins may help to better define strategies against pro-inflammatory changes or oxidative stress. If further studies would confirm a clinical benefit with evidence-based rationale, alpha-tocopherol enriched lipid emulsions may be used to guarantee a sufficient alpha-tocopherol supply in acute conditions associated with fewer alpha-tocopherol transporters and increased requirements due to high risk of oxidative tissue injury.

Successful treatment of myocardial infarction requires anearly and accurate diagnosis. Recent studies have shown thatacute myocardial scintigraphy has a high predictive value forprognosis of myocardial events. Three dimensional (3D)perfusion data obtained with SPECT are however very rare in theemergency department (ED). We have developed a mobile tomographic system for myocardialscintigraphy, which can be used in the ED. The objectives ofthe studies presented were:     To develop software and hardware for a mobile tomographicgamma camera system: the Cardiotom     To demonstrate that a mobile tomographic system can beused in a clinical situation     To evaluate the limitations of Ectomography when usingfiltered back projection for reconstruction     To develop a method of reconstruction that compensatesfor the incomplete data acquisition associated with theacquisition geometry of Ectomography Three prototypes of a mobile tomographic gamma camera systemhave been designed and built at the Division of MedicalEngineering, which all have been used in a clinical setting.The systems are based on Ectomography, a limited view anglemethod, also developed by us. Instead of rotating the entiregamma camera detector around the patient as in SPECT, a slanthole collimator is rotated in front of a stationary detector.Since short imaging times are important in the ED and the heartonly occupies a small area of the detector, system sensitivityhas been increased by dividing the collimator into segmentswith different projection directions. In myocardial imaging, 4segments are used and within 10 minutes from the start ofacquisition, reconstructed short axis view sections areavailable for interpretation. Using the Cardiotom in an experimental animal study, weverified that the system could be used to quantify myocardialarea at risk and final infarct size. This conclusion was madefrom a comparison of images obtained from the Cardiotom andpathological staining of the myocardium, analysedpost-mortem. Inherent limitations of Ectomography were evaluated withboth phantom studies and computer simulated data, reconstructedusing filtered back-projection Results show that moderatedeviation from optimal position of the detector with respect tothe myocardium will have little or no influence on thediagnostic information when assessed from short axis sectionimages and polar tomograms. However, long axis section imagesappear elongated when reconstructed using filteredback-projection. We have shown that this elongation distortion can besuppressed using iterative reconstructions techniques, and wehave implemented such an algorithm, called three-dimensionalTotal Variation Expectation Maximisation (3DTV-EM). Resultswere that elongation distortion was reduced and depthresolution improved. The reconstruction technique was alsoevaluated for SPECT reconstruction and was found to decreasethe noise in reconstructed images, when compared to thetwo-dimensional TV-EM algorithm. Noise pattern were also foundto be more uniform for the 3DTV-EM algorithm compared totwo-dimensional TV-EM. In conclusion, we have shown that the Cardiotom may beuseful in a clinical acute setting, providing valuablediagnostic information. Rapid positioning is possible, sincemoderate deviation from optimal positioning will cause few orno artefacts. Image quality can be improved if iterativetechniques are used for image reconstruction instead offiltered back-projection. <b>Keywords</b>: acute studies, myocardial infarction,scintigraphy, mobile gamma camera, tomography.

Objective: To describe the walking characteristics of a sample of ambulatory subjects with sub-acute incomplete spinal cord injury (iSCI). Methods: 52 subjects were included in a secondary analysis of clinical and spatiotemporal measures of walking. The study sample was described as a whole and subsequently divided into subgroups on the basis of 3 clinical factors (etiology, severity, and neurological level of injury) and 4 gait factors (gait aid, velocity, symmetry, and variability). Results: Clinical and spatiotemporal parameters were highly variable across the study population. Sub–groups with unique gait features were best identified by velocity and variability. Conclusions: Spatiotemporal measures of walking provide augmented description of walking in the sub-acute iSCI population. Sub-grouping by gait factors warrants further investigation with respect to their ability to act as predictors and modifiers of treatment effect.

Objective: To describe the walking characteristics of a sample of ambulatory subjects with sub-acute incomplete spinal cord injury (iSCI). Methods: 52 subjects were included in a secondary analysis of clinical and spatiotemporal measures of walking. The study sample was described as a whole and subsequently divided into subgroups on the basis of 3 clinical factors (etiology, severity, and neurological level of injury) and 4 gait factors (gait aid, velocity, symmetry, and variability). Results: Clinical and spatiotemporal parameters were highly variable across the study population. Sub–groups with unique gait features were best identified by velocity and variability. Conclusions: Spatiotemporal measures of walking provide augmented description of walking in the sub-acute iSCI population. Sub-grouping by gait factors warrants further investigation with respect to their ability to act as predictors and modifiers of treatment effect.

