Biological Understanding Of The Disease And Clinical Management

According to Professor John Neoptolemos, "There are approximately 7,000 new cases each year - but it is one of the most lethal cancers." The main reason for the low survival rate from pancreatic cancer is due to its difficulty in finding this cancer early. By the time a person has symptoms, the cancer has often reached a large size and spread to other organs. Because the pancreas is deep inside the body, the doctor cannot see or feel tumors during a routine physical exam. There are currently no blood tests or other tests that can easily find this cancer early in people without symptoms. Tests for certain genes in people with a family history of the disease can help tell if they are at higher risk for cancer. There are some new tests for finding pancreatic cancer early in people with a strong family history of the disease, but these tests are complicated and expensive. Some symptoms of pancreatic cancer include jaundice, a yellow color of the eyes and skin caused by a substance buildup in the liver, pain in the belly area or in the middle of the back, significant weight loss over a number of months, loss of appetite, digestive problems including nausea, vomiting, pain that tends to be worse after eating, a swollen gallbladder that is enlarged, blood clots that form in the veins or cause problems with fatty tissue under the skin, and diabetes. If the doctor has any reason to suspect pancreatic cancer, certain tests will be done to see if the disease is really

The American Diabetes Association (2004) defines diabetes as a subset of metabolic diseases associated with hyperglycemia secondary to insulin failing to release, act, or both. Complications related to chronic diabetes can be detrimental to one’s health including but not limited to: heart disease, stroke, kidney disease, amputations, blindness, and other optical diseases. Furthermore, the prevalence of diabetes is rising at an astronomical rate within the United States as well as internationally. According to the Center for Disease Control and Prevention (CDC) (2016) an estimated 29 million people suffer with diabetes and 86 million are prediabetic within the United States (US). Without major interventions from the healthcare community,

Type 1 diabetes is a disease that is most commonly diagnosed in children, is rarely diagnosed in adulthood, and “Diabetes at a glance” (2016) reveals that nearly two million people were newly diagnosed with the disease in 2016 in the U.S. alone, and one of the people included in that two million is myself. Throughout the

So, with this increase in toxicity over single agent inhibition of the PD-1 checkpoint, an increase in efficacy would be required to support development of the combination. At the doses of tremelimumab considered tolerable, among PD-L1 positive patients (based on staining in 25% of the cancer cells), the response rate does not appear superior to single agent PD-1 inhibition.2,4 However, among those without high level PD-L1 expression, 4 of 14 patients responded to the combination, while with approved agents, no more than 2 patients would anticipated to respond.2,4

The Chapter, "The Mystery of Disease," starts off with questions about natural selection and the evolution theory. Asking questions that most people would not think of, like, " If we can live a 100 years, why not two hundred?" or " If evolution by natural selection can shape sophisticated mechanisms such as the eye, heart, and brain, why hasn't it shaped ways to prevent nearsightedness, heart attacks and Alzheimer’s disease?". These questions make the reader wonder, what is causing the human race to continue the pattern of diseases? The authors believe there is, "a deep evolutionary view reveals the bodies of all organisms as bundles of tradeoffs, compromises and limitations that ensure that perfection is impossible." which is controversial

30). According to Brunstein (2016), individual tests can be moved to a patient’s bedside or in other less formal settings to provide faster diagnosis, allowing for quicker response times when medical interventions are needed (p. 30). Bedside testing uses a method called point-of-care testing (POCT) and presents both new possibilities as well as challenges (Brunstein, 2016, p. 30). Brunstein (2016) points out some of the challenges are decreased sensitivity, specificity, or sometimes both, especially when compared to the testing that is done in the core lab (p.30). However, POCT can prove to be advantageous because of reduced response times for medical interventions. POCT with moderate sensitivity and high specificity have proven to be convenient, cost effective first-line screening tools (Brunstein, 2016, p. 30). Molecular POCT has positive implications for the future but there are some limitations. POCT used for molecular diagnosis (Madix) are limited to only

Subjects with undiagnosed Type 2 diabetes are at superior risk of developing coronary artery disease and stroke. Therefore it is significant to screen for diabetes in a cost efficient manner in subjects who demonstrate major risk factors for diabetes.

