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Biomedical subjects

S R Durham

Publications and source records attributed to S R Durham.

174 records · Page 10Linked to original sources
PubMed1980

The influence of protein binding upon tissue fluid levels of six beta-lactam antibiotics.

The effect of protein binding upon the penetration of six-beta-lactam (three penicillins and three cephalosporins) antibiotics into tissue fluid was studied in humans. A cantharides blister technique was used. It was found that there was a linear relationship between the percentage of protein binding and the penetration into the blister fluid of the antibiotic as measured by the area under the curve of the protein-free fraction. This finding is further evidence that protein binding may have important influence upon the likely efficacy of an antimicrobial agent.

Adult↗
PubMed1979

Interference of cefoxitin in the creatinine estimation and its clinical relevance.

Serum creatinine and creatinine clearance were measured in 10 healthy volunteers before and after an intravenous injection of 2 g cefoxitin sodium. Results were compared with in vitro work which demonstrated a positive interference by cefoxitin in the Jaffé reaction, the routine laboratory method of creatinine measurement. The serum creatinine estimation should be delayed until at least 2 hours after cefoxitin administration. The creatinine clearance may appear to be falsely high.

Cefoxitin↗
PubMedDate not supplied

Phenotype of cells positive for interleukin-4 and interleukin-5 mRNA in allergic tissue reactions.

We have investigated the phenotype of cells positive for IL-4 and IL-5 mRNA in the nasal mucosa of subjects with allergic rhinitis and in bronchoalveolar lavage and bronchial biopsies from atopic asthmatic subjects. The method employed was immunochemistry followed by in situ hybridization using either 35S- or digoxigenin-labelled riboprobes. With nasal and bronchial tissue, this double ICC/ISH method revealed that more than 70% of IL-4 and IL-5 mRNA+ cells were T cells. The remaining IL-4 and IL-5 signals were co-localized to tryptase-positive mast cells and EG2+ eosinophils. Occasional IL-4 and IL-5 mRNA cells were observed in non-asthmatic control subjects, the large majority being CD3+ cells. These results indicate that CD3+ cells are the principal cellular source of IL-4 and IL-5 transcripts in atopic asthma and allergic rhinitis.

Antigens, CD↗
PubMedDate not supplied

Changes in allergic inflammation associated with successful immunotherapy.

Allergen injection immunotherapy in selected patients is effective and has wide ranging anti-inflammatory effects. These include modulation of serum (and presumably local) IgE and IgG antibody responses, a reduction in mast cell numbers in the target organ and inhibition of mast cell mediator release. Tissue eosinophilia and eosinophil activation are also reduced. We have compared and contrasted the effects of immunotherapy and topical corticosteroids on allergen-induced late nasal responses. Both treatments inhibit allergen-induced late nasal symptoms and associated CD4+ T cell and eosinophil recruitment, possibly by distinct mechanisms. Whereas topical corticosteroids may act by suppressing cytokine mRNA expression for Th2-type cytokines, particularly interleukin-4, immunotherapy induces a local Th1 response with an increase in interferon-gamma.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Local IgE production in nasal allergy.

IgE mediates allergic reactions by binding to the high-affinity receptor, Fc epsilonR1, on mast cells and basophils at mucosal surfaces; then cross-linking of the receptor by multivalent antigen triggers the allergic response. We demonstrate here that B cells in the nasal mucosa of patients with hay fever express IgE. The results also suggest that allergen-induced heavy-chain switching to IgE occurs locally within the nasal mucosa. Local IgE synthesis may explain why some 'atopic' patients develop rhinitis whereas others have either no clinical manifestations or develop atopic disease elsewhere.

Adult↗
PubMedDate not supplied

Eosinophils and eosinophil-associated cytokines in allergic inflammation.

Eosinophils are major effector cells in allergic tissue reactions. Their capacity to synthesize and store cytokines, particularly Th2-type cytokines, which may have autocrine effects such as increased cell survival in tissues, is of particular current interest. We have shown that eosinophils infiltrating the site of human cutaneous late-phase reactions (LPR) express mRNA and protein product for IL-4 and IL-5. Stimulation of peripheral blood eosinophils in vitro with either IgG or sIgA produces time-dependent induction of IL-4 and IL-5 transcription, indicating that mature cells may undergo local cytokine synthesis. We also demonstrated that bronchial biopsies from patients with both atopic and non-atopic (intrinsic) asthma express IL-4 and IL-5 mRNA which mainly co-localized to T cells, although clear hybridization signals were also obtained with eosinophils and mast cells. On the other hand, immunoreactivity for the corresponding protein was detectable predominantly in eosinophils and mast cells; a finding believed to reflect granule storage of cytokines. We also studied the resolution of the cutaneous LPR. Apoptosis of eosinophils persisted slightly longer than neutrophils in the tissues. The eventual decline in both neutrophil and eosinophil numbers followed on from the peak of the LPR. This was associated with terminal-deoxynucteotidyl-transferase-mediated nick and labelling positive (TUNEL+) (apoptotic) cells with the subsequent removal of apoptotic neutrophils and eosinophils by tissue macrophages. Thus, IL-4 and IL-5 production by eosinophils may amplify local allergic inflammatory responses and, in the case of IL-5, may prolong local tissue survival. However, in the allergen-induced LPR, inflammation rapidly resolves, possibly through the initiation of programmed cell death and phagocytosis of apoptotic cells by macrophages.

