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Biomedical subjects

R Lever

Publications and source records attributed to R Lever.

At least 19 recordsLinked to original sources

Narrowband ultraviolet B (UVB) phototherapy in children.

BACKGROUND: While narrowband ultraviolet B (UVB) phototherapy is a well-established treatment for a range of skin conditions in adults, there is little in the literature about its use in children and data regarding its long-term carcinogenic potential are lacking. AIM: We undertook a retrospective review of the use of narrowband UVB phototherapy in a paediatric population attending two Glasgow Hospitals. METHODS: Phototherapy case notes for all children aged 16 years and under at time of treatment were reviewed at two hospital sites between 1996 and 2002. RESULTS: In total, 77 children had been treated (median age 12 years, range 4-16). The conditions treated most frequently were psoriasis (45%) and atopic eczema (32%). Other dermatoses treated included alopecia areata, acne, hydroa vacciniforme and polymorphic light eruption. Treatment courses for atopic conditions were longer than those required for psoriatic conditions: median number of treatments 24 for atopic eczema (range 3-46), and 17.5 for psoriasis (range 9-35). By the end of treatment, 68% of the atopic patients and 63% of the patients with psoriasis had cleared. The adverse event profile was similar to that in adults, with erythema, herpes simplex reactivation and PLE all recorded. Anxiety was a problem for five patients. CONCLUSION: We conclude that narrowband UVB phototherapy is a useful and well-tolerated treatment for children with severe or intractable inflammatory skin disease, but concerns remain regarding long-term side-effects.

Adolescent↗

The effect of selective phosphodiesterase isoenzyme inhibition on neutrophil function in vitro.

Neutrophil-derived proteases such as neutrophil elastase (NE) and matrix metalloproteinase (MMP) are implicated in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). In this study, the effects of selective phosphodiesterase (PDE) inhibition on NE and MMP-9 release, as well as Myeloperoxidase (MPO) activity and integrin-mediated neutrophil adhesion to human umbilical vein endothelial cells (HUVECs), were investigated. Human neutrophils were treated with PDE inhibitors (10(-11)-10(-4)M) in the absence and presence of TNF-alpha (tumour necrosis factor) (100 U ml(-1)) for 30 min, prior to fMLP activation. After 45 min, the cells were removed and NE, MPO and MMP-9 release assessed. In the adhesion studies, the neutrophils were radio-labelled with 51Cr, stimulated and immediately transferred to cultured HUVEC monolayers for 30 min, prior to assessment of adhesion. TNF-alpha (100 U ml(-1)) acted synergistically with fMLP in stimulating azurophil degranulation with respect to both MPO activity (P<0.01) and NE release (P<0.01). In contrast, an additive effect was observed with TNF-alpha and fMLP with regard to MMP-9 release and neutrophil adhesion to HUVECs. The PDE4 inhibitors, roflumilast, roflumilast N-oxide, cilomilast and rolipram significantly suppressed MPO, NE and MMP-9 release in both the presence and absence of TNF-alpha (P<0.05; n=6-10) and also reduced neutrophil adhesion to HUVECs. In contrast, milrinone, a PDE3 inhibitor and the non-selective PDE inhibitor, theophylline did not inhibit azurophil degranulation under any of the experimental conditions. These data provide further evidence that selective PDE4 isoenzyme inhibitors can inhibit neutrophil degranulation, effects not shared by PDE3 inhibitors or theophylline.

3',5'-Cyclic-AMP Phosphodiesterases↗

Glycosaminoglycans, airways inflammation and bronchial hyperresponsiveness.

