Identification of the Genotype – Phenotype Correlation in the Inosine Monophosphate Dehydrogenase Enzyme

PhDMycophenolate mofetil (MMF) is widely used to minimise acute rejection following solid organ transplantation as it inhibits inosine monophosphate dehydrogenase (IMPDH) and thereby reduces lymphocyte activation. The effects of MMF and azathioprine on renal allograft outcome were examined by analysis of the national transplant database held at National Health Service (NHS) Blood and Transplant, Stoke Gifford, Bristol, UK. In a paired kidney analysis, MMF treated patients had a 3 year death censored graft survival of 91% (n=217) contrasts to 97% (n=231) in azathioprine treated patients (p=0.07) with an increased acute rejection rate in the first year after transplantation (44 v 31%, n=105 v 74, p<0.01). In a further study, 13% (n=71) of patients were found to be taking less than 1 g of MMF which was associated with a 3-fold increased risk of graft failure and inferior graft function up to 36 months. One strategy to improve graft outcome would entail targeting MMF dose according to pre-transplant IMPDH activity, which is known to display wide variability between patients, in order to maximize efficacy and minimize toxicity. Therefore, it was decided to measure pre-transplant IMPDH activity and to investigate associations with renal allograft outcome and MMF dose tolerated after transplantation. IMPDH activity was measured by detection of generated XMP by a validated HPLC method in the peripheral mononuclear cells of 55 patients waiting for renal transplantation and was found to exhibit a 4-fold variation of IMPDH activity. Black males had significantly increased IMPDH activity contrasts to Black females (p=0.01). Within the first year of transplantation, 71% (n=12) patients required a reduction in MMF dose. There was no association between pre-transplant IMPDH activity and MMF dose achieved at 1 year or MMF associated side effects or eGFR up to 36 months.It was proposed that the inter-individual variability of IMPDH activity may be associated with genetic polymorphisms and therefore sequencing of the exons of IMPDH I and II was undertaken. Two novel single nucleotide polymorphisms (SNPs), Leu244Leu and Ala285Thr, were identified in the IMPDH I gene. Patients with these variants did not exhibit differential IMPDH activity. Genotyping for established intronic SNPs was undertaken in our patient cohort as well as a random sample of 1040 recipients from the Collaborative Transplant Study DNA bank based at the University of Heidelberg, Germany. The presence of these SNPs did not increase the risk of rejection or affect graft function or MMF dose tolerated at 1 year after transplantation and there was no association between pre-transplant IMPDH activity, 5 year graft and patient survival and genotype. In our study, MMF treatment did not result in improved renal allograft outcomes in comparison to azathioprine therapy. Furthermore, we suggest that measurement of pre-transplant IMPDH activity or genotyping of the IMPDH enzymes is unlikely to assist in optimizing MMF dose and renal allograft outcome

Potentials and limitations of microorganisms as renal failure biotherapeutics

Renal insufficiency leads to uremia, a complicated syndrome. It thus becomes vital to reduce waste metabolites and regulate water and electrolytes in kidney failure. The most common treatment of this disease is either dialysis or transplantation. Although these treatments are very effective, they are extremely costly. Recently artificial cells, microencapsulated live bacterial cells, and other cells have been studied to manage renal failure metabolic wastes. The procedure for microencapsulation of biologically active material is well documented and offers many biomedical applications. Microencapsulated bacteria have been documented to efficiently remove urea and several uremic markers such as ammonia, creatinine, uric acid, phosphate, potassium, magnesium, sodium, and chloride. These bacteria also have further potential as biotherapeutic agents because they can be engineered to remove selected unwanted waste. This application has enormous potential for removal of waste metabolites and electrolytes in renal failure as well as other diseases such as liver failure, phenylketonuria, and Crohn’s disease, to name a few. This paper discusses the various options available to date to manage renal failure metabolites and focuses on the potential of using encapsulated live cells as biotherapeutic agents to control renal failure waste metabolites and electrolytes

A MATHEMATICAL MODEL TO STUDY THE SIMILARITIES OF BLOOD FLUID MODELS THROUGH INCLINED MULTI-STENOSED ARTERY

A mathematical model is presented to comparative steady of the flow behavior of Casson’s and Bingham Plastic fluid model through an inclined tube of non-uniform cross-section with multiple stenoses. The equation describing the flow has been solved and the expressions parameters on flow variables have been studied. The present study may be helpful for better understanding the flow characteristics of blood having multiple stenoses. The graphical representations have been made to validate the analytical findings with a view of its applicability to stenotic diseases. It is found that the flow of resistance increases with the height of the stenosis but decreases with the angle of inclination. The flow characteristics namely, velocity, pressure gradient, flow rate, resistance to flow have been derived. It is shown that the resistance to flow increases with the height of the secondary stenosis as well as with the yield stress. The results are compared with the available data presented by previous researchers

Methotrexate induced ventricular arrhythmia as a medication error: a case report

Methotrexate (MTX) is the most widely used drug in clinical practice for long term treatment of connective tissue disorders. As this drug has narrow therapeutic index, if it goes unmonitored can lead to life threatening complications. Herein we are describing the case of a patient who presented with ventricular arrhythmia, due to failure to execute MTX therapy in the prescribed frequency and took daily dose of MTX which was meant to be taken as a weekly dose pointing to failure of patient education or patient comprehension regarding MTX and finally succumbed due to cardiogenic shock. We concluded this causality as probable/likely category according to WHO-UMC causality categories.

