Review Article

The role of genetic mutations in genes LMNA, PPARG, PLIN1, AKT2, CIDEC in Kobberling–Dunnigan Syndrome

Shahin Asadi* and Mahsa Jamali

Köbberling-Dunnigan syndrome, also known as partial familial lipodystrophy, is a rare genetic disorder characterized by abnormal distribution of adipose tissues. Many people with Köbberling-Dunnigan syndrome develop insulin resistance, a condition in which body tissues cannot adequately respond to insulin hormone. Insulin is a hormone that helps regulate the level of your blood glucose. Köbberling-Dunnigan syndrome can be due to mutations in several different genes. However, type 2 Köbberling-Dunnigan syndrome is caused by the mutation of the LMNA gene, which is located on the long arm of chromosome 1 as 1q22.

Case Report

Hypocomplementemic interstitial nephritis with long-term follow-up

Alyssa Penning, M.D, Claire Kassakian, M.D, Donald C Houghton, M.D and Nicole K Andeen, M.D*

Prednisone-sensitive hypocomplementemia, renal insufficiency, and kidney biopsy demonstrating severe tubulointerstitial nephritis (TIN), storiform fibrosis, and tubulointerstitial immune deposits are typical of IgG4-related tubulointerstitial nephritis and hypocomplementemic interstitial nephritis. A diagnosis of hypocomplementemic interstitial nephritis requires clinical and pathologic exclusion of IgG4-related tubulointerstitial nephritis. We describe a patient with hypocomplementemic interstitial nephritis who did not develop diagnostic features of IgG4 related disease (RD) over 2-year follow-up. We conclude that hypocomplementemic interstitial nephritis could be on a biologic spectrum with IgG4-related disease, but not all cases will develop the abundance of IgG4-positive plasma cells, systemic manifestations, or elevated immunoglobulin levels characteristic of IgG4-RD.

Research Article

Diagnostic accuracy of TIMI versus GRACE score for prediction of death in patients presenting with Acute Non-ST Elevation Myocardial Infarction (NSTEMI)

Syed Haseeb Raza Naqvi, Tariq Abbas, Han Naung Tun*, Ali Ahmad Naqvi, Zubair Zaffar, Badar ul Ahad Gill and Nisar Ahmad

Background: Acute Coronary Syndrome describes a spectrum of disease ranging from unstable angina through non-ST-Elevation Myocardial Infarction (NSTEMI) to ST-Elevation Myocardial Infarction (STEMI). Early death in NSTEMI is usually due to an arrhythmia. Patients should be admitted immediately to hospital, preferably to a cardiac care unit because there is a signifi cant risk of death.

Objective: To compare the diagnostic accuracy of TIMI versus GRACE for prediction of death in patients presenting with Acute Non-ST elevation Myocardial Infarction.

Material & Methods: This present cross sectional study was conducted at Department of Cardiology, CPEIC, Multan. All patients assessed according to given scores in the two scoring system i.e. TIMI risk score and GRACE score. Then patients were labeled as high or low risk for death. Data was collected by using pre-designed proforma. 2x2 tables were generated to measure the sensitivity, specificity, positive predictive value, negative Predictive value and diagnostic accuracy of TMI Risk score and GRACE Score for prediction of death in NSTEMI patients.

Results: In our study the mean age of the patients was 55.73±9.78 years. The male to female ratio of the patients was 1.6:1. The diabetes as risk factor was found in 145(39%) patients, smoking as risk factor was found in 53(14.2%) patients and hypertension as risk factor was found in 174(46.8%) patients. the sensitivity of TIMI risk was 97.7% with specificity of 92.93% and the diagnostic accuracy was 95.16%, similarly the sensitivity of GRACE risk was 100% with specificity of 95.96% and the diagnostic accuracy was 97.85%.

Conclusion: Our study results concluded that both the TIMI risk and GRACE risk are good predictor of death in patients presenting with Acute Non-ST elevation Myocardial Infarction with higher sensitivity and diagnostic accuracy. However the GRACE risk showed more accurate results as compared to TIMI risk.

