Donation of kidneys after brain death:Protective proteins, profiles, and treatment strategies

Niertransplantatie is de voorkeursbehandeling voor patiënten met eindstadium nierfalen. Er is echter een ernstig tekort aan donornieren. Om dit tekort aan te pakken, worden er steeds meer suboptimale donornieren gebruikt om dit tekort op te lossen.Het doel van dit proefschrift is het verbeteren van de kwaliteit van de overleden hersendode donornier door de expressie van beschermende eiwitten te verhogen, en tevens meer inzicht te krijgen in het mechanisme dat resulteert in de orgaan kwaliteit van hersendode donornieren.In dit proefschrift laten we zien dat er tijdens hersendood een verhoogde expressie van Heat Shock Proteins (HSP's) is. De hoeveelheid expressie van deze eiwitten kan worden verhoog door toediening van een geneesmiddel genaamd Geranylgeranylaceton, en wij tonen aan dat de toediening van dat geneesmiddel de donornier beschermt tegen ontsteking.In dit proefschrift verdiepen we ook in het mechanisme achter de schade in hersendode donornieren. We laten zien dat er een molecuulprofiel van de donornier is die verband houdt met de orgaanfunctie na transplantatie. In de toekomst zou een dergelijk diagnostisch hulpmiddel kunnen worden geïmplementeerd om te helpen bij de beslissing om een ​​donornier wel of niet te accepteren. In het laatste deel van dit proefschrift laten we zien dat het ook mogelijk is om bloed in plaats van nierweefsel te gebruiken als ontdekkingsinstrument voor biomarkers bij nierdonatie.Kidney transplantation is the preferred treatment of patient with end-stage renal disease for those in good enough health to undergo such an operation. There is however a severe shortage of donor kidneys. To cope with this shortage more extended criteria donor kidneys and more inferior donors are used. The aim of this thesis is to improve the quality of the deceased brain dead donor kidney by increasing the expression of protective proteins, while also gaining more insight in the mechanism that results in inferior graft quality after kidney transplantation.In this thesis we show that during brain death there is an increased expression of heat shock proteins (HSPs). The protective property of these proteins can also be increased by administration of a drug called Geranylgeranylacetone, and we show that administration of that drug prevents detrimental inflammatory changes in the brain dead donor kidney.In this thesis we also deepen into the mechanism behind injury in the deceased brain death donated kidney. We show that there is a molecular profile of the donor kidney that is associated with the function of the transplant post transplantation. In the future such a diagnostic tool could be implemented to help with the decision whether to accept or decline a donor kidney. In the last part of this thesis we show that it is also feasible to use blood instead of kidney tissue as a biomarker discovery tool for diagnostic proteins in kidney donation

The resilience of children of HIV positive mothers with regard to the mother-child relationship

The purpose of this study was to explore and describe themes of resilience in the expressions and behaviours of six-year-old children with regard to the mother-child relationship, where the mothers are infected with HIV&AIDS. Themes of resilience were investigated within the framework of positive psychology. A study of limited scope was conducted from a phenomenological paradigm. I followed a mixed method methodological paradigm based on a case study design. I purposefully selected eleven six-year-old participants whose mothers are infected with HIV&AIDS from a five-year randomised control trail study (Kgolo Mmogo). Qualitative data collection methods included the transcriptions of structured baseline interviews relating to the Kinaesthetic Family Drawing (KFD), as well as the KFD per se. I utilised the scores from the Vineland Adaptive Behavior Scale (Vineland) as uantitative data collection strategy. The transcriptions were analysed by means of an inductive thematic analysis. For the analysis of the KFD I developed and piloted a framework of analysis. The raw scores from the Vineland were compared with the appropriate age norms and compared with themes of resilience identified from the KFD as well as the transcripts of the interviews. I identified both internal and external resources of resilience. The findings of my study illustrate the presence of themes of resilience as well as non-resilience within the participants and the mother-child relationships. More factors of resilience (protective factors) than non-resilience (risk factors) were identified. Secondly, it seems possible to use the KFD with the Vineland when exploring resilience as insights from both mother and child participants are measured. The integrated results from the different data sources indicate that although the results of the KFD and the transcriptions did not correlate with the results obtained from the Vineland, the results from the different data sources supplement one another. The use of the KFD as a measure to generate data related to resilience made it possible to evaluate adaptation and resilience in a specific cultural context unlike the Vineland. The results from the data sources indicate resilience and/or non-resilience in the mother-child relationship in terms of three categories namely, protective factors (Expressive Language Skills, Interpersonal Relationships and Play and Leisure Time), risk factors (Coping Skills and Gross Motor Skills) and a balance between protective and risk factors (Receptive Language, Daily Living Skills, personal and domestic, as well as Fine Motor Skills). It is feasible to use the KFD as a measure to identify themes of resilience and non-resilience when the drawing is accompanied by an interview.Dissertation (MEd)--University of Pretoria, 2010.Educational Psychologyunrestricte

