Hamdan Medical Journal (Hamdan Med J) ..................................................................................................................................REVIEW ARTICLE Extraoesophageal reflux manifestations of gastro-oesophageal reflux disease p. 1 Berit Schneider-Stickler DOI:10.4103/HMJ.HMJ_8_19 Gastro-oesophageal reflux disease (GERD) is defined as a condition when the reflux of gastric content causes troublesome symptoms or complications. Gastro-oesophageal reflux is associated with numerous pathologic conditions of the upper aerodigestive tract. GERD can be subclassified into oesophageal and extraoesophageal syndromes. Extraoesophageal manifestations can be either pulmonary or otorhinolaryngological. This review provides an overview of most important extra-oesophageal reflux manifestations in GERD patients. [ABSTRACT] [HTML Full text] [PDF] [Mobile Full text] [EPub] [Sword Plugin for Repository]Beta ORIGINAL ARTICLES Top Investigating the role of th

REVIEW ARTICLE
	Extraoesophageal reflux manifestations of gastro-oesophageal reflux disease	p. 1
	Berit Schneider-Stickler DOI:10.4103/HMJ.HMJ_8_19   Gastro-oesophageal reflux disease (GERD) is defined as a condition when the reflux of gastric content causes troublesome symptoms or complications. Gastro-oesophageal reflux is associated with numerous pathologic conditions of the upper aerodigestive tract. GERD can be subclassified into oesophageal and extraoesophageal syndromes. Extraoesophageal manifestations can be either pulmonary or otorhinolaryngological. This review provides an overview of most important extra-oesophageal reflux manifestations in GERD patients.
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ORIGINAL ARTICLES
	Investigating the role of the histone deacetylases-inhibitor suberanilohydroxamic acid in the differentiation of stem cells into insulin secreting cells	p. 10
	Ibrahim Elsharkawi, Divyasree Sandeep, Ahmed El-Serafi DOI:10.4103/HMJ.HMJ_29_18   Introduction: The United Arab Emirates has the second incidence of diabetes in the world. The current diabetes management plans are associated with many complications and do not provide a cure. Stem cells offer hope for permanent alleviation of this health problem through the possible differentiation into insulin-secreting cells. The current methods for the differentiation do not produce homogeneous beta-cell populations. Histone deacetylation is an epigenetic silencing mechanism that can render many genes irresponsive to the induction protocols. This study aimed at investigating the effect of the histone deacetylase inhibitor suberanilohydroxamic acid (SAHA) on the production of functional beta cells, based on a mesenchymal stem cells model. Methods: MG63 cells were treated for three consecutive days with SAHA, followed by a three-steps of beta cells differentiation protocol, with media-contained retinoic acid, epidermal growth factor, nicotinamide and exendin-4 at different stages. Then, glucose-stimulated insulin secretion was conducted to assess the functional state of the differentiated cells. Results: Pretreating the cells with SAHA enhanced the insulin production and secretion in comparison to the control (PBS) and the vehicle dimethyl sulfoxide, as shown by the immunofluorescence detection of insulin and the transcription factor "PDX1", as well as an increase in insulin secretion in the media. Gene expression analysis showed that SAHA pretreated cells had more induction of the studied markers when challenged with high glucose level. Conclusion: Such findings indicate a novel approach to enhance the ability of stem cells to differentiate into insulin-producing cells with potential therapeutic implications.
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	Prevalence of opioid misuse, abuse and dependence among chronic pain patients on opioids followed in chronic pain clinic in a tertiary care hospital Riyadh, Saudi Arabia	p. 15
