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Biomedical subjects

G P Morris

Publications and source records attributed to G P Morris.

At least 19 recordsLinked to original sources
PubMed2006

Getting strategic about the environment and health.

Historically, the physical environment has been a target for public health policy across the globe. This remains the case in developing countries where the enduring infectious and toxic challenge posed by the environment is tangible and its health impact is manifest. However, in Western societies, the relevance of the environment to health has become obscured. Even when this is not the case, the perspective is usually narrow, centering on specific toxic, infectious or allergenic agents in particular environmental compartments. It is rare for importance to be given to a health-determining role for the environment acting through broader psychosocial mechanisms. The result is that environmental manipulation is seen as a cornerstone of the public health response for comparatively few health concerns. This paper considers how public health policies and action on the physical environment may be pursued more optimally. The need for a more strategic approach, which employs a new conceptual model that recognizes the complexity and contextual issues affecting the relationship between the environment and health but retains sufficient flexibility and simplicity to have practical application, is identified. Building on recent work, a model is proposed and pointers are given for its use in a practical context.

Causality↗
PubMed2003

Effects of acid-induced esophagitis on esophageal smooth muscle.

Acid-induced esophagitis is associated with sustained longitudinal smooth muscle (LSM) contraction and consequent esophageal shortening. In addition, LSM strips from opossums with esophagitis are hyper-responsive, while the circular smooth muscle (CSM) contractility is impaired. To determine the origin of these changes, studies were performed on esophageal smooth muscle cells isolated from opossum esophagi perfused intraluminally on 3 consecutive days with either saline (control; n = 8) or HCl (n = 9). CSM and LSM cells, obtained by enzymatic digestion, were exposed to various concentrations of carbachol (CCh) and fixed. CCh induced concentration-dependent contraction of both LSM and CSM cells. CCh-induced LSM cell contraction was not different between control and esophagitis animals; however, there was marked attenuation in the CCh-induced contraction of CSM cells from esophagitis animals. Morphological studies revealed significant hypertrophy of the CSM cells. These findings suggest that impaired CSM contractility can be attributed at least in part to alterations to the CSM cell itself. In contrast, hyper-contractility demonstrated in LSM strips is likely related to factors in the surrounding tissue.

Animals↗
PubMed2001

Role of substance P and calcitonin gene-related peptide in acid-induced augmentation of opossum esophageal blood flow.

Increased esophageal blood flow may protect against damaging refluxed gastric juices. We have shown that mast cells, histamine, and nitric oxide increase esophageal blood flow in the opossum during acid perfusion. This study examined the roles of substance P and calcitonin gene-related peptide on acid-induced hyperemia and whether the effects of substance P are mediated by mast cells. The opossum distal esophagus was perfused with saline, acid, or capsaicin while blood flow and histamine release were determined. Neuropeptides and neurokinin antagonists were administered parenterally. Only acid or calcitonin gene-related peptide (not substance P or capsaicin) significantly increased blood flow, which was prevented by neurokinin or calcitonin-gene-related peptide antagonists. Acid, substance P, and capsaicin all increased histamine release. Pretreatment with neurokinin antagonists did not affect acid-induced histamine release. We conclude that calcitonin-gene-related peptide is an important mediator of acid-induced esophageal hyperemia, while substance P plays an indirect role.

Animals↗
PubMed2001

Impairment of deglutition reflex by acid-induced esophageal mucosal injury.

Swallowing is an important defense mechanism against reflux esophagitis as it helps clear refluxed gastric contents from the esophagus, while bicarbonate in the saliva acts to neutralize acid. The purpose of the present study was to examine the effect of esophagitis on the deglutition reflex in anesthetized opossums. Animals perfused with either an acidified pepsin solution for 45 min or with 100 mM hydrochloric acid for 45 min on each of three consecutive days exhibited a significantly impaired deglutition reflex in comparison to baseline. Control animals perfused with 0.9% saline showed no impairment. Bilateral cervical vagotomy in animals perfused with acidified pepsin attenuated the impaired deglutition reflex. Taken together, these results suggest that esophagitis causes an impairment in the deglutition reflex that is mediated by vagal afferent pathways.

Animals↗
PubMed2001

Esophagitis-related esophageal shortening in opossum is associated with longitudinal muscle hyperresponsiveness.

