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Modified three-step empirical therapy was as efficacious as primary three-step therapy for chronic cough, but was preferable because it had fewer side-effects.
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Sixty cases of allergic rhinitis were selected and randomized into DSQFD group (30 cases) and cetirizine group (30 cases), and the patients were orally administered DSQFD and cetirizine respectively. The integrals of patients' symptoms, such as sneezing, nose running, nasal occlusion and nasal itching, signs in the nasal conchae and peripheral blood eosinophil (EOS) count were abserved count before and after treatment.
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A series of N1-(substituted)aryl-5,7-dimethyl-2-(substituted)pyrido(2,3-d)pyrimidin-4(3H)-one was designed on the basis of the triangular pharmacophoric requirement of histamine H1-receptor antagonists. The designed series was synthesized by cyclo-condensation of monoaryl thiourea with ethyl cyanoacetate in the presence of dry HCl gas to give N1-(substituted aryl)-2-mercaptopyrimidine-4(3H)-one, which on cyclo-condensation with acetylacetone gave the pyridopyrimidinone. Further methylation of the mercapto group at C-2 with methyl iodide followed by nucleophilic displacement of the methylmercapto group by various amines gave the targeted compounds. All the synthesized compounds were screened for histamine H1-receptor antagonistic activity by the in vitro method of inhibition of the isotonic contraction induced by histamine on isolated guinea pig ileum using cetirizine as a standard drug. All the compounds exhibited potent histamine H1-receptor antagonistic activity with pA2 values from 7.30- 9.75 (cetirizine, pA2 value 9.40). The potent compounds were screened for their in vivo antihistaminic activity by protection of animal from asphyxic shock. The sedative potential of potent compounds was checked on albino mice by photoactometer and they had comparative sedative potential to the standard drug cetirizine. None of the compound exhibited anticholinergic activity in the in vitro rat ileum model.
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To compare the central and peripheral H1 inhibitory effects of acute and sub-chronic doses of levocetirizine (L-CTZ), cetirizine (CTZ), loratadine (LOR) and promethazine (PRM) versus placebo, using a battery of psychomotor and cognitive tests together with measures of the weal and flare reaction. PRM was included in the study as a positive internal control to validate the sensitivity of the psychometric test battery to the CNS effects of the various treatments.
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Hydroxyzine HCl is used in oral formulations for the treatment of urticaria and atopic dermatitis. Dizziness, blurred vision, and anticholinergic responses, represent the most common side effects. It has been shown that controlled release of the drug from a delivery system to the skin could reduce the side effects while reducing percutaneous absorption. Therefore, the aim of the present study was to produce an effective drug-loaded dosage form that is able to control the release of hydroxyzine hydrochloride into the skin. The Microsponge Delivery System is a unique technology for the controlled release of topical agents, and it consists of porous polymeric microspheres, typically 10-50 μm in diameter, loaded with active agents. Eudragit RS-100 microsponges of the drug were prepared by the oil in an oil emulsion solvent diffusion method using acetone as dispersing solvent and liquid paraffin as the continuous medium. Magnesium stearate was added to the dispersed phase to prevent flocculation of Eudragit RS-100 microsponges. Pore inducers such as sucrose and pregelatinized starch were used to enhance the rate of drug release. Microsponges of nearly 98% encapsulation efficiency and 60-70% porosity were produced. The pharmacodynamic effect of the chosen preparation was tested on the shaved back of histamine-sensitized rabbits. Histopathological studies were driven for the detection of the healing of inflamed tissues.
