Gastric myoelectrical and neurohormonal changes associated with nausea during tilt-induced syncope.

BACKGROUND: Nausea is a common prodromal symptom of neurally mediated syncope, but the biological factors linking nausea with syncope have not been studied. We aimed to characterize nausea during tilt-induced syncope by exploring related changes in gastric myoelectrical activity and plasma epinephrine, norepinephrine, and vasopressin concentrations across study phases of recumbency, tilt, syncope, and recovery. METHODS: Electrogastrographic and plasma hormone changes were compared between patients with tilt-induced syncope and nausea (n = 18) and control subjects (n = 6) without symptoms or hemodynamic changes during tilt-table testing. KEY RESULTS: Over a 4-minute period preceding syncope, sequential electrogastrography epochs demonstrated an increase over time in bradygastria (P = .003) and tachygastria (P = .014) power ratios, while the dominant frequency (P < .001) and the percent normogastria (P = .004) decreased. Syncope led to significant differences between cases and controls in electrogastrographic power ratios in each frequency range: bradygastria (P = .001), tachygastria (P = .005), and normogastria (P = .03). Nausea always followed electrogastrographic changes, and nausea resolution always preceded electrogastrographic normalization. Plasma vasopressin (676.5 ± 122.8 vs 91.2 ± 15.3 pg/mL, P = .012) and epinephrine (434 ± 91.3 vs 48.7 ± 2.5 pg/mL, P = .03), but not norepinephrine (P > .05), also differed with syncope between cases and controls. CONCLUSIONS AND INFERENCES: The nausea related to tilt-induced syncope is temporally associated with changes in gastric myoelectrical activity and increases in plasma vasopressin and epinephrine. The biological mechanisms that induce syncope are physiologically distinct from other experimental models of nausea such as illusory self-motion, yet nausea with syncope appears to have similarly associated electrogastrographic and hormone changes. Thus, tilt-induced syncope could serve as an informative experimental model for nausea research.

Seasonal Variation in Emergency Department Visits Among Pediatric Headache Patients.

OBJECTIVE: To ascertain whether seasonal variation occurs in emergency department (ED) visits for headache among children and adolescents. METHODS: A retrospective review was conducted using the electronic medical records of ED visits for headache at a tertiary children's hospital through calendar years 2010-2014. Using ICD-9 diagnostic codes for headache and migraine, the numbers of headache visits were determined and compared by season and during school months vs summer months. RESULTS: A total of 6572 headache visits occurred. Headache visits increased during the fall season (133 ± 27 visits per month) compared with other seasons (101 ± 19 visits per month), P ≤ .002, but did not differ when comparing school months (113 ± 25 visits per month) and summer months (100 ± 24 visits per month), P = .1. CONCLUSIONS: The corresponding increase in ED visits during the fall season coincides with the start of the school year. Academic stressors and the change in daily schedule may lead to more headaches and more ED headache visits among school-aged youth.

Visualization of High-Dimensional Point Clouds Using Their Density Distribution's Topology.

We present a novel method to visualize multidimensional point clouds. While conventional visualization techniques, like scatterplot matrices or parallel coordinates, have issues with either overplotting of entities or handling many dimensions, we abstract the data using topological methods before presenting it. We assume the input points to be samples of a random variable with a high-dimensional probability distribution which we approximate using kernel density estimates on a suitably reconstructed mesh. From the resulting scalar field we extract the join tree and present it as a topological landscape, a visualization metaphor that utilizes the human capability of understanding natural terrains. In this landscape, dense clusters of points show up as hills. The nesting of hills indicates the nesting of clusters. We augment the landscape with the data points to allow selection and inspection of single points and point sets. We also present optimizations to make our algorithm applicable to large data sets and to allow interactive adaption of our visualization to the kernel window width used in the density estimation.

A prospective study of PHACE syndrome in infantile hemangiomas: demographic features, clinical findings, and complications.