Research Article

Biological dose calculation using variable RBE in Single- and Multi-field Optimization IMPT plans for 3 Brain Tumor patients

Ryosuke Kohno*, Wenhua Cao, Pablo Yepes, Xuemin Bai, Falk Poenisch, David R Grosshans, Tetsuo Akimoto and Radhe Mohan

Purpose: The purpose of this study was to evaluate biological dose in single-field optimization (SFO) and multi-field optimization (MFO) intensity-modulated proton therapy (IMPT) plans for brain tumor patients that used a fixed relative biological effectiveness (FRBE) and those that used a variable RBE (VRBE).

Materials and methods: SFO and MFO IMPT plans were planned by the Varian Eclipse treatment planning system for three brain tumor patients. Dose and linear energy transfer (LET) distributions for each plan were recomputed using an in-house fast Monte Carlo dose calculator system, and then biological dose distributions were calculated with a FRBE of 1.1 or with a previously published VRBE model. We then compared biological dose distributions obtained by the VRBE with those obtained by the FRBE.

Results: Doses obtained by the VRBE for the gross tumor volume and clinical target volume in all plans were 1%-2% larger than those obtained by the FRBE. The minimum dose obtained by the VRBE for the brainstem in the SFO IMPT of one patient was 140% larger than that obtained by the FRBE, but the difference was only 5.3 cGy (RBE). The difference in maximum dose for the optic chiasm in the MFO IMPT of another patient was less than 3.2%, but the dose difference was 149.2 cGy (RBE). We also found that no major differences were seen between the biological dose differences in the SFO IMPT plans and those in the MFO IMPT plans.

Conclusion: We could observe biological dose differences between the FRBE and the VRBE in the SFO and the MFO IMPT plans for brain tumor patients.


Research Article

Biliary reflux gastritis after Mini Gastric Bypass: The effect of Bilirubin level

Mohamed Lasheen, Mohamed Mahfouz, Tamer Salama* and Hossam El-Deen M Salem

Background: Minigastric bypass is gaining popularity worldwide as an effective bariatric surgery which has fewer complications than RYGB. There is raising concerns about biliary reflux and its effect on gastric mucosa. In this study we tried to find the link between the presence of bile in the stomach and the incidence of gastritis after MGB.

Methods: This prospective study was conducted in Ain Shams university hospitals from January 2017 to May 2018 including 40 patients. All patients underwent MGB with a 12-month follow-up, UGI endoscopy was performed 9 months after MGB for all patients, where multiple biopsies and gastric aspirate were obtained for bilirubin level.

Results: Mean age at operation was 32 years (18–60) and preoperative BMI 44.31 kg/m2. The mean operative time was 95 (± 18 min), Mean % EWL was 81.2% at 12 months. Complete resolution occurred of hypertension in 8 patients (80%) and of Diabetes type 2 in 11 patients (84.2%). Level of bilirubin in gastric aspirate was elevated in 8 patients (20%) all of them had different levels pouch gastritis confirmed by histopathological examination.

Conclusion: Biliary reflux reached about 20% after MGB, the severity of biliary gastritis is related to the elevation of bilirubin level in the gastric aspirates, this results need to be confirmed by further studies on the MGB.

Research Article

Application of autologous adipose-derived stem cells for thin endometrium treatment in patients with failed ART programs

