Search results for: Vesiculobullous lesions

Authors: U. Bottigli, D.Cascio, F. Fauci, B. Golosio, R. Magro, G.L. Masala, P. Oliva, G. Raso, S.Stumbo

Abstract:

Purpose of this work is the development of an automatic classification system which could be useful for radiologists in the investigation of breast cancer. The software has been designed in the framework of the MAGIC-5 collaboration. In the automatic classification system the suspicious regions with high probability to include a lesion are extracted from the image as regions of interest (ROIs). Each ROI is characterized by some features based on morphological lesion differences. Some classifiers as a Feed Forward Neural Network, a K-Nearest Neighbours and a Support Vector Machine are used to distinguish the pathological records from the healthy ones. The results obtained in terms of sensitivity (percentage of pathological ROIs correctly classified) and specificity (percentage of non-pathological ROIs correctly classified) will be presented through the Receive Operating Characteristic curve (ROC). In particular the best performances are 88% ± 1 of area under ROC curve obtained with the Feed Forward Neural Network.

Keywords: Neural Networks, K-Nearest Neighbours, SupportVector Machine, Computer Aided Diagnosis.

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Authors: Abder-Rahman Ali, Antoine Vacavant, Manuel Grand-Brochier, Adélaïde Albouy-Kissi, Jean-Yves Boire

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In this paper, we present a new segmentation approach for liver lesions in regions of interest within MRI (Magnetic Resonance Imaging). This approach, based on a two-cluster Fuzzy CMeans methodology, considers the parameter variable compactness to handle uncertainty. Fine boundaries are detected by a local recursive merging of ambiguous pixels with a sequential forward floating selection with Zernike moments. The method has been tested on both synthetic and real images. When applied on synthetic images, the proposed approach provides good performance, segmentations obtained are accurate, their shape is consistent with the ground truth, and the extracted information is reliable. The results obtained on MR images confirm such observations. Our approach allows, even for difficult cases of MR images, to extract a segmentation with good performance in terms of accuracy and shape, which implies that the geometry of the tumor is preserved for further clinical activities (such as automatic extraction of pharmaco-kinetics properties, lesion characterization, etc.).

Keywords: Defuzzification, floating search, fuzzy clustering, Zernike moments.

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Authors: Lina Paola Orozco-Marín, Yuliet Montoya, John Bustamante

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Ischemic events can culminate in acute myocardial infarction with irreversible cardiac lesions that cannot be restored due to the limited regenerative capacity of the heart. Tissue engineering proposes therapeutic alternatives by using biomaterials to resemble the native extracellular medium combined with healthy and functional cells. This research focused on developing a natural thermosensitive hydrogel, its physical-chemical characterization and in vitro biocompatibility determination. Hydrogels’ morphological characterization was carried out through scanning electron microscopy and its chemical characterization by employing Infrared Spectroscopy technic. In addition, the biocompatibility was determined using fetal human ventricular cardiomyocytes cell line RL-14 and the MTT cytotoxicity test according to the ISO 10993-5 standard. Four biocompatible and thermosensitive hydrogels were obtained with a three-dimensional internal structure and two gelation times. The results show the potential of the hydrogel to increase the cell survival rate to the cardiac cell therapies under investigation and lay the foundations to continue with its characterization and biological evaluation both in vitro and in vivo models.

Keywords: cardiac cell therapy, cardiac ischemia, natural polymers, thermosensitive hydrogel

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Authors: S. Shanthi, V. Muralibhaskaran

Abstract:

Mammography has been one of the most reliable methods for early detection of breast cancer. There are different lesions which are breast cancer characteristic such as microcalcifications, masses, architectural distortions and bilateral asymmetry. One of the major challenges of analysing digital mammogram is how to extract efficient features from it for accurate cancer classification. In this paper we proposed a hybrid feature extraction method to detect and classify all four signs of breast cancer. The proposed method is based on multiscale surrounding region dependence method, Gabor filters, multi fractal analysis, directional and morphological analysis. The extracted features are input to self adaptive resource allocation network (SRAN) classifier for classification. The validity of our approach is extensively demonstrated using the two benchmark data sets Mammographic Image Analysis Society (MIAS) and Digital Database for Screening Mammograph (DDSM) and the results have been proved to be progressive.

