Flare Area Research Articles

Multi-wavelength observations of a giant flare on CN Leonis

Aims. In M dwarfs, optical emission lines and continua are sensitive to changing chromospheric conditions, e.g., during flares. To study flare conditions for an observed spectrum, a comparison to synthesised spectra from model atmospheres is needed. Methods. Using the stellar atmosphere code PHOENIX, we computed a set of 41 1D NLTE parameterised chromospheric models including the photosphere and parts of the transition region. By comparison of a linear combination of the synthesised spectra and a quiescent (observed) chromosphere to observed UVES/VLT spectra of a giant flare of the M 5.5 dwarf CN Leo (Gl406), we find the best-fitting flare model chromosphere. Results. Our model spectra give a fairly good overall description of the observed continua and emission lines. In the best-fitting model, the temperature minimum is deep in the atmosphere resulting in high electron pressure for the chromospheric flaring area. The inferred chromospheric filling factor of the flare is about 3 percent, which declines during the flare. The photospheric flare filling factor is about 0.3 percent.

Validation, reproducibility and safety of trans dermal electrical stimulation in chronic pain patients and healthy volunteers.

BackgroundSurrogate pain models have been extensively tested in Normal Human Volunteers (NHV). There are few studies that examined pain models in chronic pain patients. Patients are likely to have altered pain mechanisms. It is of interest to test patient pain responses to selective pain stimuli under controlled laboratory conditions.MethodsThe Institutional Ethic Committee approved the study. 16 patients with chronic neuropathic radiculopathy and 16 healthy volunteers were enrolled to the study after obtaining informed consent. During electrical stimulation (150 minutes for volunteers and 75 minutes for patients) the following parameters were measured every 10 minutes:Ongoing pain: Visual Analogue Scale (VAS) and Numeric Rate Scale (NRS)Allodynia (soft foam brush)Hyperalgesia (von Frey monofilament 20 g)FlareFor each endpoint, the area under the curve (AUC) was estimated from the start of stimulation to the end of stimulation by the trapezoidal rule. The individual AUC values for both periods were plotted to show the inter- and intra-subject variability. For each endpoint a mixed effect model was fitted with random effect subject and fixed effect visit. The estimate of intra-subject variance and the mean value were then used to estimate the sample size of a crossover study required to have a probability of 0.80 to detect a 25% change in the mean value. Analysis was done using GenStat 8th edition.ResultsEach endpoint achieved very good reproducibility for patients and NHV. Comparison between groups revealed trends towards:Faster habituation to painful stimuli in patientsBigger areas of hyperalgesia in patientsSimilar area of allodynia and flare (no statistical significance)ConclusionThe differences demonstrated between patients and NHVs suggest that the electrical stimulation device used here may stimulate pathways that are affected in the pathological state.

Altered C-Fiber Function as an Indicator of Early Peripheral Neuropathy in Individuals With Impaired Glucose Tolerance

OBJECTIVEThis study explored the importance of glycemic burden compared with features of the metabolic syndrome in the pathogenesis of diabetic neuropathy by comparing C-fiber function in people with type 1 diabetes to that in people with impaired glucose tolerance (IGT).RESEARCH DESIGN AND METHODSThe axon reflex–elicited flare areas (LDIflares) were measured with a laser Doppler imager (LDI) in age-, height-, and BMI-matched groups with IGT (n = 14) and type 1 diabetes (n = 16) and in healthy control subjects (n = 16).RESULTSThe flare area was reduced in the IGT group compared with the control (2.78 ± 1.1 vs. 5.23 ± 1.7 cm2, P = 0.0001) and type 1 diabetic (5.16 ± 2.3 cm2, P = 0.002) groups, whereas the flare area was similar in the type 1 diabetic and control groups.CONCLUSIONSThis technique suggests that small-fiber neuropathy is a feature of IGT. The absence of similar small-fiber neuropathy in those with longstanding type 1 diabetes suggests that glycemia may not be the major determinant of small-fiber neuropathy in IGT.