Acute intraluminal acid perfusion induces esophageal shortening in humans and opossums. Lower esophageal sphincter (LES) hypotension and peristaltic dysfunction occur in patients and animal models of reflux esophagitis. This study examined whether similar shortening and motor dysfunction occur in anesthetized opossums after repeated esophageal acid exposure and whether this is associated with longitudinal muscle (LM) hyperresponsiveness. Manometry used before and after 3 consecutive days of 45-min perfusion with 100 mmol/l HCl or normal saline measured esophageal length and motor responses to induced swallows. LM electrical and mechanical responses were assessed using standard isometric tension and intracellular recording techniques. Compared with controls, repeated acid perfusion induced erosive esophagitis and significant esophageal shortening, associated with enhanced LM responses to carbachol, a significantly depolarized resting membrane potential, and abnormal spike patterns. LES resting pressure and swallow-induced peristalsis were unaffected. In this model of reflux esophagitis, marked persistent esophageal shortening and associated LM hyperresponsiveness occur before significant LES or peristaltic dysfunction, suggesting that esophageal shortening is the earliest motor disorder induced by acid injury.

Animals↗
PubMed2000

Difficult tracheal intubation following midface distraction surgery.

A case of difficult intubation in a patient with Apert syndrome, who had recently undergone bilateral internal midface distraction, is described. The 14-year-old boy had no antecedent history of such difficulty, despite numerous previous anaesthetics. We suggest that trismus due to temporalis muscle fibrosis, and the altered relationships of the maxilla and mandible following midface advancement, were causal.

Acrocephalosyndactylia↗
PubMed2000

A novel in vitro model of Brunner's gland secretion in the guinea pig duodenum.

A novel in vitro model that combined functional and morphological techniques was employed to directly examine pathways regulating Brunner's gland secretion in isolation from epithelium. In vitro submucosal preparations were dissected from guinea pig duodenum. A videomicroscopy technique was used to measure changes in luminal diameter of glandular acini as an index of activation of secretion. Carbachol elicited concentration-dependent dilations of the lumen (EC(50) = 2 microM) by activating muscarinic receptors on acinar cells. Ultrastructural and histological analyses demonstrated that dilation was accompanied by single and compound exocytosis of mucin-containing granules and the accumulation of mucoid material within the lumen. Inflammatory mediators (histamine, PGE(1), PGE(2)) and intestinal hormones (CCK, gastrin, vasoactive intestinal polypeptide, secretin) also stimulated glandular secretion, whereas activation of submucosal secretomotor neurons by 5-hydroxytryptamine did not. This study directly demonstrates that multiple hormonal, inflammatory, and neurocrine agents activate Brunner's glands, whereas many have dissimilar effects on the epithelium. This suggests that Brunner's glands are regulated by pathways that act both in parallel to and in isolation from those controlling epithelial secretion.

Animals↗
PubMed2000

Anaesthesia and fatigue: an analysis of the first 10 years of the Australian Incident Monitoring Study 1987-1997.

The Australian Incident Monitoring Study (AIMS) database of the Australian Patient Safety Foundation (APSF) was reviewed from its inception in April 1987 to October 1997. A total of 5600 AIMS reports were lodged in that period. Reports in which fatigue was listed as a Factor Contributing to Incident were examined. This occurred in 152 reports, or 2.7% of all reports. Confidence interval analysis suggested that fatigue was associated with various concurrently reported factors. These included pharmacological incidents (especially syringe swaps) and time of day. Other factors significantly associated with fatigue reports were haste, distraction, inattention and failure to check equipment. Relieving anaesthetists and healthy patients were reported more often as factors minimizing incidents. Anaesthetists reporting fatigue more often reported incidents during induction. These data suggest that fatigue alleviation strategies and equipment checking routines, improved workplace design (including drug ampoule and syringe labelling protocols) and regulation of working hours will facilitate minimization of fatigue-related incidents. Definitive prospective studies might be most usefully targeted at these and related interventions.

Anesthesiology↗
PubMed1998

Identification, assessment and management of food-related microbiological hazards: historical, fundamental and psycho-social essentials.

