Search PubMed⌕ Search

Biomedical subjects

M Ennis

Publications and source records attributed to M Ennis.

At least 19 recordsLinked to original sources
PubMed2006

A randomized controlled trial of a health promotion education programme for people with multiple sclerosis.

OBJECTIVE: To evaluate the effectiveness of a health promotion education programme for people with multiple sclerosis (the OPTIMISE programme) in terms of increasing the level of health-promoting activity undertaken, improving self-efficacy and enhancing quality of life. DESIGN: A randomized controlled single blinded trial. Non-parametric analysis was undertaken to test for significant differences between treatment and control groups change scores. SUBJECTS AND SETTING: Sixty-two adults (32 treatment and 30 control subjects) with multiple sclerosis of any type, Expanded Disability Status Scale (EDSS) 1-7. INTERVENTION: An eight-week multidisciplinary outpatient health promotion education programme aimed at increasing knowledge, skills and confidence in undertaking health promotion activities. OUTCOME MEASURES: Health Promoting Lifestyle Profile, Self-Rated Abilities for Health Practices Scale and the Short Form 36 Item Health Survey. RESULTS: Following completion of the programme, treatment subjects had significantly higher levels of health promotion activity undertaken (P < 0.01) and self-efficacy for health promotion activities (P < 0.01). These benefits were sustained for at least three months after the programme ceased. Certain domains of quality of life also improved in treatment subjects more than controls (physical P = 0.03, mental health and general health P = 0.01), although only mental health and general health showed further improvement at three months. Participants provided positive feedback regarding the usefulness of the intervention and demonstrated observable changes to their health promotion behaviours. CONCLUSIONS: The OPTIMISE programme produced significant changes in health-promoting behaviours.

Female↗
PubMed2005

Alterations in stress-associated behaviors and neurochemical markers in adult rats after neonatal short-lasting local inflammatory insult.

Recently, there has been a growing interest in long-term consequences of neonatal pain because modern neonatal intensive care units routinely employ procedures that cause considerable pain and may be followed by local inflammation and hyperalgesia lasting for several hours or even days. To address this question, we developed a rat model of short lasting (<2 days) early local inflammatory insult produced by a single injection of 0.25% carrageenan (CAR) into the plantar surface of a hindpaw. Previously, we demonstrated that rats receiving this treatment within the first week after birth grow into adults with a global reduction in responsiveness to acute pain. Here, we report that these animals also manifest a low anxiety trait associated with reduced emotional responsiveness to stress. This conclusion is based in the following observations: (a) rats in our model display reduced anxiety on an elevated plus-maze; (b) in the forced swim test, these rats exhibit behavioral characteristics associated with stronger ability for stress coping; and (c) these animals have reduced basal and stress-induced plasma levels of such stress-related neuroendocrine markers as corticotropin-releasing factor, vasopressin, and adrenocorticotrophic hormone. In addition, we used DNA microarray and real-time reverse-transcriptase polymerase chain reaction to profile long-term changes in gene expression in the midbrain periaqueductal gray (PAG; a region involved in both stress and pain modulation) in our animal model. Among the affected genes, serotonergic receptors were particularly well represented. Specifically, we detected increase in the expression of 5-HT1A, 5-HT1D, 5-HT2A, 5-HT2C and 5-HT4 receptors. Several of these receptors are known to be involved in the anxiolytic and analgesic activity of the PAG. Finally, to determine whether neonatal inflammatory insult induces elevation in maternal care, which may play a role in generating long-term behavioral alterations seen in our model, we examined maternal behavior for 3 days following CAR injection. Indeed, we observed a substantial increase in maternal attention to the pups at the time of inflammation, but this increase was not without its cost: a period of significant maternal neglect afterward.

Adrenocorticotropic Hormone↗
PubMed2005

A brainstem substrate for analgesia elicited by intraoral sucrose.