	Sameeh Al Maharbi, Abdullah Abolkhair, Hani Al Ghamdi, Mamdouh Haddara, Bjarni Valtysson, Yasser Tolba, Raghad Alaujan, Shadi Abu-Khait DOI:10.4103/HMJ.HMJ_30_18   Background: Opioids have proven very useful for treatment of acute pain and cancer pain, and in the developed countries, opioids are increasingly used for the treatment of chronic non-malignant pain patients as well. Treatment of chronic pain patients with opioids may have several long-term consequences; especially, addiction that has been a feared complication. Objective: The objective of the study was to estimate the prevalence of opioid misuse, abuse and dependence amongst chronic pain patients on opioids followed in chronic pain clinic. Study Design and Settings: This is a cross-sectional study that carried out in chronic pain clinic in a tertiary care hospital Riyadh, Saudi Arabia (King Faisal Specialist Hospital and Research Centre [KFSH and RC]). All chronic pain patients on opioids, apart from acute pain patients and children, were eligible for the study. The Alcohol, Smoking and Substance Involvement Screening Test (Opioid ASSIST) screening questionnaire in Arabic was used as a screening tool for opioid misuse, abuse and dependence. Results: A total of 219 chronic pain patients participated in the study. There were 80 males (36.5%) and 139 females (63.5%). Prevalence of opioids misuse, abuse and dependence in chronic pain patients attending chronic pain clinic in KFSH and RC is 12.8%, 9.1% and 3.2%, respectively, based on opioids ASSIST questionnaire cut points. Conclusion: Opioid use disorders are common in pain clinics. They should be considered as serious complications of using opioids in managing chronic pain patients. Considering the high risk of opioid misuse, abuse and dependence amongst chronic pain patients, more screening and rehabilitation services are necessary.
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	Prevalence of vestibular migraine in Dubai	p. 19
	Teja Deepak Dessai, Samer Sakka Amini, Faisal Asad, Helen Kutty DOI:10.4103/HMJ.HMJ_42_18   Introduction: A vast number of adult persons suffering from vertigo associated with migraine are reported on a daily clinical practice. However, clinical identification of VM still remains hindered in Dubai due to dearth of agreement in diagnostic criteria. Aim: The aim of this study is to determine the prevalence of VM in the general population of Dubai. Methods: A total of 218 adult persons who visited outpatient otolaryngology and rhinology clinic in a given year 2017 with a complaint of vertigo were retrospectively studied and accounted in research. Further, labelling of each person was done based on the presented symptoms. Results and Discussion: To calculate the prevalence of VM, total number of each diagnosis was counted and was further subjected to a formula to calculate prevalence. Out of the 218 persons considered in the study, 30 were diagnosed with migraine (2 persons with migraine alone and 28 persons with VM). This accounts to a prevalence of 0.9% migraine alone and 12.8% VM in a clinical setting for 1 year. Conclusion: The high prevalence of VM in a clinical setup for 1 year hints toward the need for careful diagnosis of a person.
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	Knowledge and attitude of post-natal mothers in al ain medical district about hereditary blood disorders (sickle cell disease, thalassemia and glucose-6-phosphate dehydrogenase deficiency)	p. 23
	Faisal Abdulla AlShamsi, Falah Abdulla Al Mahmmod, Ali Hussain Al Hammadi DOI:10.4103/HMJ.HMJ_60_18   Background: Hereditary haemolytic anaemia has been considered as a major health problem in many countries including the United Arab Emirates (UAE), while the prevalence is not decreasing due to lack of knowledge, unorganised teamwork and services, lack of support groups and inadequate research in the fields of prevention and control. Aim and Objectives: The study aimed at assessing the knowledge and attitude of post-natal mothers in Al-Ain medical district towards common hereditary haemolytic anaemias (glucose-6-phosphate dehydrogenase [G6PD] deficiency, thalassemia and sickle cell anaemia), as a step towards decreasing the prevalence of these diseases amongst the population. Our main objective was to assess understanding of common hereditary haemolytic anaemias as well as to measure the attitude of mothers in Al Ain towards these diseases. Methods: The study was analytical cross-section survey conducted in the period from 23 August to 16 September 2003, in Al Ain Medical District, UAE, in three main hospitals: Al Ain Hospital, Tawam Hospital and Oasis Hospital. An interview-administered questionnaire was used for data collection. Data analysis was done using SPSS version 11. Results: Analysis of the study showed a significant difference amongst participants who heard about G6PD deficiency, according to different age groups, the (18–24) age group had more knowledge about G6PD deficiency when compare with other age groups (P = 