The Outcomes of Endoanal Ultrasound and Three-Dimensional, High-Resolution Anorectal Manometry do not Predict Fecal Incontinence

Endoanal ultrasound (EUS) is the gold standard for diagnosing anal sphincter defects often seen in patients with fecal incontinence (FI). Threedimensional, high-resolution anorectal manometry (3D-HRARM) is a newer technique that might also be used to diagnose sphincter defects. We aimed to investigate whether FI is associated with anal sphincter defects detected by EUS and 3D-HRARM. Retrospectively, we included all adult patients who had undergone EUS and 3D-HRARM for FI, between January 2012 and February 2015 (N = 37). During 3D-HRARM, the presence of sphincter defects was examined in rest and during maximal anal sphincter contraction. All patients also underwent a balloon retention test to objectively determine whether they suffered from FI for solid stool. Of the 37 patients, 12 patients (32%) suffered from FI. The presence of a sphincter defect detected with EUS, and with 3D-HRARM during contraction, was not associated with the prevalence of FI and no significant correlations were found between these variables. The presence of a sphincter defect, detected by 3D-HRARM in rest, was negatively correlated with the presence of FI (rs -.372, P = .024). Moreover, the prevalence of sphincter defects was lower in patients with FI, detected by 3D-HRARM in rest, than in patients without FI (13% versus 88%, P = .035). FI is not associated with anal sphincter defects detected by EUS and 3D-HRARM. The outcomes of EUS and 3D-HRARM do not thus predict the presence of FI. Instead, extensive anorectal function tests should be performed to form a complete picture of a patient’s anorectal functions and to determine the underlying causes of FI

Does Health Insurance Premium Exemption Policy for Older People Increase Access to Health Care? Evidence from Ghana

Aging in Sub-Saharan Africa causes major challenges for policy makers in social protection. Our study focuses on Ghana, one of the few Sub-Saharan African countries that passed a National Policy on Aging in 2010. Ghana is also one of the first Sub-Saharan African countries that launched a National Health Insurance Scheme (NHIS; NHIS Act 650, 2003) with the aim to improve access to quality health care for all citizens, and as such can be considered as a means of poverty reduction. Our study assesses whether premium exemption policy under the NHIS that grants non-payments of annual health insurance premiums for older people increases access to health care. We assessed differences in enrollment coverage among four different age groups (18-49, 50-59, 60-69, and 70+). We found higher enrollment for the 70+ and 60-69 age groups. The likelihood of enrollment was 2.7 and 1.7 times higher for the 70+ and 60-69 age groups, respectively. Our results suggest the NHIS exemption policy increases insurance coverage of the aged and their utilization of health care services

Prognostic factors and patterns of recurrence in esophageal cancer assert arguments for extended two-field transthoracic esophagectomy