Previous studies demonstrated that nursing or intraoral infusion of certain components of mother's milk (e.g. sugars and fats) produces calming and opiate receptor-dependent analgesia in newborn rats and humans. However, the neural circuitry underlying such analgesia is unknown. The aim of the present study was to specify the central pathways by which taste stimuli engage neural antinociceptive mechanisms. For this purpose, midcollicular transactions were used to investigate the role of the forebrain in analgesia elicited by intraoral infusion of 0.2 M sucrose in neonatal rats. Sucrose-induced analgesia persisted, and was enhanced, following midcollicular transection, indicating that it did not require neural circuits confined to the forebrain. Fos immunohistochemistry was used to identify brainstem neurons activated by a brief (90 s) intraoral infusion of a small volume (90 microl, 0.2M) of sucrose or a salt solution (0.1 M ammonium chloride) in 10-day-old rat pups. Compared with control groups (intact, cannula, distilled water), both sucrose and ammonium chloride induced Fos expression in the rostral nucleus tractus solitarius, the first relay in the ascending gustatory pathway. Sucrose also elicited Fos expression in several brainstem areas associated with centrally mediated analgesia, including the periaqueductal gray and the nucleus raphe magnus. Taken together, these findings demonstrate that analgesia elicited by intraoral sucrose does not require involvement of the forebrain. Intraoral sucrose activates neurons in the periaqueductal gray and nucleus raphe magnus, two key brainstem sites critically involved in descending pain modulation.

Administration, Oral↗
PubMed2005

Properties of external plexiform layer interneurons in mouse olfactory bulb slices.

In the external plexiform layer (EPL) of the main olfactory bulb, apical dendrites of inhibitory granule cells form large numbers of synapses with mitral and tufted (M/T) cells, which regulate the spread of activity along the M/T cell dendrites. The EPL also contains intrinsic interneurons, the functions of which are unknown. In the present study, recordings were obtained from cell bodies in the EPL of mouse olfactory bulb slices. Biocytin-filling confirmed that the recorded cells included interneurons, tufted cells, and astrocytes. The interneurons had fine, varicose dendrites, and those located superficially bridged the EPL space below several adjacent glomeruli. Interneuron activity was characterized by high frequency spontaneous excitatory postsynaptic potential/currents that were blocked by the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and largely eliminated by the voltage-sensitive Na+ channel blocker, tetrodotoxin. Interneuron activity differed markedly from that of tufted cells, which usually exhibited spontaneous action potential bursts. The interneurons produced few action potentials spontaneously, but often produced them in response to depolarization and/or olfactory nerve (ON) stimulation. The responses to depolarization resembled responses of late- and fast-spiking interneurons found in other cortical regions. The latency and variability of the ON-evoked responses were indicative of polysynaptic input. Interneurons expressing green fluorescent protein under control of the mouse glutamic acid decarboxylase 65 promoter exhibited identical properties, providing evidence that the EPL interneurons are GABAergic. Together, these results suggest that EPL interneurons are excited by M/T cells via AMPA/kainate receptors and may in turn inhibit M/T cells within spatial domains that are topographically related to several adjacent glomeruli.

Action Potentials↗
PubMed2005

Precut papillotomy versus persistence in difficult biliary cannulation: a prospective randomized trial.

BACKGROUND AND STUDY AIMS: Failed biliary cannulation occurs in up to 10% of patients undergoing ERCP. There is some controversy as to the safety and efficacy of using precut techniques to achieve biliary cannulation in difficult cases. To date, no randomized trial has compared the success and complication rates of precut with the rates for persistence when biliary cannulation is difficult. The aim of this study was to compare the success rates and complication rates of precut with the success rates and complication rates of persistence in cases of difficult biliary cannulation. PATIENTS AND METHODS: Patients without prior sphincterotomy who required biliary cannulation were screened. A "difficult biliary cannulation" was arbitrarily defined as failed cannulation after 12 minutes. These patients were then randomized to continue treatment by needle-knife cut over the roof of the papilla or by persistence with a non-wire-guided, single-lumen papillotome. "Primary" success was defined as deep cannulation within 15 minutes of randomization. Primary and final success rates and complication rates within 30 days after ERCP were compared. RESULTS: Over a 38-month period a total of 642 patients were screened. Patients in whom biliary cannulation was successful within a time period of 12 minutes or less formed the reference group (n = 580). The remainder of the patients were randomly assigned to the "precut" arm (n = 32) or to the "persistence" arm (n = 30). Primary success rates and complication rates were similar in the precut and persistence arms (75% and 4% respectively for the precut arm vs. 73% and 9% for the persistence arm). The final successful cannulation rate in the entire group of 642 patients was 99.5%. CONCLUSIONS: In experienced hands, precut papillotomy and persistence in cannulation are equally effective in cases of difficult cannulation, with a similar complication rate.

