scispace - formally typeset
Search or ask a question
Author

Michael D. Cashman

Bio: Michael D. Cashman is an academic researcher from University of Illinois at Chicago. The author has contributed to research in topics: Pancreatic cysts & Endoscopic ultrasound. The author has an hindex of 3, co-authored 9 publications receiving 263 citations.

Papers
More filters
Journal ArticleDOI
TL;DR: Central Sensitization (CS) would offer a way to conceptualize an integration of life experience and psychologic response into a biopsychosocial framework of pathophysiology, diagnosis and treatment of IBS.
Abstract: Symptoms of irritable bowel syndrome (IBS) are common in population studies including chronic abdominal pain associated with altered bowel habits. Patients often have associated gastrointestinal and somatic symptoms suggesting a possible common contributing mechanism, but the heterogeneous symptom patterns of individual patients make generalizations difficult. The pathophysiology of IBS is incompletely understood but includes disturbances of the brain-gut axis. Central mechanisms are: the psychosocial history and environment, dysfunctional brain processing of peripheral signals attributed to the intestine including the enteric nervous system, the microbiome and the innate and adaptive immune system. As a result there is visceral hypersensitivity and disturbed intestinal secretory and motor activity. Some mechanisms of visceral pain hypersensitivity may overlap with other pain syndromes including fibromyalgia (FMS). Central Sensitization (CS) would offer a way to conceptualize an integration of life experience and psychologic response into a biopsychosocial framework of pathophysiology, diagnosis and treatment of IBS. Corticotropin-releasing factor, a principle regulator in the stress and pain response may contribute to a neuroendocrine mechanism for the brain-gut interaction. The positive diagnostic approach to IBS symptoms to avoid excess testing and enhance the patient-provider therapeutic relationship requires the recognition of the "cluster" of IBS symptoms while identifying "alarm" symptoms requiring specific attention. The severity of the symptoms and other individual psychosocial factors characterize patients who seek medical care. The presence of significant psychosocial comorbidities adds to the complexity of management which often requires a multidisciplinary approach. Several treatment options exist but no single method is effective for all the symptoms of IBS. The therapeutic benefit of the well-executed physician-patient relationship is considered essential to success in managing IBS symptoms over the long term.

300 citations

Journal ArticleDOI
TL;DR: EUS-guided ethanol ablation may be a safe alternative treatment modality for pancreatic cysts, with acceptable intraprocedural and postprocesural complications, however, due to the limited data available, prospective randomized controlled trials with a long follow up period are required.
Abstract: Endoscopic ultrasound (EUS)-guided ethanol ablation has emerged as an efficacious and safe alternative management option for pancreatic cysts. We undertook a meta-analysis and systematic review to assess the overall safety and efficacy of EUS-guided ethanol ablation of pancreatic cysts. EUS-guided ethanol ablation of pancreatic cysts. Articles were searched in Medline, Pubmed, and Ovid journals. Fixed and random effects models were used to calculate the pooled proportions. Initial search identified 1,319 reference articles, in which 120 relevant articles were selected and reviewed. Data was extracted from seven studies (n = 152) of EUS-guided ethanol ablation of pancreatic cysts, which met the inclusion criteria. With EUS-guided ethanol ablation, the pooled proportion of patients with complete cyst resolution was 56.20 % (95 % CI = 48.16 to 64.08) and partial cyst resolution was 23.72 % (95 % CI = 17.24 to 30.89). Postprocedural complications after ablation were significant for abdominal pain in 6.51 % (95 % CI = 3.12 to 11.04) and pancreatitis in 3.90 % (95 % CI = 1.39 to 7.60) of the pooled percentage of patients. Publication bias calculated using Harbord-Egger bias indicator gave a value of -1.09 (95 % CI = 10.21 to 8.03, p = 0.77). The Begg-Mazumdar indicator gave a Kendall’s tau b value of 0.05 (p ≥ 0.99). EUS-guided ethanol ablation may be a safe alternative treatment modality for pancreatic cysts, with acceptable intraprocedural and postprocedural complications. However, due to the limited data available, prospective randomized controlled trials with a long follow up period are required in this area.

21 citations

Journal ArticleDOI
TL;DR: Observations of a patient with botulism requiring mechanical ventilatory support for 59 days and hospitalization for approximately 3 months are reported, finding azoturia decreased allowing a positive nitrogen balance with a rebuilding of skeletal muscle.
Abstract: Observations of a patient with botulism requiring mechanical ventilatory support for 59 days and hospitalization for approximately 3 months are reported. During the time of greatest muscular paralysis, urinary urea nitrogen excretion exceeded 20 g per day. This degree of azoturia was thought to be due to obligate loss of lean body tissue secondary to paralysis and not to stress or starvation related demands. A contributing factor to the magnitude of azoturia was the presence of a large premorbid body frame and muscle mass. The nutritional goal was not to achieve nitrogen balance but to maintain visceral protein stores. As the patient improved neurologically, the azoturia decreased allowing a positive nitrogen balance with a rebuilding of skeletal muscle.

3 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: This review will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted, and draw on both clinical and preclinical evidence to support this concept.
Abstract: The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a "leaky gut" may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function.

