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Biomedical subjects

F Shanahan

Publications and source records attributed to F Shanahan.

238 records · Page 14Linked to original sources
PubMedDate not supplied

Acromegaly and colorectal cancer: a comprehensive review of epidemiology, biological mechanisms, and clinical implications.

Acromegaly is an endocrine disorder characterised by sustained hypersecretion of growth hormone (GH) with concomitant elevation of insulin-like growth factor (IGF)-I, and is associated with malignancy and premature mortality from cardiovascular and respiratory diseases. In particular, there may be an increased risk of colorectal neoplasia, but the exact extent of this is contentious. Colonoscopy-based studies of adenoma prevalence rates in acromegalic patients are misleading, but population-based studies on colorectal cancer risk are more consistent - a meta-analysis estimated a pooled risk ratio of 2.04 (95 % CI: 1.32, 3.14). Possible mechanisms underlying this increased risk include direct actions as a consequence of elevated levels of circulating GH and IGF-I and/or other perturbations within the IGF system. Other possible mechanisms include altered bile acid secretion, altered cellular immunity, hyperinsulinaemia, shared genetic susceptibility and increased bowel length. However, most explanations only offer indirect evidence, and the expectation of acromegaly as a natural model of colorectal carcinogenesis has not materialised. From a clinical perspective, it seems reasonable to consider a once-only colonoscopic screening at approximately age 55 years, but potential risks and benefits should be balanced.

Acromegaly↗
PubMedDate not supplied

Mucosal substance P receptor expression in HIV infection and inflammatory bowel disease.

Gastrointestinal (GI) disease is a common manifestation of HIV infection. Symptoms may result from the acquisition of intestinal infection, but in certain cases functional and mucosal abnormality may result from mucosal HIV infection. The pathogenesis of HIV enteropathy is poorly understood, but a range of neuroenteric disturbances has been described including a reduction in mucosal substance P (SP). Inflammatory bowel disease (IBD) is a generic term used to describe two major clinical entities; Crohn's disease (CD) and ulcerative colitis (UC). Dysregulation of mucosal neuropeptide expression has been implicated in the pathogenesis of CD and UC. Mucosal SP expression has been variously described as increased, normal or reduced in intestinal tissue from patients with IBD. In contrast, uniform increases in mucosal SP receptor (SPR) have been described in patients with IBD using quantitative autoradiography. The purpose of this study was to characterize intestinal mucosal SPR mRNA expression in control, HIV and IBD patients using semiquantitative reverse transcription PCR. Intestinal tissue was obtained during diagnostic colonoscopy from 7 control, 9 HIV-infected and 28 (12 CD and 16 UC) IBD patients. RNA was isolated from the tissue biopsies, reverse transcribed and amplified with primers specific for SPR. SPR mRNA expression was detected in 7/7 (100%) of control, 2/9 (22%) of HIV-infected, 12/12 (100%) of CD and 11/16 (69%) of UC intestinal biopsies. These data demonstrate that SPR mRNA expression is significantly reduced in patients with HIV infection. Reduced mucosal SPR expression may contribute to the mucosal abnormality, altered intestinal motility and GI symptoms associated with HIV infection.

Adult↗
PubMedDate not supplied

Probiotics: from myth to reality. Demonstration of functionality in animal models of disease and in human clinical trials.

The enteric flora comprise approximately 95% of the total number of cells in the human body and are capable of eliciting immune responses while also protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract (GIT) may also be implicated in the pathogenesis of several chronic conditions such as inflammatory bowel disease (IBD). The University College Cork-based Probiotic Research Group has successfully isolated and identified lactic acid bacteria (LAB) which exhibit beneficial probiotic traits. These characteristics include the demonstration of bile tolerance; acid resistance; adherence to host epithelial tissue; and in vitro antagonism of potentially-pathogenic micro-organisms or those which have been implicated in promoting inflammation. The primary objective of this report is to describe the strategy adopted for the selection of potentially effective probiotic bacteria. The study further describes the evaluation of two members of the resulting panel of micro-organisms (Lactobacillus salivarius subsp. salivarius UCC118 and Bifidobacterium longum infantis 35624) under in vitro conditions and throughout in vivo murine and human feeding trials. Specifically, an initial feeding study completed in Balb/c mice focused upon (i) effective delivery of the probiotic micro-organisms to the GIT and evaluation of the ability of the introduced strains to survive transit through, and possibly colonise, the murine GIT; (ii) accepting the complexity of the hostile GIT and faecal environments, development of a method of enumerating the introduced bacterial strains using conventional microbiological techniques; and (iii) assessment of the effects of administered bacterial strains on the numbers of specific recoverable indigenous bacteria in the murine GIT and faeces. Additional research, exploiting the availability of murine models of inflammatory bowel disease, demonstrated the beneficial effects of administering probiotic combinations of Lactobacillus salivarius UCC118 and Bifidobacterium longum infantis 35624 in prevention of illness-related weight loss. A further ethically-approved feeding trial, successfully conducted in 80 healthy volunteers, demonstrated that yoghurt can be used as a vehicle for delivery of Lactobacillus salivarius strain UCC118 to the human GIT with considerable efficacy in influencing gut flora and colonisation.

Animals↗