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Biomedical subjects

S Durham

Publications and source records attributed to S Durham.

At least 19 recordsLinked to original sources
PubMed2003

Significant enhancement of gastric mucin content after rabeprazole administration: its potential clinical significance in acid-related disorders.

Rabeprazole is the only proton pump inhibitor that enhances the content of gastric mucin in experimental animals. We have studied, therefore, the effect of rabeprazole on the content of gastric mucin, mucus, and its viscosity in 21 asymptomatic volunteers in a double-blind study. The mucus content during rabeprazole administration significantly increased both in pentagastrin-stimulated (3.36 +/- 0.39 vs 1.50 +/- 0.32 mg/ml, P < 0.001) and basal (3.31 +/- 0.38 vs 2.28 +/- 0.36 mg/ml, P < 0.01) conditions. The content of mucin during rabeprazole was 2.6-fold (0.96 +/- 0.08 vs 0.36 +/- 0.06 mg/ml, P < 0.0001) and 41% (0.82 +/- 0.09 vs 0.58 +/- 0.09 mg/ml, P < 0.05) higher in stimulated and basal conditions, respectively. The viscosity of gastric juice during rabeprazole administration was also significantly higher both in stimulated (P < 0.01) and basal (P < 0.05) conditions. In conclusion, the unique pharmacological property of rabeprazole, significantly augmenting production of gastric mucus and mucin, may translate to additional clinical benefits in protecting the upper alimentary tract mucosa during the acid-related challenge.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Randomised controlled trial of single, subacromial injection of methylprednisolone in patients with persistent, post-traumatic impingment of the shoulder.

OBJECTIVE: To evaluate the impact on recovery, of single subacromial injection of methylprednisolone in patients with persistent, post-traumatic impingement of the shoulder. DESIGN: Randomised, controlled study. SETTING: Large accident and emergency department in Leicester, UK. PARTICIPANTS: 98 patients with persistent, post-traumatic impingement of the shoulder. INTERVENTION: Single subacromial injection of methylprednisolone with bupivicaine (group S, n=54) or bupivicaine only (group C, n=44). MAIN OUTCOME MEASURES: Pain using a 10 cm visual analogue scale (VAS) and active shoulder abduction. RESULTS: Comparison of pain scores by the 10 cm VAS between group and group C showed no statistical difference at 3, 6, or 12 weeks. Mean patient pain scores at 12 weeks were 1.38 in both groups (p=0.99). There were 16 patients in group S (mean age 52 years) with a 10 cm VAS greater than 1 (95% CI CI 0.17 to 0.43), compared with 13 patients (mean age 57 years) in group C (95% CI 0.17 to 0.45). Comparison of active shoulder abduction between group S and group C showed no statistical difference at 3, 6, or 12 weeks. Mean active abduction at 12 weeks was 168.9 degrees in group S and 170.3 degrees in group C (p=0.8). There were 10 patients in group S (mean age 60.5) with active abduction less than 170 at 12 weeks (95% CI 0.09 to 0.31), compared with five patients (mean age 62 years) in group C (95% CI 0.04 to 0.24). CONCLUSIONS: Single subacromial injection of methylprednisolone has no beneficial impact on reducing the pain, or the duration of immobility in patients with persistent post-traumatic impingement of the shoulder

Adolescent↗
PubMed2002

Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial.