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The aim of this study was to compare both the behavioral and physiological effects of 2 drug regimens in children: chloral hydrate (CH), meperidine (M), and hydroxyzine (H) (regimen A) versus midazolam (MZ), M, and H (regimen B). Patients between 24 and 54 months of age were examined by crossover study design. Behavior was analyzed objectively by the North Carolina Behavior Rating System and subjectively through an operator and monitor success scale. Physiological data were recorded every 5 minutes and at critical points throughout the appointment. Sixteen patients completed this study. No significant differences in behavior were noted by the North Carolina Behavior Rating System or the operator and monitor success scale. A quiet or annoyed behavior was observed 93% and 90% of the time for regimen A and regimen B, respectively. Using the operator and monitor success scale, 63% of regimen A and 56% of regimen B sedations were successful. No statistically significant differences were noted in any of the physiological parameters between the 2 regimens. Ten episodes of hemoglobin desaturation were detected with regimen A sedations. There were no differences between the sedative drug regimens CH/M/H and MZ/M/H for behavioral outcomes or physiological parameters.
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The present study provides evidence that the P-gp transporter is involved in central antihistamine effects in humans. Participants were less alert during the combined treatment of cetirizine and verapamil as indicated by longer reaction times and decreased blood oxygen level-dependent response in the right superior temporal gyrus.
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This study was a double-blind, placebo-controlled, randomized clinical trial. Treatments were administrated on days 1, 2, 3, and 4, 3 hours before the start of the laboratory test battery (performed on days 1 and 4), comprising a word-learning test, the Sternberg Memory Scanning Test, a tracking test (easy and hard version), and a divided attention test (tracking and memory scanning simultaneously). Statistical analyses were performed separately for days 1 and 4 by using analysis of variance.
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A 16-year-old boy presented to the emergency department with rapidly progressing extremity pain, edema, and ecchymosis after envenomation by a copperhead. Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) was infused. Six vials were placed in 250 mL of normal saline solution, and the infusion was gradually increased. Fifty minutes after beginning, the infusion was increased to 640 mL/h. Within minutes of the rate increase, the patient experienced full-body urticaria, facial edema, voice change, and tachycardia. The infusion was stopped. Hydroxyzine pamoate, famotidine, methylprednisolone, and a 1-L bolus of normal saline solution were administered intravenously. The symptoms abated, and the remaining FabAV was infused at a slower rate without return of this reaction. This immediate hypersensitivity reaction was most likely a rate-related anaphylactoid reaction that has not been previously reported with FabAV.[Holstege CP, Wu J, Baer AB. Immediate hypersensitivity reaction associated with the rapid infusion of Crotalidae polyvalent immune Fab (ovine). Ann Emerg Med. June 2002;39:677-679.]
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After some positive results with prostaglandin inhibitors, we undertook a study in which we randomly placed patients on four different forms of therapy for their pruritus. The therapies included hydroxyzine with or without doxepin at night, pentoxifylline, indomethacin and topical moisturization with medium-strength topical steroids. All patients were evaluated for both subjective relief as well as side effects.
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Randomized, controlled multicenter trial. (ClinicalTrials.gov: NCT00610584)
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The systemic therapies which may modulate the pattern of immune dysregulation seen in HIV-1 disease may be beneficial in the pruritus seen in late-stage patients.
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Isolated canine cutaneous mast cells.
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Intubation was easily realized but it was necessary to assist ventilation in patients presenting prolonged apnea lasting more than 30 s (5 out of 9 patients who presented apnea during procedure). Intubation was quickly realized (T+ 4 +/- 3 min). Haemodynamics and saturation were not altered during procedure. Inhalatory induction using sevoflurane costs 6 10 versus 16 80 for intravenous target controlled propofol anesthesia (using only one preconditionned syringe).
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A double-blind, placebo-controlled clinical trial was undertaken for two weeks to evaluate three dosing schedules for administration of cetirizine in patients with seasonal allergic rhinitis. Average severity scores from the patients' ratings for sneezing and nasal itching were significantly reduced in all three cetirizine groups (10 mg QAM or QHS and 5 mg BID), compared with placebo. The effectiveness of cetirizine in once-daily dosing schedules indicates that significant antihistaminic activity is delivered over a full 24 hours. The possibility for flexibility in dosing combined with its relatively short half-life and low incidence of adverse effects make cetirizine an important second-generation H1-antihistamine for the management of seasonal allergic rhinitis.