Keywords: Feature extraction, fractal analysis, Gabor filters, multiscale surrounding region dependence method, SRAN.

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Authors: Justina I. R. Udotong

Abstract:

Toxicity of copper (Cu), lead (Pb) and iron (Fe) to Tilapia guinensis was carried out for 4 days with a view to determining their effects on the liver and muscle tissues. Tilapia guinensis samples of about 10 - 14cm length and 0.2 – 0.4kg weight each were obtained from University of Calabar fish ponds and acclimated for three (3) days before the experimental set up. Survivors after the 96-hr LC50 test period were selected from test solutions of the heavy metals for the histopathological studies. Histological preparations of liver and muscle tissues were randomly examined for histopathological lesions. Results of the histological examinations showed gross abnormalities in the liver tissues due to pathological and degenerative changes compared to liver and muscle tissues from control samples (tilapia fishes from aquaria without heavy metals). Extensive hepatocyte necrosis with chronic inflammatory changes was observed in the liver of fishes exposed to Cu solution. Similar but less damaging effects were observed in the liver of fishes exposed to Pb and Fe. The extent of lesion observed was therefore heavy metal-related. However, no pathologic changes occurred in the muscle tissues.

Keywords: Degenerative changes, heavy metal, hepatocyte necrosis, histopathology, toxicity.

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Authors: U. Bottigli, R.Chiarucci, B. Golosio, G.L. Masala, P. Oliva, S.Stumbo, D.Cascio, F. Fauci, M. Glorioso, M. Iacomi, R. Magro, G. Raso

Abstract:

Purpose of this work is to develop an automatic classification system that could be useful for radiologists in the breast cancer investigation. The software has been designed in the framework of the MAGIC-5 collaboration. In an automatic classification system the suspicious regions with high probability to include a lesion are extracted from the image as regions of interest (ROIs). Each ROI is characterized by some features based generally on morphological lesion differences. A study in the space features representation is made and some classifiers are tested to distinguish the pathological regions from the healthy ones. The results provided in terms of sensitivity and specificity will be presented through the ROC (Receiver Operating Characteristic) curves. In particular the best performances are obtained with the Neural Networks in comparison with the K-Nearest Neighbours and the Support Vector Machine: The Radial Basis Function supply the best results with 0.89 ± 0.01 of area under ROC curve but similar results are obtained with the Probabilistic Neural Network and a Multi Layer Perceptron.

Keywords: Neural Networks, K-Nearest Neighbours, Support Vector Machine, Computer Aided Detection

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Authors: Giovanni Luca Masala

Abstract:

Pattern recognition is the research area of Artificial Intelligence that studies the operation and design of systems that recognize patterns in the data. Important application areas are image analysis, character recognition, fingerprint classification, speech analysis, DNA sequence identification, man and machine diagnostics, person identification and industrial inspection. The interest in improving the classification systems of data analysis is independent from the context of applications. In fact, in many studies it is often the case to have to recognize and to distinguish groups of various objects, which requires the need for valid instruments capable to perform this task. The objective of this article is to show several methodologies of Artificial Intelligence for data classification applied to biomedical patterns. In particular, this work deals with the realization of a Computer-Aided Detection system (CADe) that is able to assist the radiologist in identifying types of mammary tumor lesions. As an additional biomedical application of the classification systems, we present a study conducted on blood samples which shows how these methods may help to distinguish between carriers of Thalassemia (or Mediterranean Anaemia) and healthy subjects.

