Preeclampsia : an accelerator–brake defect disorder

Life's perfect partnership starts with the placenta. If we get this right, we have the best chance of healthy life. In preeclampsia, we have a failing placenta. Preeclampsia kills one pregnant woman every minute and the life expectancy of those who survive is greatly reduced. Preeclampsia is treated roughly the same way it was when Thomas Edison was making the first silent movie. Globally, millions of women risk death to give birth each year and almost 300,000 lose their lives in this process. Over half a million babies around the world die each year as a consequence of preeclampsia. Despite decades of research, we lack pharmacological agents to treat it. Maternal endothelial dysfunction is a central phenomenon responsible for the clinical signs of preeclampsia. In the late nineties, we discovered that vascular endothelial growth factor (VEGF) stimulated nitric oxide release. This led us to suggest that preeclampsia arises due to the loss of VEGF activity, possibly due to a rise in soluble Flt-1 (sFlt-1), the natural antagonist of VEGF. Researchers have shown that high sFlt-1 elicits preeclampsia-like signs in pregnant rats and sFlt-1 increases before the clinical signs of preeclampsia in pregnant women. We demonstrated that removing or reducing this culprit protein from preeclamptic placenta restored the angiogenic balance. Heme oxygenase-1 (HO-1 or Hmox1) that generates carbon monoxide (CO), biliverdin (rapidly converted to bilirubin) and iron is cytoprotective. We showed that the Hmox1/CO pathway prevents human placental injury caused by pro-inflammatory cytokines and suppresses sFlt-1 and soluble endoglin release, factors responsible for preeclampsia phenotypes. The other key enzyme we identified is the hydrogen sulfide generating cystathionine-gamma-lyase (CSE or Cth). These are the only two enzyme systems shown to suppress sFlt-1 and to act as protective pathways against preeclampsia phenotypes in animal models. We also showed that when hydrogen sulfide restores placental vasculature, it also improves lagging fetal growth. These molecules act as the inhibitor systems in pregnancy and when they fail, this triggers preeclampsia. Discovering that statins induce these enzymes led us to an RCT to develop a low-cost therapy (StAmP Trial) to prevent or treat preeclampsia. If you think of pregnancy as a car then preeclampsia is an accelerator–brake defect disorder. Inflammation, oxidative stress and an imbalance in the angiogenic milieu fuel the ‘accelerator’. It is the failure in the braking systems (the endogenous protective pathway) that results in the ‘accelerator’ going out of control until the system crashes, manifesting itself as preeclampsia.

The role of the English language in the context of national development vision 2025 with specific reference to agriculture in Tanzania

After thirty years of vacillation, the Tanzanian government has made a firm decision to Swahilize its secondary education system. It has also embarked on an ambitious economic and social development programme (Vision 2025) to transform its peasant society into a modern agricultural community. However, there is a faction in Tanzania opposed to Kiswahili as the medium of education. Already many members of the middle and upper class their children to English medium primary schools to avoid the Kiswahili medium public schools and to prepare their children for the English medium secondary system presently in place. Within the education system, particularly at university level, there is a desire to maintain English as the medium of education. English is seen to provide access to the international scientific community, to cutting edge technology and to the global economy. My interest in this conflict of interests stems from several years' experience teaching English to students at Sokoine University of Agriculture. Students specialise in agriculture and are expected to work with the peasant population on graduation. The students experience difficulties studying in English and then find their Kiswahili skills insufficient to explain to farmers the new techniques and technologies that they have studied in English. They are hampered by a complex triglossic situation in which they use their mother tongue with family and friends, Kiswahili, the national language for early education and most public communication within Tanzania, and English for advanced studies. My aim in this thesis was - to study the language policy in Tanzania and see how it is understood and implemented; - to examine the attitudes towards the various languages and their various roles; - to investigate actual language behaviour in Tanzanian higher education. My conclusion is that the dysfunctionality of the present study has to be addressed. Diglossic public life in Tanzania has to be accommodated. The only solution appears to be a compromise, namely a bilingual education system which supports from all cases of society by using Kiswahili, together with an early introduction of English and its promotion as a privileged foreign language, so that Tanzania can continue to develop internally through Kiswahili and at the same time retain access to the globalising world through the medium of English.