Microbiological risk assessment aimed at devising measures of hazard management, should take into account all perceived hazards, including those not empirically identified. It should also recognise that safety cannot be "inspected into" a food. Rather hazard management should be the product of intervention strategies in accordance with the approach made mandatory in the EU Directive 93/43 and the USDA FSIS Pathogen Reduction HACCP system; Final Rule. It is essential too that the inherent variability of the biological attributes affecting food safety is recognised in any risk assessment. The above strategic principles may be conceptualised as a four-step sequence, involving (i) identification and quantification of hazards; (ii) design and codification of longitudinally integrated ("holistic") technological processes and procedures to eliminate, or control growth and metabolism of, pathogenic and toxinogenic organisms; (iii) elaboration of microbiological analytical standard operating procedures, permitting validation of "due diligence" or responsible care, i.e. adherence to adopted intervention strategies. This should be supported by empirically assessed reference ranges, particularly for marker organisms, while the term "zero tolerance" is refined throughout to tolerable safety limit; (iv) when called for, the need to address concerns arising from lay perceptions of risk which may lack scientific foundation. In relation to infectious and toxic hazards in the practical context the following general models for quantitative holistic risk assessment are presented: (i) the first order, basic lethality model; (ii) a second approximation taking into account the amount of food ingested in a given period of time; (iii) a further adjustment accounting for changes in colonization levels during storage and distribution of food commodities and the effects of these on proliferation of pathogens and toxin production by bacteria and moulds. Guidelines are provided to address: (i) unsubstantiated consumer concern over the wholesomeness of foods processed by an innovative procedure; and (ii) reluctance of small food businesses to adopt novel strategies in food safety. Progress here calls for close cooperation with behavioural scientists to ensure that investment in developing measures to contain risk deliver real benefit.

Animals↗
PubMed1998

Identification, assessment and management of food-related microbiological hazards: historical, fundamental and psycho-social essentials.

Microbiological risk assessment aimed at devising measures of hazard management, should take into account all perceived hazards, including those not empirically identified. It should also recognise that safety cannot be "inspected into" a food. Rather hazard management should be the product of intervention strategies in accordance with the approach made mandatory in the EU Directive 93/43 and the USDA FSIS Pathogen Reduction HACCP system; Final Rule. It is essential too that the inherent variability of the biological attributes affecting food safety is recognised in any risk assessment. The above strategic principles may be conceptualised as a four-step sequence, involving (i) identification and quantification of hazards; (ii) design and codification of longitudinally integrated ("holistic") technological processes and procedures to eliminate, or control growth and metabolism of, pathogenic and toxinogenic organisms; (iii) elaboration of microbiological analytical standard operating procedures, permitting validation of "due diligence" or responsible care, i.e. adherence to adopted intervention strategies. This should be supported by empirically assessed reference ranges, particularly for marker organisms, while the term "zero tolerance" is refined throughout to tolerable safety limit; (iv) when called for, the need to address concerns arising from lay perceptions of risk which may lack scientific foundation. In relation to infectious and toxic hazards in the practical context the following general models for quantitative holistic risk assessment are presented: (i) the first order, basic lethality model; (ii) a second approximation taking into account the amount of food ingested in a given period of time; (iii) a further adjustment accounting for changes in colonization levels during storage and distribution of food commodities and the effects of these on proliferation of pathogens and toxin production by bacteria and moulds. Guidelines are provided to address: (i) unsubstantiated consumer concern over the wholesomeness of foods processed by an innovative procedure; and (ii) reluctance of small food businesses to adopt novel strategies in food safety. Progress here calls for close cooperation with behavioural scientists to ensure that investment in developing measures to contain risk deliver real benefit.

Consumer Advocacy↗
PubMed1998

Gastric cytoprotection is secondary to increased mucosal fluid secretion: a study of six cytoprotective agents in the rat.

We tested the hypothesis that rapidly developing gastric cytoprotection produced by topical application of exogenous compounds is a result of increased gastric mucosal fluid secretion. Ex vivo gastric chambers were prepared in rats which were subsequently exposed topically to one of the prostaglandin (PG) E1 analogues misoprostol or rioprostil, PGE2, nicotine, N-ethylmaleimide (NEM), 0.25 M HCl, or to their respective vehicles. All agents were added to empty chambers to avoid complications resulting from dilution by gastric contents. Effects of these agents on intraluminal volume changes, blood flow, juxtamucosal pH, histology, and on the mucosal damage resulting from necrotizing agents were studied. All six agents were cytoprotective and each increased net secretion of fluid by the chambered mucosae. Gastric blood flow was not significantly increased by NEM, by 0.25 M HCl, or by nicotine compared to controls, and the juxtamucosal pH was not significantly increased by any of the three agents for which this was studied. Vacuole formation in surface epithelial cells and subepithelial edema were seen after exposure to some agents, but none of the agents led to formation of a thick barrier of exfoliated cells and mucus. Ablation of primary afferent nerves with capsaicin abolished both protection by 0.25 M HCl and the net increase in fluid secretion by the mucosae. Capsaicin ablation did not alter either the protection afforded by NEM or the increase in volume of secretion. We conclude that increased mucosal fluid secretion is the common factor present with all six cytoprotective agents and hence may be the predominant mechanism of cytoprotection against topically applied necrotizing agents.

