1,721,000 research outputs found
Treating allergic rhinitis: continuous versus on-demand regime? Executive summary of the supportive initiatives for the global management of allergy (SIGMA): report from the Belgian working group
No full textThis Supportive Initiative for the Global Management of Allergy (SIGMA) initiative gathered together four multidisciplinary and inter-university groups of Belgian experts in the treatment of allergic rhinitis to review the literature and come to a consensus opinion on the global management of allergy. Their conclusions were as follows. Group 1 concluded that in children suffering from allergic rhinitis, there is sufficient expert opinion in favour of continuous treatment with both H1-antihistamines and corticosteroids for controlling symptoms during periods of allergen exposure, but not to support continuous treatment during periods when symptoms are negligible in an attempt to prevent the development of new allergic diseases. Group 2 came to similar conclusions in adults. Group 3 considered adults with concomitant asthma and stressed the crucial necessity to screen each asthmatic for allergic rhinitis and institute appropriate therapy for both conditions. Even though efficacious treatment algorithms are available for both rhinitis and asthma, an integrated management of these frequently concomitant diseases is not always prescribed even though there is a proven clinical advantage of adequate treatment of the nose of asthmatics. Group 4 concluded that for both H1-antihistamines and nasal corticosteroids, safety data indicate that continuous treatment may be given without fears of adverse consequences. With regard to the cost implications of continuous therapy versus on-demand therapy, there are indications that effective treatment of allergic rhinitis by continuous treatment reduces overall drug costs, particularly that of escape medication and indirect costs in the form of days absent from work and school
Investigation into the mechanisms by which nedocromil sodium, frusemide and bumetanide inhibit the histamine-induced itch and flare response in human skin in vivo
No full textBackground In a previous study, iontophoresis of nedocromil sodium into human skin in vivo was shown to reduce histamine-induced itch and flare. In asthma, the Na+/K+/2Cl cotransporter inhibitors, frusemide and bumetanide, have been reported to have many similar actions to nedocromil sodium.Objective To compare the effects of these drugs in the histamine-induced itch, flare and weal response in human skin in vivo and elucidate their site of action.Methods Nedocromil sodium, frusemide bumetanide and reversed osmosis water (control), were introduced by iontophoresis into the forearm skin of 10 volunteers in each of two single-blind studies. In study 1, histamine (20 ?L of 100 ?m) or vehicle was injected into the area of iontophoresis 10 min later. In study 2, histamine or vehicle was injected 5 mm outside the area of iontophoresis so the flare developed over the area of iontophoresis. Itch was scored on a visual analogue scale every 20 s for 5 min, flare areas were assessed using scanning laser Doppler imaging up to 10 min and weal was assessed by planimetry at 10 min.Results In study 1, nedocromil sodium, frusemide and bumetanide reduced itch scores by 36%, 48% and 34%, respectively, and flare areas by 17%, 26% and 15% respectively (all P<0.05). Weal areas and blood flux in the flare were unaffected. In study 2, itch scores, flare areas and weal areas were not inhibited. Also, blood flux values in areas of drug and water iontophoresis were not different.Conclusion This study has provided evidence to support the hypothesis that nedocromil sodium, frusemide and bumetanide inhibit sensory nerve activation to reduce the itch and flare responses induced by histamine in human skin in vivo. It is likely that inhibition of a Na+/K+/2Cl cotransporter in the sensory nerve membrane is a possible mechanism of action
Effects of blood flow on the in vivo recovery of a small diffusible molecule by microdialysis in human skin
