ASSESMENT OF CLINICAL EFFECTIVENESS OF LOSARTAN AND AMLODIPINE IN HYPERTENSIVE PATIENT WITH LEFT VENTRICULAR HYPERTROPHY

Objective: Hypertension is an important worldwide public health challenge because of its high frequency and concomitant risks of cardiovascular and kidney diseases. Left ventricular hypertrophy (LVH) is defined as an increase in the mass of the LV, which can be secondary to an increase in wall thickness, an increase in cavity size, or both. Relevant study reported that LVH is one of the major and independent risk factors for coronary artery disease, heart failure, serious dysrhythmias, and sudden death. Thus, regression of LVH is a primary pharmacologic objective. The objective of this study is to assess the effectiveness of losartan and amlodipine in regression of LVH and to monitor the adverse effects of these drugs on monotherapy. The study also focused to estimate the clinical effectiveness of specified drugs in lowering hypertension.Methods: The study conducted was retrospective, prospective, comparative study extended over 1 year on 28 patients based on inclusion and exclusion criteria.Results: Both these drugs cause regression of LVH with a decrease in LV mass index value; it is seen that amlodipine is better in controlling elevated blood pressure (BP), especially diastolic BP. In statistical analysis, regression of LVH was found to be correlated with reduction of BP.Conclusion: Incidence of adverse effect was found to be prominent in amlodipine group. Thus, losartan was found to be better in regressing LVH than amlodipine.Â

Genome sequencing in esophageal squamous cell carcinoma

Technological advances in the form of next-generation sequencing allow sequencing of large numbers of different DNA sequences in a single/parallel reaction compared to conventional sequencing. It is a powerful tool which has enabled comprehensive characterization of esophageal squamous cell carcinoma. Whole-genome sequencing is the most comprehensive but expensive, whereas whole-exome sequencing is cost-effective, but it only works for the known genes. Thus, second-generation sequencing methods can provide a complete picture of the esophageal squamous cell carcinoma genome by detecting and discovering different type of alterations in the cancer which may lead to the development of effective diagnostic and therapeutic approaches for esophageal squamous cell carcinoma

Review of sequencing platforms and their applications in phaeochromocytoma and paragangliomas

Genetic testing is recommended for patients with phaeochromocytoma (PCC) and paraganglioma (PGL) because of their genetic heterogeneity and heritability. Due to the large number of susceptibility genes associated with PCC/PGL, next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening of these individuals. New generations of DNA sequencing technologies facilitate the development of comprehensive genetic testing in PCC/PGL at a lower cost. Whole-exome sequencing and targeted NGS are the preferred methods for screening of PCC/PGL, both having precise mutation detection methods and low costs. RNA sequencing and DNA methylation studies using NGS technology in PCC/PGL can be adopted to act as diagnostic or prognostic biomarkers as well as in planning targeted epigenetic treatment of patients with PCC/PGL. The designs of NGS having a high depth of coverage and robust analytical pipelines can lead to the successful detection of a wide range of genomic defects in PCC/PGL. Nevertheless, the major challenges of this technology must be addressed before it has practical applications in the clinical diagnostics to fulfill the goal of personalized medicine in PCC/PGL. In future, novel approaches of sequencing, such as third and fourth generation sequencing can alter the workflow, cost, analysis, and interpretation of genomics associated with PCC/PGL

Genital herpes zoster as a consequence of cancer chemotherapy-induced immunosuppression: report of a case

Herpes zoster (HZ) is a clinical manifestation of the reactivation of the varicella zoster virus (VZV). HZ of the male genital area is a rarely reported condition. The exact mechanism of latency and reactivation of VZV in these patients is unknown. The incidence of HZ can be associated with various conditions such as malignancies, immune deficiencies, autoimmune diseases, psychological conditions, and human immunodeficiency infection or HIV disease. In this report, we describe a rare case of HZ on male genitalia following the administration of immunosuppressant drugs for bowel cancer. The patient developed classical features of HZ during chemotherapy, 2 years after the initial chemotherapy for his bowel cancer. The ulcers of HZ lesions were treated with chlorhexidine (Curasept) ointment to prevent secondary bacterial infection. All the lesions subsided gradually and in 2 weeks with no later symptoms or pain. Genitalia are an unusual site of eruption in HZ. Patients with malignancy and iatrogenic immunodeficiency have an increased risk of reactivation of VZV and development of HZ