0.008). Another significant difference amongst individuals who heard about G6PD deficiency, according to different educational level was as follows: 31% less than secondary school, 60.6% completed secondary school and 50% for higher educational level (P = 0.033). Similarly, for G6PD deficiency, mothers from GCC countries were more aware of G6PD deficiency when compare with other nationals (P = 0.006). Of the total participants, 90% agreed on the importance of genetic counselling before marriage. As the best method of increasing knowledge about hereditary anaemias, media campaigns were the preferred approach having 70.6% voting for it, followed by the approach of educating schoolchildren with 43.1% approval. Conclusion: There is a lack of knowledge amongst post-natal mothers in Al Ain Medical District about common hereditary anaemias compared to a good attitude towards prevention of these disorders.
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	Comparative study between haemorrhagic and ischaemic strokes in hadramout: A hospital-based study	p. 29
	Rasheed Mohammed Bamekhlah, Mohammed Rasheed Bamekhlah, Hussain Saeed Al-Ghazali, Abdulraheem Abdullah Bahishwan DOI:10.4103/HMJ.HMJ_62_18   Aim: The aim of this study was compare between haemorrhagic stroke (HS) and ischaemic stroke (IS) stroke in relation to risk factors and clinical presentation among stroke patients admitted to a tertiary teaching hospital over a 5-year period. Materials and Methods: This was a retrospective, cross-sectional, hospital-based study. We reviewed the medical files of patients admitted with the diagnosis of stroke at Ibn Sina Teaching Hospital, from January 2011 to December 2015 to compare between HS and IS patients. Results: From a total of 1678 stroke patients, IS constituted 81.2% of them and 18.8% were HS, males were 57.7% and females 42.3%. HS patients were significantly younger than IS patients, (odds ratio [OR] 0.4; 95% confidence interval [CI] 0.31–0.51, P= 0.000), and there was no significant difference in gender (males 61.6% vs. 56.8%, P = 0.12). Hypertension and smoking were significantly higher among HS than IS patients (OR 5.51; 95% CI 3.98–7.62, P < 0.0001) and (OR 1.84; 95% CI, 1.37–2.46, P= 0.003), respectively, whereas diabetes mellitus (OR, 0.75 95% CI, 0.58–0.96, P= 0.024), transient ischaemic attacks (TIA) (OR, 0.23; 95% CI 0.14–0.38, P < 0.0001), hyperlipidaemia (OR, 0.35; 95% CI 0.19–0.66, P = 0.007) and family history of stroke (OR, 0.64; 0.42–0.97, P= 0.033) were significantly higher in IS than HS patients. Sudden onset of stroke attack and impaired consciousness including coma was significantly more frequent in HS than IS patients (98.7% vs. 86.8%, P= 0.000) and (77.5% vs. 34.2%, P = 0.000), respectively. In-hospital fatality was higher among HS than IS victims (46.3% vs. 26.5%, P = 0.000). Conclusion: Younger age, hypertension and smoking were higher in HS than IS patients, and increasing age, diabetes, TIA, hyperlipidaemia and family stroke history were higher in IS patients, sex did not favour any type, HS was more presented with impaired consciousness and had a higher in-hospital fatality than IS.
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CASE REPORT
	Simultaneous bilateral nephrectomy of hugely enlarged polycystic kidneys	p. 34
	Fariborz Bagheri, Senthil Kumar, Hamzeh Esmaeilpour, Mohammad Hassan, Akos Pytel DOI:10.4103/HMJ.HMJ_36_18   This case is the first of its kind of simultaneous bilateral nephrectomy of the largest size of autosomal dominant polycystic kidneys in the United Arab Emirates. A 57-year-old man referred to our department with abdominal pain and distension, difficulty in walking and breathing, and edema of both legs caused by hugely enlarged bilateral polycystic kidneys. He was on hemodialysis for the past 3 years. Any type of operation was refused by him. In October 2016, he was admitted to the hospital due to deterioration of his general condition and intolerable quality of life caused by severe compression to the abdominal organs. After obtaining written consent, simultaneous open bilateral nephrectomy was done successfully. Mass of both kidneys removed was 13,050 g which is, to our knowledge, the largest polycystic kidneys removed simultaneously so far. Early bilateral nephrectomy is advisable in patients with end-stage renal failure with the tendency of progressive enlargement of the kidney size.
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Molecular Imaging, vol. 12