Glycosaminoglycans (GAGs) are large, polyanionic molecules expressed throughout the body. The GAG heparin, co-released with histamine, is synthesised by and stored exclusively in mast cells, whereas the closely related molecule heparan sulphate is expressed, as part of a proteoglycan, on cell surfaces and throughout tissue matrices. These molecules are increasingly thought to play a role in regulation of the inflammatory response and heparin, for many years, has been considered to hold potential in the treatment of diseases such as asthma. Heparin and related molecules have been found to exert antiinflammatory effects in a wide range of in vitro assays, animal models and, indeed, human patients. Moreover, the results of studies carried out to date indicate that the antiinflammatory activities of heparin are dissociable from its well-established anticoagulant nature, suggesting that the separation of these characteristics could yield novel antiinflammatory drugs which may be useful in the future treatment of diseases such as asthma

Animals↗

The effects of heparin on the adhesion of human peripheral blood mononuclear cells to human stimulated umbilical vein endothelial cells.

1. The effects of unfractionated heparin (UH) and a selectively O-desulphated derivative of heparin (ODSH), lacking anticoagulant activity, on the adhesion of human peripheral blood mononuclear cells (HPBMNC) to human stimulated umbilical vein endothelial cells (HUVECs), were investigated. 2. For comparison, the effects of poly-L-glutamic acid (PGA), a large polyanionic molecule without sulphate groups and two different molecular weight sulphated dextrans (DS 5 k and DS 10 k) were studied. 3. UH (50 - 1000 u ml(-1)) significantly (P<0.05) inhibited the adhesion of HPBMNC to HUVECs, stimulated with IL-1beta (100 u ml(-1)), TNF-alpha (1000 u ml(-1)) or LPS (100 microg ml(-1)), when the drugs were added together with stimuli to HUVECs and coincubated for 6 h. Such effects on adhesion occurred with limited influence on expression of relevant endothelial adhesion molecules (ICAM-1 and VCAM-1). 4. UH (100 - 1000 u ml(-1)), when added to prestimulated HUVECs, significantly (P<0.05) increased adhesion of mononuclear cells to endothelium at the higher concentrations tested, without any effect on adhesion molecule expression. In contrast, the opposite effect was observed when human polymorphonuclear leucocyte adhesion was examined, under the same experimental conditions, suggesting that the observed potentiation of HPBMNC adhesion is cell specific. 5. The effects of UH on HPBMNC adhesion were shared by the non-anticoagulant ODSH (600 - 6000 microg ml(-1)) but not by sulphated dextrans or PGA (300 - 6000 microg ml(-1)). 6. Heparin affects the adhesion of HPBMNC to stimulated endothelium, in both an inhibitory and potentiating manner, effects which are unrelated to its anticoagulant activity and not solely dependent on molecular charge characteristics.

Cell Adhesion↗

The effects of heparin and related molecules upon the adhesion of human polymorphonuclear leucocytes to vascular endothelium in vitro.

1. The effects of an unfractionated heparin preparation (Multiparin), a low molecular weight heparin preparation (Fragmin) and a selectively O-desulphated derivative of heparin lacking anticoagulant activity, have been investigated for their effects on the adhesion of human polymorphonuclear leucocytes (PMNs) to cultured human umbilical vein endothelial cells (HUVECs) in vitro. The effect of poly-L-glutamic acid, a large, polyanionic molecule was also studied. 2. Unfractionated heparin (50-1000 U ml-1), the O-desulphated derivative (0.3-6 mg ml-1) and the low molecular weight heparin (50 U-1000 U ml-1) all inhibited significantly the adhesion of 51Cr labelled PMNs to HUVECs stimulated with interleukin-1 beta (IL-1 beta; 10 U ml-1), bacterial lipopolysaccharide (LPS; 2.5 micrograms ml-1) or tumour necrosis factor-alpha (TNF-alpha; 125 U ml-1) for 6 h, whereas poly-L-glutamic acid had no effect. In addition, the three heparin preparations in the same concentration range inhibited significantly the adhesion of f-met-leu-phe-stimulated PMNs to resting HUVECs. 3. The effects of unfractionated heparin upon the expression of adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and E-selection were also investigated, as were the effects of unfractionated heparin upon adhesion of human PMNs to previously stimulated HUVECs. Heparin had little effect upon levels of expression of these adhesion molecules on stimulated HUVECs. However, a profound effect upon PMN adhesion to previously stimulated HUVECs was demonstrated using the same preparation, suggesting that inhibition of adhesion molecule expression is not a major component of the described inhibitory effects of heparin. 4. Pre-incubation of PMNs with heparin followed by washing inhibited their adhesion to HUVECs, under different conditions of cellular activation, implying that heparin can bind to these cells and exert its anti-adhesive effects even when not directly present in the system. 5. These observations would suggest that both heparin and a low molecular weight heparin are capable of inhibiting adhesion of human PMNs to endothelial cells, an effect not dependent solely upon the polyanionic nature of these molecules, nor dependent upon their ability to act as anticoagulants.

