scholarly journals From gastric aspiration to airway inflammation

2016 ◽  
Vol 73 (2) ◽  
Author(s):  
I.A. Brownlee ◽  
A. Aseeri ◽  
C. Ward ◽  
J.P. Pearson
Keyword(s):  
Disease Progression ◽  
Disease Onset ◽  
Intrathoracic Pressure ◽  
Experimental Models ◽  
Pharmacological Intervention ◽  
Symptom Improvement ◽  
Physiological Factors ◽  
Gastric Aspiration ◽  
Food Antigens ◽  
Microbial Agents

The airways are poorly protected from potentially damaging agents contained within gastric contents. While digestive factors are obvious damaging agents, gastric aspiration may also deliver microbial agents, cytokines or food antigens to airway tissues. Direct damage or the triggering of the inflammatory cascade by gastric aspiration is believed to drive airways disease onset and/or progression. Evidence exists from experimental models demonstrating direct instillation of damaging factors to a range of airways epithelia causes damage and/or an inflammatory response. Clinical longitudinal studies have also noted an association between the presence of biomarkers of reflux in airways samples and disease progression. A shared pathophysiology of many chronic airways diseases is a more negative intrathoracic pressure. Such changes would drive an increased abdominothoracic pressure gradient. These changes in respiratory mechanics mean that chronic lung disease patients may be predisposed to reflux and subsequent aspiration. Therefore, it appears that gastric aspiration and airways disease progression may be linked not solely as cause and effect, but seemingly within a vicious cycle. A range of physiological factors govern both occurrence of gastric reflux into the pharynx/larynx and could also increase the susceptibility of certain individuals to disease progression. A range of long-term surgical and pharmacological intervention studies are necessary to test the benefit of such therapies in reducing disease progression or driving symptom improvement. Such studies may be hampered by the reliability of available therapies in halting gastric aspiration and the difficulty in the clinical or biochemical assessment of gastric aspiration.

scholarly journals Gastric Aspiration and Its Role in Airway Inflammation

2018 ◽  
Vol 12 (1) ◽  
pp. 1-10 ◽  
Author(s):  
E.B. Hunt ◽  
A. Sullivan ◽  
J. Galvin ◽  
J. MacSharry ◽  
D.M. Murphy
Keyword(s):  
Wide Spectrum ◽  
Experimental Models ◽  
Clinical Syndrome ◽  
Pharmacological Intervention ◽  
Symptom Improvement ◽  
Gastric Aspiration ◽  
Airway Response ◽  
Clinical Benefits ◽  
The Individual ◽  
Chronic Airway

Gastro-Oesophageal Reflux (GOR) has been associated with chronic airway diseases while the passage of foreign matter into airways and lungs through aspiration has the potential to initiate a wide spectrum of pulmonary disorders. The clinical syndrome resulting from such aspiration will depend both on the quantity and nature of the aspirate as well as the individual host response. Aspiration of gastric fluids may cause damage to airway epithelium, not only because acidity is toxic to bronchial epithelial cells but also due to the effect of digestive enzymes such as pepsin and bile salts. Experimental models have shown that direct instillation of these factors to airways epithelia cause damage with a consequential inflammatory response. The pathophysiology of these responses is gradually being dissected, with better understanding of acute gastric aspiration injury, a major cause of acute lung injury, providing opportunities for therapeutic intervention and potentially, ultimately, improved understanding of the chronic airway response to aspiration. Ultimately, clarification of the inflammatory pathways which are related to micro-aspirationviapepsin and bile acid salts may eventually progress to pharmacological intervention and surgical studies to assess the clinical benefits of such therapies in driving symptom improvement or reducing disease progression.