The principal cause of non-ST-segment myocardial infarction (NSTEMI), a subclass of acute coronary syndrome (ACS), is thrombosis and the underlying cause is atherosclerosis. Percutaneous coronary intervention (PCI) is one of the treatments to attenuate the ischemic effects of severe coronary artery stenosis. However, restenosis following PCI (post-PCI) is a major problem for the long-term success of the procedure. Recently, the interaction of advanced glycation end products (AGE) with the receptor for advanced glycation end products (RAGE) has been implicated in the development of atherosclerosis in animal models. Interaction of AGE with RAGE results in activation of nuclear factor kappa-B (NF-êB), release of cytokines including tumor necrosis factor-alpha (TNF-á), the expression of adhesion molecules including soluble vascular adhesion molecule-1 (sVCAM-1) and induction of oxidative stress all of which have been implicated in the development of atherosclerosis. The soluble receptor for advanced glycation end products (sRAGE) acts as a decoy for RAGE ligands (AGEs) and this occurs by competing with RAGE. In animal models, balloon inflation and de-endothelialization of the carotid artery increase the concentration of AGE and RAGE in the arterial wall and induces neointimal hyperplasia and stenosis. Treatment with sRAGE in animal models reduces neointimal growth and decreases smooth muscle cell migration and proliferation and expression of extracellular matrix.<p> It is hypothesized that NSTEMI and post-PCI restenosis may be due to low levels of serum sRAGE resulting in increased AGE and RAGE interactions. Low levels of sRAGE would also increase the levels of serum TNF-á and sVCAM-1.<p> The objectives of this study were to determine whether: (1) the levels of serum sRAGE are lower and the levels of AGE, TNF-á and sVCAM-1 are higher in NSTEMI patients compared to control; (2) the levels of serum sRAGE are lower and the levels of AGE, TNF-á and sVCAM-1 are higher in NSTEMI patients with restenosis compared to those without restenosis; and (3) sRAGE or AGE/sRAGE ratio may serve as a biomarker/ predictor of NSTEMI and post-PCI restenosis.<p> The study objectives include 46 consecutive NSTEMI patients undergoing elective PCI and 28 healthy age-matched male controls. Pre-PCI and 6 month post-PCI angiography were performed in all NSTEMI patients. Blood samples were collected at designated intervals for the measurement of sRAGE, AGE, TNF-á, and sVCAM-1 using commercially available enzyme-linked immunosorbent assay (ELISA) kits.<p> The levels of serum sRAGE were lower and those of TNF-á, sVCAM-1, AGE and AGE/sRAGE were higher in NSTEMI patients compared to control subjects. (sRAGE, 884.55 ± 50 vs. 1287 ± 41.5 pg/mL{p<0.001}; TNF-á, 23.1 ± 2.3 vs. 10.3 ± 0.8 pg/mL {p<0.002}; sVCAM-1, 1059.62 ± 70.8 vs. 651 ± 35.5 ng/mL {p<0.0003}, AGE, 1192.50 ± 82.6 vs. 669.40 ± 47.9 ng/mL {p<0.001}; and AGE/sRAGE, 1.75 ± 0.17 vs. 0.52 ± 0.06 {p<0.001}).<p> The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the sRAGE biomarker test were 59%, 100%, 100%, 100% and 74% respectively, while those of the AGE/sRAGE test were 85%, 91%, 97%, 67% and 86%, respectively, in the diagnosis of patients with NSTEMI acute coronary syndrome. The pre-PCI levels of serum sRAGE in patients with restenosis were significantly lower (p<0.001) than in patients without restenosis (610.6 ± 24.1 vs. 1143.8 ± 52.5 pg/mL). The post-PCI levels of serum sRAGE were significantly lower (p<0.0001) in patients with restenosis compared to those without restenosis (477 ± 18.6 vs. 1106.7 ± 41.9 pg/mL). The pre-PCI levels of serum TNF-á and sVCAM-1 were significantly higher (p<0.001 and p<0.001) in patients with restenosis compared to those without restenosis (TNF-á, 37.9 ± 2.5 vs. 11.6 ± 0.41 pg/mL; sVCAM-1, 1381.8 ± 63.5 vs. 811.37 ± 26.5 ng/mL). The post PCI levels of serum TNF-á and sVCAM-1 were also significantly higher (p<0.0001 and p<0.0001) in patients with restenosis than in patients without restenosis (TNF-á, 48.4 ± 1.4 vs. 12.5 ± 0.44 pg/mL; sVCAM-1, 1381.8 ± 63.5 vs. 762.2 ± 26.4 ng/mL). The post-PCI levels sRAGE were lower while those of TNF-á and sVCAM-1 were higher compared to the pre-PCI levels in patients with restenosis. However, the pre- and post-PCI levels of serum sRAGE, TNF-á and sVCAM-1 were similar in patients without restenosis. The pre-PCI levels of serum AGE and AGE/sRAGE were significantly higher (p<0.001 and p<0.001) in patients with restenosis compared to those without restenosis (AGE, 1512.1 ± 84.53 vs. 891.7 ± 92.4 ng/mL; 2.39 ± 0.20 vs. 1.03 ± 0.17).<p> The sensitivity, specificity, PPV, NPV, and accuracy of the pre-PCI sRAGE tests were 73%, 100%, 100%, 80%, and 87%, respectively while those of the AGE/sRAGE tests were 81%, 94%, 93%, 84% and 88%, respectively in identifying patients with post-PCI restenosis.<p> In conclusion the results suggest that: (1) the levels of serum sRAGE are lower while those of TNF-á, sVCAM-1, AGE and AGE/sRAGE are higher in NSTEMI patients compared to control subjects; (2) serum levels of sRAGE are negatively correlated with the number of diseased vessels; (3) Both low sRAGE and high AGE/sRAGE may serve as a biomarker/predictor of NSTEMI, but AGE/sRAGE has a greater sensitivity compared to sRAGE; (4) the pre-PCI levels of serum sRAGE are lower while those of AGE/sRAGE are higher in patients with restenosis compared to those without restenosis; and (5) both low sRAGE and high AGE/sRAGE may serve as a predictor/ biomarker of post-PCI restenosis; however, AGE/sRAGE has a greater sensitivity than sRAGE.