Keywords: Computer Aided Detection, mammary tumor, pattern recognition, dissimilarity

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Authors: A. Ben Abdallah, H. Essabbah, M. H. Bedoui

Abstract:

The myocardial sintigraphy is an imaging modality which provides functional informations. Whereas, coronarography modality gives useful informations about coronary arteries anatomy. In case of coronary artery disease (CAD), the coronarography can not determine precisely which moderate lesions (artery reduction between 50% and 70%), known as the “gray zone", are haemodynamicaly significant. In this paper, we aim to define the relationship between the location and the degree of the stenosis in coronary arteries and the observed perfusion on the myocardial scintigraphy. This allows us to model the impact evolution of these stenoses in order to justify a coronarography or to avoid it for patients suspected being in the gray zone. Our approach is decomposed in two steps. The first step consists in modelling a coronary artery bed and stenoses of different location and degree. The second step consists in modelling the left ventricle at stress and at rest using the sphercical harmonics model and myocardial scintigraphic data. We use the spherical harmonics descriptors to analyse left ventricle model deformation between stress and rest which permits us to conclude if ever an ischemia exists and to quantify it.

Keywords: Spherical harmonics model, vascular bed, 3D reconstruction, left ventricle, myocardial scintigraphy.

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Authors: Giovanni Luca Masala

Abstract:

Pattern recognition is the research area of Artificial Intelligence that studies the operation and design of systems that recognize patterns in the data. Important application areas are image analysis, character recognition, fingerprint classification, speech analysis, DNA sequence identification, man and machine diagnostics, person identification and industrial inspection. The interest in improving the classification systems of data analysis is independent from the context of applications. In fact, in many studies it is often the case to have to recognize and to distinguish groups of various objects, which requires the need for valid instruments capable to perform this task. The objective of this article is to show several methodologies of Artificial Intelligence for data classification applied to biomedical patterns. In particular, this work deals with the realization of a Computer-Aided Detection system (CADe) that is able to assist the radiologist in identifying types of mammary tumor lesions. As an additional biomedical application of the classification systems, we present a study conducted on blood samples which shows how these methods may help to distinguish between carriers of Thalassemia (or Mediterranean Anaemia) and healthy subjects.

Keywords: Computer Aided Detection, mammary tumor, pattern recognition, thalassemia.

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Authors: Laila Seada, Nouf Al Gharbi, Shaimaa Dawa

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Although skin cancers are prevalent worldwide, it is uncommon in Ha’il region in the Kingdom of Saudi Arabia, mostly non-melanoma sub-type. During a 4-year period from 2014 to 2017, out of a total of 120 cases of skin lesions, 29 non-melanoma cancers were retrieved from histopathology files obtained from King Khalid Hospital. As part of the study, all cases of skin cancer diagnosed during 2014 -2017 have been revised and the clinicopathological data recorded. The results show that Basal cell carcinoma (BCC) was the most common neoplasm (36%), followed by cutaneous lymphomas (mostly mycosis fungoides 25%), squamous cell carcinoma (SCC) (21%) and dermatofibrosarcoma protuberans (DFSP) (11%). Only one case of metastatic carcinoma was recorded. BCC nodular type was the most prevalent, with a mean age 57.6 years and mean size 2.73 cm. SCC was mostly grade 2, with mean size 1.9 cm and an older mean age of 72.3 cm. Increased size of lesion positively correlated with older age (p = 0.001). Non-melanoma skin cancer in Ha’il region is not frequently encountered. BCC is the most frequent followed by cutaneous T-cell lymphomas and SCC. The findings in this study were in accordance with other parts of, but much lower than other parts of the world.

Keywords: Non melanoma skin cancer, Hail Region, histopathology, BCC.