BACKGROUND: Previous studies suggest that sublingual immunotherapy (SLIT) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed. OBJECTIVE: To evaluate the efficacy and safety of SLIT in grass pollen-induced seasonal rhinoconjunctivitis. METHODS: A randomized, placebo-controlled trial in 56 adults over 18 months. Outcome measures included diary scores of seasonal symptoms and medication use, overall assessments, conjunctival and intradermal provocation tests and serum antibody measurements. To investigate possible mechanisms, sublingual biopsies were taken for measurement of local T cells, antigen-presenting cells and IL-12 mRNA expression. RESULTS: There were no significant differences between the immunotherapy (IT) and placebo groups for diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients' overall assessment of hayfever severity compared with previous years showed a highly significant improvement in favour of the IT group (P < 0.02). After treatment the late skin response was smaller (P = 0.003) and the ratio of serum allergen-specific IgG4/IgE was higher (P = 0.05) in the IT group. Both of these variables correlated with the clinical response to SLIT. There were no differences between groups in either the sublingual epithelium or lamina propria for numbers of CD3+ cells (epithelium: P = 0.9, lamina propria: P = 0.2), CD1a+ cells (P = 0.3, P = 0.25), CD68+ cells (P = 0.9, P = 1.0) or IL-12 mRNA+ cells (P = 0.6, P = 0.4). Local side-effects were minor and there were no serious treatment-related adverse events. CONCLUSION: Grass pollen sublingual immunotherapy was well tolerated. Although there was no significant change in diary scores, the improvement in overall assessments, which correlated with inhibition of the late skin response and increases in serum IgG4 : IgE ratio, indicates the need for larger, dose-ranging studies.

Administration, Sublingual↗
PubMed2001

T cell phenotypes of the normal nasal mucosa: induction of Th2 cytokines and CCR3 expression by IL-4.

Mucosal environments such as that of the nose are points of first contact between the human organism and its environment. At these sites the immune system must be regulated to differentiate between and respond appropriately to pathogens and harmless contaminants. T cell-driven immune responses broadly fall into Th1- or Th2-type phenotypes, with increasing evidence that the recruitment of these T lymphocyte subsets is mediated by selective expression of specific chemokine receptors. We have investigated the immunology of the normal nasal mucosa. We show that nasal T cell lines from normal individuals, expanded by culture in IL-2, show reduced expression of the Th2-type cytokines IL-4 and IL-5 compared with lines derived from the blood of the same subjects. These T cells also show reduced expression of the Th2-selective chemokine receptor, CCR3, but similar levels of CCR4 compared with the blood-derived lines. This apparent suppression of Th2 cytokine and CCR3 expression by nasal T cells was reversed by addition of IL-4 to the culture medium. These data are consistent with the presence of a nasal mucosal microenvironment that suppresses Th2 responses and may represent a protective measure against atopic allergic disease in humans and a favoring of Th1 responses to infectious agents. In contrast, T cell expression of CCR1 was higher in the nose than in the blood regardless of the culture medium cytokine environment in keeping with a role for this receptor in tissue homing or lymphocyte activation.

Adult↗
PubMed2001

A comparison of intramuscular ketamine with high dose intramuscular midazolam with and without intranasal flumazenil in children before suturing.

OBJECTIVES: (a) To compare the use of high dose intramuscular midazolam with and without intranasal flumazenil in children after suturing. (b) To compare the use of high dose intramuscular midazolam with low dose intramuscular ketamine in children before suturing. METHODS: 87 children, aged between 1 and 7 years, presenting with simple wounds needing sedation, were studied. Children considered combative (n=47) were given ketamine (2.5 mg/kg intramuscularly). The remaining 40 children were given midazolam (0.4 mg/kg intramuscularly) with and without flumazenil (25 microg/kg, intranasally). RESULTS: The median oxygen saturation was 97% in both midazolam groups. Flumazenil significantly reduced the amount of agitation during recovery (p=0.048) and also the time at which children were ready for discharge (median 55 versus 95 minutes, p value <0.001). After discharge both midazolam groups had an unsteady gait (75%) and there was no significant difference in the duration. As expected because of the deliberate selection of combative children into the ketamine group, the pre-sedation behaviour was slightly more disturbed compared with the midazolam group (p=0.10). However, the ketamine group was less agitated during local anaesthetic and suturing p<0.001. CONCLUSION: Intramuscular midazolam (0.4 mg/kg) did not effectively sedate the children, in that a significant number still had to be restrained. However, none could remember the suturing. Intranasal flumazenil seems to be effective in shortening the time to discharge. If midazolam is to be used then a dose high enough to produce full amnesia should be used, there seems to be no advantage in increasing the dose further. Low dose intramuscular ketamine remains the drug of choice.