Inflammatory diseases such as hypertension are associated with high levels of oxidative stress. Characteristic of oxidative stress is the inflammatory acute phase protein response. Oxidative stress and its accompanied inflammation can be reduced via phase 2 enzyme induction. Broccoli sprouts, a rich source of phase 2 enzyme inducers such as isothiocyanates, can be incorporated into the diet to increase phase 2 enzymes. <p> The hypothesis of this study is that, the dietary intake of dried broccoli sprouts, by inducing liver phase 2 enzymes, will decrease oxidative stress and the acute phase response in the blood of spontaneously hypertensive stroke-prone rats. <p> Spontaneously hypertensive stroke-prone rats (SHRsp) and Sprague Dawley (SD) rats were placed either on a control diet of modified AIN-93G or an experimental diet of modified AIN-93G supplemented with dried broccoli sprouts. The following parameters were examined: 1. Isothiocyanate absorption (an increased level of dithiocarbamates is reflective of ITC absorption), 2. Oxidative stress (a reduction in oxidative stress is evidenced by an increase in plasma protein thiols and blood glutathione (GSH)), 3. Acute phase proteins (a decreased APR is reflected by an increase in plasma albumin and a decrease in ceruloplasmin), 4. Activity of phase 2 enzymes (increased phase 2 enzyme induction results in higher activities of liver quinone reductase (QR), glutathione-S-transferase (GST) and glutathione reductase (GR)). <p> My experimental results demonstrated that broccoli sprout feeding results in higher protein thiol levels in female SHRsp and higher blood GSH levels in males but no acute phase protein changes were observed in either male or female SHRsp. Broccoli sprout feeding caused higher QR and lower GST activities in female SHRsp but did not affect the activities of phase 2 enzymes in male SHRsp. The activities of GST and QR were higher in SD rats than in SHRsp. Levels of dithiocarbamates were higher in the broccoli fed group than in the control fed group. <p> The results from this study do not present a clear pattern to support the hypothesis that dietary intake of broccoli sprouts by inducing phase 2 enzymes will decrease parameters of oxidative stress and the acute phase response. <p> In conclusion, there is an interactive role played by animal gender and the induction of phase 2 enzymes by dried broccoli sprouts.