Responses to Intradermal Injections of Substance P in Psoriasis Patients with Pruritus

Background: Various mediators have been suggested for the pathogenesis of pruritus in psoriasis. Methods: To investigate cutaneous responses of substance P in pruritic lesional and nonlesional areas of psoriasis patients and in healthy controls, substance P, saline and histamine were injected intradermally. After each injection, pruritus, flare and wheal were recorded. Results: There was no statistical difference in the latency period, duration, area under the curve and maximum intensity of pruritus evoked by substance P (10^–5 and 10^–6 mol/l) between psoriasis and healthy control skin. Substance P (10^–5 mol/l) induced a tendency to a greater intensity of pruritus in lesional compared to nonlesional psoriatic skin (p = 0.08). Histamine produced a shorter itch latency period (p < 0.05) and a lower maximum intensity of pruritus (p = 0.05) in lesional psoriasis skin than in healthy control skin. No significant difference in flare area was observed between the psoriasis patients and healthy controls. The histamine-induced wheal was smaller in psoriasis patients than in healthy individuals (p < 0.05). Conclusion: Intradermally injected substance P induced pruritus, flare and wheal in psoriasis patients. However, these responses did not differ significantly from those of the healthy controls.

A comparison of two formulations of intradermal capsaicin as models of neuropathic pain in healthy volunteers

To compare the dose-response relationships of two formulations [Tween- or hydroxypropyl-b-cyclodextrin (HP-b-CD)-based] of intradermal capsaicin in healthy volunteers and to assess the effect of potential covariates of response. One, 10, 30 and 100 microg in 10 ml were compared for the outcomes of flare, spontaneous pain, mechanical allodynia and hyperalgesia in eight healthy men and eight healthy women. The formulations produced comparable responses at doses 1, 10 and 30 microg, but in all parameters the response was less at 100 microg with the Tween formulation.Mean area for hyperalgesia was 9 cm(2) [95% confidence interval (CI) 5, 13] higher with the HP-beta-CD formulation. Flare area was 5 cm(2) (95% CI 8, 13) greater with the HP-beta-CD formulation. There was a significant difference between pain responses from the injection site on the upper forearm compared with the lower forearm on all four pain assessments. In contrast, significant differences were seen in pain response between nondominant and dominant arm for flare, allodynia and hyperalgesia but not for spontaneous pain. A significant difference in sex was seen only for hyperalgesia. The nominal 100-microg dose of the Tween formulation contained only 39% of label strength in the aqueous phase, which may explain the lower pharmacodynamic response. The formulations are comparable over the dose range 1-30 microg. The significantly lower pain response at the 100 microg dose in the Tween compared with the HP-beta-CD formulation is likely to be due to limitations in solubility at the 100 microg level. Given the greater ease of formulation and the superior dose-response relationship, the HP-beta-CD formulation is preferable for use in the model in future studies.

The investigation of the Neupert effect in two solar flares

The Neupert effect suggests a flare model in which the nonthermal emissions are produced by energetic electrons which heat lower corona and chromosphere to produce the thermal emissions. Based on this concept, we investigate the Neupert effect to test the correlation between the hard X-ray spectral index and the time rate of the UV flare area at 1600 or 171 Å. Using the TRACE and RHESSI observations, we explore these quantities for two solar flares, one on March 14, 2002 and the other on November 1, 2003. The negative dependence between the spectral index and the time rate of the UV flare area is found, especially during the hard X-ray sub-peaks. This finding indicates that the electron-beam-driven heating plays a prominent role in the UV emission of these two flares.

Pharmacokinetic-Pharmacodynamic Modelling of the Antihistaminic (H1) Effect of Bilastine