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Authors: Rahil Garnavi, Mohammad Aldeen, M. Emre Celebi, Alauddin Bhuiyan, Constantinos Dolianitis, George Varigos

Abstract:

Automatic segmentation of skin lesions is the first step towards the automated analysis of malignant melanoma. Although numerous segmentation methods have been developed, few studies have focused on determining the most effective color space for melanoma application. This paper proposes an automatic segmentation algorithm based on color space analysis and clustering-based histogram thresholding, a process which is able to determine the optimal color channel for detecting the borders in dermoscopy images. The algorithm is tested on a set of 30 high resolution dermoscopy images. A comprehensive evaluation of the results is provided, where borders manually drawn by four dermatologists, are compared to automated borders detected by the proposed algorithm, applying three previously used metrics of accuracy, sensitivity, and specificity and a new metric of similarity. By performing ROC analysis and ranking the metrics, it is demonstrated that the best results are obtained with the X and XoYoR color channels, resulting in an accuracy of approximately 97%. The proposed method is also compared with two state-of-theart skin lesion segmentation methods.

Keywords: Border detection, Color space analysis, Dermoscopy, Histogram thresholding, Melanoma, Segmentation.

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Authors: Aicha Majda, Abdelhamid El Hassani

Abstract:

Lung CT image segmentation is a prerequisite in lung CT image analysis. Most of the conventional methods need a post-processing to deal with the abnormal lung CT scans such as lung nodules or other lesions. The simplest similarity measure in the standard Graph Cuts Algorithm consists of directly comparing the pixel values of the two neighboring regions, which is not accurate because this kind of metrics is extremely sensitive to minor transformations such as noise or other artifacts problems. In this work, we propose an improved version of the standard graph cuts algorithm based on the Patch-Based similarity metric. The boundary penalty term in the graph cut algorithm is defined Based on Patch-Based similarity measurement instead of the simple intensity measurement in the standard method. The weights between each pixel and its neighboring pixels are Based on the obtained new term. The graph is then created using theses weights between its nodes. Finally, the segmentation is completed with the minimum cut/Max-Flow algorithm. Experimental results show that the proposed method is very accurate and efficient, and can directly provide explicit lung regions without any post-processing operations compared to the standard method.

Keywords: Graph cuts, lung CT scan, lung parenchyma segmentation, patch based similarity metric.

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Authors: M. Yadegari

Abstract:

The thyroid gland is the largest classic endocrine organ that effects many organs of the body and plays a significant role in the process of Metabolism in animals. The aim of this study was to investigate the prevalence of thyroid disorders diagnosed by ultrasound and microscopic Lesions of the thyroid during the slaughter of apparently healthy One Humped Camels (Camelus dromedarius) in Iran. Randomly, 520 male camels (With an age range of 4 to 8 years), were studied in 2012 to 2013. The Camels’ thyroid glands were evaluated by sonographic examination. In both longitudinal and transverse view and then tissue sections were provide and stained with H & E and finally examined by light microscopy. The results obtained indicated the following: hyperplastic goiter (21%), degenerative changes (12%), follicular cysts (8%), follicular atrophy (4%), nodular hyperplasia (3%), adenoma (1%), carcinoma (1%) and simple goiter colloid (1%). Ultrasound evaluation of thyroid gland in adenoma and carcinoma showed enlargement and irregular of the gland, decreased echogenicity, and the heterogeneous thyroid parenchyma. Also, in follicular cysts were observed in the enlarged gland with no echo structures of different sizes and decreased echogenicity as a local or general. In nodular hyperplasia, increase echogenicity and heterogeneous parenchymal were seen. These findings suggest the use of sonography and pathology as a screening test in the diagnosis of complications of thyroid disorders.

Keywords: One humped camel, pathology, sonography, thyroid gland.