I Sudoma, L Pylyp, Y Kremenska and Y Goncharova*

One of the factors of assisted reproduction technology (ART) success is an adequate growth and development of endometrium. At the end of follicular phase of menstrual cycle endometrium reaches its greatest thickness. It is believed that there is a critical limit of endometrial thickness beyond which the implantation of embryo is unlikely or impossible [1-5]. In practice of ART programs ultrasound measurement of endometrial thickness is used to evaluate uterine lining growth. Scientific literature is debatable as to what thickness of endometrium should be considered optimal, some researchers emphasize the negative impact of “thin endometrium” on the success of ART programs [1-12], while others do not agree [6,7,9]. Nevertheless, when endometrial thickness in ART program does not exceed 6 mm the chance of pregnancy occurring is very low (Kumbak B, et al. 2009). Endometrium is a unique tissue that has thousands of cycles of growth, differentiation and detachment during woman’s life [13-15]. Various organs and tissues are believed to contain stem cells populations that ensure the recovery of these tissues. Cells with multipotent properties were also found in endometrium [16,17]. A group of scientists from Australia detected and identified population of mesenchymal stem cells (MSCs) and epithelial progenitor cells in human endometrium [13,18-20]. It may be assumed that the absence, lack and defects of MSCs or the absence of signals needed to push their proliferation and differentiation lead to the fact that endometrium is not renewed, thin and unable to provide the implantation of embryo. Endometrial MSCs are adult stem cells similar to those found in other tissues. Therefore, in case of their lack or absence it is logical to assume that endometrial niche can be colonized by autologous stem cells derived from other tissues. In some areas of medicine, autologous stem cells are already used in clinical practice for the repair of damaged tissues and organs, although these methods are still experimental [21,22]. There were several publications about the use of stem cells for improving the endometrium growth and structure in experimental (animal) models (Zhao Jing et al. 2014) and in clinical practice in patients with Asherman syndrome and endometrial athrophy refractory to other types of therapy [23,24], (Singh N, et al. 2014; Santamariya X, et al. 2016). The main source of autologous stem cells is bone marrow. However, lately adipose tissue becomes popular because the procedure of its extraction - liposuction is less traumatic and better tolerated by patients compared to spongy bone puncture for bone marrow obtaining [25]. First MSCs were derived from adipose tissue during its cosmetic extraction in 2001 [26]. These adipose-derived mesenchymal stem cells (ASCs) have rather high capacity for differentiation (multipotency) and proliferation.

The aim of this work was to study the possibility of autologous ASCs use for the treatment of “thin endometrium” in patients with unsuccessful ART programs.

The protocol of treatment was approved by local ethical committee and patient’s informed consent was obtained for it.

Research Article

Association of Toll-like receptor 2, 4, and 9 gene polymorphism with high altitude induced thrombosis patients in Indian population

Swati Sharma#, Iti Garg*#, Gauri Mishra, Babita Kumari, Lilly Ganju and Bhuvnesh Kumar

Venous Thromboembolism (VTE) is a multifactorial disease that is influenced by individual genetic background and various environmental factors, high altitude (HA) being the one. HA exposure may cause release of several damage associated molecular patterns (DAMPs), which act as ligand for various immune receptors. Previous studies on western population involving SNPs analysis of TLRs demonstrated that TLRs are involved in development and progression of several cardiovascular diseases. But, no such study has been done in Indian population in context of HA exposure. TLRs, being receptors play a significant role in manifestation and elimination of diseases by recognition of specific ligands and downstream signal transduction therefore; the genetic variation in TLRs could be implicated for imparting varying response of individuals to discrete diseases.

Therefore, in accordance with it, in present study changes in protein structures of TLR2 and TLR4 due to presence of SNP were accessed by in-silico tools to observe whether the mutation has effect on protein structure and integrity which further influencing its function. The results showed that SNP harbouring protein has decreased functional pockets, thus may be protective for disease. Taking this lead further to genotypic level, first time association between Toll-like receptor genes polymorphism and risk of high altitude induced venous thrombosis is analyzed in Indian population by PCR RFLP method. Though the result showed initial trend that TLR2 and TLR9 SNP are monomrphic in distribution and for TLR4 there was no significant difference in distribution of SNP between healthy and HA-DVT group, these SNPs have potential to be used as susceptibility markers if studied in large population size. 

Clinical Image

New technique of imaging cellular change to squmous cells metaplsia of cervix

Salwa Samir Anter*

Flexible magnifying endoscopy with narrow band imaging (ME-NBI) has outstanding diagnostic correctness for gastrointestinal metaplsia and is hope for to be highly useful for imaging stage cervixcal metaplsia beginning by imaging the first stage of metaplasia by imaging single layer of subcolmnar reserve cells reserve cells hyperplasia, the reserve cells are round to cuboid with large oval or round nuclei, seen below the surface columnar cells and the columnar within the endocervical gland
figure page (1).