Abdominal Pain↗
PubMed2005

Children with stable asthma have reduced airway matrix metalloproteinase-9 and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio.

BACKGROUND: Childhood asthma is characterized by inflammation of the airways. Structural changes of the airway wall may also be seen in some children early in the course of the disease. Matrix metalloproteinases (MMPs) are key mediators in the metabolism of the extracellular matrix (ECM). OBJECTIVE: To investigate the balance of MMP-8, MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1 in the airways of children with asthma. METHODS: One hundred and twenty-four children undergoing elective surgical procedures also underwent non-bronchoscopic bronchoalveolar lavage (BAL). MMP-8, MMP-9 and TIMP-1 were measured by ELISA. RESULTS: There was a significant reduction in MMP-9 in atopic asthmatic children (n=31) compared with normal children (n=30) [median difference: 0.57 ng/mL (95% confidence interval: 0.18-1.1 ng/mL)]. The ratio of MMP-9 to TIMP-1 was also reduced in asthmatic children. Levels of all three proteins were significantly correlated to each other and to the relative proportions of particular inflammatory cells in BAL fluid (BALF). Both MMP-8 and MMP-9 were moderately strongly correlated to the percentage neutrophil count (r=0.40 and 0.47, respectively, P<0.001). CONCLUSIONS: An imbalance of MMPs and their inhibitors occurs in children with well-controlled asthma, which may indicate early derangement of the metabolism of the ECM.

Adolescent↗
PubMed2005

Neutrophil cell death, activation and bacterial infection in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterised by chronic endobronchial bacterial infection and neutrophil mediated inflammation. Neutrophil apoptosis is essential for the resolution of inflammation. This study assessed the relationship between levels of neutrophil apoptosis and sputum microbiology in matched clinically stable patients with CF. METHODS: Sputum was induced from 34 patients (nine with no Gram negative infection, 10 colonised with Pseudomonas aeruginosa, 10 with Burkholderia cenocepacia, and five with other infections). Apoptotic neutrophils measured by flow cytometric Annexin V/propidium iodide staining and morphology were similar in all groups. RESULTS: Patients infected with P aeruginosa or B cenocepacia had a significantly lower percentage of viable neutrophils in the sputum than those with no Gram negative infection (Kruskal-Wallis p = 0.01, median (interquartile range (IQR)) 14.2% (9.4-21.6), 15.8% (12.3-19.5), and 48.4% (23.0-66.4); p = 0.003 and p = 0.002, respectively). They also had significantly higher levels of secondary necrotic granulocytes in sputum than patients with no Gram negative infection (Kruskal-Wallis p<0.0001, median (IQR) 55.5% (48.4-64.5), 50.4% (44.6-61.9), and 24.8% (14.4-30.5); p<0.0001 and p<0.0001, respectively). Neutrophils (x 10(6)/g sputum) in P aeruginosa infected patients (Kruskal-Wallis p = 0.05, median (IQR) 6.3 (3.5-12.7)) and B cenocepacia infected patients (5.7 (1.5-14.5)) were significantly higher than in the group with no Gram negative infection (0.5 (0.5-4.3), p = 0.03 and 0.04, respectively). CONCLUSION: These results suggest that cell death and clearance may be altered in patients with CF colonised with P aeruginosa and B cenocepacia compared with those with no Gram negative infection.

Adult↗
PubMed2005

Neutrophils and eosinophils: clinical implications of their appearance, presence and disappearance in asthma and COPD.

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic disorders. Traditionally, asthma has been associated with an eosinophilic inflammation and COPD with neutrophilic inflammation. In this review we will highlight the maturation, recruitment, activation, action and apoptosis of these cells. In addition we will focus on the evidence for their presence in disease and suggest potential new therapeutic interventions.

Animals↗
PubMed2004

Adverse reactions to drugs: in vitro studies with isolated cells.

