Magnitude and causes of childhood blindness and severe visual impairment in Sekoru District, Southwest Ethiopia: a survey using the key informant method

There are very few population-based data on childhood blindness in the Horn of Africa. In Sekoru district, Ethiopia, we performed a whole-of-population cross-sectional survey using the key informant method to determine the magnitude and causes of childhood blindness (presenting visual acuity <3/60 in the better eye) and severe visual impairment (SVI; presenting visual acuity <6/60 but ≥3/60 in the better eye). Forty-two key informants were trained to identify blind/SVI children aged <16 years. Identified children were examined by an ophthalmologist. Causes of blindness/SVI were established by clinical examination. Key informants visited 94% of 22 666 households, identifying 112 children, of whom 36 (32%) were confirmed to be blind/SVI by the ophthalmologist. Twenty (56%) of the 36 were male. The mean age was 10.7 years. The district prevalence of childhood blindness/SVI was 0.062% (95% CI 0.042-0.082%). Lens-related abnormalities (mainly congenital cataract) were the commonest causes. Avoidable causes of blindness accounted for 89% of cases. Paediatric ophthalmic services are required here, as elsewhere in rural Ethiopia. Assessment by key informants has an acceptable positive predictive value in this setting. This method warrants further evaluation as a tool for measuring the prevalence of other rare conditions in rural and remote populations.     

Thermochromic tissue-mimicking phantom for optimisation of thermal tumour ablation

Purpose The purpose of this study was to (1) develop a novel tissue-mimicking thermochromic (TMTC) phantom that permanently changes colour from white to magenta upon heating above ablative temperatures, and (2) assess its utility for specific applications in evaluating thermal therapy devices.

Materials and methods Polyacrylamide gel mixed with thermochromic ink was custom made to produce a TMTC phantom that changes its colour upon heating above biological ablative temperatures (> 60?°C). The thermal properties of the phantom were characterised, and compared to those of human tissue. In addition, utility of this phantom as a tool for the assessment of laser and microwave thermal ablation was examined.

Results The mass density, thermal conductivity, and thermal diffusivity of the TMTC phantom were measured as 1033?±?1.0?kg/m³, 0.590 ± 0.015 W/m.K, and 0.145?±?0.002?mm²/s, respectively, and found to be in agreement with reported values for human soft tissues. Heating the phantom with laser and microwave ablation devices produced clearly demarcated regions of permanent colour change geographically corresponding to regions with temperature elevations above 60?°C.

Conclusion The TMTC phantom provides direct visualisation of ablation dynamics, including ablation volume and geometry as well as peak absolute temperatures within the treated region post-ablation. This phantom can be specifically tailored for different thermal therapy modalities, such as radiofrequency, laser, microwave, or therapeutic ultrasound ablation. Such modality-specific phantoms may enable better quality assurance, device characterisation, and ablation parameter optimisation, or optimise the study of dynamic heating parameters integral to drug device combination therapies relying upon heat.     

Evaluation of in vivo antihypertensive and in vitro vasodepressor activities of the leaf extract of Syzygium guineense (Willd) D.C

The aim of this work was to evaluate the antihypertensive activity of the hydroalcohol extract of the leaves of Syzygium guineense (Willd) D.C. (Myrtaceae) in a 1-kidney-1-clip rat model and its vasorelaxant effect on isolated aorta. The extract reduced blood pressure in a dose and time dependent fashion. Following 3 days of treatment, single oral daily doses of 50, 100 and 150 mg/kg caused an overall reduction (p < 0.05) of systolic blood pressure by 6.9, 34.0 and 40.8 mmHg, respectively. The diastolic blood pressure was, however, significantly reduced (p < 0.05) by 100 mg/kg (10.3 mmHg) and 150 mg/kg (18.4 mmHg) doses only. The mean blood pressure was reduced by 5.0, 18.3 and 25.9 mmHg by the respective doses. The extract also caused a dose-dependent relaxation of aorta precontracted with KCl at a concentration of 5-70 mg/mL, with a maximum relaxation of 56.22% achieved at 70 mg/mL concentration. The relaxation mechanism was found to be independent of the endothelium system, muscarinic receptors, histamine receptors, ATP dependent K(+) channels, cyclooxygenase enzymes and cGMP/NO pathway. The findings suggest that the extract had an antihypertensive effect most likely caused by dilation of the blood vessels, a confirmation for the folkloric use of the plant.     

Lyso-thermosensitive liposomal doxorubicin for treatment of bladder cancer

Purpose: To evaluate lyso-thermosensitive liposomal doxorubicin (LTLD, ThermoDox^®) in combination with loco-regional mild hyperthermia (HT) for targeted drug delivery to the bladder wall and potential treatment of bladder cancer.

Material and methods: Porcine in vivo studies were performed with the following groups: (i) intravenous (IV) LTLD with hyperthermia (LTLD?+?HT); (ii) IV doxorubicin (DOX) with hyperthermia (IV DOX?+?HT) and (iii) IV LTLD without hyperthermia (LTLD – HT). Drug formulations were delivered via 30?min IV infusion coinciding with 1-h bladder irrigation (45?°C water for HT groups, 37?°C for non-HT group), followed by immediate bladder resection. DOX concentrations were measured in consecutive sections parallel to the bladder lumen by liquid chromatography following drug extraction. Computer models were developed to simulate tissue heating and drug release from LTLD.