Anticoagulants↗

Mission to Honduras.

I have volunteered for many years for a woman's organization raising money to build trade and technical schools around the world, but I had never been asked to use my education as a nurse for this purpose. When the opportunity came for me and my classmates to join a volunteer mission to Honduras we jumped at the chance. Since we were all nurses we knew how to deliver patient care. This mission gave us the opportunity to use our newly acquired nurse practitioner skills. It also gave us the opportunity to see first hand how much need there is in other countries, as well as our own, for professional volunteers to help in multicultural settings.

Education, Nursing, Graduate↗

Randomised controlled trial of advice on an egg exclusion diet in young children with atopic eczema and sensitivity to eggs.

BACKGROUND: The role of exclusion diets in the management of atopic eczema in young children is uncertain. This randomised controlled trial evaluates the effect of excluding egg from the diet in young children with atopic eczema and sensitivity to eggs. Fifty-five such children were randomised either to a 4-week regimen, in which mothers were given general advice on care of eczema and additional specific advice from a dietician about an egg exclusion diet (diet group), or to a control group in which general advice only was given. Both groups continued conventional topical treatment. Disease activity was assessed by estimates of the surface area affected by eczema and by an arbitrary severity score. Possible egg sensitivity was identified by RAST before randomisation and after the trial by double-blind placebo-controlled egg challenge. RESULTS: The mean reduction in surface area affected by eczema was significantly greater (p = 0.02) in the group receiving dietary advice (from 19.6% to 10.9% area affected) than in the control group (from 21.9% to 18.9%). A significant improvement also occurred in severity score (p = 0.04): from 33.9 to 24.0 units for the diet group compared with a decrease from 36.7 to 33.5 in the control group. The study suggests that advice on the dietary exclusion of eggs is useful as part of the overall management of young children with atopic eczema and sensitivity to eggs.

Dermatitis, Atopic↗

A controlled study of gold contact hypersensitivity.

1203 patients attending for routine patch testing at 3 hospitals and 105 volunteers were tested with 0.5% and 0.05% gold sodium thiosulfate (GST). 38 patients (3.2%) and 5 volunteers (4.8%) had positive patch tests to GST. There were no significant differences between volunteers and patients with respect to age, sex, atopy or exposure to gold in dental restorations, jewellery or through occupation. There were no significant differences in prevalence of GST hypersensitivity in the 3 hospitals, or between patients and controls. This is the 1st controlled study of hypersensitivity to GST, and suggests that routine patch testing to gold is of limited clinical benefit.

Adolescent↗

Allergic contact dermatitis in atopic dermatitis.

Of 73 adult patients attending a clinic specially provided to treat patients with atopic dermatitis, 31 (42%) showed one or more positive patch reaction on contact testing. There was a striking female preponderance in the patch test positive group (26F:5M) in contrast to those with negative test results (9F:17M). The commonest allergens identified were fragrances in 13 patients, nickel (7), rubber (5), lanolin (4) and formaldehyde (3). In 21 patients, topical preparations, cosmetic or medically prescribed, could be implicated. Contact sensitivity seems to be relatively common in adult patients who have a continuing problem with their atopic dermatitis. Recognizing this sensitization may be important in their management.

Adolescent↗