No full textThe aim of this study was to investigate the impact of changes in local blood flow on the recovery of a small, diffusible molecule (sodium fluorescein) from the extravascular tissue space of the skin, by microdialysis in vivo. Loss and recovery of fluorescein by linear microdialysis probes (5-kDa molecular mass cutoff, 0.2 mm diameter) inserted 1 mm apart in pairs, at three sites in the skin of the volar surface of the forearm of healthy volunteers, was measured under conditions of basal, reduced (noradrenaline, 0.005 mg/ml), and increased (glyceryl trinitrate, patch) blood flow. Whereas loss of tracer from the delivery probe appeared unaffected by changes in local blood flow, retrieval of fluorescein by the second probe was directly related to blood flux, measured using scanning laser Doppler imaging. Steady-state recovery at vasoconstricted sites was 4.0 ± 0.7 µg · ml1 compared with 1.8 ± 0.7 µg · ml1 at control sites (p < 0.001). Local vasodilatation reduced the retrieval of fluorescein by ~50% to give a steady-state concentration of fluorescein in the dialysate at 40 to 50 min after the start of perfusion of 0.9 ± 0.3 µg · ml1 (p = 0.05). These studies in the skin are consistent with microdialysis theory. They suggest that clearance of solute by the blood will have a significant impact on microdialysis probe recovery and that, in the skin, the magnitude of this clearance is directly related to blood flow. <br/
Comparison of the effects of desloratadine and levocetirizine on histamine-induced wheal, flare and itch in human skin
No full textObjective:
A previous study showed the inhibitory effects of loratadine on histamine-induced wheal, flare and itch in human skin to be very variable between individuals. It was hypothesised that this variability may have been due to differences in the rates of metabolism of loratadine to its active form, desloratadine. This double blind, crossover study examined the effects of desloratadine in 12 healthy volunteers. Levocetirizine was used as a comparator.Methods:
Desloratadine (5 mg), levocetirizine (5 mg) or placebo was taken orally 4 h before an intradermal injection of histamine (20 l, 100 M) or vehicle control into the forearm skin. Flare areas were assessed by scanning laser Doppler imaging before and at 30 s intervals for a period of 9 min. Wheal areas were measured by planimetry at 10 min. Itch was scored every 30 s for 5 min using a visual analogue scale.Results:
Following placebo administration, the mean (± SEM) wheal area at 10 min was 79.3 ± 6.9 mm2, mean flare area for the first 5 min following challenge 26.6 ± 2.7 cm2, and itch score for the same period 48.5 ± 7.6%. The effects of desloratadine were variable between individuals, mean reductions in the wheal and flare areas being 17% (P = 0.033) and 12% (P = 0.036). Desloratadine did not reduce itch significantly. Levocetirizine was more consistent in its effects, mean reductions in wheal, flare and itch being 51%, 67% 78% respectively (all P < 0.001).Conclusions:
A single dose of 5 mg levocetirizine produced more consistent and greater inhibitory effects on histamine-induced wheal, flare and itch than did 5 mg desloratadine. The difference is suggested to reflect the basic pharmacokinetics of the two drugs
Reduced structural proteins in the conjunctival epithelium in allergic eye disease..
No full textAims: Allergic eye disease affects up to 20% of the population with varying severity. The conjunctival epithelium plays a key role in allergic eye disease. The purpose of this study was to determine whether the conjunctival epithelium is abnormal in allergic eye disease. Methods: Conjunctival biopsy samples were taken from patients with seasonal allergic conjunctivitis (SAC) 'in' and 'out of season' and nonatopic control subjects. Specimens were fixed in glycol methacrylate, 2 microm serial sections cut and Image-J used to assess the sites and areas of immuno-staining. Results: E-cadherin, CD44, keratins K5/6, K8, K13, K14, K18 and pan-keratin immuno-staining were all significantly lower in patients 'out of season' compared with normal controls. No structural differences in the epithelium were observed between the two groups. The epithelium of patients 'in season' was thicker and immuno-staining of the above markers similar to controls. Conclusions: The expression of a wide spectrum of epithelial cell adhesion proteins and cytoskeletal elements is downregulated in the conjunctiva of SAC patients 'out of season' compared with normal controls. We suggest that this could have an important impact on the ability of the epithelium to protect itself against allergen penetration, potentially influencing the development and course of allergic eye disease and offering a novel area for therapeutic control
Inhibition by glucocorticoids of the mast cell-dependent weal and flare response in human skin in vivo
No full textThis study examines the relative contributions made by inhibition of mast cell degranulation, reduction of mast cell recruitment and maturation, and lowering the responsiveness of the vasculature to histamine, in the inhibition by glucocorticoids of the weal and flare in human skin.