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A 2-week, single-center, randomized, open, parallel group comparative clinical study between rupatadine and levocetirizine in patients with seasonal allergic rhinitis.
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Experimental data suggest that there is an imbalance between Th1 and Th2 cells in atopic dermatitis (AD) skin compared to allergic contact dermatitis (ACD). This imbalance (Th2 and Th1 predominance, respectively) implies the production of different cytokines in these two conditions leading to different expression of adhesion molecules on skin endothelial cells.
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Sensitivity and specificity were 50 % [95 % confidence interval (CI) 23.66-76.34] and 90 % (95 % CI 59.58-98.21), respectively, for single drugs. Our algorithm confirmed a previously identified signal concerning clarithromycin and calcium-channel blockers (unadjusted odds ratio (ORu) 2.92; 95 % CI 1.11-7.69, p = 0.04). Among the 45 drug pairs investigated, we identified a signal concerning 55 patients in association with bromazepam and hydroxyzine (ORu 1.66; 95 % CI 1.23-2.23). This signal was not confirmed after a chart review. Even so, AKI and co-prescription were confirmed for 96 % (95 % CI 88-99) and 88 % (95 % CI 76-94) of these patients, respectively.
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d-CPA 4 mg·kg(-1) i.p. increased non-rapid eye movement (REM) sleep whereas 10-40 mg·kg(-1) d-CPA decreased non-REM sleep at dark onset time. Nocturnal i.c.v. infusions of d-CPA (10 µmol·100 µL(-1)·10 h(-1)) increased drowsiness but not non-REM sleep, whereas the same i.c.v. infusions of cetirizine significantly increased non-REM sleep, abolished REM sleep, and decreased wakefulness for more than 10 h. The medial preoptic area contained the greatest fluorescent labelling after i.c.v. cetirizine/DBD-pz infusions. Histamine-induced Ca(2+) increases in medial preoptic neurons were blocked by d-CPA or cetirizine, whereas d-CPA, but not cetirizine, increased Ca(2+) irrespective of antihistaminergic activity at ≥ 100 µM.
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The purpose of this prospective, randomised study was to determine whether passive smoking influences the outcome of therapies in paediatric patients with allergic respiratory diseases.
The failure of the second-generation antihistamines cetirizine and fexofenadine to prevent motion sickness suggests that the therapeutic actions of this class of antihistamines against motion sickness may be mediated through central versus peripheral receptors. The sedative effect of other antihistamines, such as hydroxyzine, may play a more significant role in alleviating motion sickness than previously thought.
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Data were pooled from six clinical trials, in which cetirizine was administered orally in various formulations and in single and multiple dosage regimens. The population consisted of 112 children (33 female and 79 male) aged 6 months to 12 years. A one-compartment open model with first-order absorption and elimination was fitted to the plasma concentration-time profiles using nonlinear mixed effects modelling with first-order estimation.
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In order to further evaluate the role of cytokines in the induction of atopic pruritus, leukocytes from 10 atopic eczema patients or 10 nonallergic controls were stimulated in vitro with mite or birch pollen antigen for 1 and 4 days. Subjects were prick-tested with the supernatants, and whealing and itching were evaluated 20 and 60 min later. The supernatants were also examined for the contents of GM-CSF, IL-2, IL-6 and IL-8 by ELISA and TNFalpha. Two hours prior to testing, the antihistamine cetirizine (20 mg) or a placebo tablet were given to the patients according to a randomized, double-blind study protocol. After pricking with antigen-stimulated leukocyte supernatants, 6 of 10 patients but no controls reacted mostly at 20 min with whealing and/or pruritus. In the cetirizine-treated group, no decrease in these skin reactions was seen compared to placebo. Analysis for cytokines showed increased levels of IL-8 in allergen-stimulated samples, with no correlation to the induction of itching or whealing by these supernatants. IL-6 levels were low and variable, and GM-CSF, IL-2 and TNFalpha levels were always below standard values. These data show that leukocytes selectively release IL-8 in response to in vitro antigen stimulation. They furthermore provide additional support for the concept that as yet to be identified products play a role in atopic pruritus.