2. 3D Fusion Framework for Infarction and Angiogenesis Analysis in a Myocardial Infarct Minipig Model

   Xu Zhenzhen, PhD¹, Bo Tao, PhD, MD², Yu Li, MSc¹, Jun Zhang, PhD¹, Xiaochao Qu, PhD¹, Feng Cao, PhD², Jimin Liang, PhD¹
   Molecular Imaging, vol. 16, First Published May 11, 2017.
   Abstract

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   Abstract

   The combination of different modality images can provide detailed and comprehensive information for the prognostic assessment and therapeutic strategy of patients with ischemic heart disease. In this study, a 3D fusion framework is designed to integrate coronary computed tomography (CT) angiography (CTA), 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]DG) positron emission tomography (PET)/CT, and [⁶⁸Ga]-1,4,7-triazacyclononane-1,4,7-triacetic acid-(Arg-Gly-Asp)2 ([⁶⁸Ga]-NOTA-PRGD2) PET/CT images of the myocardial infarction model in minipigs. First, the structural anatomy of the heart in coronary CTA and CT is segmented using a multi-atlas-based method. Then, the hearts are registered using the B-spline-based free form deformation. Finally, the [¹⁸F]DG and [⁶⁸Ga]-NOTA-PRGD2 signals are mapped into the heart in coronary CTA, which produces a single fusion image to delineate both the cardiac structural anatomy and the functional information of myocardial viability and angiogenesis. Heart segmentation demonstrates high accuracy with good agreement between manual delineation and automatic segmentation. The fusion result intuitively reflects the extent of the [¹⁸F]DG uptake defect as well as the location where the [⁶⁸Ga]-NOTA-PRGD2 signal appears. The fusion result verified the occurrence of angiogenesis based on the in vivo noninvasive molecular imaging approach. The presented framework is helpful in facilitating the study of the relationship between infarct territories and blocked coronary arteries as well as angiogenesis.
    
3. 

   Whole-Body Distribution of Leukemia and Functional Total Marrow Irradiation Based on FLT-PET and Dual-Energy CT

   Taiki Magome, PhD¹², Jerry Froelich, MD³, Shernan G. Holtan, MD⁴, Yutaka Takahashi, PhD²⁵, Michael R. Verneris, MD⁴, Keenan Brown, PhD⁶, Kathryn Dusenbery,MD⁷, Jeffrey Wong, MD⁸, Susanta K. Hui, PhD²⁷⁸
   Molecular Imaging, vol. 16, First Published September 26, 2017.
   Abstract

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   Abstract

   This report describes a multimodal whole-body 3′-deoxy-3′[(18)F]-fluorothymidine positron emission tomography (FLT-PET) and dual-energy computed tomography (DECT) method to identify leukemia distribution within the bone marrow environment (BME) and to develop disease- and/or BME-specific radiation strategies. A control participant and a newly diagnosed patient with acute myeloid leukemia prior to induction chemotherapy were scanned with FLT-PET and DECT. The red marrow (RM) and yellow marrow (YM) of the BME were segmented from DECT using a basis material decomposition method. Functional total marrow irradiation (fTMI) treatment planning simulations were performed combining FLT-PET and DECT imaging to differentially target irradiation to the leukemia niche and the rest of the skeleton. Leukemia colonized both RM and YM regions, adheres to the cortical bone in the spine, and has enhanced activity in the proximal/distal femur, suggesting a potential association of leukemia with the BME. The planning target volume was reduced significantly in fTMI compared with conventional TMI. The dose to active disease (standardized uptake value >4) was increased by 2-fold, while maintaining doses to critical organs similar to those in conventional TMI. In conclusion, a hybrid system of functional–anatomical–physiological imaging can identify the spatial distribution of leukemia and will be useful to both help understand the leukemia niche and develop targeted radiation strategies.
    