Animals↗
PubMed1998

Cellular pathways of mast cell- and capsaicin-sensitive nerve-evoked ileal submucosal arteriolar dilations.

This study characterized mast cell- and capsaicin-sensitive sensory nerve vasodilator mechanisms regulating submucosal arterioles in the guinea pig ileum. The outside diameter of arterioles in in vitro submucosal preparations from milk-sensitized guinea pigs was monitored using videomicroscopy. Superfusion of the cow's milk protein, beta-lactoglobulin (beta-Lg; 5 microM), evoked large dilations, which became completely desensitized. beta-Lg-evoked dilations were blocked by pyrilamine or NG-monomethyl-L-arginine plus indomethacin but not by TTX. Electron microscopic studies revealed that mast cells, in preparations receiving beta-Lg, demonstrated significant reductions of the dispersed and intact granule areas compared with preparations not exposed to beta-Lg. Paired experiments were conducted to determine if capsaicin-sensitive, nerve-evoked responses involved mast cell degranulation. One preparation received capsaicin (200 nM) followed by beta-Lg (5 microM); the other preparation received the drugs in reverse order. Prior treatment with capsaicin or beta-Lg had no effect on subsequent dilations evoked by the alternate treatment. Electron microscopy showed that nerve-arteriole associations were 10 times closer than nerve-mast cell associations. Mast cell numbers were not increased by milk sensitization. These findings suggest that mast cell- and capsaicin-sensitive nerve-evoked vasodilator mechanisms act independently in a model in which mast cell numbers are not increased.

Alprostadil↗
PubMed1997

Gastrointestinal transit and prolonged ambulatory colonic motility in health and faecal incontinence.

BACKGROUND: Colonic motor function has not been studied in the ambulatory setting over a prolonged period in the unprepared state. Furthermore, the disturbance of this function in patients with faecal incontinence is unknown. AIM: To study colonic function over two to three days in the ambulatory, unprepared state in health and in patients with idiopathic faecal incontinence. METHODS: Six healthy women and six women with faecal incontinence and a structurally intact anal sphincter ingested a dual radioisotope meal, and had a six sensor, solid state manometric probe colonoscopically inserted into the left colon. Scanning was performed until radioisotope left the gut and pressure was recorded for a median of 44 hours. RESULTS: Three of six patients showed abnormal gastric emptying. Patients showed no disturbance of colonic radioisotope transit. Controls had a median of 12, whereas patients had a median of 16, high amplitude propagated waves per 24 hours. In three patients urge incontinence was associated with high amplitude (up to 500 cm water) propagated waves which often reached the rectum. These high pressure waves were identical to those occurring in healthy subjects, the only difference being the lack of adequate sphincter response. Passive incontinence was not associated with colonic motor activity. Defaecation in all subjects was associated with identical propagated waves, and distal movement of 13% (median) of right colonic content and excretion of 32% from the left colon and rectum. The urge to defaecate was associated with either propagated waves (45%) or non-propagated contractions (55%). Rectal motor complexes were recorded in both groups of subjects, but similar rhythmic activity was also recorded in the sigmoid and descending colon. CONCLUSIONS: Normal colonic function consists of frequent high pressure propagated waves. Rhythmic activity occurs both proximal to and in the rectum. Defaecation is characterised by high pressure propagated waves associated with coordinated anal sphincter relaxation. Patients with faecal incontinence may have a widespread disturbance of gut function. Urge incontinence, an urge to defaecate, and defaecation can all be associated with identical high amplitude propagated pressure waves.

Aged↗
PubMed1997

Esophagitis as the outcome of progressive failures of the defensive repertoire.