To model the pharmacokinetic and pharmacodynamic relationship of bilastine, a new histamine H(1) receptor antagonist, from single- and multiple-dose studies in healthy adult subjects. The pharmacokinetic model was developed from different single-dose and multiple-dose studies. In the single-dose studies, a total of 183 subjects received oral doses of bilastine 2.5, 5, 10, 20, 50, 100, 120, 160, 200 and 220 mg. In the multiple-dose studies, 127 healthy subjects received bilastine 10, 20, 40, 50, 80, 100, 140 or 200 mg/day as multiple doses during a 4-, 7- or 14-day period. The pharmacokinetic profile of bilastine was investigated using a simultaneous analysis of all concentration-time data by means of nonlinear mixed-effects modelling population pharmacokinetic software NONMEM version 6.1. Plasma concentrations were modelled according to a two-compartment open model with first-order absorption and elimination. For the pharmacodynamic analysis, the inhibitory effect of bilastine (inhibition of histamine-induced wheal and flare) was assessed on a preselected time schedule, and the predicted typical pharmacokinetic profile (based on the pharmacokinetic model previously developed) was used. An indirect response model was developed to describe the pharmacodynamic relationships between flare or wheal areas and bilastine plasma concentrations. Finally, once values of the concentration that produced 50% inhibition (IC(50)) had been estimated for wheal and flare effects, simulations were carried out to predict plasma concentrations for the doses of bilastine 5, 10 and 20 mg at steady state (72-96 hours). A non-compartmental analysis resulted in linear kinetics of bilastine in the dose range studied. Bilastine was characterized by two-compartmental kinetics with a rapid-absorption phase (first-order absorption rate constant = 1.50 h(-1)), plasma peak concentrations were observed at 1 hour following administration and the maximal response was observed at approximately 4 hours or later. Concerning the selected pharmacodynamic model to fit the data (type I indirect response model), this selection is attributable to the presence of inhibitory bilastine plasma concentrations that decrease the input response function, i.e. the production of the skin reaction. This model resulted in the best fit of wheal and flare data. The estimates (with relative standard errors expressed in percentages in parentheses) of the apparent zero-order rate constant for flare or wheal spontaneous appearance (k(in)), the first-order rate constant for flare or wheal disappearance (k(out)) and bilastine IC(50) values were 0.44 ng/mL/h (14.60%), 1.09 h(-1) (15.14%) and 5.15 ng/mL (16.16%), respectively, for wheal inhibition, and 11.10 ng/mL/h (8.48%), 1.03 h(-1) (8.35%) and 1.25 ng/mL (14.56%), respectively, for flare inhibition. The simulation results revealed that bilastine plasma concentrations do not remain over the IC(50) value throughout the inter-dose period for doses of 5 and 10 mg. However, with a dose of 20 mg of bilastine administered every 24 hours, plasma concentrations remained over the IC(50) value during the considered period for the flare effect, and up to 20 hours for the wheal effect. Pharmacokinetic and pharmacodynamic relationships of bilastine were reliably described with the use of an indirect response pharmacodynamic model; this led to an accurate prediction of the pharmacodynamic activity of bilastine.

Botulinum toxin type A reduces histamine-induced itch and vasomotor responses in human skin

Clinical evidence has revealed the antipruritic effect of botulinum toxin type A (BoNT/A). BoNT/A is believed to be effective against itch as it inhibits the release of acetylcholine as well as some other substances that may be involved in itch. To investigate the effect of subcutaneous administration of BoNT/A on experimentally histamine-induced itch in human skin. In this double-blind, placebo-controlled study, 14 healthy men (mean +/- SD age 26.3 +/- 2.6 years) received BoNT/A (Botox; Allergan, Irvine, CA, U.S.A.; 5 U) and isotonic saline on the volar surface of either forearm. Histamine prick tests were performed four times at the treatment sites (before treatment, and days 1, 3 and 7 after treatment). The itch intensity (as rated on a 0-10 visual analogue scale), itch area, neurogenic inflammation (visible flare area), blood flow (laser Doppler) and cutaneous temperature (thermographic images) were measured over the course of the trials. BoNT/A reduced the histamine-induced itch intensity (F(1,39) = 30.2, P < 0.001) and itch area (F(1,39) = 8.8, P = 0.011) compared with saline at all time points after treatment. The duration of itch was also shorter for BoNT/A-treated areas (F(1,39) = 19.4, P < 0.001), with a peak effect at day 7. The flare area was smaller in the BoNT/A-treated arm compared with the saline-treated arm at all time points after treatment (F(1,39) = 15.4, P = 0.002). Findings from blood flow (F(1,26) = 177.3, P < 0.001) and temperature measurements (F(1,26) = 27.6, P < 0.001) clearly showed the suppressive effect of BoNT/A on vasomotor reactions, with the maximal effect on days 3 and 7. BoNT/A reduced the itch intensity, blood flow and neurogenic inflammation in response to the histamine prick test in human skin. The findings could be applicable in the treatment of some pruritic conditions that can be difficult to treat with conventional treatments.