Asthma↗
PubMedDate not supplied

Local IgE production.

Recent data from a number of groups have confirmed that IgE antibody may be produced, at least in part, locally within the nasal mucosa. Our data support the theory that B cell switching may also occur locally, although this remains to be confirmed. Local IgE may account for local disease expression in atopic subjects, although it is not clear which step is rate-limiting in this process. Our results highlight the importance of developing local strategies targeted against IgE for treatment of allergic diseases.

B-Lymphocytes↗
PubMedDate not supplied

Late asthmatic reactions and changes in histamine responsiveness provoked by occupational agents.

The temporal and quantitative relationship between increases in airway responsiveness and late asthmatic reactions provoked by inhalation challenge with occupational agents was studied in nine individuals who underwent a total of thirteen active inhalation challenge tests with one of the following agents: toluene diisocyanate (TDI), maleic anhydride (MA), trimellitic anhydride (TMA), carmine, or colophony (pine wood resin). Airway responsiveness to inhaled histamine (histamine PC20) was measured before and at approximately 3 and 24 h after control and active challenge exposure, when, on all but four occasions, FEV1 was within 10% of pre-challenge values. Significant increases (p less than 0.02) in histamine responsiveness were present at 3 h following challenge exposures which subsequently provoked a definite late asthmatic reaction (FEV1 decrease greater than 15% 3-11 h post challenge). These increases in histamine responsiveness were significantly greater than those at 3 h following the challenges which provoked an isolated early (FEV1 decrease less than 6% 3-11 h post-challenge) or equivocal late asthmatic reaction (FEV1 decrease 6-15% 3-11 h post-challenge) (p less than 0.03). Although histamine responsiveness remained high at 24 h after challenges provoking late asthmatic reactions (p less than 0.05), this was less than the increase at 3 h and not significantly different from the PC20 at 24 h after challenges provoking either single early or equivocal late asthmatic reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗
PubMedDate not supplied

Comparison of the immunopathology of extrinsic, intrinsic and occupational asthma.

Using immunohistochemistry and a panel of monoclonal antibodies we have compared T lymphocyte, eosinophil, macrophage and neutrophil infiltration and expression of adhesion receptors (ICAM-1, E-selectin and VCAM-1) in bronchial biopsies from 10 intrinsic asthmatics, 9 isocyanate-induced asthmatics, 10 extrinsic asthmatics and 12 normal healthy nonatopic controls. There was a significant increase in the number of CD25+ (interleukin-2 receptor [IL-2R]-bearing) cells (p < 0.01) in isocyanate-induced asthma compared with that of controls. There were also significant increases in MBP+ cells (p < 0.02) and EG2+ cells (p < 0.01), which represent total and activated eosinophils. CD25+ (p < 0.01), MBP+ (p < 0.03) and EG2+ (p < 0.01) cells were also elevated in extrinsic asthma. An intense mononuclear cell infiltrate was identified in intrinsic asthmatics with an increase in the number of CD45+ cells (total leukocytes), CD3+ and CD4+ T lymphocytes and CD68+ macrophages (p < 0.03, p < 0.01, p < 0.03 and p < 0.03, respectively), compared with normal controls. CD25+ cells (IL-2R+) and the number of MBP+ and actively secreting eosinophils were also increased in intrinsic asthmatics compared with normal controls (p < 0.01, p < 0.01 and p < 0.01, respectively). EG2+ cell numbers in intrinsic asthma correlated with the Aas symptom score (r = 0.65, p < 0.05), where EG2+ cell numbers in intrinsic and extrinsic asthmatics correlated with airways methacholine responsiveness (r = -0.5, p < 0.03) and the Aas symptom score (r = 0.54, p < 0.03). There was constitutive expression of ICAM-1, E-selectin and VCAM-1 in patients with asthma (intrinsic and extrinsic) and normal controls. Compared with controls, ICAM-1 and E-selectin staining in the submucosa was increased in intrinsic asthma both for intensity (p < 0.02, p < 0.05) and extent of staining (p < 0.01, p < 0.05). Epithelial expression of ICAM-1 was more frequent in asthmatics than control subjects (p < 0.05). These results suggest that T cell activation and eosinophil infiltration are features common to asthma of diverse etiology. There appears to be a complex pattern in in vivo of regulation for ICAM-1, E-selectin and VCAM-1, where they may reflect the degree of ongoing inflammation in asthma.

Adult↗
PubMedDate not supplied

Medical approach to rhinitis.

Rhinitis is a common and important cause of morbidity and impairment of quality of life. An accurate diagnosis, although usually straightforward, is important before commencing treatment. There have been major advances in diagnostic aids, including specific allergen extracts for skin testing, computed tomography of the nose and paranasal sinuses and the availability of flexible and rigid rhinoscopes. Advances in treatment include the availability of topical corticosteroids and non-sedative antihistamines, and the use of minimally invasive surgical techniques. Immunotherapy retains a place in carefully selected pollen-sensitive patients.

Diagnosis, Differential↗