Linguistic Landscape of Languages Used in Signboards in Larkana, Sindh

The present study investigates the use of local, official and national languages and the incessant use of English on the localized Sindhi Roman script. Linguistic landscape is the study of written language on public road Signs, advertisements, billboards or front shops. Bilingualism is very common on the public signboards of Larkana city, where English language is used as market language. Many local people consider it as foreign language still English is used on every local and public signboard of Larkana city. The study used semi-structured interviews from different businesspeople, shopkeepers and owners of the institutions. The results show that Romanized Sindhi language/ Sindhlish and Bilingualism is influenced and dominant on the linguistic landscape of Larkana. In the comparison of English language the local/ native languages of the particular area of Larkana city seem missed or least used on signboards. Keywords: Linguistic Landscape, Multilingualism, Bilingualism, Official Language, Roman Sindhi DOI: 10.7176/JLLL/80-03 Publication date:June 30th 202

Investigating Attitudes of EFL Learners Towards Standard English (SE) and Pakistani English (PE) at a Public Sector University, Sindh Jamshoro

This study deals with the attitudes of EFL learners towards accent of Standard English and Pakistani English at public sector University Jamshoro. There are not much studies have done in Pakistani context, in order to investigate the attitudes of EFL learners towards accent of Pakistani English and Standard English. University of Sindh was selected as site of the study. Quantitative research method was used for this study and the close ended questionnaire was adopted from Parveen and Mehmood (2013) was used as a tool of the study. The random selection of the participants was done. They participants were 200 in number and they were the students of Institute of English Language and Literature, University of Sindh, Jamshoro. The data was collected online through google form. The data was analyzed using statistical methods. SPSS version 22 was employed to carry out the statistical operations. Quantitative data was analyzed through SPSS to draw mean, median mode and percentages for each item in the questionnaire. It was found that EFL learners’ attitude towards the accent of Standard English and Pakistani English was positive. If one is acquiring a standard accent of English as an additional ingredient to one's linguistic knowledge that would be okay in multiple concerns. On the other hand if it is being given exaggerated significance and is learned discriminatively, that would be matter of great debate around the globe to cease language crisis. Keywords: Attitudes, Quantitative, EFL learners, Standard English, Pakistani English, Accent DOI: 10.7176/JLLL/83-04 Publication date: November 30th 202

Study of various treatment modalities of caesarean scar pregnancy

Background: Caesarean scar pregnancy (CSP) can be defined as the implantation of the gestational sac within the scar of a previous caesarean surgery. Incidence of CSP is 1 in 1800 pregnancies.Methods: It is a retrospective study based on clinical diagnosis and management of CSP of women who presented to the obstetrics and gynaecology department SVP hospital from January 2008 to August 2021. Total number of cases of CSP were 28. Incidence, gestational age, ultrasound findings, serum β-human chorionic gonadotropin (β-hCG) levels, flow profiles of color Doppler, and different methods of treatment were recorded. Diagnosis was confirmed by ultrasound.Results: In this study, all 28 cases of CSP considered were offered definitive management. In present study 5 cases (17.88%) showed torrential haemorrhage during dilatation and evacuation (D and E) which was treated by various methods like 1 (3.57%) Foley’s tamponade, 1 (3.57%) uterine artery embolization (UAE) and 3 (10.71%) hysterectomy. Hysterotomy was performed in 13 cases (46.42%) and (7.69%) of heterotrophic CSP (HCSP). One case (3.84%) of CSP presented at 26 weeks of gestation with haemorrhagic shock, underwent obstetric hysterectomy.Conclusions: There is a rise in the incidence of CSP because of increase in the global rate of caesarean sections and early transvaginal USG in pregnancy. Transvaginal sonography is the best diagnostic tool. Medical management can be offered when diagnosis is made at gestational age of 7 weeks of gestational age. Surgical management has an advantage of shorter follow up.

Analysis of drug related electrolyte disturbances in emergency medicine department

Background: Electrolytes play an important role in various physiological functions of the body. Electrolyte disturbances are one of the most common problems encountered in critically ill patients. Drugs are also known to cause adverse electrolyte consequences. These drugs could be anti-hypertensive agents, hormones, antipsychotics or steroids. There is paucity of published literature on electrolyte disturbances caused by drugs. The purpose of our study was to evaluate the electrolyte disturbances caused by various drugs in critically ill patients.Methods: Following approval of the Institutional Ethics Committee, data collection was started. Adverse Drug Reactions (ADRs) presenting as an electrolyte disturbance in emergency medicine department or occurring in hospitalized patients in the Intensive care unit (ICU) of our hospital was be collected. ADRs resulting into electrolyte disturbances were identified and analysed in detail for demographic details, types of electrolyte disturbances, seriousness, severity, causality and preventability of ADRs. Fisher's exact test was done to find out the statistical difference between the electrolyte disturbances and different drugs.Results: Total 58 ADRs were reported as an electrolyte disturbance. Mean age of the patients affected was 52.48 years. Highest number of ADRs were observed in the age group of 61 to 70 years. Hypokalemia constituted 32 cases (55.2%) followed by hyponatremia (25.9%), hyperkalemia (6.9%), hypernatremia (6.9%), hypocalcemia (1.7%), hypomagnesemia (1.7%) and hypophosphatemia (1.7%). Insulin was associated with maximum cases of ADRs (27.6%).Conclusions: Electrolyte disturbances constitutes a major chunk of ADRs especially in critically ill patients. The physicians must be well-versed with the dynamics of fluid-electrolyte balance