Temporal comparison of nonthermal flare emission and magnetic-flux change rates

To test the standard flare model (CSHKP-model), we measured the magnetic-flux change rate in five flare events of different GOES classes using chromospheric/photospheric observations and compared its progression with observed nonthermal flare emission. We calculated the cumulated positive and negative magnetic flux participating in the reconnection process, as well as the total reconnection flux. Finally, we investigated the relations between the total reconnection flux, the GOES class of the events, and the linear velocity of the flare-associated CMEs. Using high-cadence H-alpha and TRACE 1600 A image time-series data and MDI/SOHO magnetograms, we measured the required observables (newly brightened flare area and magnetic-field strength inside this area). RHESSI and INTEGRAL hard X-ray time profiles in nonthermal energy bands were used as observable proxies for the flare-energy release rate. We detected strong temporal correlations between the derived magnetic-flux change rate and the observed nonthermal emission of all events. The cumulated positive and negative fluxes, with flux ratios of between 0.64 and 1.35, were almost equivalent to each other. Total reconnection fluxes ranged between 1.8 x 10^21 Mx for the weakest event (GOES class B9.5) and 15.5 x 10^21 Mx for the most energetic one (GOES class X17.2). The amount of magnetic flux participating in the reconnection process was higher in more energetic events than in weaker ones. Flares with more reconnection flux were associated with faster CMEs.

Segmentation of White Matter Flaring Areas in Ultrasound Images of Very-Low-Birth-Weight Preterm Infants

In this article, we present an interactive algorithm segmenting white brain matter, visible as hyperechoic flaring areas in ultrasound (US) images of preterm infants with periventricular leukomalacia (PVL). The algorithm combines both the textural properties of pathological brain tissue and mathematical morphology operations. An initial flaring area estimate is derived from a multifeature multiclassifier tissue texture classifier. This area is refined based on the structural properties of the choroid plexus, a brain feature known to have characteristics similar to flaring. Subsequently, a combination of a morphological closing, gradient and opening by reconstruction operation determines the final flaring area boundaries. Experimental results are compared with a gold standard constructed from manual flaring area delineations of 12 medical experts. In addition, we compared our algorithm to an existing active contour method. The results show our technique agrees to the gold standard with statistical significance and outperforms the existing method in accuracy. Finally, using the flaring area as a criterion we improve the sensitivity of PVL detection up to 98% as compared with the state of the art. (E-mail: ervsteen@telin.ugent.be)

Experimental forearm immobilization in humans reduces capsaicin-induced pain and flare

In a recent study we found that 4 weeks of human experimental forearm immobilization induced hypersensitivity to mechanical and cold stimuli and a higher skin temperature on the immobilized hand. Identical findings are reported in immobilization studies in rats where increased substance P signaling is suggested to play a central role. Capsaicin releases substance P from axon collaterals in the periphery initiating vasodilatation and plasma extravasation. The effect of immobilization on capsaicin-induced responses is, however, not known. Therefore, the present study examined the effect of experimental forearm immobilization on capsaicin-induced pain and flare responses in healthy subjects. Twenty-seven human volunteers were exposed to 4 weeks of scaphoid cast immobilization of the left forearm. Before and after immobilization, skin temperature and blood flow were measured at the thumbs of both hands during 5 min of rest. Subjects then received topical capsaicin (5%) randomly on the dorsum of the right and left hands. Time to sensory detection of capsaicin and pain onset was significantly increased on the immobilized left hand. Immobilization significantly reduced capsaicin-evoked pain, neurogenic flare area, and skin blood flow (perfusion units), and the reduced capsaicin-evoked pain was significantly correlated to an increase in peripheral skin temperature but not to skin blood flow. The correlation between reduced capsaicin-evoked pain and increased skin temperature suggests an increased substance P release while the delayed onset and diminished magnitude of capsaicin-induced pain may be due to reduced penetration of capsaicin into the epidermis.