Inflammatory diseases such as hypertension are associated with high levels of oxidative stress. Characteristic of oxidative stress is the inflammatory acute phase protein response. Oxidative stress and its accompanied inflammation can be reduced via phase 2 enzyme induction. Broccoli sprouts, a rich source of phase 2 enzyme inducers such as isothiocyanates, can be incorporated into the diet to increase phase 2 enzymes. <p> The hypothesis of this study is that, the dietary intake of dried broccoli sprouts, by inducing liver phase 2 enzymes, will decrease oxidative stress and the acute phase response in the blood of spontaneously hypertensive stroke-prone rats. <p> Spontaneously hypertensive stroke-prone rats (SHRsp) and Sprague Dawley (SD) rats were placed either on a control diet of modified AIN-93G or an experimental diet of modified AIN-93G supplemented with dried broccoli sprouts. The following parameters were examined: 1. Isothiocyanate absorption (an increased level of dithiocarbamates is reflective of ITC absorption), 2. Oxidative stress (a reduction in oxidative stress is evidenced by an increase in plasma protein thiols and blood glutathione (GSH)), 3. Acute phase proteins (a decreased APR is reflected by an increase in plasma albumin and a decrease in ceruloplasmin), 4. Activity of phase 2 enzymes (increased phase 2 enzyme induction results in higher activities of liver quinone reductase (QR), glutathione-S-transferase (GST) and glutathione reductase (GR)). <p> My experimental results demonstrated that broccoli sprout feeding results in higher protein thiol levels in female SHRsp and higher blood GSH levels in males but no acute phase protein changes were observed in either male or female SHRsp. Broccoli sprout feeding caused higher QR and lower GST activities in female SHRsp but did not affect the activities of phase 2 enzymes in male SHRsp. The activities of GST and QR were higher in SD rats than in SHRsp. Levels of dithiocarbamates were higher in the broccoli fed group than in the control fed group. <p> The results from this study do not present a clear pattern to support the hypothesis that dietary intake of broccoli sprouts by inducing phase 2 enzymes will decrease parameters of oxidative stress and the acute phase response. <p> In conclusion, there is an interactive role played by animal gender and the induction of phase 2 enzymes by dried broccoli sprouts.

SAMMANFATTNING Buksmärtor är en av de vanligaste orsakerna till att människor söker sjukvård. Historiskt sett har smärtlindring till patienter med buksmärta varit restriktiv. Otillräcklig smärtlindring kan bero på rädsla för att smärtlindrande läkemedel ska dölja viktiga kliniska tecken som kan leda till diagnostiska svårigheter. Syfte: Att undersöka i vilken omfattning ambulanssjuksköterskan smärtlindrar patienter med buksmärta, i vilken utsträckning patienter smärtskattas samt om det föreligger någon skillnad mellan män och kvinnor när det gäller administrering av smärtlindrande läkemedel och omfattning av smärtskattning prehospitalt. Metod: En retrospektiv jämförande deskriptiv journalgranskning med kvantitativ ansats. Ett konsekutivt urval gjordes och sammanlagt granskades 200 journaler, varav 100 omfattade kvinnor och 100 omfattade män. Resultat: 21 % (n=42) av patienterna smärtlindrades. Det fanns ingen statistisk signifikans som visade att kvinnor och män smärtlindrades i olika omfattning. Det var 34,5 % (n=69) av patienterna som smärtskattades, och ingen skillnad mellan könen påvisades. Denna studie är av betydelse för specialistsjuksköterskor och andra personalkategorier som omhändertar patienter med buksmärta. Studien bidrar med kunskap som kan leda till att det prehospitala omhändertagandet av patienter med buksmärta utvecklas och förbättras. / ABSTRACT Abdominal pain is one of the most common reasons for seeking medical care. Historically, pain relief in patients with abdominal pain has been restrictive. Causes of inadequate pain relief could be fear that analgesics will mask important clinical signs that can lead to diagnostic difficulties. Aim: To investigate to what extent patients with abdominal pain receive analgesics, the extent to which patients’ pain is rated and if there is any difference between men and women in the administration of analgesics and the extent of prehospital pain measurement. Method: A retrospective comparative descriptive medical record review with quantitative data. A consecutive selection was made and a total of 200 medical records were reviewed, 100 involved women and 100 involved men. Result: 21 % (n=42) of the patients were given analgesics. Men and women were treated equally in terms of pain relief. There were 34,5 % (n=69) of the patients who were asked to estimate their pain, and no difference between sexes was detected. This study is relevant to healthcare professionals who treat patients with abdominal pain. The result of this study can be used in the development and the improvement of the prehospital care of patients with abdominal pain.