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Authors: Sharan Badiger, Prema T. Akkasaligar, Deepak Kadeli, M. Vishok

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Neurological disorders are the most debilitating of manifestations seen in patients infected with HIV. The clinical profile of neurological manifestations in HIV patients has undergone a shift in recent years with opportunistic infections being controlled with combination anti-retroviral therapy and the advent of drugs which have higher central nervous system penetrability. The aim of this paper is to study the clinical, investigation profile and various neurological disorders in HIV patients on anti‐retroviral therapy. Fifty HIV patients with neurological manifestations were studied. A complete neurological examination including neurocognitive functioning using Montreal Cognitive Assessment and HIV Dementia scale were assessed. Apart from relevant investigations, CD4 count, cerebrovascular fluid analysis, computed tomography (CT) and magnetic resonance imaging (MRI) of brain were done whenever required. Neurocognitive disorders formed the largest group with 42% suffering from HIV associated Neurocognitive Disorders. Among them, asymptomatic neurocognitive impairment was seen in 28%; mild neurocognitive disorder in 12%, and 2% had HIV‐associated dementia. Opportunistic infections of the nervous system accounted for 32%, with meningitis being the most common. Four patients had space occupying lesions of central nervous system; four tuberculomas, and one toxoplasmosis. With the advent of highly active retroviral therapy, HIV patients have longer life spans with suppression of viral load leading to decrease in opportunistic infections of the nervous system. Neurocognitive disorders are now the most common neurological dysfunction seen and thus neurocognitive assessment must be done in all patients with HIV.

Keywords: Anti retroviral therapy, cognitive dysfunction, dementia, neurological manifestations, opportunistic infections.

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Authors: H. M. Abdelmoneim, N. A. Babtain, A. S. Barhamain, A. Z. Kufiah, A. S. Malibari, S. F. Munassar, R. S. Rawa

Abstract:

Introduction: Prostate cancer is one of the most common causes of morbidity and mortality in men in developed countries. Cancer Stem Cells (CSCs) could be responsible for the progression and relapse of cancer. Therefore, CSCs markers could provide a prognostic strategy for human malignancies. Aldehyde dehydrogenase 1A1 (ALDH1A1) activity has been shown to be associated with tumorigenesis and proposed to represent a functional marker for tumor initiating cells in various tumor types including prostate cancer. Material & Methods: We analyzed the immunohistochemical expression of ALDH1A1 in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma and assessed their significant correlations in 50 TURP sections. They were microscopically interpreted and the results were correlated with histopathological types and tumor grade. Results: In different prostatic histopathological lesions we found that ALDH1A1 expression was low in BPH (13.3%) and PIN (6.7%) and then its expression increased with prostatic adenocarcinoma (40%), and this was statistically highly significant (P value = 0.02). However, in different grades of prostatic adenocarcinoma we found that the higher the Gleason grade the higher the expression for ALDH1A1 and this was statistically significant (P value = 0.02). We compared the expression of ALDH1A1 in PIN and prostatic adenocarcinoma. ALDH1A1 expression was decreased in PIN and highly expressed in prostatic adenocarcinoma and this was statistically significant (P value = 0.04). Conclusion: Increasing ALDH1A1 expression is correlated with aggressive behavior of the tumor. Immunohistochemical expression of ALDH1A1 might provide a potential approach to study tumorigenesis and progression of primary prostate carcinoma.

Keywords: ALDH1A1, BPH, PIN, prostatic adenocarcinoma.

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Authors: Hye-Young Shin, Chan Kee Park

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Background: To compare the thinning patterns of the ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) as measured using Cirrus high-definition optical coherence tomography (HD-OCT) in patients with visual field (VF) defects that respect the vertical meridian. Methods: Twenty eyes of eleven patients with VF defects that respect the vertical meridian were enrolled retrospectively. The thicknesses of the macular GCIPL and pRNFL were measured using Cirrus HD-OCT. The 5% and 1% thinning area index (TAI) was calculated as the proportion of abnormally thin sectors at the 5% and 1% probability level within the area corresponding to the affected VF. The 5% and 1% TAI were compared between the GCIPL and pRNFL measurements. Results: The color-coded GCIPL deviation map showed a characteristic vertical thinning pattern of the GCIPL, which is also seen in the VF of patients with brain lesions. The 5% and 1% TAI were significantly higher in the GCIPL measurements than in the pRNFL measurements (all P < 0.01). Conclusions: Macular GCIPL analysis clearly visualized a characteristic topographic pattern of retinal ganglion cell (RGC) loss in patients with VF defects that respect the vertical meridian, unlike pRNFL measurements. Macular GCIPL measurements provide more valuable information than pRNFL measurements for detecting the loss of RGCs in patients with retrograde degeneration of the optic nerve fibers.