Space inhomogeneity and evolution of magnetic field in the area of weak solar flare

Space inhomogeneity and evolution of magnetic field in the area of weak solar flare

Subcutaneous Botulinum toxin type A reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin

The present human study aimed at investigating the effect of subcutaneous administration of Botulinum toxin type A (BoNT/A) on capsaicin-induced trigeminal pain, neurogenic inflammation and experimentally induced cutaneous pain modalities. Fourteen healthy males (26.3±2.6 years) were included in this double-blind and placebo-controlled trial. The subjects received subcutaneous BoNT/A (22.5U) and isotonic saline in the mirror sides of their forehead. Pain and neurogenic inflammation was induced by four intradermal injections of capsaicin (100μg/μL) (before, and days 1, 3 and 7 after treatments). The capsaicin-induced pain intensity, pain area, the area of secondary hyperalgesia, the area of visible flare and vasomotor reactions were recorded together with cutaneous heat, electrical and pressure pain thresholds. BoNT/A reduced the capsaicin-induced trigeminal pain intensity compared to saline (F=37.9, P<0.001). The perceived pain area was smaller for the BoNT/A-treated side compared to saline (F=7.8, P<0.05). BoNT/A reduced the capsaicin-induced secondary hyperalgesia (F=5.3, P<0.05) and flare area (F=10.3, P<0.01) compared to saline. BoNT/A reduced blood flow (F1,26=109.5, P<0.001) and skin temperature (F1,26=63.1, P<0.001) at the capsaicin injection sites compared to saline and its suppressive effect was maximal at days 3 and 7 (P<0.05, post hoc test). BoNT/A elevated cutaneous heat pain thresholds (F=17.1, P<0.001) compared to saline; however, no alteration was recorded for electrical or pressure pain thresholds (P>0.05). Findings from the present study suggest that BoNT/A appears to preferentially target Cfibers and probably TRPV1-receptors, block neurotransmitter release and subsequently reduce pain, neurogenic inflammation and cutaneous heat pain threshold.

Use of olopatadine ophthalmic solution and reactivity of histamine skin testing

The significant morbidity of allergic rhinitis and allergic conjunctivitis necessitates that diagnosis must be as accurate as possible. However, the very drugs used to treat allergic symptoms have been found to suppress histamine-induced skin testing, making the diagnosis very challenging. Oral formulations of antihistamines are well known to diminish skin test reactivity, but ocular application has never been studied to our knowledge. This study was performed to evaluate whether olopatadine hydrochloride 0.2% ophthalmic solution suppressed histamine-induced wheals and flares on skin-prick testing. A randomized, double-blinded, placebo-controlled, single-center, cross-over pilot study was performed that compared histamine-induced wheal and flare areas after 7-10 days of treatment with both olopatadine 0.2% ophthalmic solution and artificial tears, allowing for a 7- to 10-day washout period between medications. From a total of 24 patients randomized, 21 subjects completed the study, 86% of whom were female. There were no statistically significant differences among both the wheal and the flare areas when comparing treatment with olopatadine and placebo, under the 5% significance level. Although characterized by a small sample size and a preponderance of female subjects, our data suggest that olopatadine does not suppress wheal and flare areas during allergy testing, and discontinuation in preparation for skin-prick testing does not appear to be necessary.

Ultraviolet-B induced inflammation of human skin: Characterisation and comparison with traditional models of hyperlagesia

The effect on human skin of over-exposure to solar ultraviolet radiation (UVR) has been well described. The erythema produced is commonly referred to as ‘sunburn’. Recently UVR induced inflammation has been utilised as a human model of sub-acute pain. Our aim was to characterise the sensory phenotype of UVB inflammation in human volunteers. We delivered UVB to small areas of volar forearm skin in healthy volunteers and found that the degree of inflammation and concomitant increase in sensitivity to cutaneous stimuli were UVB dose and time dependant. We directly compared UVB induced inflammation and the more established thermal burn and topical capsaicin pain models. UVB inflammation produced precisely demarcated erythematous lesions without secondary flare. Both thermal burns and topical capsaicin produced large areas of flare, indistinguishable in character from the primary lesions. Moreover, UVB inflammation induced large reductions in mechanical pain threshold restricted to the primary lesion site, whereas the more established inflammatory pain models produced not only primary hypersensitivity but also significant areas of secondary mechanical hypersensitivity. Taken together these findings suggest that UVB inflammation, at least using moderate doses produces sensory changes primarily by sensitising peripheral pain processing in the relative absence of alterations in central pain processing.