PHACE (OMIM no. 606519) is a neurocutaneous syndrome that refers to the association of large, plaque-like, "segmental" hemangiomas of the face, with one or more of the following anomalies: posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral developmental defects, specifically sternal defects and/or supraumbilical raphe. The etiology and pathogenesis of PHACE is unknown, and potential risk factors for the syndrome have not been systematically studied. The purpose of this study was thus to determine (1) the incidence of PHACE and associated anomalies among a large cohort of hemangioma patients, (2) whether certain demographic, prenatal or perinatal risk factors predispose infants to this syndrome, and (3) whether the cutaneous distribution of the hemangioma can be correlated to the types of anomalies present. We undertook a prospective, cohort study of 1,096 children with hemangiomas, 25 of whom met criteria for PHACE. These 25 patients represented 20% of infants with segmental facial hemangiomas. Compared to previous reports, our PHACE patients had a higher incidence of cerebrovascular and cardiovascular anomalies. Two developed acute arterial ischemic stroke during infancy, while two with cardiovascular anomalies showed documented evidence of normalization, suggesting that both progressive and regressive vascular phenomena may occur in this syndrome. Correlation to the anatomic location of the hemangioma appears to be helpful in determining which structural abnormalities might be present. A comparison of demographic and perinatal data between our PHACE cases and the hemangioma cohort overall showed no major differences, except a trend for PHACE infants to be of slighter higher gestational age and born to slightly older mothers. Eighty-eight percent were female, a finding which has been noted in multiple other reports. Further research is needed to determine possible etiologies, optimal evaluation, and outcomes.

Painful stimuli evoke itch in patients with chronic pruritus: central sensitization for itch.

BACKGROUND: Central sensitization for pain is important for patients with chronic pain. The authors investigated a possible role of central sensitization for itch in patients with chronic pruritus. METHODS: Noxious stimuli were applied in lesional and visually nonlesional skin areas of 25 patients with atopic dermatitis, in lesional skin areas of 9 patients with psoriasis vulgaris, and in 20 healthy subjects. The stimuli included mechanical pinpricks, electrical stimuli, contact heat, and injection of low-pH solution. Intensities of itch and pain were assessed separately on a numeric rating scale. RESULTS: All the noxious stimuli primarily evoked pain in control subjects and patients with psoriasis vulgaris. In patients with atopic dermatitis, however, itch was evoked instead of burning pain. In their lesional skin, itch was the predominant sensation. Chemical stimuli evoked intense itch in lesional and visually healthy skin areas (the area under the curve of itch rating compared with the control, mean +/- SEM, 668 +/- 166 and 625 +/- 192 vs 38 +/- 23; p < 0.001; p < 0.01). Chemically induced itch also was observed in healthy subjects after a conditioning histamine stimulus of 15 minutes, but not after a conditioning histamine stimulus of 2 minutes. CONCLUSION: The chronic barrage of pruriceptive input may elicit central sensitization for itch so that nociceptive input no longer inhibits itch but on the contrary is perceived as itch. In contrast to the well-known A-fiber-mediated alloknesis and hyperknesis, this type of central sensitization appears to be elicited by C-nociceptors.

Efficacy of naltrexone on acetylcholine-induced alloknesis in atopic eczema.

Atopic eczema (AE) is a chronically pruritic inflammatory skin disease. Although the mediators and exact mechanisms eliciting and sustaining pruritus are not completely known, AE patients in clinical trials have been shown to benefit under treatment with morphine antagonists. Naltrexone (NAL) is a relatively pure morphine antagonist that blocks the effects of opioids twice as much as naloxone. NAL exhibits minimal pharmacological activity and displaces endorphines at mu- and kappa-receptors without its own intrinsic activity. NAL's excellent oral bioavailability and linear increases in the area under plasma concentration-time curve make it ideal for use in experimental studies. We designed our present experiments similar to former experiments evaluating both peripheral cutaneous sensations and central itch procession in order to gain more information about the possible distribution of opioid receptors and their involvement in the pathophysiology of pruritus. Eleven AE patients participated in our double-blind study. Either 25 mg of NAL (Nemexin) or a placebo (PLA) was given to the participants 60 min prior to the acetylcholine (ACH) injection [intracutaneous (i.c.) injection of 0.02 ml of 0.55 M]. A PLA stimulus with buffered saline served as control on the opposite forearm. We used laser Doppler flowmetry to measure the vasomotoric changes after ACH injection and recorded the duration and intensity of itch with a visual analogue scale (VAS). Following the evaluation of wheal and flare sensation, we obtained the area of itchy skin around the injection site (alloknesis) by gently stroking the surrounding skin with a brush in the centripetal direction towards the injection site. The results were planimetrically evaluated. Oral NAL reduced the perifocal itch significantly (P < 0.009). In four of our observations the area of alloknesis completely disappeared. Itch duration was reduced by 20 s and the intensity of itch was diminished, yet not significantly. NAL had no significant effects on cholinergic vasoreactions measured by the laser Doppler (P > 0.50) and especially failed to decrease the initial flux response, which is a typical sign of an altered vascular reaction (P > 0.25). The decrease of wheal (P = 0.008) and flare (P = 0.01) extension indicates an appropriate dosage of our treatment for this experiment. The most significant effects of NAL were observed in parameters of itch processing such as alloknesis (P = 0.009) and flare extension (P = 0.01). Therefore we favour the concept that NAL might have a stronger impact on central nervous mechanisms than on peripheral nociceptive structures.