Results: Comparing mean DOX concentrations at increasing depths from the lumen to outer surface of the bladder wall, the ranges for LTLD?+?HT, IV DOX?+?HT and LTLD – HT, respectively, were 20.32–3.52?μg/g, 2.34–0.61?μg/g and 2.18–0.51?μg/g. The average DOX concentrations in the urothelium/lamina and muscularis, respectively, were 9.7?±?0.67 and 4.09?±?0.81?μg/g for IV LTLD?+?HT, 1.2?±?0.39 and 0.86?±?0.24?μg/g for IV DOX?+?HT, and 1.15?±?0.38 and 0.62?±?0.15?μg/g for LTLD – HT. Computational model results were similar to measured DOX levels and suggest adequate temperatures were reached within the bladder wall for drug release from LTLD.

Conclusions: Doxorubicin accumulation and distribution within the bladder wall was achieved at concentrations higher than with free IV doxorubicin by mild bladder hyperthermia combined with systemic delivery of LTLD.     

Utility of diffusion-weighted imaging in the diagnosis of inguinal lymph node metastasis with malignant melanoma

Malignant melanoma is a malignancy of pigment-producing cells (melanocytes) located predominantly in the skin. Nodal metastases are an adverse prognostic factor compromising long term patient survival. Therefore, accurate detection of regional nodal metastases is required for optimization of treatment. Computed tomography (CT) and magnetic resonance imaging (MRI) remain the primary imaging modalities for regional staging of malignant melanoma. However, both modalities rely on size-related and morphological criteria to differentiate between benign and malignant lymph nodes, decreasing the sensitivity for detection of small metastases. Surgery is the primary mode of therapy for localized cutaneous melanoma. Patients should be followed up for metastases after surgical removal. We report here a case of inguinal lymph node enlargement with a genital vesicular lesion with a history of surgery for malignant melanoma on her thigh two years ago. CT and diffusion weighted-MRI (DW-MRI) were applied for the lymph node identification. DW-MRI revealed malignant lymph nodes due to malignant melanoma metastases correlation with pathological findings.     

Megakaryocytic cells synthesize and platelets secrete alpha5-laminins, and the endothelial laminin isoform laminin 10 (alpha5beta1gamma1) strongly promotes adhesion but not activation of platelets

Following vascular injury, basement membrane (BM) components of the blood vessels are exposed to circulating cells and may contribute to hemostasis and/or thrombosis. Laminins 8 (LN-8) (alpha4beta1gamma1) and 10 (LN-10) (alpha5beta1gamma1) are major laminin isoforms of the endothelial BM, and LN-8 is also secreted by activated platelets. In the present study, we demonstrate synthesis of alpha5-laminins LN-10 and LN-11 (alpha5beta2gamma1) by megakaryocytic cells, and intracellular expression of these laminin isoforms in blood platelets. In contrast to platelet LN alpha4 chain that had an apparent molecular weight of 180 kDa and associated mostly to LNbeta1 chain, platelet LNalpha5 consisted of 300/350 kDa polypeptides and associated mainly to LNbeta2. Both alpha4- and alpha5-laminins were secreted by platelets following stimulation. When compared to recombinant human (rh) LN-8, rhLN-10 was much more adhesive to platelets, though adhesion to both proteins was largely mediated via alpha6beta1 integrin. In spite of their adhesive properties, rhLN-8 and rhLN-10 induced neither P-selectin expression nor cell aggregation, two signs of platelet activation. This study demonstrates synthesis/expression of heterotrimeric alpha5-laminins in hematopoietic/blood cells, and provides evidence for the adhesive, but not activating, role of endothelial laminin isoforms in platelet biology.     

Non-invasive detection of biliary leaks using Gd-EOB-DTPA-enhanced MR cholangiography: comparison with T2-weighted MR cholangiography

Objective

To evaluate the added role of T1-weighted (T1w) gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance cholangiography (MRC) compared with T2-weighted MRC (T2w-MRC) in the detection of biliary leaks.

Methods

Ninety-nine patients with suspected biliary complications underwent routine T2w-MRC and T1w contrast-enhanced (CE) MRC using Gd-EOB-DTPA to identify biliary leaks. Two observers reviewed the image sets separately and together. MRC findings were compared with those of surgery and percutaneous transhepatic cholangiopancreatography. The sensitivity, specificity and accuracy of the techniques in identifying biliary leaks were calculated.

Results

Accuracy of locating biliary leaks was superior with the combination of Gd-EOB-DTPA-enhanced MRC and T2w-MRC (P?<?0.05).The mean sensitivities were 79 % vs 59 %, and the mean accuracy rates were 84 % vs 58 % for combined CE-MRC and T2w-MRC vs sole T2w-MRC. Nineteen out of 21 patients with biliary-cyst communication, 90.4 %, and 12/15 patients with post-traumatic biliary extravasations, 80 %, were detected by the combination of Gd-EOB-DTPA-enhanced MRC and T2w-MRC images, P?<?0.05.

Conclusions

Gd-EOB-DTPA-enhanced MRC yields information that complements T2w-MRC findings and improves the identification and localisation of the bile extravasations (84 % accuracy, 100 % specificity, P?<?0.05). We recommend Gd-EOB-DTPA-enhanced MRC in addition to T2w-MRC to increase the preoperative accuracy of identifying and locating extravasations of bile.

Key Points

? Magnetic resonance cholangiography (MRC) does not always detect bile leakage and cysto-biliary communications. ? Gd-EOB-DTPA-enhanced MRC helps by demonstrating extravasation of contrast material into fluid collections. ? Gd-EOB-DTPA-enhanced MRC also demonstrates the leakage site and bile duct injury type. ? Combined Gd-EOB-DTPA-enhanced and T2w-MRC can provide comprehensive information about biliary system. ? Gd-EOB-DTPA-enhanced MRC is non-invasive and does not use ionising radiation.