Second stage reserve cells proliferate the cells gain more cytoplasm, and the nuclei decrease in size figure page (3)

Third stage, the surface columnar cells degenerate and sloughed, figure page (1)

The fourth stage stratified cells develop squmous characteristics and acquire glycogen figure page (4)

Third stage, the surface columnar cells degenerate and sloughed, figure page (1)
The fourth stage stratified cells develop squmous characteristics and acquire glycogen figure page (4)
The endocervical gland solidify

Research Article

Risk definition in Laparoscopic versus Open Cholecystectomy

Abdelhamid MS, Nabil TM, Nafady HA, Garib AZ, Soliman SS

Nothing without risk. As cholecystectomy is one of the most common procedures, any minor risk will be a mass volume. This study was to define the magnitude of that risk. In the study were 1486 patients between Feb. 2009 and April. 2018. Open in 292 (19.6%), 1194 (80.4%) laparoscopically, 1086 [91%] completed so and 108 (9%) converted. There were 18 (1.2%) with bile duct injury. 1 (0.3%) in the open group and 17 (1.4%) in the laparoscopic group. 9 diagnosed during surgery, 4 with jaundice, 2 early and 2 late, 5 with leak. Statistically the operative injury is insignificance in the 2 groups (P<0.3). The jaundice was significantly high in the laparoscopic group of patients (P<0.045). Also the bile leak (P<0.028). The same for morbidity (P<0.01. The revers was for mortality (P<0.04).
Conclusion: The incidence of CBD injury in the literature is less than the actual rate. Laparoscopic interventions have a higher rate of injury and the proximal ducts are at higher risk.

Case Report

Squamous cell carcinoma developed on neglected, mistreated and delayed diagnosed chronic venous leg ulcer

Laura Maria Curic* and Marino Cordellini

Chronic venous leg ulcers (VLU), especially long-lasting non-healing ulcers, are among the risk factors for squamous cell carcinoma (SCC) with particularly aggressive behaviour. We present a case of a 71-year-old female patient with a relevant personal history of multiple SCC and basal cell carcinoma (BCC) excision and chronic venous insufficiency showing for about three years a ulcerated lesion located on the anteromedial distal third of the left leg non-responsive to specific treatment, which subsequently increased their size and merged. Biopsy sample was taken. Histopathology revealed a G2 SCC in all biopsy samples. After the staging, a left inguino-femoral lymphadenectomy and the excision were done. The treatment of bone exposure with a soleus muscle flap in the upper half of the defect and skin graft for all the defect and a specific oncologic treatment were proposed as possible curative solutions. Patients with chronic venous leg ulcers and clinically suspicious lesions should be evaluated for malignant transformation of the venous lesion. When diagnosed, malignancy complicating a chronic venous leg ulcer requires a resolute treatment as it may be fatal.

Research Article

Naphazoline nitrate treat the Frey effect of microwave and other sonic weapon’s damages in Human’s Internal, Endogenous Organs

Robert Skopec*

State Department had evacuated a number of Americans from the U.S. consulate in Guangzhou, China after they experienced unexplained health issues. A group of U.S. diplomats stationed in China have been brought back to the states after being inflicted by a mystery illness that reportedly resembles the brain injuries previously suffered by staff in Cuba. At the end of the December 2018 we have found a medicine fully treating the damages caused the Frey Effect of Microwave and other types of Sonic Weapons in Human’s internal, endogenous organs. I am proposing to use Naphasoline nitrate, (former) nasal decongestant, to treat Carcinogenesis of the Human’s internal, endogenous organs caused by Sonic Weapons through the release and cleaning of the Lymphatic ways in patients with colorectal, colon, pancreatic, breast, etc., cancer. I have proved this healing effect of the Naphazoline nitrate on myself during treatment in last months of the year 2018.

Review Article

Renal function during exercise and recovery

Javier Calderón Montero*

This review paper analyzes the response of renal function during two types of exercise: 1) exercise of increasing intensity and 2) exercise of submaximal intensity and prolonged duration. During an effort of increasing intensity there is a decrease in renal blood flow that, theoretically, could compromise renal function.However, several studies seem to show that the kidney has self-regulatory mechanisms that allow maintaining the filtration fraction. On the other hand, ultra resistance exercises, such as ironman, are becoming more frequent. Knowing the renal response to this type of exercise is essential to apply knowledge to emergency situations such as dehydration or hyponatremia.