Incidence, predictors, and significance of abnormal cardiac enzyme rise in patients treated with bypass surgery in the arterial revascularization therapies study (ARTS).

BACKGROUND: Although it has been suggested that elevation of CK-MB after percutaneous coronary intervention is associated with adverse clinical outcomes, limited data are available in the setting of coronary bypass grafting. The aim of the present study was to determine the incidence, predictors, and prognostic significance of CK-MB elevation following multivessel coronary bypass grafting (CABG). METHODS AND RESULTS: The population comprises 496 patients with multivessel coronary disease assigned to CABG in the Arterial Revascularization Therapies Study (ARTS). CK-MB was prospectively measured at 6, 12, and 18 hours after the procedure. Thirty-day and 1-year clinical follow-up were performed. Abnormal CK-MB elevation occurred in 61.9% of the patients. Patients with increased cardiac-enzyme levels after CABG were at increased risk of both death and repeat myocardial infarction within the first 30 days (P=0.001). CK-MB elevation was also independently related to late adverse outcome (P=0.009, OR=0.64). CONCLUSIONS: Increased concentrations of CK-MB, which are often dismissed as inconsequential in the setting of multivessel CABG, appear to occur very frequently and are associated with a significant increase in both repeat myocardial infarction and death beyond the immediate perioperative period.

Arterial access site closure with a novel sealing device: Duett.

Management of arterial access sites following percutaneous endovascular procedures is associated with patient discomfort and local complications. A new vascular sealing device, comprised of a balloon delivery catheter and a flowable procoagulant consisting of thrombin and collagen, was tested. Immediately following catheterization 200 patients (age, 66.1 +/- 11.2 years) were treated with the sealing device (Duett). Of these 200 patients, 132 underwent diagnostic catheterization, 67 underwent percutaneous transluminal coronary angioplasty, and one underwent percutaneous transluminal angioplasty. The sheath sizes included 2-5 Fr, 166-6 Fr, 25-7 Fr and 7-8 Fr. All patients undergoing diagnostic procedures received at least 5,000 U of intravenous heparin during the procedure. The Duett was used successfully in 198/200 (99%) patients immediately following completion of the endovascular procedure. In two patients a device malfunction resulted in uncomplicated crossover to manual compression. The time to hemostasis ranged from 3 to 5 minutes. All patients were walking 2 to 5 hours following the procedure unless a complication had occurred. No patient experienced leg ischemia, required surgical repair of the arterial access site, or had an infection at the site. In three patients (1.5%), a pseudoaneurysm occurred and was successfully treated with ultrasound-guided compression and three patients received a blood transfusion. No late complications were observed following hospital discharge. This novel vascular sealing device successfully achieves rapid hemostasis and allows early ambulation following percutaneous endovascular procedures with a low incidence of complications.

Doxepin affects acetylcholine induced cutaneous reactions in atopic eczema.