Administration, Intranasal↗
PubMed2001

Mitochondrial abnormalities in ageing macular photoreceptors.

PURPOSE: To evaluate somatic mitochondrial (mt)DNA mutations in the macula during ageing. METHODS: Ten 30-microm cryostat sections from the macula (foveal and perifoveal regions) and peripheral retina of 14 donors (aged 14-94 years) were cut for cytochrome c oxidase cytochemistry. The photoreceptor layer was microdissected and DNA extracted for 4977-bp mtDNA (mtDNA(4977)) quantification using PCR. Dual cytochemistry for cytochrome c oxidase and succinate dehydrogenase allowed the detection of cytochrome c oxidase-deficient cones. RESULTS: Findings showed a progressive accumulation of mtDNA(4977) from ages 14 to 94 years. From ages 14 to 60 years there was an increase from 0.006% to 0.25%, and from ages 60 to 94 years there was a steeper increase from 0.25% to 5.39%. Counts of cones in the dual-reacted preparations showed more cytochrome c oxidase-deficient cones in the foveal region than elsewhere. CONCLUSIONS: The results show that mitochondrial DNA deletions and cytochrome c oxidase-deficient cones accumulate in the ageing retina, particularly in the foveal region. These defects may contribute to the changes in macular function observed in ageing and age-related maculopathy.

Adolescent↗
PubMed2000

Molecular pathology of allergic disease. II: Upper airway disease.

Allergic upper airway diseases such as allergic rhinitis and chronic sinusitis are an increasing problem. Although the pathogenesis remains elusive, an individual's genetic predisposition as well as exposure to the allergen are currently considered factors in their development. Clinical symptoms of sneezing, rhinorrhea, and congestion are primarily a consequence of granulocyte release of chemical mediators such as histamine, prostanoids, and leukotrienes as well as the infiltration of inflammatory cells. Observations subsequent to allergen provocation are comparable to natural exposure and as such much of our understanding of allergic responses is derived from this model. A prominence of CD4(+) T cells and eosinophils, synthesis and release of T(H)2 cytokines, and the coordinate expression of chemokines and adhesion molecules are all characteristic of the allergic response observed in rhinitis and sinusitis. Corticosteroids and immunotherapy target these inflammatory processes and have been observed to successfully reduce and shift the predominantly T(H)2 environment toward T(H)1 cytokine expression. As our understanding of the pathophysiologic features of allergic upper airway disease improves, as well as the relationship between their development and that of lower airway disease, new strategies of diagnosis and treatment will allow for more effective modulation of the allergic process and associated morbidity.

Animals↗
PubMed2000

Local synthesis of epsilon germline gene transcripts, IL-4, and IL-13 in allergic nasal mucosa after ex vivo allergen exposure.

BACKGROUND: The production of epsilon germline gene transcripts (Iepsilon(+)/Cepsilon(+) RNA) precedes class switch recombination to IgE and is induced by IL-4 and/or IL-13. Although Iepsilon and Cepsilon RNA(+) B cells have been identified within nasal tissue after in vivo allergen exposure, suggesting local germline transcription, whether these were resident or infiltrating B lymphocytes was not clear. OBJECTIVE: We sought to examine whether B cells resident to the nasal mucosa undergo epsilon germline transcription. METHODS: Nasal mucosal biopsy specimens were obtained from asymptomatic patients with seasonal allergic rhinitis and exposed to allergen ex vivo. Using immunocytochemistry, B lymphocytes were enumerated; with in situ hybridization, the number of cells expressing Iepsilon, Cepsilon, IL-4, and IL-13 messenger (m)RNA(+) cells was examined. RESULTS: Tissue cultured in medium containing specific allergen exhibited significantly more Iepsilon and Cepsilon RNA(+) cells compared with medium alone (P <.05). IL-4 and IL-13 mRNA synthesis also resulted from ex vivo allergen exposure; there were significantly more cells expressing transcripts for these cytokines within allergic nasal mucosal tissue cultured with allergen than medium alone (P <.05). Within allergen-stimulated tissue obtained from allergic patients, 30% of total B cells were Iepsilon RNA(+), and the majority of IL-4 and IL-13 mRNA(+) cells were T cells (68% and 44%, respectively) and mast cells (32% and 19%, respectively). CONCLUSION: These results demonstrate that the nasal mucosa is a site of epsilon germline gene transcription and suggest that local T cell and mast cell production of IL-4 and IL-13 may regulate this event.

