Comparative immune profiling of pancreatic ductal adenocarcinoma progression among South African patients.

Background: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer characterized by an immunosuppressive microenvironment. Patients from specific ethnicities and population groups have poorer prognoses than others. Therefore, a better understanding of the immune landscape in such groups is necessary for disease elucidation, predicting patient outcomes and therapeutic targeting.

Proteomic analysis identifies dysregulated proteins and associated molecular pathways in a cohort of gallbladder cancer patients of African ancestry.

Background: Gallbladder cancer (GBC) is a lethal cancer with a poor prognosis. The lack of specific and sensitive biomarkers results in delayed diagnosis with most patients presenting at late stages of the disease. Furthermore, there is little known about the molecular mechanisms associated with GBC, especially in patients of African ancestry.

Serum Metabolomic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry.

Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance.

Pancreatic cancer is one of the most deadly cancers, ranking amongst the top leading cause of cancer related deaths in developed countries. Features such as dense stroma microenvironment, abnormal signaling pathways, and genetic heterogeneity of the tumors contribute to its chemoresistant characteristics. Amongst these features, growth factors have been observed to play crucial roles in cancer cell survival, progression, and chemoresistance.

Breast Cancer Cells Induce a Pro-inflammatory Response to Mitigate Immune Mediation in a 3D Culture Model.

Background: Growth factors and cytokines mediate complex interactions between cells within the breast tumour microenvironment. In advanced cancer, an excess of regulatory T (T) lymphocytes and lack of natural killer (NK) cells in tumour-infiltrating lymphocyte populations may reflect a shift to pro-tumorigenic adaptive immune mechanisms. To facilitate targeted assessment of the interactions between tumour and immune cells ex vivo, three-dimensional (3D) culture systems are able to better recapitulate the in vivo microenvironment, recreating the anatomy of tumours.

SWATH-MS based proteomic profiling of pancreatic ductal adenocarcinoma tumours reveals the interplay between the extracellular matrix and related intracellular pathways.

Pancreatic cancer accounts for 2.8% of new cancer cases worldwide and is projected to become the second leading cause of cancer-related deaths by 2030. Patients of African ancestry appear to be at an increased risk for pancreatic ductal adenocarcinoma (PDAC), with more severe disease and outcomes.

Immunotherapeutic strategies in pancreatic ductal adenocarcinoma (PDAC): current perspectives and future prospects.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest human malignancies with a dismal prognosis. During PDAC progression, the immune response is affected as cancer cells evade detection and elimination. Recently, there have been advances in the treatment of PDAC using immunotherapy, although a lot more work is yet to be done.

Increased expression of plakoglobin is associated with upregulated MAPK and PI3K/AKT signalling pathways in early resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types, and it is associated with a 5-year survival rate of <10% due to limited early detection methods and ineffective therapeutic options. Thus, an improved understanding of the mechanisms involved in the early stages of PDAC tumorigenesis is crucial in order to identify potential novel diagnostic and therapeutic targets. The most common signalling aberrations in PDAC occur in the Wnt/Notch signalling pathway, as well as within the epidermal growth factor receptor (EGFR) pathway and its associated ligands, EGF and transforming growth factor-β.

Transient Expression of Interleukin-21 in the Second Hit of Acute Pancreatitis May Potentiate Immune Paresis in Severe Acute Pancreatitis.

Objectives: Interleukin-21 (IL-21) is a cytokine associated with tissue inflammation, autoimmune and infectious diseases. Organ dysfunction and death can occur in patients with acute pancreatitis (AP) in two distinct clinical phases. Initially, a systemic inflammatory response syndrome may be followed by systemic sepsis from infected pancreatic necrosis, known as the "second hit.

The thick left ventricular wall of the giraffe heart normalises wall tension, but limits stroke volume and cardiac output.

Giraffes--the tallest extant animals on Earth--are renowned for their high central arterial blood pressure, which is necessary to secure brain perfusion. Arterial pressure may exceed 300 mmHg and has historically been attributed to an exceptionally large heart. Recently, this has been refuted by several studies demonstrating that the mass of giraffe heart is similar to that of other mammals when expressed relative to body mass.

