A ten-year study of Retinoblastoma in Uganda: An approach to improving outcome with limited resources.

BACKGROUND: Survival of children with cancer in resource-limited regions is very poor compared to better-resourced regions. Retinoblastoma (RB) is a childhood cancer that is commonly reported in many regions of Africa. RB may be safely and effectively treated by non-specialists, which could facilitate more widespread availability of treatment in under-resourced areas. METHODS: A ten-year consecutive series of children with RB treated at Ruharo Eye Centre between December 2009 and November 2019 was prospectively followed up. Chemoreduction followed by surgery is the standard approach to therapy. Costs of therapy and also of travel and food are borne by the program which is unaffordable to most families and necessitates donors. Survival by stage of RB and number of eyes affected was described using Kaplan-Meier plots. Visual acuity was assessed for all children with bilateral disease and the retention of sight during follow-up assessed. RESULTS: Among 665 children with RB, 18.2 % (121 children) presented with metastatic (Stage 4) RB with only two of these children surviving >24 months. Five-year survival was 60.2 % among all children with RB rising to 93.3 % and 87.2 % for children with unilateral and bilateral Stage 1 disease, respectively. Among 184 children with bilateral disease, 130 (70.7 %) retained some level of sight following primary treatment with 91 of those (49.5 % of all bilateral children) retaining vision up to their death or to the end of follow-up. CONCLUSION: Many children in Uganda present with advanced RB and curative treatment is not possible in this setting. Children diagnosed and treated early have good prospects of survival. Retention of sight among many bilaterally affected children is achievable, facilitating access to normal education. Therefore, the strategic priorities for improving survival are changing community perceptions so that children with eye problems are brought without delay, and widening access to modern treatment by using genereal health workers with standard drugs, backed by financial, social and peer support.

Application of Bayesian statistics to estimate nitrous oxide emission factors of three nitrogen fertilisers on UK grasslands.

Trapezoidal integration by linear interpolation of data points is by far the most commonly used method of cumulative flux calculations of nitrous oxide (N2O) in studies that use flux chambers; however, this method is incapable of providing accurate uncertainty estimates. A Bayesian approach was used to calculate N2O emission factors (EFs) and their associated uncertainties from flux chamber measurements made after the application of nitrogen fertilisers, in the form of ammonium nitrate (AN), urea (Ur) and urea treated with Agrotain® urease inhibitor (UI) at four grassland sites in the UK. The comparison between the cumulative fluxes estimated using the Bayesian and linear interpolation methods were broadly similar (R2 = 0.79); however, the Bayesian method was capable of providing realistic uncertainties when a limited number of data points is available. The study reports mean EF values (and 95% confidence intervals) of 0.60 ±â€¯0.63, 0.29 ±â€¯0.22 and 0.26 ±â€¯0.17% of applied N emitted as N2O for the AN, Ur and UI treatments, respectively. There was no significant difference between N2O emissions from the Ur and UI treatments. In the case of the automatic chamber data collected at one site in this study, the data did not fit the log-normal model, implying that more complex models may be needed, particularly for measurement data with high temporal resolution.

Seasonal fluxes of carbon monoxide from an intensively grazed grassland in Scotland.

Fluxes of carbon monoxide (CO) were measured using a fast-response quantum cascade laser absorption spectrometer and the eddy covariance method at a long-term intensively grazed grassland in southern Scotland. Measurements lasted 20 months from April 2016 to November 2017, during which normal agricultural activities continued. Observed fluxes followed a regular diurnal cycle, peaking at midday and returning to values near zero during the night, with occasional uptake observed. CO fluxes correlated well with the meteorological variables of solar radiation, soil temperature and soil moisture content. Using a general additive model (GAM) we were able to gap fill CO fluxes and estimate annual fluxes of 0.38 ±â€¯0.046 and 0.35 ±â€¯0.045 g C m-2 y-1g C m-2 y-1 for 2016 and 2017, respectively. If the CO fluxes reported in this study are representative of UK grasslands, then national annual emissions could be expected to be in the order of 61.91 (54.3-69.5) Gg, which equates to 3.8% (3.4-4.3%) of the current national inventory total.

The effect of hyaluronidase on ultrasound-measured dispersal of local anaesthetic following sub-Tenon injection.

PURPOSE: To determine by B-scan ultrasonography if the addition of hyaluronidase affects the dispersal of anaesthetic fluid after sub-Tenon's injection. DESIGN: Single-centre prospective randomised double-blind study. MATERIALS AND METHODS: We performed a trial in 19 patients who were randomised to receive 5 ml of lidocaine 2% alone, or with hyaluronidase 15 IU/ml. A pre-anaesthetic B-scan ultrasound was performed followed by a standard infero-nasal sub-Tenon's injection. Further B-scan ultrasound studies were performed at 1, 3, and 5 min recording depth of local anaesthetic fluid. Data was analysed with Fisher's exact test and Student's t-test where appropriate. Results were considered significant when P<0.05. RESULTS: The maximum depth of local anaesthetic was significantly less in the hyaluronidase group than the control group at 3 and 5 min (0.79 vs1.65 mm, P-value 0.01 and 0.43 vs1.52 mm, P-value 0.002 respectively). There were no statistically significant differences in the akinesia, pain and surgical satisfaction scores between the two groups. CONCLUSIONS: The addition of hyaluronidase significantly augments the dispersal of local anaesthetic fluid, as measured by B-scan ultrasonography.