Zoonotic potential of Giardia lamblia and control of giardiasis

Maria Fantinatti*

Giardia is the most common pathogenic intestinal flagellate protozoan in the world. The most studied species is Giardia lamblia (syn. Giardia intestinalis, Giardia duodenalis) that infects mammals, including humans.About the other seven species the scientific literature is very scarce and little is known about its characteristics and epidemiological importance. The exception is Giardia muris species that is frequently used in experimental infection to attempt to understand the parasite-host interaction in G. lamblia infection [1].

The classification of G. lamblia has been made based on the host of origin and morphomolecular characteristics [2,3]. The first divisions in G. lamblia assemblages were performed according to the host specificity from which the isolate originated [4]. This subdivision was corroborated in analyzes of intrinsic characteristics of the parasite, such as antigenic factors, isoenzymes, but mainly through DNA analysis that allows to reaffirm the heterogeneity of G. lamblia [4,5]. Eight assemblages are known, distributed with denominations A to H. Assemblages A and B are potentially zoonotic, as they infect humans and other mammalian hosts, including non-human primates, canids, felines, rabbits, beavers, muskrats, mustelids, rodents, marsupials, wild ruminants and livestock animals. Assemblages C to H are still considered host-specific. Assemblages C and D have already been described in canids; assemblage E was isolated from hoofed animals, as horses, swine, cattle; assemblage F, specific for felines; Assemblage G is found exclusively in mice and rats; Assemblage H was described from pinnipeds feces [1,5].

Research Article

Phylogenetic analysis of metalloprotease from transcriptome of venom gland of Hemiscorpius lepturus

Fatemeh Kazemi-Lomedasht*, Delavar Shahbazzadeh and Mahdi Behdani

Hemiscorpius lepturusis a dangerous scorpion and referred to health concern issue in Khuzestan, Iran. The venom of H.lepturus is cytotoxic and its effect is similar to spider Loxosceles reclusa. Metalloproteinases are the important class of enzymes in the venom that has hemorrhagic activity. The early finding suggests the existence of metalloproteases in the transcriptome of venom gland of H.lepturus. Phylogenetic analysis was accomplished to reveal the evolutionary relationship of identified metalloproteases. The phylogenetic tree was constructed by Molecular Evolutionary Genetics Analysis software and neighbor-joining method. Results showed among three sequences, two metalloproteinases named HLMP1 and HLMP3 of H.lepturus were most close to spider P. tepidariorum. The third sequence named HLMP2 was different and formed an independent clade in the phylogenetic tree. The results suggest that the sequence of metalloproteases in the venom component of H.lepturus is similar to the spider than the scorpion.

Research Article

Angioarchitectonics of acute pneumonia

Klepikov Igor*

The article presents the results of x-ray anatomical studies of 56 whole lung preparations, which were carried out immediately after the autopsy of children who died from АP. In 47 cases it was carried out the contrast of the vessels and in 9 cases the bronchial tree. The results allowed
to clarify some details of the pathogenesis of АP and were additional arguments in support of the new doctrine of the disease.

Research Article

Acute pneumonia: Facts and realities against etiological hypotheses and beliefs

Klepikov Igor

Modern AP concepts are focused exclusively on the infectious nature of the disease and the presence of certain pathogens. This belief determines the principles of treatment, the lack of effectiveness of which remains a concern of health professionals. The article presents a fragment of the study devoted to the etiology of АP. 994 children aged 4 months to 14 years with various forms of so-called community-acquired pneumonia were examined and treated. Bacteriological examination of the material from the inflammation zone was carried out in 542 patients. Experiments on modeling АP and its pleural complications were performed on 44 animals. The obtained results and critical analysis of the literature data and scientific facts allow us to consider bacteria only as one of the etiological elements of АP, which is not mandatory in all cases of the disease. Scientifically based revision of existing ideas about the causes and mechanisms of AP development leads to the need for a radical change in the principles of treatment and is a strategic direction in solving the problem.