The clinical aggressiveness observed in PDA is due, in part, to its cellular complexity and its ability to survive in a harsh tumor microenvironment. These factors likely contribute to therapeutic resistance to many therapies. First, PDA is associated with a dense stromal reaction. The tumor mass is composed mainly of the tumor microenvironment and it includes mostly non-neoplastic cells, such as fibroblasts and lymphocytes, and well as non-cellular connective tissue (6, 7). Additionally, the PDA tumor microenvironment also includes a vasculature, but this cancer is classically hypovascular (8). This is evident when these tumors are visualized with contrast-enhanced computed tomography imaging, which shows hypoattenuated lesions when compared to the well-enhancing surrounding pancreatic parenchyma (9). PDAs are also genetically complex. Though common driver-mutations are present in essentially all PDAs (i.e., high-frequency mutations, such as KRAS), there are a significant number of

Pancreatic cancer and military service. PDAC cases can be categorized into 3 clinical phases: 1) primary localized resectable tumor; 2) locally advanced unresectable disease; and 3) metastatic disease. All cases of PDAC are eventually metastatic which accounts for the poor prognosis. Accumulating evidence indicates that military service per se may be a risk factor for PDAC, since military personnel and Veterans have a higher incidence of PDAC , and Veteran patients are more frequently seen with unresectable diseases . There is a 40% increased risk overall and a 90% increased risk in men between ages 48-52, indicating an association of PDAC oncogenesis with military service (Moore, S. 2009. Thesis. The Univ. of Texas School of Public Healt.). One reason

Although the study provides valuable information by adding to what is known about the pharmacokinetics, efficacy and safety of Nilotinib in PD, there are some flaws in this research. First, the basis for this study is the assumption that Nilotinib, being a c-ABL inhibitor (Manley et al., 2010), can prevent the build-up of neurotoxic substrates in the brains of PD patients, thus improving symptoms (Karuppagounder

The treatment aim of PBC is to achieve symptomatic relief and to encourage lifequality free from pruritis and fatigue,once this target has been attained regular follow-up is to be adviced . the chronic treatment costs ,transplantation needs of the patients with PBC mean that this disease accounts for a ample proportion of clinical hepatology workload, as prognosis is improved by earlier diagnosis and therapy ,more focus is to be pointed on the symptomatic treatment. with more supporting evidence on UDCA and recent development over PBC, It has now become even more convenient for physicians treating this disease.

Most PD-1/PD-L1 inhibitory drugs have been shown to be relatively safe, with very little evidence of toxicity in patients who receive these drugs (37). In some instances, however, drug related toxicity has occurred. For example, Rosenberg et. al. administered 1200 mg of Atezolizumab daily for a period of 21 days to 315 patients with metastatic urothelial carcinoma. At the end of the study, 310 patients discontinued treatment and of those 193 patients had died. Additionally, 8 patients withdrew and 1 discontinued for other reasons. Adverse events were reported in 300 of the 310 patients which included: fatigue, rash and dyspnoea. A total of 55% of patients experienced a grade 3-4 adverse event , 69% had treatment related adverse events, however, no treatment related deaths occurred.(55)

Overall Goal: Determine challenges in developing a clinically meaningful model of PD heterogeneity, subtypes, a progression model and the high-level method for a roadmap around these challenges

Creating cellular model has been a challenging task of a genetic engineer. However, cellular model became a favorite model for biologists due to its inexpensive in generation and maintenance of culture, avoid risk of losing any precious biological material and expedite the various inherent intriguing biological mechanisms at first instance before testing for the in vivo application. Cellular models also provide a great avenue for studying the disease mechanism and drug discovery. To generate the cellular genetic model, TALENs with the reporters are transfected in human cell line to induce targeted genome modification. Genetically modified mammals can serve as valuable models of human genetic disorders, but the majority of disease-associated alleles represent single-nucleotide replacement that lead to missense, nonsense, and silent mutations (Sauna and Kimchi-Sarfaty, 2011). Compared with other animal models, mice are preferred because of their small body size, their fertilization cycle, and genetically close relationship to human genome. To unravel the function of disease-related genes and to understand the mechanism of disease progression, mouse mutants were generated by pronuclear microinjection of TALEN mRNA targeted to the mouse homologs of human disease genes into one-cell embryos to generate novel Knockout and Knockin mutants. Frontotemporal lobar degeneration (FTLD) is a common cause of presenile dementia caused by the degeneration of neurons in frontal and temporal

Chronic pancreatitis (CP) is a persistent inflammatory state of the pancreas. This disease is characterized by progressive damage to the pancreas that leads to extensive fibrosis, loss of the lobular morphology, and changes in the arrangement and composition of the islets. This is an irreversible damage that results in impairment of endocrine and exocrine functions. The incidence of chronic pancreatitis ranges from 3.5 to 10 cases per 10,000. (A. Catharine Ross, Benjamin Caballero, Robert J. Cousins, Katherine L. Tucker, Thomas R. Ziegler, 2014). Risk factors of chronic pancreatitis are associated with environment and genetic factors such as alcohol consumption, nicotine-consumption, hereditary factors, nutritional factors, and immunological