Pre-epithelial defences include the coordinated actions of the lower esophageal sphincter and the esophageal muscles, which minimize reflux of gastric contents and promote clearance of refluxed material. The esophageal epithelium also possesses innate resistance to luminal damaging agents and may be protected luminally by a mucus or 'mucus bicarbonate' barrier and possibly a layer of hydrophobic surfactants. These components are derived from submucosal glands located in the submucosal connective tissue and from salivary secretions that may bind to the esophageal surface. Epithelial defences include the glycocalyx, permeability properties of the epithelial cell plasma membrane, junctional barriers to proton permeation through the paracellular pathway and ion transport processes for regulation of intracellular pH. Subepithelial defences involve mainly regulation of blood supply via responses of nerves, mast cells and blood vessels to influxing protons. Although the epithelium can withstand prolonged exposure to physiologically relevant concentrations of acid, the presence of pepsin or bile salts may overcome the permeability barrier, which probably resides in the superficial layers of epithelial cells. Focal destruction of these cells allows access of luminal acid and other aggressive agents to the vulnerable basolateral cell membranes and to the submucosa. The result is lesion production, although an efflux of alkaline plasma may protect the underlying submucosa and allow healing. Salivary-derived epidermal growth factor (EGF) is present in the luminal fluid, and lesion development may also provide access of EGF to receptors within the epithelium and in the underlying vasculature. Accelerated cell proliferation would then contribute to healing. Inflammation and healing should also be viewed as defensive responses, as can the development of Barrett's esophagus, in which the stratified squamous epithelium is replaced by a potentially acid-resistant columnar epithelium. Chronic inflammation and esophagitis only result when this multilayered set of defences is overcome. The challenge for research is to identify those components of the defensive repertoire that are defective in individuals who suffer from chronic esophagitis.

Animals↗
PubMed1996

Mast cells mediate acid-induced augmentation of opossum esophageal blood flow via histamine and nitric oxide.

BACKGROUND & AIMS: Increased esophageal blood flow during reflux episodes may play an important role in mucosal resistance to injury, although the mechanism remains unclear. Decreased stainable mast cells and increased luminal histamine release during acid exposure has been previously documented. Therefore, the role of mast cells, nerves, histamine, and nitric oxide in mediating increased blood flow during acid challenge of the distal esophagus was investigated. METHODS: The effects of the mast cell stabilizers disodium cromoglycate and doxantrazole, the neurotoxin tetrodotoxin, the histamine H1 receptor antagonist promethazine, and the NO synthase inhibitor N omega-nitro-L-arginine methyl ester were examined by monitoring opossum esophageal histamine release and blood flow during perfusion with 100 mmol/L HCl. RESULTS: Luminal acid challenge significantly increased both histamine release and blood flow (P < 0.05). Disodium cromoglycate, promethazine, and N omega-nitro-L-arginine methyl ester attenuated the increase in blood flow to basal (saline-perfused) levels. Tetrodotoxin did not prevent an acute increase in blood flow that rapidly returned to baseline, likely from the ensuing hypotension. CONCLUSIONS: These findings provide evidence that mast cell-derived histamine, acting through an NO-dependent mechanism, plays a central role in the response of the esophageal microcirculation to luminal acid.

Animals↗
PubMed1996

Sump bay fever: inhalational fever associated with a biologically contaminated water aerosol.

OBJECTIVE: To investigate the clinical, serological, and environmental features of a work related inhalational fever associated with exposure to an aerosol generated from a biologically contaminated 130,000 gallon water pool in a building used for testing scientific equipment. METHOD: Cross sectional survey of all exposed subjects (n = 83) by symptom questionnaire, clinical examination, spirometry, and serology for antibody to Pseudomonads, pool water extract, and endotoxin. In symptomatic patients diffusion capacity was measured, and chest radiology was performed if this was abnormal. Serial peak flow was recorded in those subjects with wheeze. Bacterial and fungal air sampling was performed before and during operation of the water pool pump mechanism. Endotoxin was measured in the trapped waters and in the pumps. Serum cotinine was measured as an objective indicator of smoking. RESULTS: Of the 20 symptomatic subjects, fever was most common in those with the highest exposure (chi 2 42.7, P < 0.001) in the sump bay when the water was (torrentially) recirculated by the water pumps. Symptoms occurred late in the working day only on days when the water pumps were used, and were independent of the serum cotinine. Pulmonary function was normal in most subjects (spirometry was normal in 79/83, diffusion capacity was low in five subjects, chest radiology was normal). Peak flow recording did not suggest a work relation. The bacterial content of the aerosol rose from 6 to > 10,000 colony forming units per cubic metre (cfu/m3) (predominantly environmental Pseudomonads) when the pumps were operating. High endotoxin concentrations were measured in the waters and oil sumps in the pumps. Low concentrations of antibody to the organisms isolated were detected (apart from two subjects with high antibody) but there was no relation to exposure or the presence of symptoms and similar antibody was found in the serum samples from a non-exposed population. The fever symptoms settled completely with the simple expedient of changing the water and cleaning the pumps. CONCLUSION: Given the results of our study, the development of inhalational fever in this unique environment and clearly restricted cohort was closely related to the degree of exposure to contaminated aerosol and mainly occurred in the absence of distinct serological abnormality and independent of cigarette smoking.

Adult↗