Allergens↗
PubMed2000

Spectrum of occipitoatlantoaxial injury in young children.

OBJECT: Injuries of the occipitoatlantoaxial (Oc-C2) region are the predominant form of cervical injury in children younger than 10 years of age. Magnetic resonance (MR) imaging can be used to visualize directly the traumatic ligamentous and soft-tissue abnormalities of the Oc-C2 region. A retrospective review was undertaken to examine the spectrum of pediatric Oc-C2 injuries seen on MR imaging, their correlation with plain x-ray film and computerized tomography findings, and their clinical course. METHODS: Seventy-one consecutive children younger than 10 years of age underwent cervical MR imaging for evaluation of traumatic injury. Magnetic resonance imaging was used to document abnormalities in 23 children; 20 of these injuries involved the Oc-C2 region. Abnormalities in the Oc-C2 region included disruptions of the musculature, apical ligament, atlantooccipital joint(s), tectorial membrane, and spinal cord. A spectrum of injury with progressive involvement of these structures was seen, ranging from isolated muscular injury to the multiple soft-tissue and ligamentous disruptions with craniocervical dislocation. Involvement of the tectorial membrane was the critical threshold in the transition from stable to unstable injury. Analysis of plain x-ray films revealed that a novel interspinous C1-2:C2-3 ratio criteria of greater than or equal to 2.5 was predictive of tectorial membrane abnormalities on MR imaging, with 87% sensitivity and 100% specificity. In patients with tectorial membrane abnormalities who underwent immobilization alone, interim platybasia was demonstrated on follow-up MR images. Conclusions. A progressive spectrum of distinct Oc-C2 injuries can occur in young children; the tectorial membrane is a critical stabilizing ligamentous structure in the Oc-C2 complex; and tectorial membrane abnormalities may be identified by a C1-2:C2-3 ratio of greater than or equal to 2.5.

Atlanto-Axial Joint↗
PubMed1998

Enhanced reduction of atherosclerosis in hamsters treated with pravastatin and captopril: ACE in atheromas provides cellular targets for captopril.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase and angiotensin-converting enzyme (ACE) reduce experimental atherosclerosis by different mechanisms. To determine whether dual-drug therapy additively retards the progression of early lesions, control hyperlipidemic hamsters were compared with those treated with pravastatin, captopril, and pravastatin plus captopril. After 8 weeks of treatment, pravastatin (34 mg/kg/day) reduced plasma total cholesterol and triglycerides by 41 and 84%, respectively, whereas captopril (100 mg/kg/day) reduced normal blood pressure by 21%. The combination of pravastatin and captopril (33 and 100 mg/kg/day) decreased plasma total cholesterol and triglycerides by 44 and 84%, and blood pressure was decreased by 14%. In the aortic arch, pravastatin reduced macrophage-foam cell size and fatty streak area by 21 and 31%, respectively, whereas captopril decreased macrophage-foam cell number and fatty streak area by 34 and 35%. Pravastatin plus captopril decreased macrophage-foam cell number, foam cell size, and fatty streak area by 38, 24, and 67%. ACE inhibitors were previously reported to retard atherosclerosis without affecting blood pressure, suggesting that these agents acted on the artery wall. Therefore the expression of arterial ACE was determined in normal and atherosclerotic hamster aortas. ACE messenger RNA (mRNA) and protein were detected in endothelial cells, intimal macrophage-foam cells and medial smooth-muscle cells of atherosclerotic arteries indicating an upregulation of ACE expression with hyperlipidemia and atherosclerosis. In conclusion, dual-therapy with pravastatin and captopril produced an additive reduction in fatty streak area compared with either drug alone and suggested that atherogenesis can be retarded beyond the level achieved with monotherapy. The presence of ACE in endothelial cells and intimal macrophage-foam cells provides cellular targets for captopril to directly modify the formation of early atherosclerotic lesions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