BACKGROUND: Atopic eczema (AE) is a chronic inflammatory skin disease with strong itching as the prominent symptom. The pathology of itch is still in discussion, but acetylcholine (ACH) seems to be a relevant pruritogenic mediator in AE. Since efficient benefit on pruritus and excoriations has been demonstrated with tricyclic agents, we investigated how the topical treatment with doxepin (5%, Boehringer Standard, Mannheim, Germany), a tricyclic compound with anticholinergic properties, may influence ACH induced itch and cutaneous sensations (erythema, wheal, axonreflex flare). METHODS: Eleven patients with AE were included in this double blind study. For 3 days we applied doxepin cream to a defined area on the volar forearm and basic ointment to the other side 4 times daily. On day 4, ACH and sodium chloride were i.c. injected into the pretreated arms. Vasoreactions and cutaneous sensations were measured similar to studies described in previous publications from our group. RESULTS: Doxepin treatment over 3 days reduced ACH provoked flare size more than 53% (P<0.005) and wheal size about 48% (P<0.005) whereas the maximal antipruritic effect was similiar to the basic therapy. The itch intensity, which is expressed as the mean AUC value, was rated at 6.12 arbitrary units after the neutral cream application and 5.9 arbitrary units after doxepin. CONCLUSIONS: The clinical and experimental effectiveness of doxepin as an antipruritic drug has been known for years. However, studies focusing on ACH as a pruritogenic mediator have not been performed. The duration of the doxepin application in our study seems to be appropriate since flare and wheal development were diminished. The reason why doxepin did not develop more antipruritic action compared to the vehicle cream may be due to the fact that the doxepin free cream already possessed an antipruritic action in this experimental study design. This is probably caused by rehydrating and moisturizing effects.

Mast cell mediators other than histamine induce pruritus in atopic dermatitis patients: a dermal microdialysis study.

While histamine is the crucial mediator of pruritus in type 1 allergic reactions, its role in atopic dermatitis (AD) is unclear. In this study, the role of mast cell mediators in protein extravasation and pruritus was evaluated using intradermal microdialysis. The microdialysis capillaries were used to apply the mast cell degranulating substance compound 48/80 (C48/80; 0.05%) or histamine (0.01%) and also to deliver H1-blockers (cetirizine, 200 microg mL-1) in nine AD patients and nine controls. Large pore size membranes (3000 kDa) enabled simultaneous analysis of protein extravasation. Itch sensation was measured psychophysically and weal and flare reaction were evaluated planimetrically. Protein extravasation induced by histamine and C48/80 was significantly reduced in AD patients. Blockade of H1-receptors by cetirizine significantly reduced C48/80-induced protein extravasation in AD patients and controls to an identical level. C48/80-induced pruritus was abolished by cetirizine in controls, whereas pruritus in AD patients was unchanged after H1 blockade. We conclude that mast cell mediators others than histamine are involved in C48/80-induced pruritus in AD patients. Whether the reduced capacity of AD patients to induce protein extravasation is of pathophysiological relevance for pruritus remains to be established.

Short- and long-term outcomes of Wiktor stent implantation at low versus high pressures. Austrian Wiktor Stent Study Group.

A prospective, randomized, multicenter trial was conducted to evaluate whether high-pressure postdilation of the Wiktor stent provides short- and long-term benefits compared with the conventional low-pressure implantation technique. From June 1995 through May 1996, 181 patients were randomly assigned to either low-pressure (6 to 12 atm, group A, n = 94) Wiktor stent placement or to high-pressure postdilation (> or = 13 atm, group B, n = 87) after stent deployment. All patients were followed up clinically for 7 +/- 3 months, with an angiographic follow-up in 154 patients (85%). After stent implantation, neither minimal lumen diameter (MLD) nor percent diameter stenosis (%DS) differed significantly between the 2 groups (MLD, 2.8 +/- 0.5 vs 2.9 +/- 0.5 mm; %DS, 17 +/- 8% vs 16 +/- 9% for groups A and B, respectively). However, a trend toward a larger mean lumen diameter within the stent was observed in group B (3.3 +/- 0.6 vs 3.5 +/- 0.5 mm for groups A and B, respectively; difference between means 0.14 mm, 95% confidence interval -0.01 to 0.29, p = 0.08). Angiographic follow-up revealed similar MLD and %DS in both treatment groups (MLD, 2.1 +/- 0.7 vs 2.2 +/- 0.8 mm; %DS, 31 +/- 17% vs 30 +/- 24% for groups A and B, respectively, p = NS). Acute stent thrombosis occurred in 2 patients (1%) (1 patient in each group), and subacute thrombosis in 1 patient (0.6%) in group A. There was 1 death in group A, and target lesion restenosis (> or = 50% DS) was observed in 15% of patients with no differences between the groups. In conclusion, this study demonstrated favorable short- and long-term results of Wiktor stent implantation. Despite a trend toward additional initial lumen gain by high-pressure postdilation, this did not translate into a measurable improvement in long-term outcome.

Administration of acetylcholine and vasoactive intestinal polypeptide to atopic eczema patients.