1077-P: De-escalation Treatment (DET): A Personalized Pharmacological Intervention to Stop Disease Progression in Patients with Type 2 Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1077-P
Author(s):  
ANDREAS PFÜTZNER ◽  
ANASTASIOS MANESSIS ◽  
LINDA DO ◽  
MINA HANNA
Keyword(s):  
Type 2 Diabetes ◽  
Disease Progression ◽  
Pharmacological Intervention

scholarly journals Writers Are Common among Parkinson’s Disease Patients: A Longitudinal Study

2021 ◽  
Vol 2021 ◽  
pp. 1-3
Author(s):  
Anna Aasly ◽  
Jan O. Aasly
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Longitudinal Study ◽  
General Population ◽  
Personality Disorders ◽  
Disease Progression ◽  
Medical Record ◽  
Disease Onset ◽  
Psychological Characteristics ◽  
Personality Profile

Parkinson’s disease (PD) patients may have a specific personality profile, which includes being introvert, cautious and devoted to hard work. The evaluation of psychological characteristics must be evaluated according to methods for assessments of personality disorders. Such evaluations are often time-consuming and available only in research settings. The “parkinsonian trait” may be established early in life but may change with disease progression. To overcome this long interval before onset of PD questions on literary activities were included in the medical record. Three percent of PD patients could be defined as writers, significantly higher than observed in the general population. PD writers published their first books long before onset of disease. Being a writer is an extrovert trait meaning that the patient is prepared for criticism and publicity. We suggest that questions regarding personal activities prior to disease onset add valuable information on personality which differs significantly from traits observed later in the disease period.

Progression and prognosis in multiple system atrophy presenting with REM behavior disorder

Neurology ◽  
2020 ◽  
Vol 94 (17) ◽  
pp. e1828-e1834 ◽  
Author(s):  
Giulia Giannini ◽  
Vincenzo Mastrangelo ◽  
Federica Provini ◽  
Andrea Droghini ◽  
Annagrazia Cecere ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Disease Progression ◽  
Survival Data ◽  
Disease Onset ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Rapid Progression ◽  
Sleep Behavior ◽  
Risk Of Death ◽  
Progression Of Disease

ObjectivesTo investigate (1) the prevalence of REM sleep behavior disorder (RBD) as mode of disease onset in a cohort of patients with multiple system atrophy (MSA) and (2) disease progression and prognosis in patients with MSA with RBD predating (pre-RBD) and following (post-RBD) disease onset.MethodsWe retrospectively identified all patients with a clinical diagnosis of MSA evaluated at least once a year during the disease course. Type of onset was defined by the first reported motor or autonomic symptom/sign related to MSA. The occurrence of symptoms/signs and milestone of disease progression, and their latency from disease onset, were collected. Survival data were calculated. RBD was confirmed by video-polysomnography.ResultsOf a total of 158 patients, pre-RBD represented the mode of disease onset in 27% of patients, preceding disease onset according to the international criteria with a median of 3 (2–5) years. Comparing pre-RBD and post-RBD patients, the first group showed an increased prevalence of autonomic onset of disease, a reduced prevalence of parkinsonism, an earlier onset of stridor, pyramidal signs, symptomatic orthostatic hypotension, urinary dysfunction, severe dysphagia, and wheelchair dependency. The risk of death was higher in patients with pre-RBD.ConclusionsIn our MSA cohort, RBD represented the most frequent mode of disease presentation. A more rapid progression of disease was observed in the pre-RBD group. These findings suggested a careful assessment of sleep disorders to early recognize RBD and a closer follow-up of autonomic dysfunction and stridor in patients with pre-RBD.

scholarly journals Emotional Lability at Disease Onset Is an Independent Prognostic Factor of Faster Disease Progression in Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 11 (5) ◽  
pp. 1021
Author(s):  
Krzysztof Barć ◽  
Katarzyna Szacka ◽  
Krzysztof Nieporęcki ◽  
Mamede de Carvalho ◽  
Marta Gromicho ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Prognostic Factor ◽  
Disease Progression ◽  
Disease Onset ◽  
Independent Prognostic Factor ◽  
Emotional Lability ◽  
Lateral Sclerosis