719 citations

Journal ArticleDOI
TL;DR: This review clarifies how the gut microbiota regulates Trp metabolism and identifies the underlying molecular mechanisms of these interactions.
Abstract: The gut microbiota influences the health of the host, especially with regard to gut immune homeostasis and the intestinal immune response. In addition to serving as a nutrient enhancer, L-tryptophan (Trp) plays crucial roles in the balance between intestinal immune tolerance and gut microbiota maintenance. Recent discoveries have underscored that changes in the microbiota modulate the host immune system by modulating Trp metabolism. Moreover, Trp, endogenous Trp metabolites (kynurenines, serotonin, and melatonin), and bacterial Trp metabolites (indole, indolic acid, skatole, and tryptamine) have profound effects on gut microbial composition, microbial metabolism, the host's immune system, the host-microbiome interface, and host immune system-intestinal microbiota interactions. The aryl hydrocarbon receptor (AhR) mediates the regulation of intestinal immunity by Trp metabolites (as ligands of AhR), which is beneficial for immune homeostasis. Among Trp metabolites, AhR ligands consist of endogenous metabolites, including kynurenine, kynurenic acid, xanthurenic acid, and cinnabarinic acid, and bacterial metabolites, including indole, indole propionic acid, indole acetic acid, skatole, and tryptamine. Additional factors, such as aging, stress, probiotics, and diseases (spondyloarthritis, irritable bowel syndrome, inflammatory bowel disease, colorectal cancer), which are associated with variability in Trp metabolism, can influence Trp-microbiome-immune system interactions in the gut and also play roles in regulating gut immunity. This review clarifies how the gut microbiota regulates Trp metabolism and identifies the underlying molecular mechanisms of these interactions. Increased mechanistic insight into how the microbiota modulates the intestinal immune system through Trp metabolism may allow for the identification of innovative microbiota-based diagnostics, as well as appropriate nutritional supplementation of Trp to prevent or alleviate intestinal inflammation. Moreover, this review provides new insight regarding the influence of the gut microbiota on Trp metabolism. Additional comprehensive analyses of targeted Trp metabolites (including endogenous and bacterial metabolites) are essential for experimental preciseness, as the influence of the gut microbiota cannot be neglected, and may explain contradictory results in the literature.

687 citations

Journal ArticleDOI
TL;DR: In this US trial, 40–50% of patients reported adequate relief of their IBS-D symptoms with the low FODMAP diet or a diet based on modified NICE guidelines, which led to significantly greater improvement in individual IBS symptoms, particularly pain and bloating, compared with the mNICE diet.

278 citations

Journal ArticleDOI
01 Dec 2018-Gut
TL;DR: It is found that FMT changed gut microbiota in patients with IBS, but patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 months, suggesting that altering the gut microbiota is not enough to obtain clinical improvement in IBS.
Abstract: Objective IBS is associated with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clinical outcome in patients with IBS. Design We performed this study in 52 adult patients with moderate-to-severe IBS. At the screening visit, clinical history and symptoms were assessed and faecal samples were collected. Patients were randomised to FMT or placebo capsules for 12 days and followed for 6 months. Study visits were performed at baseline, 1, 3 and 6 months, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected. Results A significant difference in improvement in IBS-SSS score was observed 3 months after treatment (p=0.012) favouring placebo. This was similar for IBS-QoL data after 3 months (p=0.003) favouring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not. Conclusion In this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 months. Altering the gut microbiota is not enough to obtain clinical improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS. Trial registration number NCT02788071.

231 citations

Journal ArticleDOI
TL;DR: The effects of a blinded low‐FODMAP vs high‐fructo‐oligosaccharides (FOS) diet on symptoms, immune activation, gut microbiota composition, and short‐chain fatty acids (SCFAs) are investigated.
Abstract: Background A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is increasingly recommended for patients with irritable bowel syndrome (IBS). We aimed to investigate the effects of a blinded low-FODMAP vs high-fructo-oligosaccharides (FOS) diet on symptoms, immune activation, gut microbiota composition, and short-chain fatty acids (SCFAs). Methods Twenty patients with diarrhea-predominant or mixed IBS were instructed to follow a low-FODMAP diet (LFD) throughout a 9-week study period. After 3 weeks, they were randomized and double-blindly assigned to receive a supplement of either FOS (FODMAP) or maltodextrin (placebo) for the next 10 days, followed by a 3-week washout period before crossover. Irritable bowel syndrome severity scoring system (IBS-SSS) was used to evaluate symptoms. Cytokines (interleukin [IL]-6, IL-8, and tumor necrosis factor alpha) were analyzed in blood samples, and gut microbiota composition (16S rRNA) and SCFAs were analyzed in fecal samples. Key Results Irritable bowel syndrome symptoms consistently improved after 3 weeks of LFD, and significantly more participants reported symptom relief in response to placebo (80%) than FOS (30%). Serum levels of proinflammatory IL-6 and IL-8, as well as levels of fecal bacteria (Actinobacteria, Bifidobacterium, and Faecalibacterium prausnitzii), total SCFAs, and n-butyric acid, decreased significantly on the LFD as compared to baseline. Ten days of FOS supplementation increased the level of these bacteria, whereas levels of cytokines and SCFAs remained unchanged. Conclusions and Inferences Our findings support the efficacy of a LFD in alleviating IBS symptoms, and show changes in inflammatory cytokines, microbiota profile, and SCFAs, which may have consequences for gut health.

160 citations