Responses to acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) were investigated in atopic eczema (AE) patients. To elucidate the involvement of histamine to ACh-provoked vasoreactions and sensations, we applied a selective H1-antagonist (cetirizine) 3 h prior to the ACh-administration. Solutions of acetylcholine (ACh, 0.55 M) and vasoactive intestinal polypeptide (VIP, 1.5x 10(-5) M) were injected (10 microl) intracutaneously into the volar forearm of 14 healthy subjects and 14 atopic eczema (AE) patients. The substances were applied as single stimulus as well as in combination. Sensations evoked by the stimulation were recorded using 2 visual analog scales (VAS). Vasoreactions were analyzed with the new technique of computer assisted video image analysis. With this method we measured the dynamics of the flare development and the extension of the final flare size independent of the observer's assessment. In control subjects the development and extension of the final flare size was almost similar, regardless whether ACh and VIP were applied in combination or separately. Compared to healthy controls, after injection of ACh, VIP and the combination of VIP and ACh smaller flare sizes were recorded in AE patients. After VIP was given, the control subjects reported pruritus, which was significantly augmented compared to AE patients. In contrast, controls reported a burning pain after the injection of ACh, whereas AE patients felt predominantly pruritus. Itch sensation after the combined application of VIP and ACh was significantly elevated in AE patients. Consequently, we assume that mediators of sudomotor neurons, i.e., VIP and ACh meet in AE patients apparently sensitized nociceptive primary afferents and induce exaggerated itch, pain and flare responses. When pretreated with the selective H1-antagonist cetirizine before ACh was injected, pain and erythema due to ACh was diminished in healthy controls. In contrast, cetirizine did not influence the size of erythema and the magnitude of sensation in AE patients. We conclude, that the release of histamine is not involved in ACh-induced erythema and pruritus in AE. These data provide evidence that pruritus can be elicited in atopic eczema by a cholinergic, histamine independent mechanism.

Recent studies of cutaneous nociception in atopic and non-atopic subjects.

Itching reflects a distinct quality of cutaneous nociception elicited by chemical or other stimuli to neuronal receptors at the superficial layers of the skin and muco-cutaneous orifices. Although recent experimental studies of the conduction and perception of itch have yielded deeper insight into the physiology of this sensory quality, little is known about the neuromechanisms involved in pruritus accompanying many inflammatory skin diseases, in particular, in atopic eczema. Previous case-control studies of our research group with patients suffering from atopic eczema (AE) revealed significantly diminished itch perception after iontophoretic application of different doses of histamine as well as substance P (i.c. injected). Further experiments using acetylcholine (ACh, i.c.) clearly demonstrated that ACh elicits pruritus instead of pain in patients with AE. The first part of the present review deals with the results of our most recent case-control studies on histamine-induced itch perception in atopics devoid of eczema as well as in patients with urticaria or psoriasis compared to atopics with or without manifest eczema. We demonstrated that both focal itch and perifocal alloknesis (i.e., itch elicited by a slight mechanical, otherwise non-itching stimulus) were significantly reduced in eczema-free atopics yet were normal in non-atopics suffering from urticaria or psoriasis. In further studies using ACh i.c. injected into the uninvolved skin of patients with AE, lichen ruber, psoriasis, type IV contact eczema, or non-specific nummular eczema (n = 10/each group), all the atopics and 6/10 psoriatics felt itch instead of burning pain, but none of the others did. Different doses of vasoactive intestinal peptide (VIP) i.c. applied to the controls and the atopics with or without eczema did not markedly increase the intensity of nociceptive sensations. However, ACh induced pain in the controls, pure pruritus in the atopics with acute eczema, and a 'mixture' of pain and itch in the atopics just free from eczema. Obviously, the quality of sensations evoked by ACh and VIP depends on the inflammatory or non-inflammatory state of the atopic skin. In a placebo-controlled, double blind study on histamine-induced focal itch and alloknesis with healthy subjects (n = 15) using naltrexone (opioid receptor antagonist) and cetirizine (H1-blocking agent), naltrexone was found to significantly reduce both itching and alloknesis. Cetirizine reduced focal itch but failed to influence the alloknesis phenomenon. The wheal and flare reaction was suppressed only by cetirizine. These different effects point to a mainly CNS-based activity of naltrexone but a peripheral level effect of cetirizine. Due to long-lasting experience with group sport as a supporting adjuvant for inpatients with AE, we evaluated, by clinical, psychometric, and physiological studies, the therapeutic efficacy of controlled physical exercise in addition to otherwise equal anti-eczematous therapy for both voluntary participants and non-participants in sports by performing several case-control studies, one followed-up to 6 months after the patients' discharge from the hospital. Regular moderate exercises neither deteriorated nor impeded the recovery from AE, ameliorated the participants' scratch controlling ability and significantly their depressed emotional mood. The non-participants failed to achieve these aims. Sweating-induced itch was inhibited in almost all participants if simple skin care (clearing by warm shower, ointment) and short-term rest were used by informed patients. In conclusion, there are several indications that itching is elicited in individuals inclined to cutaneous atopy, regardless of their eczematous or just eczema-free state, by a different physiological pathway from that in non-atopic individuals. Therefore, antipruritic agents influencing the centrally altered nociception of atopics are needed and may be expected in near future. (ABSTRACT TRUNCATED)