Neuroblastoma with orbital metastasis: ophthalmic presentation and role of ophthalmologists.

INTRODUCTION: Neuroblastoma is predominantly a tumour of early childhood, which metastasises to the orbits. In such cases, ophthalmologists are involved in the multidisciplinary management. This unique series from a tertiary referral centre is used to elaborate the ophthalmic associations and the ophthalmologist's role in this rare condition. METHODS: A review of case notes was performed on six patients who presented to the paediatric ophthalmology - oncology liaison service at the Leeds teaching hospitals between 1998 and 2003. The ophthalmic outcome and role of the ophthalmologist were assessed. RESULTS: Average age of presentation was 29.8 months (range 15-69 months). Average duration of follow-up was 19.5 months (range 2-58 months). One child died during treatment. Two have completed treatment and are under follow-up. Presenting features of the six children were proptosis in four, periorbital ecchymosis in two, ocular motility restriction in two, and subconjunctival haemorrhage in one. Only one case developed blindness. CONCLUSIONS: The role of the ophthalmologist in patients with metastatic orbital neuroblastoma can vary from a supportive role to one of active intervention and management of ophthalmic complications. The ophthalmologist is involved in diagnosis and staging as well as monitoring response to treatment of both the primary disease and secondary ophthalmic complications.

Technique to prevent limb ischemia during peripheral cannulation for extracorporeal membrane oxygenation.

Prolonged extracorporeal support using femoral cannulation may cause limb ischemia. A technique is described using antegrade, retrograde arterial perfusion and venous drainage to prevent limb ischemia.

Do corneal endothelial dystrophies represent ocular neurocristopathies? A discussion on the available evidence.

Current thinking on the embryological origin of human corneal endothelium has it that this cellular population stems from neural crest precursors. There are arguments in support of this assumption but equally persuasive ones against it. We present a discussion of the evidence for and against a neural crest origin for human corneal endothelial cells. In suggesting that caution be applied to extrapolating from non-human work, we would question the fallibility of the current thinking on this subject. To denote human corneal dystrophies as neurocristopathies may be a premature assumption.

Optic nerve breast metastasis mimicking meningioma.

PURPOSE: We report on an optic nerve breast metastasis masquerading initially as a central retinal vein occlusion and later as an optic nerve meningioma. METHODS: A 60-year-old female presented with a left central retinal vein occlusion (CRVO). She represented 7 months later with left upper ptosis, proptosis and painful rubeotic glaucoma Computed tomography (CT) and magnetic resonance imaging suggested an optic nerve meningioma. On referral to the regional orbital unit a mild left external ophthalmoplegia was noted and, in view of previous right mastectomy and chemotherapy 3 years earlier, the left optic nerve was biopsied simultaneously with left enucleation of her painful eye. RESULTS: Histopathology showed infiltration of the optic nerve and meningeal sheath spreading into the subretinal space and vitreous by malignant epithelial cells, consistent with breast origin. Further CT imaging and bone scans revealed no other metastases. Single field left orbit radiotherapy of 20 Gy was given in five fractions and Arimidex (Zeneca Pharmaceuticals, Cheshire, England) was commenced with the cessation of tamoxifen. The patient was also given an ocular prosthesis. Sadly, she lost vision in her other eye due to retrograde malignant invasion of her optic chiasm and died 6 weeks later. CONCLUSIONS: Orbital and choroidal metastases are relatively common but isolated optic nerve metastases are extremely rare. Progressive infiltration of the nerve is likely to enhance CRVO ischaemia and resultant rubeotic glaucoma. In the diagnosis of CRVO, proptosis or external ophthalmoplegia, the presence of pre-existing malignant disease should raise concerns, as delay in diagnosis may affect outcome, particularly if the metastases are sensitive to pharmacological therapy.

Carbon monoxide poisoning causes optic neuropathy.

PURPOSE: To describe the electrophysiological and psychophysical effects of carbon monoxide (CO) poisoning on visual function. METHODS: Three patients are presented who suffered CO poisoning, two due to suicide attempts and one in the course of a road traffic accident. After a full ocular examination, Goldmann visual fields, flash and pattern visual evoked potentials (VEPs) and flash and pattern electroretinograms (ERGs) were tested. RESULTS: Electrophysiology showed reduced or absent N95 components of the pattern ERG and delayed, reduced VEPs. A positive-negative-positive (PNP) VEP waveform was seen in two cases. In one case, where presentation occurred at an early stage, visual and electrophysiological function was improved with hydroxycobalamine. CONCLUSIONS: The combination of ERG and VEP findings suggest that CO poisoning can cause a toxic optic neuropathy that may have a similar aetiological mechanism to that in tobacco amblyopia. Early treatment with hydroxycobalamine may be of some benefit.