One forearm of healthy human volunteers was treated for 24 h (n=6) or daily for 21 days (n=10) with 0.05% clobetasol propionate. The other arm served as control. Weal and flare responses were elicited by intradermal injection of 20 l of 0.3 mM codeine. The areas of the responses were measured using scanning laser Doppler imaging. Microdialysis was used to assess histamine release. Mast cell numbers and tissue histamine content were assessed in 4-mm punch biopsies. Histamine (20 l of 1 M i.d.) was used to assess the status of the vasculature.
No significant effects were seen at 24 h. At 21 days, clobetasol reduced the areas of the codeine-induced weal and flare responses by 59 and 58% respectively (both P=0.006). Mast cell numbers were reduced by 47%, (P=0.014) and total tissue histamine content by 52% (P=0.006). Codeine-induced histamine release was reduced by 44% (P=0.022). The weal, but not the flare, induced by histamine was significantly inhibited (P=0.019). Echography revealed a 15% thinning of the skin by clobetasol.
These results demonstrate that reduction of the weal and flare responses to codeine following clobetasol treatment, results primarily from reduced mast cell numbers and tissue histamine content rather than inhibition by corticosteroids of mast cell degranulation
Comparison of the effects of levocetirizine and loratadine on histamine-induced wheal, flare, and itch in human skin
No full textBackground: This randomized, double-blind, crossover study compared the effects of the R-enantiomer of cetirizine, levocetirizine, with those of loratadine on the wheal, flare, and itch response to histamine in human skin.Methods: Levocetirizine (5 mg), loratadine (10 mg), or placebo was taken orall_y 4 h before the intradermal injection of histamine (20 µl, 100 µM) or the control vehicle into the forearm skin of healthy volunteers. Flare areas were assessed by scanning laser Doppler imaging before and at 30-s intervals for a period of 9 min. Wheal areas were measured by planimetry at 10 min. Itch was scored every 30 s with a visual analogue scale.Results: After placebo administration, the mean peak flare area was 23.01±1.94 cm2, the wheal area 248±27 mm2, and the cumulative itch score 28.8±4.6% (mean±SEM). Levocetirizine reduced the flare, wheal, and itch by 60%, 68%, and 91%, respectively (all_ P<0.001, Student's t-test for paired data). The effects of loratadine were variable and not statisticall_y significant.Conclusions: Levocetirizine (5 mg) is a potent inhibitor of the effects of histamine in human skin with an efficacy that exceeded that of loratadine (10 mg) when single doses of the drugs were administered 4 h before the test
Raised parenchymal interleukin-6 levels correlate with improved outcome after traumatic brain injury
No full textPrevious studies have suggested that an increased production of the pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) can influence patient outcome following a severe head injury. However, these studies have relied upon measurements of cytokine levels in CSF or serum, rather than the brain parenchyma itself. Recently, a method of intracranial microdialysis has been developed which permits the efficient recovery of macromolecules from the parenchyma. We have used this technique to investigate whether there is a correlation between patient outcome and parenchymally derived cytokines. Fourteen patients who were admitted to the Wessex Neurological Centre with severe head injury were selected for the study. This group of patients consisted of seven males and seven females with an age range of 21-77 years. Patients were treated according to standard protocols including emergency craniotomy where necessary. Microdialysis probes were implanted into the frontal region contralateral to the site of the primary injury. Approximately 200 micro l of dialysate was recovered every 8-12 h, and the concentrations of IL-6, IL-1beta and nerve growth factor (NGF) were determined by commercial enzyme-linked immunosorbent assays. Patients were assessed initially using the Glasgow coma score, and survivors were assessed after 6 months using the Glasgow outcome scale. Significantly (P = 0.04) higher levels of IL-6 were found in patients who survived compared with those who died. Also, there was a significant correlation between peak IL-6 levels and Glasgow outcome scores (r(2) = 0.34, P = 0.03, n = 14). The levels of IL-1beta and NGF were similar in both groups of patients. From these data, we suggest that IL-6 is an endogenous neuroprotective cytokine produced in response to severe head trauma.Abbreviations: IL-1ß= interleukin-1ß; IL-6 = interleukin-6; NGF = nerve growth factor; TBI = traumatic brain injur
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