Effect of topical capsaicin on the cutaneous reactions and itching to histamine in atopic eczema compared to healthy skin.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is thought to produce analgesic and possibly also antipruritic effects when applied topically. Capsaicin 0.05% was applied three times daily over a 5-day period to the same infrascapular region. The effects of the pretreatment upon the pruritogenic and wheal and flare reactions to subsequent histamine iontophoresis (20 mC) were evaluated on the following day. The antipruritic effects of the pretreatment were compared with the effects of placebo pretreatment and no pretreatment. Wheal and flare areas were evaluated planimetrically. Itch or pain were rated every minute over a 24-min period. The areas of alloknesis, i.e. the induction of perifocal itch sensation by usually nonitching (e.g. mechanical) stimuli, were also evaluated. In control subjects, but not in atopic eczema (AE) patients, capsaicin pretreatment significantly reduced the flare area. Compared with control subjects, AE patients showed a lack of alloknesis or significantly smaller areas of alloknesis in pretreated and nonpretreated skin. In control subjects, capsaicin pretreatment significantly reduced itch sensations compared with nonpretreated skin, whereas in AE patients no differences were seen. Itch sensations in capsaicin-pretreated skin were significantly lower in control subjects than in AE patients. We conclude that capsaicin does effectively suppress histamine-induced itching in healthy skin but has less effect in AE. The diminished itch sensations and the absence of alloknesis in atopic individuals indicate that histamine is not the key factor in itching in AE.

Cutaneous reactions and sensations after intracutaneous injection of vasoactive intestinal polypeptide and acetylcholine in atopic eczema patients and healthy controls.

We analysed vasoreactions and sensations of atopic eczema (AE) patients and healthy controls after intracutaneous (i.c.) injection of vasoactive intestinal polypeptide (VIP) and acetylcholine (ACh). Blood flow was measured by laser Doppler flowmetry (LDF). Plasma extravasation and flare size were evaluated planimetrically, and sensations were recorded using visual analog scales. Three groups of subjects (controls, AE patients suffering from acute eczema and AE patients during a symptom-free period) were investigated. We administered VIP separately at concentrations of 1.5 x 10(-7), 1.5 x 10(-6) and 1.5 x 10(-5) M and in combination with ACh (5.5 x 10(-6) M) into the volar forearm of the subjects. Both substances led to an increase in LDF measurements and induced a wheal and flare reaction. Blood flow was elevated as a function of dose after a single VIP application in all groups. Compared with healthy controls, a significant increase in blood flow was measured after combined VIP and ACh administration in AE patients suffering from acute AE, whereas flare area and plasma extravasation were significantly reduced after single VIP and combined VIP and ACh injections, respectively. In all groups, VIP induced dose-dependent pruritus. Compared with a control stimulus (0.9% sodium chloride and ACh), combined injections of VIP and ACh had no additional effect on the magnitude of the sensation. In AE patients, the intensity was similar to that experienced by the control subjects, but the quality of sensation was different: ACh induced pain in the control subjects, pruritus in AE patients, and a mixture of pain and itching in AE patients showing no symptoms. Our results suggest that VIP- and ACh-induced skin reactions and the quality of the sensations depend on the activity of the atopic eczema. Confirming our former studies, AE patients develop a different quality of sensation after ACh administration and also after administration of VIP combined with ACh. Therefore, we suggest that ACh might be involved in the pathomechanisms of pruritus in AE.