Establishment of a heterotypic 3D culture system to evaluate the interaction of TREG lymphocytes and NK cells with breast cancer.

Three-dimensional (3D) culture approaches to investigate breast tumour progression are yielding information more reminiscent of the in vivo microenvironment. We have established a 3D Matrigel system to determine the interactions of luminal phenotype MCF-7 cells and basal phenotype MDA-MB-231 cells with regulatory T lymphocytes and Natural Killer cells. Immune cells were isolated from peripheral blood using magnetic cell sorting and their phenotype validated using flow cytometry both before and after activation with IL-2 and phytohaemagglutinin.

Cystatin C- and creatinine-based equations in the assessment of renal function in HIV-positive patients prior to commencing Highly Active Antiretroviral Therapy.

Background: We evaluated the accuracy and precision of creatinine- and cystatin C-based prediction equations for estimating glomerular filtration rate compared to measured glomerular filtration rate in an antiretroviral-naive human immunodeficiency virus population.

Methods: The study population consisted of 100 treatment-naive HIV patients. Glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, as well as cystatin C-based equations (CKD-EPIcystatin C, cystatin Cvan Deventer and CKD-EPIcombined)) compared to (51)Cr-EDTA plasma clearance-measured glomerular filtration rate.

Enuresis in South African children: prevalence, associated factors and parental perception of treatment.

Unlabelled: Study Type--Symptom Prevalence (prospective cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Nocturnal enuresis is a common childhood problem. Although its prevalence is known in many countries, no data are available from South Africa and it is difficult to extrapolate data from developed countries to a population with such diverse conditions and resource-poor settings.

Prevalence of residual left ventricular structural changes after one year of antihypertensive treatment in patients of African descent: role of 24-hour pulse pressure.

Objectives: One year of antihypertensive therapy may normalise left ventricular (LV) structure in 51% of hypertensive patients of European descent. Whether similar effects can be achieved in patients of African descent, who have a high prevalence of concentric LV hypertrophy (LVH) and remodelling, is unknown.

Methods: In 103 hypertensive patients in the Baragwanath Hypertension study we evaluated the prevalence of residual LV structural changes (echocardiography) after four and 13 months of stepwise antihypertensive therapy.

Modeling of cellular arginine uptake by more than one transporter.

Determining the kinetic constants of arginine uptake by endothelial cells mediated by more than one transporter from linearization of data as Eadie-Hofstee plots or modeling which does not include the concentration of trace radiolabeled amino acid used to measure uptake may not be correct. The initial rate of uptake of trace [³H]L-arginine by HUVECs and ECV₃₀₄ cells in the presence of a range of unlabeled arginine and modifiers was used in nonlinear models to calculate the constants of arginine uptake using GraphPad Prism. Theoretical plots of uptake derived from constants determined from Eadie-Hofstee graphs overestimated uptake, whereas those from the nonlinear modeling approach agreed with experimental data.

Multimodality scar management program.

Background: This trial was undertaken to assess the efficacy of a multimodality management regime used for the prevention of hypertrophic scars. It follows previous research and experience (A.D.

Assessment of the medial head of the gastrocnemius muscle in functional compression of the popliteal artery.

Objective: Nonfunctional popliteal entrapment is due to embryologic maldevelopment within the popliteal fossa. Functional entrapment occurs in the apparent absence of an anatomic abnormality. Gastrocnemius hypertrophy has been associated with the latter.

Lavage drain extension for local anaesthetic instillation into abdominal wounds.

Background: A new device made by ThebeMedicare allows efficient local anaesthetic washout of wound areas, by utilising an attachment to an existing drain. The aim of this trial was to explore 'proof of concept' in patients undergoing abdominoplasty procedures.

Patients And Methods: Thirty-one patients who had undergone abdominoplasty procedures were selected for instillation of a local anaesthetic preparation, ropivacaine (Naropin, AstraZeneca) into the wound site on day 1 and 2 after surgery, followed by early mobilisation.