BACKGROUND: High recurrence rates determine the dismal outcome in esophageal cancer. We reviewed our experiences and defined prognostic factors and patterns of recurrences after curatively, intended transthoracic esophagectomy. METHODS: Between January 1991 and December 2005, 212 consecutive patients underwent a radical transthoracic esophagectomy with extended 2-field lymphadenectomy. Recurrence rates, survival, and prognostic factors were analyzed (minimal follow-up period, 2 y). RESULTS: Radicality was obtained in 85.6%. The median follow-up period was 26.6 months. The overall recurrence rate at I, 3, and 5 years was 28%, 44%, and 64%, respectively, and locoregional recurrence rate was 17%, 27%, and 43%, respectively. Overall survival rates, including postoperative deaths, were 45% and 34% at 3 and 5 years, respectively. pT stage and lymph node (LN) ratio greater than .20 were independent prognostic factors for survival and recurrences. Radicality was most prognostic for survival, and for N+ greater than 4 positive LN for recurrences. CONCLUSIONS: Radicality and LN ratio are strong prognostic factors. High radicality and adequate nodal assessment are guaranteed by an extended transthoracic approach. (C) 2010 Elsevier Inc. All rights reserved

Trajectories of Fatigue in Inflammatory Bowel Disease

BACKGROUND: Fatigue is one of the most frequently reported symptoms by patients with inflammatory bowel disease (IBD), both during active disease phases as well as during clinical remission. This study addressed whether different trajectories of fatigue over time can be identified among patients with IBD. Subsequently, we compared the demographic and clinical characteristics between trajectories. METHODS: The current study included 849 patients with IBD diagnosed with either Crohn disease (CD; n = 511) or ulcerative colitis (UC; n = 338) who visited the University Medical Center in Groningen (the Netherlands) at least 3 times during a 9-year follow-up. We conducted latent class growth analyses to identify distinct trajectories. RESULTS: In all patients with IBD (and in the subgroup with CD), we found 5 trajectories for fatigue. In the UC subgroup, we found 4 fatigue trajectories. One trajectory present in both patients with CD (11.45%) and patients with UC (4.75%) was characterized by chronic elevated levels of fatigue across time. Women and parents were more prevalent in trajectories with higher fatigue severity. We also found significant associations among the fatigue trajectories with disease activity and psychological well-being. CONCLUSIONS: The results clearly showed the existence of distinct fatigue paths over time in patients with IBD. Those reporting more chronic elevated levels of fatigue also reported greater disease activity and reduced well-being. Therefore, reducing disease activity may be important for the treatment of fatigue. In addition, given the significant association with well-being, it is possible that reducing fatigue may improve self-reported well-being

A Critical Appraisal of Circumferential Resection Margins in Esophageal Carcinoma

In esophageal cancer, circumferential resection margins (CRMs) are considered to be of relevant prognostic value, but a reliable definition of tumor-free CRM is still unclear. The aim of this study was to appraise the clinical prognostic value of microscopic CRM involvement and to determine the optimal limit of CRM.To define the optimal tumor-free CRM we included 98 consecutive patients who underwent extended esophagectomy with microscopic tumor-free resection margins (R0) between 1997 and 2006. CRMs were measured in tenths of millimeters with inked lateral margins. Outcome of patients with CRM involvement was compared with a statistically comparable control group of 21 patients with microscopic positive resection margins (R1).A cutoff point of CRM at a parts per thousand currency sign1.0 mm and &gt; 1.0 mm appeared to be an adequate marker for survival and prognosis (both P &lt;0.001). The outcome in patients with CRMs a parts per thousand currency sign1.0 and &gt; 0 mm was equal to that in patients with CRM of 0 mm (P = 0.43). CRM involvement was an independent prognostic factor for both recurrent disease (P = 0.001) and survival (P &lt;0.001). Survival of patients with positive CRMs (a parts per thousand currency sign1 mm) did not significantly differ from patients with an R1 resection (P = 0.12).Involvement of the circumferential resection margins is an independent prognostic factor for recurrent disease and survival in esophageal cancer. The optimal limit for a positive CRM is a parts per thousand currency sign1 mm and for a free CRM is &gt; 1.0 mm. Patients with unfavorable CRM should be approached as patients with R1 resection with corresponding outcome.</p