An alternative to "brutacaine": a comparison of low dose intramuscular ketamine with intranasal midazolam in children before suturing.

OBJECTIVE: To compare the use of low dose intramuscular ketamine with high dose intranasal midazolam in children before suturing. METHODS: Altogether 102 children with simple wounds between 1 and 7 years old were allocated to the two study groups. RESULTS: Two children were excluded from the study because of deviation from the agreed protocol. The 50 children in the ketamine group were less likely to cry or need to be restrained during the procedure than those in the midazolam group (p < 0.01). The median oxygen saturation was 97% in both groups. There was no difference in the recovery behaviour and the range of time at which children were ready for discharge, although the median time for the latter was shorter in the midazolam group (75 v 82 minutes). Vomiting occurred in nine of the ketamine and four of the midazolam group. After discharge both groups had an unsteady gait (73% v 71%) which usually resolved within two hours. CONCLUSION: Intranasal midazolam (0.5 mg/kg) effectively sedated the children in that none could remember the suturing. However a significant number still had to be restrained (86% v 14%). Intramuscular ketamine (2.5 mg/kg) produced dissociative anaesthesia in the majority of cases and was the preferred drug of nurse, doctor, and parent.

Administration, Intranasal↗
PubMed1998

Granulocyte/macrophage-colony stimulating factor in allergen-induced rhinitis: cellular localization, relation to tissue eosinophilia and influence of topical corticosteroid.

BACKGROUND: Allergen-induced late nasal responses are associated with recruitment of T lymphocytes and eosinophils, and preferential messenger RNA (mRNA) expression of 'TH2-type' cytokines. We previously showed that topical steroid inhibited the late response and associated tissue eosinophilia. In this study we tested the hypothesis that granulocyte/macrophage-colony stimulating factor (GM-CSF) may contribute to late-responses and tissue eosinophilia and is inhibitable by topical corticosteroid. METHODS: Nasal biopsies were taken before and 24 h after nasal allergen provocation following 6 weeks of treatment with either a nasal corticosteroid spray (fluticasone propionate) or a matched placebo nasal spray twice daily. Cryostat sections were processed by immunohistochemistry and in situ hybridization to assess cytokine mRNA expression for GM-CSF. RESULTS: Increases in T lymphocytes and eosinophils were seen in the nasal mucosa after allergen challenge (p = 0.01) which were accompanied by a 5-fold increase in cells expressing mRNA for GM-CSF (p = 0.01). Double immunohistochemistry/in situ hybridization demonstrated that the majority of GM-CSF mRNA+ cells were co-localized to CD68+ (40%), or T cells (40%) with a lesser contribution from eosinophils (<20%). Topical steroid treatment was accompanied by a decrease in both the CD3+ and major basic protein (MBP+) cells expressing GM-CSF mRNA (p = 0.01) with a corresponding proportionate increase in the % of macrophages expressing GM-CSF. CONCLUSIONS: The results indicate that after allergen provocation, eosinophils are recruited to the nasal mucosa and that, at least in part, this may be due to GM-CSF. Topical nasal corticosteroid inhibits late responses and the associated eosinophilia, possibly indirectly by decreasing GM-CSF from T lymphocytes or reducing autocrine production of GM-CSF from eosinophils.

Administration, Intranasal↗