Is Degenerative Spondylolisthesis a Contraindication for Total Disc Replacement? Kineflex Lumbar Disc Replacement in 7 Patients With 24-Month Follow-up.

Background: Degenerative spondylolisthesis is associated with a significant segmental kyphosis at the level of the listhesis. We treated 7 disc spaces with Grade 2 listhesis and/or kyphosis of the slipped disc level with Kineflex disc replacement.

Methods: Out of a single-center prospective registry, involving 310 lumbar disc replacement patients, 7 patients underwent a single-level Kineflex disc replacement at the level of a degenerative spondylolisthesis with either segmental kyphosis or a Grade 2 slip.

Lumbar disc replacement for junctional decompensation after fusion surgery: clinical and radiological outcome at an average follow-up of 33 months.

Background: Failed fusion surgery remains difficult to treat. Few published data on disc replacement surgery after failed fusion procedures exist. Our objective was to evaluate outcomes of junctional lumbar disc replacement after previous fusion surgery and to correlate outcome with radiological changes to parameters of sagittal balance.

Functional variants of the angiotensinogen gene determine antihypertensive responses to angiotensin-converting enzyme inhibitors in subjects of African origin.

Objective: To determine whether the response to angiotensin-converting enzyme inhibitor (ACEI) monotherapy in subjects of African origin is determined by genetic variants within the angiotensinogen (AGT) gene.

Methods: A total of 194 hypertensive patients of African ancestry were recruited from district clinics in Johannesburg, South Africa. Eighty patients received open-label ACEI (enalapril or lisinopril) monotherapy, and 114 open-label calcium antagonist (nifedipine) as a drug class comparator.

Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure.

Objectives: The purpose of this research was to evaluate the therapeutic value of initiating a beta-blocker before an angiotensin-converting enzyme inhibitor (ACEI) in the treatment of heart failure.

Background: Although ACEI and carvedilol produce benefits in heart failure, whether the order of initiation of therapy determines the impact on left ventricular (LV) function and New York Heart Association functional class (NYHA FC) has not been determined.

Methods: A single-center, prospective, randomized, open-label study was performed.

Effect of slow-release indapamide and perindopril compared with amlodipine on 24-hour blood pressure and left ventricular mass in hypertensive patients of African ancestry.

Background: In the treatment of hypertension in subjects of African origins, although hydrochlorothiazide (HCTZ) is not as effective as calcium channel blockers, indapamide is superior to HCTZ. In the present study we therefore compared the effects of slow release (SR) indapamide with the calcium channel blocker amlodipine, when used as initial therapy, on blood pressure (BP) and left ventricular mass (LVM) during 6 months of treatment in this group.

Methods: Patients with a mean daytime ambulatory diastolic BP > or =90 mm Hg and < or =110 mm Hg (n = 125, aged 53 +/- 11 years, 68% women) were randomized to receive open-label 1.

Therapy of ischemic cardiomyopathy with the immunomodulating agent pentoxifylline: results of a randomized study.

Background: Inflammatory immune activation commonly occurs in heart failure and may perpetuate this syndrome. We sought to determine whether the immunomodulating agent pentoxifylline enhances left ventricular function in patients with ischemic cardiomyopathy. We also investigated the effect of therapy on levels of brain natriuretic peptide (NT-pro BNP), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and the marker of apoptosis, Fas/Apo-1.

Impact of renin-angiotensin-aldosterone system gene variants on the severity of hypertension in patients with newly diagnosed hypertension.

Background: The severity of hypertension has prognostic significance. Previous studies have assessed the relationship between renin-angiotensin-aldosterone system (RAAS) genotype and the severity of hypertension in either treated patients or those who have only recently discontinued treatment.

Methods: We assessed the impact of RAAS genotype on ambulatory and office blood pressure (BP) in 231 newly diagnosed hypertensive patients of African ancestry who had never received therapy.