A randomized study of enzalutamide in patients with localized prostate cancer undergoing active surveillance (ENACT).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS5097-TPS5097
Author(s):  
Neal D. Shore ◽  
Srinivas Vourganti ◽  
Jonathan L. Silberstein ◽  
Bruce A. Brown ◽  
Samuel Wilson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Active Surveillance ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Pharmacological Intervention ◽  
Intermediate Risk ◽  
Open Label ◽  
Group Status ◽  
End Points

TPS5097 Background: Prostate cancer (PC) patients (pts) who select active surveillance (AS) are a heterogeneous population with varying risks for disease progression. Studies have estimated that approximately 31–42% of pts electing AS have experienced disease progression (pathological or therapeutic) over 1.8 and 2.3 years. There is no evidence-based pharmacological intervention which has effectively lessened this progression event. Pharmacological intervention with enzalutamide (ENZ), an androgen receptor inhibitor approved for treatment of metastatic castration-resistant PC, may lessen this progression. The aims of this study are to evaluate the efficacy of ENZ versus AS alone for delaying time to progression in pts with clinically localized PC undergoing AS. This study examines the effects of ENZ on progression in a subset of pts with low- or intermediate-risk PC who would otherwise elect an AS protocol. Methods: This is a multicenter, randomized, open-label study (NCT02799745). Eligibility criteria include histologically confirmed prostate adenocarcinoma within 6 months of screening, low or intermediate risk PC (T1c−T2c, prostate-specific antigen [PSA] < 20, N0, M0, Gleason score ≤7 [3+4 pattern only]), Eastern Cooperative Oncology Group status ≤2 and estimated life expectancy > 5 years. Exclusion criteria include any prior PC intervention. Pts will be randomized to receive open-label oral ENZ 160 mg/day once daily or to AS during the 1-year study treatment period. After the first year, all pts will be followed for one additional year with no other intervention. All pts will undergo prostate biopsy at 1 and 2 years. The primary end point is time to PC progression (pathological or therapeutic). Secondary end points include safety, incidence of negative biopsies for cancer at 1 and 2 years, percentage of cancer positive cores at 1 and 2 years, time to PSA progression, incidence of secondary rise in serum PSA, and quality-of-life questionnaires. Exploratory end points include biomarker assessment and genomic analysis. Study enrolment commenced in June 2016, with study completion expected in March 2019. Planned total enrolment is 222 pts from ~60 United States/Canadian sites. Clinical trial information: NCT02799745.

scholarly journals Pharmacological Agents Targeting the Cellular Prion Protein

Pathogens ◽  
2018 ◽  
Vol 7 (1) ◽  
pp. 27 ◽  
Author(s):  
Maria Barreca ◽  
Nunzio Iraci ◽  
Silvia Biggi ◽  
Violetta Cecchetti ◽  
Emiliano Biasini
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Cell Types ◽  
Experimental Models ◽  
Cellular Prion Protein ◽  
Pharmacological Intervention ◽  
Therapeutic Effects ◽  
Pharmacological Agents ◽  
Alternative Approach ◽  
Common Substrate

Prion diseases are associated with the conversion of the cellular prion protein (PrPC), a glycoprotein expressed at the surface of a wide variety of cell types, into a misfolded conformer (the scrapie form of PrP, or PrPSc) that accumulates in brain tissues of affected individuals. PrPSc is a self-catalytic protein assembly capable of recruiting native conformers of PrPC, and causing their rearrangement into new PrPSc molecules. Several previous attempts to identify therapeutic agents against prion diseases have targeted PrPSc, and a number of compounds have shown potent anti-prion effects in experimental models. Unfortunately, so far, none of these molecules has successfully been translated into effective therapies for prion diseases. Moreover, mounting evidence suggests that PrPSc might be a difficult pharmacological target because of its poorly defined structure, heterogeneous composition, and ability to generate different structural conformers (known as prion strains) that can elude pharmacological intervention. In the last decade, a less intuitive strategy to overcome all these problems has emerged: targeting PrPC, the common substrate of any prion strain replication. This alternative approach possesses several technical and theoretical advantages, including the possibility of providing therapeutic effects also for other neurodegenerative disorders, based on recent observations indicating a role for PrPC in delivering neurotoxic signals of different misfolded proteins. Here, we provide an overview of compounds claimed to exert anti-prion effects by directly binding to PrPC, discussing pharmacological properties and therapeutic potentials of each chemical class.