Keywords: Brain lesion, Macular ganglion cell-Inner plexiform layer, Spectral-domain optical coherence tomography.

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Authors: Sarunyoo Songkro, Naranut Rajatasereekul, Nipapat Cheewasrirungrueng

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The aim of the present study was to evaluate the mucoadhesion and the release of nicotinamide gel formulations using in vitro methods. An agar plate technique was used to investigate the adhesiveness of the gels whereas a diffusion apparatus was employed to determine the release of nicotinamide from the gels. In this respect, 10% w/w nicotinamide gels containing bioadhesive polymers: Carbopol 934P (0.5-2% w/w), hydroxypropylmethyl cellulose (HPMC) (4-10% w/w), sodium carboxymethyl cellulose (SCMC) (4-6% w/w) and methylcellulose 4000 (MC) (3-5% w/w) were prepared. The gel formulations had pH values in the range of 7.14 - 8.17, which were considered appropriate to oral mucosa application. In general, the rank order of pH values appeared to be SCMC > MC4000 > HPMC > Carbopol 934P. Types and concentrations of polymers used somewhat affected the adhesiveness. It was found that anionic polymers (Carbopol 934 and SCMC) adhered more firmly to the agar plate than the neutral polymers (HPMC and MC 4000). The formulation containing 0.5% Carbopol 934P (F1) showed the highest release rate. With the exception of the formulation F1, the neutral polymers tended to give higher relate rates than the anionic polymers. For oral tissue treatment, the optimum has to be balanced between the residence time (adhesiveness) of the formulations and the release rate of the drug. The formulations containing the anionic polymers: Carbopol 934P or SCMC possessed suitable physical properties (appearance, pH and viscosity). In addition, for anionic polymer formulations, justifiable mucoadhesive properties and reasonable release rates of nicotinamide were achieved. Accordingly, these gel formulations may be applied for the treatment of oral mucosal lesions.

Keywords: Nicotinamide, bioadhesive polymer, mucoadhesiveness, release rate, gel.

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Authors: Ireneusz Majsterek, Anna Merecz, Agnieszka Sliwinska, Marcin Kosmalski, Jacek Kasznicki, Jozef Drzewoski

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Oxidative stress is considered to be the cause for onset and the progression of type 2 diabetes mellitus (T2DM) and complications including neuropathy. It is a deleterious process that can be an important mediator of damage to cell structures: protein, lipids and DNA. Data suggest that in patients with diabetes and diabetic neuropathy DNA repair is impaired, which prevents effective removal of lesions. Objective: The aim of our study was to evaluate the association of the hOGG1 (326 Ser/Cys) and XRCC1 (194 Arg/Trp, 399 Arg/Gln) gene polymorphisms whose protein is involved in the BER pathway with DNA repair efficiency in patients with diabetes type 2 and diabetic neuropathy compared to the healthy subjects. Genotypes were determined by PCR-RFLP analysis in 385 subjects, including 117 with type 2 diabetes, 56 with diabetic neuropathy and 212 with normal glucose metabolism. The polymorphisms studied include codon 326 of hOGG1 and 194, 399 of XRCC1 in the base excision repair (BER) genes. Comet assay was carried out using peripheral blood lymphocytes from the patients and controls. This test enabled the evaluation of DNA damage in cells exposed to hydrogen peroxide alone and in the combination with the endonuclease III (Nth). The results of the analysis of polymorphism were statistically examination by calculating the odds ratio (OR) and their 95% confidence intervals (95% CI) using the ¤ç2-tests. Our data indicate that patients with diabetes mellitus type 2 (including those with neuropathy) had higher frequencies of the XRCC1 399Arg/Gln polymorphism in homozygote (GG) (OR: 1.85 [95% CI: 1.07-3.22], P=0.3) and also increased frequency of 399Gln (G) allele (OR: 1.38 [95% CI: 1.03-1.83], P=0.3). No relation to other polymorphisms with increased risk of diabetes or diabetic neuropathy. In T2DM patients complicated by neuropathy, there was less efficient repair of oxidative DNA damage induced by hydrogen peroxide in both the presence and absence of the Nth enzyme. The results of our study suggest that the XRCC1 399 Arg/Gln polymorphism is a significant risk factor of T2DM in Polish population. Obtained data suggest a decreased efficiency of DNA repair in cells from patients with diabetes and neuropathy may be associated with oxidative stress. Additionally, patients with neuropathy are characterized by even greater sensitivity to oxidative damage than patients with diabetes, which suggests participation of free radicals in the pathogenesis of neuropathy.