OBJECTIVE AND DESIGN: Drug-induced adverse reactions can be allergic or pseudoallergic in nature, in this study the histamine releasing ability of 4 radiographic contrast media and 2 opioid analgesics was tested on a variety of mast cell containing cell suspensions. MATERIAL: Mast cell containing cell suspensions were obtained from porcine lung, liver, kidneys and heart, as well as rat lung and rat peritoneal lavage. TREATMENT: Cells were incubated for 10 min with Angiographin (amidotrizoate), Hexabrix (ioxaglate), Rayvist (ioglycate) or Telebrix (ioxithalamate) all 10-500 microl/ml or with levomethadone (0.1-5 mM) or pethidine (0-10 mM). METHODS: Histamine was measured using an automated fluorometric method and percentage histamine release calculated. RESULTS: All agents caused histamine release from porcine cells and rat lung cells. However, rat peritoneal mast cells were refractory to the action of pethidine. Cardiac cells were the most sensitive to the radiographic contrast media but the least sensitive to the opioid analgesics. CONCLUSIONS: The data indicate that mast cells isolated from animal models can provide an indication of those agents likely to induce an adverse pseudoallergic reaction. However, these data should be used together with those obtained from human mast cells, in vivo animal experiments as well as studies using human volunteers and clinical trials as advocated in the Marburg Model.

Analgesics, Opioid↗
PubMed2004

Histamine dilutions modulate basophil activation.

BACKGROUND: In order to demonstrate that high dilutions of histamine are able to inhibit basophil activation in a reproducible fashion, several techniques were used in different research laboratories. OBJECTIVE: The aim of the study was to investigate the action of histamine dilutions on basophil activation. METHODS: Basophil activation was assessed by alcian blue staining, measurement of histamine release and CD63 expression. Study 1 used a blinded multi-centre approach in 4 centres. Study 2, related to the confirmation of the multi-centre study by flow cytometry, was performed independently in 3 laboratories. Study 3 examined the histamine release (one laboratory) and the activity of H(2) receptor antagonists and structural analogues (two laboratories). RESULTS: High dilutions of histamine (10(-30)-10(-38) M) influence the activation of human basophils measured by alcian blue staining. The degree of inhibition depends on the initial level of anti-IgE induced stimulation, with the greatest inhibitory effects seen at lower levels of stimulation. This multicentre study was confirmed in the three laboratories by using flow cytometry and in one laboratory by histamine release. Inhibition of CD63 expression by histamine high dilutions was reversed by cimetidine (effect observed in two laboratories) and not by ranitidine (one laboratory). Histidine tested in parallel with histamine showed no activity on this model. CONCLUSIONS: In 3 different types of experiment, it has been shown that high dilutions of histamine may indeed exert an effect on basophil activity. This activity observed by staining basophils with alcian blue was confirmed by flow cytometry. Inhibition by histamine was reversed by anti-H2 and was not observed with histidine these results being in favour of the specificity of this effect We are however unable to explain our findings and are reporting them to encourage others to investigate this phenomenon.

Alcian Blue↗
PubMed2004

Adenosine, inflammation and asthma--a review.

Adenosine is a ubiquitous molecule present in every cell of the human body. It has a wide range of physiological functions mediated predominantly through specific cell surface adenosine receptors. Adenosine has both pro- and anti-inflammatory effects and acts on inflammatory and resident immune cells and antioxidant enzymes. The elevation of adenosine in the bronchoalveolar lavage (BAL) fluid of asthmatics combined with its bronchoconstrictor effect on the airways in asthmatics has led to increased research into the contribution of adenosine in the pathophysiology of inflammation and asthma. This review looks at the airway response to adenosine and at the interaction of adenosine with mast cells and basophils.

Adenosine↗
PubMed2004

The effect of nicotine on basophil histamine release.