Posterior scleritis and polymyalgia rheumatica.

Scleritis is typically a non-infectious granulomatous inflammatory process. It may be found in conjunction with systemic disease, more commonly in those patients with necrotising anterior scleritis. We describe a patient with posterior scleritis and polymyalgia rhematica. This association has not previously been reported.

Spatial diversity in the mid-Flandrian vegetation history of North Gill, North Yorkshire.

The results of investigating a series of 11 pollen and stratigraphic profiles in peats along a 350 m stream section are described. Each profile has a small pollen catchment overlapping little with its neighbour's and the diagrams therefore show fine spatial resolution of the vegetational history. Fine temporal resolution is provided by 1 cm, or for certain sections 1 mm, interval samples. There is evidence that during the Mesolithic distinct patches of the local forest vegetation, of the order of tens rather than hundreds of metres in diameter, were managed by burning and the regular lopping of branches, for periods of up to a few hundred years each. Peat inception is thought to have occurred as early as the 9th millenium BP in some parts of the stream and up to 3000 yr later in others. Lopping and burning was the immediate cause at most sites within the channel of the gill, although fine-scale topographic and geological variation affected the timing. The developing peat was bordered by an alder carr in the lower and middle reaches of the stream. Radiocarbon dating of the mid-Flandrian Ulmus decline shows it to be asynchronous. It was caused by a combination of factors including disease and the affect the mesolithic management practices had had on the soil earlier in the Flandrian.

The relationship between Trichuris trichiura transmission intensity and the age-profiles of parasite-specific antibody isotypes in two endemic communities.

The present study compares parasite-specific antibody responses in two Caribbean communities with high and low levels of Trichuris trichiura transmission. The age-dependency of antibody levels suggest that IgG1 and IgG2 levels relate to the current intensity of infection (as assessed by density of eggs in stool (e.p.g.) and reflect the age-intensity profile at the population level. IgG4, IgE and IgA levels persist into early adulthood and the subsequent decline is gradual. In the low transmission area, lower infection levels are reflected in lower parasite-specific antibody levels (of all isotypes) in the community as a whole. Despite a significantly greater past experience of infection in the high transmission area, antibody levels are not maintained at significantly higher levels throughout adulthood. The production of IgA appears to require a threshold for triggering, and a vigorous IgA response is maintained into early adulthood only in the high transmission village where peak intensity is greatest and the age-convexity of intensity is most marked. Experimental and theoretical studies focusing on the dynamic nature of host-helminth interactions in hosts exposed to high and low infection levels, and the putative role of acquired immunity, are discussed in relation to the data presented.

Age-dependency of infection status and serum antibody levels in human whipworm (Trichuris trichiura) infection.

This study examines the age-dependency of the relationships between human infection with whipworm (Trichuris trichiura) and parasite-specific antibody level measured by ELISA against an extract of adult worms after preincubation of the sera with Ascaris lumbricoides adult worm extract. The convex age-profile of parasite infection intensity is shown to be mirrored by an age-dependent change in age-class mean levels of IgG (all subclasses except IgG3), IgA, IgM and IgE. Mean antibody levels rise with increasing acquisition of infection in childhood and decline as the intensity of infection falls in adulthood. Immunoblot analysis of selected sera from different age-classes indicates that antigen recognition is similarly dependent on infection intensity. In individual children, antibody levels correlate positively with acquisition of infection, consistent with a simple model of antigen dosage specifying the magnitude of the humoral immune response. In adults, IgG4 correlates positively and IgA negatively with intensity of infection, suggesting involvement of these isotypes in functional roles of immune blockade or effector mechanisms, respectively.

Vitamin E, lipid fractions, and fatty acid composition of colostrum, transitional milk, and mature milk: an international comparative study.

Triglycerides, cholesterol, fatty acid composition, and tocopherols were determined in colostrum, transitional milk, and mature milk in St Lucia. With progress of lactation, triglycerides and percentage medium-chain fatty acids increased whereas tocopherols, cholesterol, and percentage long-chain polyunsaturated fatty acids decreased. These changes reflect augmented de novo synthesis of fatty acids (8:0, 10:0, 12:0, and 14:0) in the mammary gland and a tendency of increasing fat-globule size as milk matures. Transitional and mature milks, but particularly colostrum, contained higher concentrations of components considered to be derived from the fat-globule membrane (cholesterol, tocopherols, percentage long-chain polyunsaturated fatty acids) compared with those reported for Western countries. Percentage medium-chain fatty acids in mature milk was two to three times higher than in developed countries. Differences from data from studies in Western countries are discussed in relation to analytical methods and possible consequences for lipid digestion, lipid absorption, growth, and brain development.