How accurate are photographic surrogate markers used to detect macular oedema in the english national Screening Programme?

Introduction: Macular oedema is not directly visible on digital photographs used in screening. Photographic surrogate markers are used to detect patients who may have macular oedema. Evidence suggests that only around 10% of patients with these surrogate markers referred to an ophthalmologist have macular oedema when examined by slit-lamp biomicroscopy. Purpose: The purpose of this audit was to determine how many patients with surrogate markers were truly identified by optical coherence tomography (OCT) as having macular oedema. Method: Data were collected from patients attending digital diabetic retinopathy screening. Patients who presented with surrogate markers for macular oedema also had an OCT scan. The fast macula scan on the Stratus OCT was used and an ophthalmologist reviewed the scans to determine whether macular oedema was present. Results: Out of 66 patients with maculopathy defined as haemorrhages or microaneurysms within one optic disc diameter (DD) of the fovea and visual acuity (VA) worse than 6/9 11 (17%) showed thickening on the OCT, only 4 (6%) had macular oedema. None required laser. Out of 155 patients with maculopathy defined as any exudate within one DD of the fovea or circinate within two DD 45 (29%) showed thickening on the OCT of these 27% required laser. Conclusion: OCT is a useful tool in screening to help identify those who need a true referral to ophthalmology for maculopathy. If exudate is present the chance of having macular oedema and requiring laser treatment is greater than the presence of microaneurysms within one DD and reduced VA.

How accurate are photographic surrogate markers used to detect macular edema in the English national screening programme?

DESIGN. Retrospective analysis PURPOSE. Macular oedema is not directly visible on two dimensional digital photographs such that surrogate markers need to be used. In the English National Screening Programme these are exudate within one optic disc diameter (DD) of the fovea, group of exudates within two DD of the fovea and haemorrhages or microaneurysms (HMA) within one DD of the fovea with best corrected visual acuity (VA) worse than 6/9. All patients who present with any of these surrogate markers at screening are referred to an ophthalmology clinic for slit lamp examination. The purpose of this audit was to determine how many patients with positive maculopathy diagnosis on photography were truly identified by optical coherence tomography (OCT) with macular oedema. METHODS. Data was collected from patients attending digital diabetic retinopathy screening. Patients who presented with surrogate markers for macular oedema also had an OCT scan. The fast macula scan on the Stratus OCT was used and an ophthalmologist reviewed the scans to determine whether macular oedema was present. RESULTS. Maculopathy by exudates: Of 155 patients 45 (29%) showed thickening on the OCT of these 12 required laser. Those who also had pre-proliferative retinopathy (n=20) were more likely to have macular oedema (75%) than those with background diabetic retinopathy. Maculopathy by HMA and VA worse than 6/9: Of 66 patients 11 (16.7%) showed thickening on the OCT. 5 (7.6%) of these had macular oedema, 5 (7.6%) epi-retinal membrane, and 1 (1.5%) age related macular degeneration. None of these patients required laser. CONCLUSIONS. The likelihood of the presence of macular oedema and requiring laser treatment is greater with macular exudation than HMA within one DD and reduced VA. Overall the surrogate markers used show low specificity for macular oedema, however combining OCT with photography does identify those with macular oedema who require a true referral for an ophthalmological slit lamp examination.

Quality of life, stress and mental health in parents of children with parentally diagnosed food allergy compared to medically diagnosed and healthy controls

Background. Food allergy is related to poorer quality of life (QoL) and mental health of caregivers. Many parents diagnose food allergy in their child without seeking medical care and there is limited research on this group. This study investigated parental QoL and mental health in parents of children with parent-diagnosed food allergy (PA), medically diagnosed food allergy (MA), and a control group with no allergy (NA). Methods. One hundred and fifty parents from a general population completed validated measures of QoL, anxiety, depression, and stress. Results. Parents of children with food allergy (PA or MA) reported higher stress, anxiety, and depression than the control group (all ). Parents of children with MA reported poorer food allergy related QoL compared to parents of children with PA (); parents of children with PA reported poorer general QoL compared to parents of children with MA (). Conclusion. Parents of children with food allergy have significantly poorer mental health compared to healthy controls, irrespective of whether food allergy is medically diagnosed or not. It is important to encourage parents to have their child medically tested for food allergy and to recognise and refer for psychological support where needed.