BACKGROUND: Changes in the immune and inflammatory response are induced by smoking tobacco but underlying mechanisms remain to be elucidated. OBJECTIVE: This study investigated the effect of nicotine agonists on histamine release from human basophils. METHODS: Peripheral blood basophils were obtained from healthy volunteers. The effect of the nicotine agonists [-]-1-methyl-2-[3-pyridyl]pyrrolidine and (+)-nicotine di-p-toluoyltartrate salt on cell viability and anti-IgE induced histamine release was investigated. RESULTS: Cell viability was not altered by preincubation with the agents for 15 min. Anti-IgE induced histamine release was significantly inhibited by preincubation (15 min, 37 degrees C) with [-]-1-methyl-2-[3-pyridyl]pyrrolidine at the highest concentration tested 10(-)3 M (p<0.01). Preincubation (15 min, 37 degrees C) with (+)-nicotine di-p-toluoyltartrate salt significantly inhibited anti-IgE induced histamine release at 10(-3)M and 10(-5) M (p<0.05). CONCLUSIONS: This study has demonstrated that nicotine agonists inhibit histamine release from human basophils. Further studies examining the effect of smoking on basophil activation are required.

Adult↗
PubMed2004

Cytokines and inflammatory mediators in cystic fibrosis.

Airway disease in cystic fibrosis (CF) is characterised by a continuous cycle of chronic infection and inflammation dominated by a neutrophilic infiltrate. This inflammation is characterised by an increased production of pro-inflammatory cytokines in the lung. The relationship between the abnormal CFTR gene product and the development of inflammation and progression of lung disease in CF is not fully understood. This review article studied the mechanisms of pulmonary inflammation in CF, the profiles of cytokines and inflammatory mediators in the lung in CF, the mechanisms that predispose to chronic Pseudomonas aeruginosa infection, cytokine involvement in diseases other than CF and reviewed current therapeutic strategies for CF. Imbalances of cytokine secretion are now better understood due to recent advances in understanding CF at a molecular level and it is increasingly thought that the normal inflammatory process is deranged in CF early in the course of the disease and may occur in the absence of detectable infection. However, the relationship between this unbalanced cytokine production, the mutations in CFTR and its actual consequence for pathogenesis need further investigation.

Anti-Inflammatory Agents↗
PubMed2004

Ontogeny of analgesia elicited by non-nutritive suckling in acute and persistent neonatal rat pain models.

Significant analgesic and calming effects in human infants and neonatal rodents are produced by orogustatory and orotactile stimuli associated with nursing. These naturally occurring analgesic stimuli may help to protect the vulnerable developing nervous system from the long-term effects of neonatal tissue injury. However, the efficacy of orotactile-induced analgesia across the pre-weaning period, as well as its effects on persistent inflammatory pain, is unknown. Here, we investigated the developmental profile of analgesia produced by orotactile stimulation during non-nutritive suckling in rats. The effects of suckling, as compared to non-suckling littermates, on nocifensive withdrawal responses to thermal and mechanical stimuli were examined at postnatal (P) days P0, P3, P10, P17 and P21. In some rats, Complete Freund's adjuvant (CFA) was injected in a fore- or hindpaw to produce inflammation. For thermal stimuli, suckling significantly increased forepaw withdrawal latencies at P3, P10 and P17, while hindpaw responses were increased at P3 and P10, but not at P17. In inflamed pups, suckling increased fore- and hindpaw response latencies at P10 and P17, but not at P0 or P21. Suckling-induced analgesia was naloxone-insensitive. For mechanical stimuli, suckling-induced analgesia was present at P3, P10 and P17, but not at P21, for both fore- and hindpaws in naïve and inflamed animals. Additionally, suckling had a small but significant effect at P0 for the forepaw in inflamed pups. In nearly all experiments, the peak effect of suckling for thermal and mechanical stimuli occurred at P10. These results indicate that orotactile analgesia, like orogustatory analgesia, is absent or minimal at P0, appears consistently at approximately P3 and is maximal at P10. Unlike gustatory analgesia in rats however, orotactile analgesia persists at least to P17. Orotactile stimulation during suckling effectively reduces transient pain elicited by thermal and mechanical stimuli, as well as persistent hyperalgesia and allodynia caused by inflammation.

Acute Disease↗
PubMed2004

Characterization of basal and re-inflammation-associated long-term alteration in pain responsivity following short-lasting neonatal local inflammatory insult.