Identification of Novel Mutations and Expressions of EPAS1 in Phaeochromocytomas and Paragangliomas

Endothelial PAS domain-containing protein 1 (EPAS1) is an oxygen-sensitive component of the hypoxia-inducible factors (HIFs) having reported implications in many cancers by inducing a pseudo-hypoxic microenvironment. However, the molecular dysregulation and clinical significance of EPAS1 has never been investigated in depth in phaeochromocytomas/paragangliomas. This study aims to identify EPAS1 mutations and alterations in DNA copy number, mRNA and protein expression in patients with phaeochromocytomas/paragangliomas. The association of molecular dysregulations of EPAS1 with clinicopathological factors in phaeochromocytomas and paragangliomas were also analysed. High-resolution melt-curve analysis followed by Sanger sequencing was used to detect mutations in EPAS1. EPAS1 DNA number changes and mRNA expressions were examined by polymerase chain reaction (PCR). Immunofluorescence assay was used to study EPAS1 protein expression. In phaeochromocytomas, 12% (n = 7/57) of patients had mutations in the EPAS1 sequence, which includes two novel mutations (c.1091A>T; p.Lys364Met and c.1129A>T; p.Ser377Cys). Contrastingly, in paragangliomas, 7% (n = 1/14) of patients had EPAS1 mutations and only the c.1091A>T; p.Lys364Met mutation was detected. In silico analysis revealed that the p.Lys364Met mutation has pathological potential based on the functionality of the protein, whereas the p.Ser377Cys mutation was predicted to be neutral or tolerated. The majority of the patients had EPAS1 DNA amplification (79%; n = 56/71) and 53% (n = 24/45) patients shown mRNA overexpression. Most of the patients with EPAS1 mutations exhibited aberrant DNA changes, mRNA and protein overexpression. In addition, these alterations of EPAS1 were associated with tumour weight and location. Thus, the molecular dysregulation of EPAS1 could play crucial roles in the pathogenesis of phaeochromocytomas and paragangliomas

Updates on the genetics and the clinical impacts on phaeochromocytoma and paraganglioma in the new era

Genetic mutations of phaeochromocytoma (PCC) and paraganglioma (PGL) are mainly classified into two major clusters. Cluster 1 mutations are involved with the pseudo hypoxic pathway and comprised of PHD2, VHL, SDHx, IDH, HIF2A, MDH2 and FH mutated PCC/PGL. Cluster 2 mutations are associated with abnormal activation of kinase signalling pathways and included mutations of RET, NF1, KIF1Bβ, MAX and TMEM127. In addition, VHL, SDHx (cluster 1 genes) and RET, NF1 (cluster 2 genes) germline mutations are involved in the neuronal precursor cell pathway in the pathogeneses of PCC/PGL. Also, GDNF, H-ras, K-ras, GNAS, CDKN2A (p16), p53, BAP1, BRCA1&2, ATRX and KMT2D mutations have roles in the development of PCC/PGLs. Overall, known genetic mutations account for the pathogenesis of approximately 60% of PCC/PGLs. Genetic mutations, pathological parameters and biochemical markers are used for better prediction of the outcome of patients with this group of tumours. Immunohistochemistry and gene sequencing can ensure a more effective detection, prediction of malignant potential and treatment of PCC/PCLs

Diffuse sclerosing variant of papillary thyroid carcinoma-an update of its clinicopathological features and molecular biology

Diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) is an uncommon variant of papillary thyroid carcinoma. The aim of this review is to critically analyse the features of this entity. A search of the literature revealed 25 clinicopathological studies with in-depth analysis of features of DSVPTC. Overall, the prevalence of DSVPTC varies from 0.7-6.6% of all papillary thyroid carcinoma. Higher prevalence of DSVPTC was noted in paediatric patients and in patients affected by irradiation. DSVPTC tends to occur more frequently in women and in patients in the third decade of life. Macroscopically, DSVPTC can involve the thyroid gland extensively without forming a dominant mass. Microscopic examination of DSVPTC revealed extensive fibrosis, squamous metaplasia and numerous psammoma bodies. The latter pathological feature can aid in the pre-operative diagnosis of the entity by fine needle aspiration and ultrasound. Compared to conventional papillary thyroid carcinoma, DSVPTC had a higher incidence of lymph node metastases at presentation. Distant metastases were noted in approximately 5% of the cases. Patients with DSVPTC were recommended to be managed by aggressive treatment protocols. It is likely that as a result of this, the prognosis of the patients with DSVPTC was noted to be similar to conventional papillary thyroid carcinoma. Overall, cancer recurrence and cancer related mortality have been reported in 14% and 3%, respectively, of patients with DSVPTC. In immunohistochemical studies, DSVPTC showed different expression patterns of epithelial membrane antigen, galectin 3, cell adhesion molecules, p53 and p63 when compared to conventional papillary thyroid carcinoma. On genetic analysis, the occurrence of BRAF and RAS mutations are uncommon events in DSVPTC and activation of RET/PTC rearrangements are common. To conclude, DSVPTC has different clinical, pathological and molecular profiles when compared to conventional papillary thyroid carcinoma

COMPARATIVE EVALUATION OF THE EFFECTS OF DEXMEDETOMIDINE-PROPOFOL AND FENTANYL-PROPOFOL ON VARIOUS PARAMETERS DURING I-GEL INSERTION

Background: Supraglottic airway devices have become inevitable for routine and difficult airway management and various induction agent are used for supraglottic airway device insertion. The present study compares the insertion conditions for I-gel, using Dexmedetomidine and Fentanyl with Propofol. Methods Sixty patients were included in the study and randomly divided into two groups. Group D received 1mcg/kg Dexmedetomidine and Group F received 1mcg/kg Fentanyl.  Mean arterial blood pressure (MAP) and heart rate (HR) were recorded at baseline and after 1’, 3’ 5’and 10’ after insertion. Result A significant decrease in HR was seen in Group D at 3’, 5’, and 10’ after insertion when compared to its respective time intervals in Group F.  However, when MAP was observed, the 5’ after insertion showed a decrease in blood pressure within the groups but when MAP between groups were compared, there was no significant variation between Group F and Group D at their respective time intervals after insertion. Heart rate was significantly reduced with Dexmedetomidine compared to that with Fentanyl.   Conclusion Co-induction of Propofol with Fentanyl or Dexmedetomidine 1 mcg/kg provides satisfactory hemodynamic stability and comparable insertion condition for I-Gel

Medical humanities research showcase: the emergence of a new trans-disciplinary field in a time of precarity

This brief showcase of the medical humanities research networks and collaborations emerging at the University of Queensland explores the role this interdisciplinary field may play in post-pandemic Australasia. Suggesting that cultural, social and historical negotiations with medicine will become increasingly important as our societies recover from the COVID-19 crisis, the showcase presents case studies and perspectives from medical educators and practitioners, historians and experts in the fields of cultural studies and communication, on the topics of medical education, historical understandings of sexual health and clashes between public health and social justice movements

Novel therapeutics against breast cancer stem cells by targeting surface markers and signaling pathways

Background: Breast cancer remains to be one of the deadliest forms of cancers, owing to the drug resistance and tumor relapse caused by breast cancer stem cells (BCSCs) despite notable advancements in radio-chemotherapies. Objectives: To find out novel therapeutics against breast cancer stem cells by aiming surface markers and signaling pathways. Methods: A systematic literature search was conducted through various electronic databases including, Pubmed, Scopus, Google scholar using the keywords "BCSCs, surface markers, signaling pathways and therapeutic options against breast cancer stem cell. Articles selected for the purpose of this review were reviewed and extensively analyzed. Results: Novel therapeutic strategies include targeting BCSCs surface markers and aberrantly activated signaling pathways or targeting their components, which play critical roles in self-renewal and defense, have been shown to be significantly effective against breast cancer. In this review, we represent a number of ways against BCSCs surface markers and hyper-activated signaling pathways to target this highly malicious entity of breast cancer more effectively in order to make a feasible and useful strategy for successful breast cancer treatment. In addition, we discuss some characteristics of BCSCs in disease progression and therapy resistance. Conclusion: BCSCs involved in cancer pathogenesis, therapy resistance and cancer recurrence. Thus, it is suggested that a multi-dimensional therapeutic approach by targeting surface markers and aberrantly activated signaling pathways of BCSCs alone or in combination with each other could really be worthwhile in the treatment of breast cancer