First-generation antihistamines are effective at ameliorating the symptoms of allergic rhinitis and CIU; however, they are associated with adverse effects due to a lack of selectivity for the histamine H(1)-receptor and an ability to bind to cerebral H(1)-receptors. Newer-generation agents, in general, possess high H(1)-receptor selectivity and a low tendency to cross the blood-brain barrier, while maintaining efficacy. In general, safety at elevated doses has been demonstrated for the newer antihistamines, although higher rates of sedation and impairment have been reported with increasing doses for some agents.
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A 54-year-old Caucasian woman with chronic HCV infection developed propranolol-induced angioedema.
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In this work, two-step hollow fiber-based liquid-phase microextraction procedure was evaluated for extraction of the zwitterionic cetirizine (CTZ) and basic hydroxyzine (HZ) in human plasma. In the first step of extraction, the pH of sample was adjusted at 5.0 in order to promote liquid-phase microextraction of the zwitterionic CTZ. In the second step, the pH of sample was increased up to 11.0 for extraction of basic HZ. In this procedure, the extraction times for the first and the second steps were 30 and 20 min, respectively. Owing to the high ratio between the volumes of donor phase and acceptor phase, CTZ and HZ were enriched by factors of 280 and 355, respectively. The linearity of the analytical method was investigated for both compounds in the range of 10-500 ng mL(-1) (R(2) > 0.999). Limit of quantification (S/N = 10) for CTZ and HZ was 10 ng mL(-1) , while the limit of detection was 3 ng mL(-1) for both compounds at a signal to noise ratio of 3:1. Intraday and interday relative standard deviations (RSDs, n = 6) were in the range of 6.5-16.2%. This procedure enabled CTZ and HZ to be analyzed simultaneously by capillary electrophoresis.
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Results show that incomplete removal of diclofenac, the compound that was found in the highest abundance, was observed via biodegradation and adsorption, and that UV photolysis was the main removal mechanism for this compound. The effect of adsorption to the secondary sludge was often negligible for the PhACs, with the exceptions of diclofenac, etofenamate, hydroxyzine and indapamide. However, the musks showed a high level of adsorption to the sludge. UV radiation had an important role in reducing the concentration of some of the target compounds (e.g. diclofenac, ibuprofen, clorazepate, indapamide, enalapril and atenolol) not removed in the activated sludge tank.
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Neurogenic cystitis was induced by the injection of Bartha's strain of PRV into the abductor caudalis dorsalis tail base muscle of female C57BL/6 mice. Therapeutic modulation of pelvic pain was assessed daily for five days using von Frey filament stimulation to the pelvic region to quantify tactile allodynia.
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A total of 120 newly diagnosed adult patients were evaluated. Patients were single blinded and randomly assigned to one of four medication groups that received the following regimens for 4 weeks: Group A, combination of sedating H1 antihistamine and non-sedating H1 antihistamine; Group B, combination of H1 antihistamine and H2 antihistamine; Group C, combination of H1 antihistamine and LRA; and Group D, matched placebo medication. The primary measure of treatment efficacy was the daily urticaria activity score (UAS) of 'wheal and itch'. A positive therapeutic response was defined as a reduction to < 25% of baseline weekly UAS, while a relapse was a return to > 75% of baseline weekly UAS.
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To study the clinical effects of integrative Chinese and Western medicine in treating chronic urticaria and its impact on peripheral blood content of interleukin-10 (IL-10) and IL-8.
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Docetaxel, at this dose and schedule, has definite antitumor activity in pretreated MBC patients. Moreover, this is the first randomized trial to show that corticosteroids have a favorable impact on docetaxel-induced FR.