scholarly journals Predicting Alzheimer’s disease progression trajectory and clinical subtypes using machine learning

2019 ◽  
Author(s):  
Vipul K. Satone ◽  
Rachneet Kaur ◽  
Anant Dadu ◽  
Hampton Leonard ◽  
Hirotaka Iwaki ◽  
...  
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Disease Onset ◽  
Machine Learning Techniques ◽  
Progression Rate ◽  
Early Stages ◽  
Age Related ◽  
Learning Techniques

AbstractBackgroundAlzheimer’s disease (AD) is a common, age-related, neurodegenerative disease that impairs a person’s ability to perform day-to-day activities. Diagnosing AD is challenging, especially in the early stages. Many patients still go undiagnosed, partly due to the complex heterogeneity in disease progression. This highlights a need for early prediction of the disease course to assist its treatment and tailor therapy options to the disease progression rate. Recent developments in machine learning techniques provide the potential to not only predict disease progression and trajectory of AD but also to classify the disease into different etiological subtypes.Methods and findingsThe work shown here clusters participants in distinct and multifaceted progression subgroups of AD and discusses an approach to predict the progression rate from baseline diagnosis. We observed that the myriad of clinically reported symptoms summarized in the proposed AD progression space corresponds directly with memory and cognitive measures, which are routinely used to monitor disease onset and progression. Our analysis demonstrated accurate prediction of disease progression after four years from the first 12 months of post-diagnosis clinical data (Area Under the Curve of 0.96 (95% confidence interval (CI), 0.92-1.0), 0.81 (95% CI, 0.74-0.88) and 0.98 (95% CI, 0.96-1.0) for slow, moderate and fast progression rate patients respectively). Further, we explored the long short-term memory (LSTM) neural networks to predict the trajectory of an individual patient’s progression.ConclusionThe machine learning techniques presented in this study may assist providers in identifying different progression rates and trajectories in the early stages of the disease, hence allowing for more efficient and personalized healthcare deliveries. With additional information about the progression rate of AD at hand, providers may further individualize the treatment plans. The predictive tests discussed in this study not only allow for early AD diagnosis but also facilitate the characterization of distinct AD subtypes relating to trajectories of disease progression. These findings are a crucial step forward for early disease detection. These models can be used to design improved clinical trials for AD research.

scholarly journals Possible mechanisms of chronic leprosy-related arthritis

1997 ◽  
Vol 115 (2) ◽  
pp. 1406-1409 ◽  
Author(s):  
Waldenise Cossermelli-Messina ◽  
Wilson Cossermelli
Keyword(s):  
Cross Reactivity ◽  
Experimental Models ◽  
Chronic Arthritis ◽  
Direct Infiltration ◽  
Cartilage Proteoglycans ◽  
Microbial Agents ◽  
Mycobacterial Protein ◽  
Reversal Reaction ◽  
Autoimmune Phenomena ◽  
Induce Arthritis

Microbial agents induce arthritis through mechanisms such as direct infiltration of tissue and by inducing autoimmune phenomena. The mechanisms involved in this last type of arthritis have been investigated. In experimental models of adjuvant and reactive arthritis, the involvement of T cells and in some cases mycobacteria in the development of arthritis have been confirmed. Cross-reactivity between the 65 kD mycobacterial protein and cartilage proteoglycans has been postulated as a possible mechanism. In this study, chronic peripheral arthritis was observed in patients with Hansen's disease, in patients with resolved Hansen's and in those with paucibacillary forms. This arthritis was not related to reactional states (erythema nodosum Ieprosum and reversal reaction), in contrast to several reports in the literature. The mechanisms by which microbes could induce chronic arthritis are discussed herein.

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