4. 

   Vulnerable Plaque Detection and Quantification with Gold Particle–Enhanced Computed Tomography in Atherosclerotic Mouse Models

   David De Wilde, Bram Trachet, Carole Van der Donckt, Bert Vandeghinste, Benedicte Descamps, Christian Vanhove, Guido R. Y. De Meyer, Patrick Segers
   Molecular Imaging, vol. 14, 6, First Published June 1, 2015.
   Abstract

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   Abstract

   Recently, an apolipoprotein E–deficient (ApoE^−/−) mouse model with a mutation (C1039G+/−) in the fibrillin-1 (Fbn1) gene (ApoE^−/−Fbn1^C1039G+/− mouse model) was developed showing vulnerable atherosclerotic plaques, prone to rupture, in contrast to the ApoE^−/− mouse model, where mainly stable plaques are present. One indicator of plaque vulnerability is the level of macrophage infiltration. Therefore, this study aimed to measure and quantify in vivo the macrophage infiltration related to plaque development and progression. For this purpose, 5-weekly consecutive gold nanoparticle–enhanced micro–computed tomography (microCT) scans were acquired. Histology confirmed that the presence of contrast agent coincided with the presence of macrophages. Based on the microCT scans, regions of the artery wall with contrast agent present were calculated and visualized in three dimensions. From this information, the contrast-enhanced area and contrast-enhanced centerline length were calculated for the branches of the carotid bifurcation (common, external, and internal carotid arteries). Statistical analysis showed a more rapid development and a larger extent of plaques in the ApoE^−/−Fbn1^C1039G+/− compared to the ApoE^−/−mice. Regional differences between the branches were also observable and quantifiable. We developed and applied a methodology based on gold particle–enhanced microCT to visualize the presence of macrophages in atherosclerotic plaques in vivo.
    
5. 

   Complementary Use of Bioluminescence Imaging and Contrast-Enhanced Micro—Computed Tomography in an Orthotopic Brain Tumor Model

   Sanaz Yahyanejad, Patrick V. Granton, Natasja G. Lieuwes, Lesley Gilmour, Ludwig Dubois, Jan Theys, Anthony J. Chalmers, Frank Verhaegen, Marc Vooijs
   Molecular Imaging, vol. 13, 4, First Published January 1, 2015.
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   Abstract

   Small animal models are crucial to link molecular discoveries and implementation of clinically relevant therapeutics in oncology. Using these models requires noninvasive imaging techniques to monitor disease progression and therapy response. Micro–computed tomography (CT) is less studied for the in vivo monitoring of murine intracranial tumors and traditionally suffers from poor soft tissue contrast, whereas bioluminescence imaging (BLI) is known for its sensitivity but is not frequently employed for quantifying tumor volume. A widely used orthotopic glioblastoma multiforme (GBM) tumor model was applied in nude mice, and tumor growth was evaluated by BLI and contrast-enhanced microCT imaging. A strong correlation was observed between CT volume and BLI-integrated intensity (Pearson coefficient (r) = .85, p = .0002). Repeated contouring of contrast-enhanced microCT-delineated tumor volumes achieved an intraobserver average pairwise overlap ratio of 0.84 and an average tumor volume coefficient of variance of 0.11. MicroCT-delineated tumor size was found to correlate with tumor size obtained via histologic analysis (Pearson coefficient (r) = .88, p = .005). We conclude that BLI intensity can be used to derive tumor volume but that the use of both contrast-enhanced microCT and BLI provides complementary tumor growth information, which is particularly useful for modern small animal irradiation devices that make use of microCT and BLI for treatment planning, targeting, and monitoring.
    