Lack of Analgesia by Oral Standardized Cannabis Extract on Acute Inflammatory Pain and Hyperalgesia in Volunteers

Cannabinoid-induced analgesia was shown in animal studies of acute inflammatory and neuropathic pain. In humans, controlled clinical trials with Delta-tetrahydrocannabinol or other cannabinoids demonstrated analgesic efficacy in chronic pain syndromes, whereas the data in acute pain were less conclusive. Therefore, the aim of this study was to investigate the effects of oral cannabis extract in two different human models of acute inflammatory pain and hyperalgesia. The authors conducted a double-blind, crossover study in 18 healthy female volunteers. Capsules containing Delta-tetrahydrocannabinol-standardized cannabis extract or active placebo were orally administered. A circular sunburn spot was induced at one upper leg. Heat and electrical pain thresholds were determined at the erythema, the area of secondary hyperalgesia, and the contralateral leg. Intradermal capsaicin-evoked pain and areas of flare and secondary hyperalgesia were measured. Primary outcome parameters were heat pain thresholds in the sunburn erythema and the capsaicin-evoked area of secondary hyperalgesia. Secondary measures were electrical pain thresholds, sunburn-induced secondary hyperalgesia, and capsaicin-induced pain. Cannabis extract did not affect heat pain thresholds in the sunburn model. Electrical thresholds (250 Hz) were significantly lower compared with baseline and placebo. In the capsaicin model, the area of secondary hyperalgesia, flare, and spontaneous pain were not altered. To conclude, no analgesic or antihyperalgesic activity of cannabis extract was found in the experiments. Moreover, the results even point to the development of a hyperalgesic state under cannabinoids. Together with previous data, the current results suggest that cannabinoids are not effective analgesics for the treatment of acute nociceptive pain in humans.

Effects of botulinum toxin type A on histamine-induced itch and vasomotor responses in human skin

Clinical evidences reveal the anti-pruritic effect of Botulinum toxin type A (BoNT/A). BoNT/A inhibits the release of acetylcholine as well as some other substances, which may be involved in pruritus. The present study investigated the effect of subcutaneous administration of BoNT/A on experimentally induced itch by histamine in human skin. Fourteen healthy male volunteers (26.3±2.6 years) received BoNT/A (5 U, BOTOX ® , Allergan, US) and isotonic saline in the volar surface of either forearm. Histamine-prick tests were performed 4 times at the treatment sites (before, day 1, day 3 and week 1 after treatments). The itch intensity (VAS0-10) and neurogenic inflammation were measured and the effect of treatments over trials was assessed by repeated ANOVA. BOTOX ® significantly reduced the histamine-induced itch intensity ( F 1,39 =30.2, P <0.001) compared to saline. Flare area was smaller in BOTOX ® -treated arm compared to saline ( F 1,39 =15.4, P =0.002). Findings from laser Doppler assessed blood flow ( F 1,26 =177.3, P <0.001) and thermo-images ( F 1,26 =27.6, P <0.001) clearly showed the suppressive effect of BOTOX ® on histamine-induced vasomotor reactions compared to saline. BoNT/A reduced itch intensity and neurogenic inflammation to histamine-prick test in human skin. The findings can be applicable in future treatments of some pruritic conditions.

Solar Flare Geometries. I. The Area Fractal Dimension

In this study we investigate for the first time the fractal dimension of solar flares and find that the flare area observed in EUV wavelengths exhibits a fractal scaling. We measure the area fractal dimension D2, also called the Hausdorff dimension, with a box-counting method, which describes the fractal area as A(L) ∝ LD2. We apply the fractal analysis to a statistical sample of 20 GOES X- and M-class flares, including the Bastille Day 2000 July 14 flare, one of the largest flares ever recorded. We find that the fractal area (normalized by the time-integrated flare area Af) varies from near zero at the beginning of the flare to a maximum of A(t)/Af = 0.65 ± 0.12 after the peak time of the flare, which corresponds to an area fractal dimension in the range of 1.0 D2(t) 1.89 ± 0.05. We find that the total EUV flux Ftot(t) is linearly correlated with the fractal area A(t) . From the area fractal dimension D2, the volume fractal dimension D3 can be inferred (subject of Paper II), which is crucial to inferring a realistic volume filling factor, which affects the derived electron densities, thermal energies, and cooling times of solar and stellar flares.