Keywords: Diabetic neuropathy, oxidative stress, gene polymorphisms, oxidative DNA damage.

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Authors: Surajit Debnath, Soma Addya

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Human genome is not only the evolutionary summation of all advantageous events, but also houses lesions of deleterious foot prints. A single gene mutation sometimes may express multiple consequences in numerous tissues and a linear relationship of the genotype and the phenotype may often be obscure. ß Thalassemia minor, a transfusion independent mild anaemia, coupled with environment among other factors may articulate into phenotypic pleotropy with Hypocholesterolemia, Vitamin D deficiency, Tissue hypoxia, Hyper-parathyroidism and Psychological alterations. Occurrence of Pancreatic insufficiency, resultant steatorrhoea, Vitamin-D (25-OH) deficiency (13.86 ngm/ml) with Hypocholesterolemia (85mg/dl) in a 30 years old male ß Thal-minor patient (Hemoglobin 11mg/dl with Fetal Hemoglobin 2.10%, Hb A2 4.60% and Hb Adult 84.80% and altered Hemogram) with increased Para thyroid hormone (62 pg/ml) & moderate Serum Ca+2 (9.5mg/ml) indicate towards a cascade of phenotypic pleotropy where the ß Thalassemia mutation ,be it in the 5’ cap site of the mRNA , differential splicing etc in heterozygous state is effecting several metabolic pathways. Compensatory extramedulary hematopoiesis may not coped up well with the stressful life style of the young individual and increased erythropoietic stress with high demand for cholesterol for RBC membrane synthesis may have resulted in Hypocholesterolemia.Oxidative stress and tissue hypoxia may have caused the pancreatic insufficiency, leading to Vitamin D deficiency. This may in turn have caused the secondary hyperparathyroidism to sustain serum Calcium level. Irritability and stress intolerance of the patient was a cumulative effect of the vicious cycle of metabolic compromises. From these findings we propose that the metabolic deficiencies in the ß Thalassemia mutations may be considered as the phenotypic display of the pleotropy to explain the genetic epidemiology. According to the recommendations from the NIH Workshop on Gene-Environment Interplay in Common Complex Diseases: Forging an Integrative Model, study design of observations should be informed by gene-environment hypotheses and results of a study (genetic diseases) should be published to inform future hypotheses. Variety of approaches is needed to capture data on all possible aspects, each of which is likely to contribute to the etiology of disease. Speakers also agreed that there is a need for development of new statistical methods and measurement tools to appraise information that may be missed out by conventional method where large sample size is needed to segregate considerable effect. A meta analytic cohort study in future may bring about significant insight on to the title comment.

Keywords: Genetic disease, Genetic epidemiology, Heterozygous, Phenotype, Pleotropy, ß Thalassemia minor, Metabolic compromises.

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