6. 

   Development and Validation of a Complete GATE Model of the Siemens Inveon Trimodal Imaging Platform

   Sanghyeb Lee, Jens Gregor, Dustin Osborne
   Molecular Imaging, vol. 12, 7, First Published October 1, 2013.
   Abstract

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   Abstract

   This article presents and validates a newly developed GATE model of the Siemens Inveon trimodal imaging platform. Fully incorporating the positron emission tomography (PET), single-photon emission computed tomography (SPECT), and computed tomography (CT) data acquisition subsystems, this model enables feasibility studies of new imaging applications, the development of reconstruction and correction algorithms, and the creation of a baseline against which experimental results for real data can be compared. Model validation was based on comparing simulation results against both empirical and published data. The PET modality was validated using the NEMA NU-4 standard. Validations of SPECT and CT modalities were based on assessment of model accuracy compared to published and empirical data on the platform. Validation results show good agreement between simulation and empirical data of approximately ± 5%.
    
7. 

   Use of eXIA 160 XL for Contrast Studies in Micro–Computed Tomography: Experimental Observations

   Inneke Willekens, Nico Buls, Michel De Maeseneer, Tony Lahoutte, Johan de Mey
   Molecular Imaging, vol. 12, 6, First Published September 1, 2013.
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   Abstract

   The purpose of this study was to evaluate the time course of contrast enhancement of spleen, liver, and blood using eXIA 160 XL in healthy mice. eXIA 160 XL was intravenously injected in C57bl/6 mice (n = 12) at a dose of 0.1 mL/20 g (16 mg iodine [I]/20 g) (n = 6) or 0.2 mL/20 g (32 mg I/20 g) (n = 6). The distribution was analyzed by repeated micro–computed tomographic scans up to 48 hours after contrast administration. Images were analyzed using Amidesoftware. Regions of interest were drawn in the spleen, liver, and left ventricle. Contrast enhancement was measured and expressed as a function of time. Peak contrast enhancement of the spleen was reached at 30 minutes, and peak contrast enhancement of the liver occurred 45 minutes after 16 mg I/20 g. Given that this contrast was found to be rather low in the spleen in comparison with former eXIA 160 products, experiments were done at a higher dose. However, the 32 mg I/20 g dose was lethal for mice. Enhancement inside the heart lasts for 1 hour. Administration of eXIA 160 XL results in long-lasting blood pool contrast with higher contrast enhancement in heart and liver in comparison with eXIA 160; however, the administered dose should be limited to 16 mg I/20 g.
    
8. 

   Comparison of Computed Tomography– and Optical Image–Based Assessment of Liposome Distribution

   Huang Huang, Michael Dunne, John Lo, David A. Jaffray, Christine Allen
   Molecular Imaging, vol. 12, 3, First Published May 1, 2013.
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   Abstract

   The use of multimodal imaging as a tool to assess the in vivo pharmacokinetics and biodistribution of nanocarriers is important in understanding the nature of their in vivo transport. The current study reports the development of a nano-sized liposomal computed tomographic (CT)/optical imaging probe carrying iohexol and Cy5.5 and its use in micro-CT and optical imaging to quantitatively assess the whole-body (macroscopic), intratumoral, and microscopic distribution over a period of 8 days. These multimodal liposomes have a vascular half-life of 30.3 ± 8.9 hours in mice bearing subcutaneous H520 non-small cell lung cancer tumors, with the maximum liposome accumulation in tumor achieved 48 hours postinjection. The in vivo liposome distribution and stability were quantitatively assessed using both micro-CT and fluorescence molecular tomography. The combination of CT and optical imaging enables visualization of the liposomes at the whole-body, tumor, and cellular scales with high sensitivity. Such noninvasive tracking of therapeutic vehicles at the macro- and microscale is important for informed and rational development of novel nanocarrier systems.