Allergy Skin Test Responses During Experimental Infection With Respiratory Syncytial Virus

Skoner DP, Gentile DA, Angelini B, Doyle WJ. Ann Allergy Asthma Immunol. 2006;96:834–839 PURPOSE OF THE STUDY. To determine if a viral upper respiratory infection affects allergy skin-test responsiveness. STUDY POPULATION. Sixteen adults experimentally exposed to respiratory syncytial virus (RSV). METHODS. Subjects without concurrent upper or lower airway disease were cloistered and inoculated with 106 plaque-forming units of RSV type B. Daily physical examination and symptom scores were recorded. Nasal lavages were performed and stored at −70°C for RSV-antigen assay and culture. Blood samples were obtained for immunoglobulin E (IgE) measurement on days 0, 2, 4, 6, 8, 10, and 21. Skin-prick testing was performed for 17 locally relevant aeroallergens and controls on days 0, 3, 6, and 21. RESULTS. Eight patients had ≥1 positive skin-test result at baseline and were considered atopic. Eleven (5 atopic, 6 nonatopic) had evidence of postinoculation RSV infection. Atopic patients had a higher IgE level at baseline as compared with nonatopic subjects (123 ± 80 vs 45 ± 36 IU/mL; P &amp;lt; .01). There was no change in total IgE level in those in the nonatopic group, but the atopic subjects had a nonsignificant increase in IgE level on days 8 and 10 (146 ± 112 IU/mL). Of the 8 nonatopic patients, only 3 had negative skin-test results to all antigens on all 3 postinoculation test days. The mean number of positive wheal responses to allergens for all patients was 1.7 ± 2.3, 4.4 ± 3.8, 3.6 ± 3.5, and 3.9 ± 3.6 at baseline and days 3, 6, and 21, respectively (P &amp;lt; .01 versus baseline for all pairings). For patients with positive skin-test results at baseline, mean wheal and flare area provoked by those allergens increased after RSV exposure. The increased number of positive responses to skin testing was noted for both seasonal and perennial aeroallergens. CONCLUSIONS. The results may have some implication in explaining complications of RSV infection such as otitis media, asthma exacerbation, and subsequent development of asthma. REVIEWER COMMENTS. There has long been a chicken-and-egg question when it comes to RSV infection in childhood and subsequent development of asthma. That is, does RSV predispose to later recurrent wheezing illnesses, or does the predisposition to wheeze lead to worse outcomes with RSV infection? Are children with an atopic predisposition more likely to have a severe RSV infection, or are those with severe infection more likely to develop atopy? This small study did not answer the question, but it provides a hint that RSV infection itself might affect immunologic responsiveness to aeroallergens, at least in the short-term. The study results cannot be extrapolated to make any long-term conclusions. Furthermore, the study was undertaken in healthy adults. It would be unethical to intentionally infect infants and toddlers with RSV at an age when they might be most susceptible to the risks of environmental influences on the development of atopy and to the risks of the infection itself.

Heritability of responses to painful stimuli in women: a classical twin study

There is as yet no conclusive evidence for the heritability of pain sensitivity in humans. We performed a classical twin study to evaluate the relative contributions of genetic and environmental factors on responses to painful stimuli in women. Ninety-eight pairs of twins, 51 monozygotic (MZ) and 47 dizygotic (DZ), were recruited from the TwinsUK adult registry held at St Thomas' Hospital, London. The correlation of quantitative sensory testing scores for the different responses to painful stimuli were compared between the MZ and DZ twin pairs and structural equation modelling was used to provide an estimate of the heritability. Statistically significant genetic components (varying between 22 and 55%) were seen for the responses to the majority of painful stimuli including: heat pain threshold (HPT), the pain rating during induction of a thermal burn, the secondary areas of punctate hyperalgesia and brush evoked allodynia following the induction of a 45 degrees C thermal burn, and the pain ratings during the iontophoresis of adenosine triphosphate (ATP) and acid. The area of skin flare following thermal burn induction did not have a significant genetic component; rather common environmental factors provided the greatest contribution (65%). In our experiment neither shared genetic nor environmental features were significant in determining the extent of thermal sensitisation. In summary we show that sensitivity to a variety of experimental thermal, mechanical and chemical pain-producing stimuli has a genetic contribution. Our study demonstrates the importance of genetic factors in determining human experimental pain sensitivity, and opens the way for its use as a phenotype in gene discovery. Since experimental pain sensitivity is known to be a predictor for pathological pain, our data imply that genetic factors have an important aetiological contribution towards clinical pain states.