Recently, several studies have suggested that neonatal noxious insult could alter future responses to painful stimuli. However, the manifestations, mechanisms, and even developmental nature of these alterations remain a matter of controversy. In part, this is due to the lack of detailed information on the neonatal sensitive period(s) during which noxious stimulation influences future nociception, and the time-course and distribution of the resultant abnormalities. The present paper describes these parameters in a rat model of short-lasting ( approximately 24 h) neonatal local inflammation of a hindpaw produced by injection of 0.25% carrageenan (1 microl/g). Examinations of paw withdrawal responses to thermal and mechanical stimulations in adult animals, which as neonates were subjected to this insult, showed that the previously-reported long-term hypoalgesia and hyperalgesia are not mutually exclusive outcomes of early noxious experience. Long-term hypoalgesia was apparent at the basal conditions and was equally strong in the previously injured and uninjured paws, which suggests a globally-driven deficit. In contrast, long-term excessive hyperalgesia had the strongest manifestation in the neonatally-injured paw after re-inflammation, indicating significant segmental involvement in its generation. The differences between mechanisms underlying the observed hypoalgesia and hyperalgesia are further underscored by the finding that, while the former is detectable only after animals reach the second month of life, the latter is elicitable immediately upon cessation of the initial neonatal inflammation. Nevertheless, we detected a significant overlap in the neonatal sensitive periods for generation of these effects (both occurring within the first postnatal week). Also, neither the basal hypoalgesia nor excessive re-inflammation-associated hyperalgesia subsided with age and were detectable in 120-125-day-old rats. These finding provide a framework within which the entire complex of long-term effects of early noxious experience can be understood and examined.

Animals↗
PubMed2004

Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis.

BACKGROUND: Lower airway secretions from patients with bronchiectasis show inflammatory cell infiltration and increased proinflammatory mediators. The aim of this study was to investigate the effects of antibiotic treatment for exacerbations on neutrophil apoptosis and necrosis. METHODS: Sputum was induced from 15 subjects with idiopathic bronchiectasis at the beginning of an acute exacerbation and after intravenous antibiotic treatment. Neutrophil apoptosis and necrosis were assessed using flow cytometry and morphology and the supernatant was analysed for concentrations of inflammatory mediators. RESULTS: Neutrophil numbers (x10(6) cells/g sputum) in sputum were significantly greater on day 0 than on day 14 (median difference (95% confidence interval (CI)) 5.14 (1.27 to 8.46), p = 0.02). Controls had a significantly higher percentage of sputum macrophages than patients with bronchiectasis (day 0, 1.35 (95% CI 0.48 to 2.89), p = 0.004; day 14, 1.09 (95% CI 0.26 to 2.86), p = 0.02). The concentrations of tumour necrosis factor alpha (pg/ml), interleukin 8 (ng/ml), and neutrophil elastase (ng/ml) in sputum supernatant were significantly reduced on day 14 compared with day 0 (median difference -94 (95% CI -158 to -27), p = 0.005; -106 (95% CI -189 to -50), p = 0.0006; and -73 451 (95% CI -135 495 to -12 303), p = 0.02 respectively). Patients with bronchiectasis had a significantly lower percentage of cells which were neither apoptotic nor necrotic than healthy controls (both days, -38.8 (95% CI -49.6 to -8.5), p = 0.002; -45.0 (95% CI -58.0 to -34.1), p = 0.0003, respectively), and on day 14 they had a significantly higher percentage of secondary necrotic cells than healthy controls (40 (95% CI 11.6 to 57.5), p = 0.004). CONCLUSIONS: This study shows that antibiotic treatment affects concentrations of proinflammatory mediators and cell death and clearance may be altered in bronchiectasis.

Anti-Infective Agents↗
PubMed2003

Liver fluke (Fasciola hepatica)-derived peptides activate rat peritoneal mast cells.

Short peptides with sequences derived from those found in the tegumental antigen of Fasciola hepatica have been synthesised. Incubation of some of these peptides with rat peritoneal mast cells resulted in the degranulation of the cells as measured by a histamine release assay. This activity was shown to be associated with the proline-lysine-proline motif, which is responsible for the induction of mast cell degranulation by the mammalian bioactive peptide substance P. Studies on the mode of action of the fluke-derived peptide indicated that it was operating through the same biochemical pathways as substance P. The implications of these findings for the development of immune responses during parasite infections are discussed.

Animals↗