[Dose-dependent pellagroid skin reaction caused by carbamazepine]. / Dosisabhängige pellagroide Hautreaktion durch Carbamazepin.

A 11-year-old girl suffering from grand mal epilepsy underwent antiepileptic therapy with carbamazepine (600 mg/daily). Two weeks after increasing the dose (900 mg/day) she suddenly developed relatively sharply limited, sunburn-like brown reddish macular lesions with central scaling and partly hyperkeratotic areas on the hands, feet, face, knees, gluteal and axillar regions. Otherwise no health disorders were found; in particular no neurological or gastrointestinal symptoms occurred. After reduction of the doses (450 mg/day) these skin lesions faded away. With exception of elevated serum levels of carbamazepine, nicotinamide and vitamin B6, all blood tests were in normal range. Interactions of carbamazepine with the vitamin B6- nicotinamide metabolism are the reason for these previously undescribed cutaneous side effects in connection with carbamazepine therapy. The present case demonstrates a toxic, non-allergic reaction during carbamazepine treatment with pellagroid skin symptoms.

Histamine and cutaneous nociception: histamine-induced responses in patients with atopic eczema, psoriasis and urticaria.

Having observed altered itch and flare reactions after histamine application in patients with atopic eczema, we tried to determine these reactions in patients with urticaria and psoriasis. We investigated 16 healthy non-atopic subjects, 16 atopics in an eczema-free interval, 16 with acute atopic eczema, 16 with urticaria and 16 with psoriasis. Histamine was iontophoretically applied. The resulting sensations were rated on a visual analogue scale. Flare areas were measured 6 min after stimulation. Itch ratings of urticaria and psoriasis patients did not differ significantly from controls, whereas both atopic groups, regardless of acute or symptom-free state, reported significantly reduced intensity of itching. Flares were significantly diminished in all subjects with acute skin disease (psoriasis, urticaria and atopic eczema), regardless of diagnosis. However, flares were "normal" in symptom-free atopics and were not significantly different from controls. In conclusion, all "acute" patients showed a diminished axon-reflex function, possibly due to a downregulation of C-fiber responsiveness to histamine or an increased turnover rate of inflammatory mediators. Both atopic groups reported weaker itching, suggesting altered central nervous processing of itch.

Acetylcholine is an inducer of itching in patients with atopic eczema.

As previous experimental studies disproved histamine as the main mediator of eliciting pruritus in atopic eczema (AE), we examined the neurocutaneous sensations in 15 patients with AE and in 15 age- and sex-matched non-atopic controls after i.c. injection of acetylcholine (Ach, 0.5 M, 20 microliters) or buffered saline. The sensory perceptions were rated by the participants of the study with regard to their quality and intensity using a visual analogue scale. Simultaneously, the vascular reactions to Ach were recorded by the examinators via laser Doppler fluxmetry as well as flare and wheal planimetry. In contrast to the approximately equal flare and wheal extensions in either group, the cutaneous sensations differed significantly. The patients complained of 'pure' itching that developed shortly after Ach injection, whereas the control subjects reported only burning pain. Moreover, the patients perceived their sensations significantly earlier and significantly longer than did the controls. The study provides evidence that Ach plays an important role in the pathogeny of pruritus in patients with AE. Further investigations of the neuronal mechanisms involved in this atopy-related effect of Ach have to be performed.

Flare responses of atopic eczema patients analysed with true colour images.

OBJECTIVE AND DESIGN: Attenuated flare responses of atopic eczema (AE) patients to histamine are well documented, but their origin is still unknown. SUBJECTS AND METHODS: Here we studied the development of erythema after histamine iontophoresis in 12 AE patients and 12 healthy volunteers by means of a RGB-camera for recording true colour images. TREATMENT: 10 mg cetirizine or placebo was administered orally 3 h before the experiment in a crossover design. RESULTS: The flare reaction was found to develop after termination of histamine iontophoresis in two phases: a first phase lasting 1-2 min in which the flare increased by about 10 mm2/s and a second phase lasting another 10-15 min characterized by a slower growth in the range of 1 mm2/s. CONCLUSIONS: Flare size was diminished in AE patients, mainly due to a slower or absent growth in the second phase. Oral application of the H1-antagonist cetirizine (Zyrtec) reduced the flare reaction in both groups of volunteers significantly, indicating that the reaction is dependent on the activation of chemosensitive nerve fibres via H1-receptors.