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Effect of cetirizine on cutaneous reactions to PAF, kallikrein and serum in patients with chronic urticaria.

The effects of oral administration of the antihistamine cetirizine on the weal and flare caused by intradermal injection of platelet activating factor (PAF-acether), kallikrein, histamine and the patient's own serum were investigated in 10 patients with chronic urticaria. Cetirizine markedly reduced the weal and flare induced by all these agents as measured 12 min after the injections. The delayed reactions observed after injection of PAF, kallikrein and serum were also inhibited by cetirizine at 6 hours. In addition, reactions which were present 20 h after injection of the agent before administration of cetirizine were found to be inhibited at the same point in time after cetirizine treatment. These effects might explain the good inhibitory clinical effect of cetirizine on the patients' urticaria. No side-effects were noted during the treatment.

Adult↗

Adrenergic urticaria and adrenergic pruritus.

We report here on 2 patients with adrenergic urticaria and adrenergic pruritus, respectively. The lesions and features developed during phases of stress and during the attacks were associated with an increase in the plasma concentrations of noradrenalin, adrenalin and prolactin. The dopamine plasma level was elevated only in the case of adrenergic urticaria. The symptoms could be reproduced by intradermal injection of adrenalin and noradrenalin and treated successfully with propanolol, a blocker of beta-adrenergic receptors. Adrenergic urticaria is a rare but distinct entity, which has to be separated from cholinergic urticaria. Adrenergic pruritus seems to be a minor variant of adrenergic urticaria.

Adult↗

Immunization with recombinant human granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant elicits both a cellular and humoral response to recombinant human granulocyte-macrophage colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important cytokine for the generation and propagation of antigen-presenting cells and for priming a cellular immune response. We report here that use of recombinant human GM-CSF (rhGM-CSF), administered as an adjuvant in a peptide-based vaccine trial given monthly by intradermal injection, led to the development of a T-cell and antibody response to rhGM-CSF. An antibody response occurred in the majority of patients (72%). This antibody response was not found to be neutralizing. In addition, by 48-hour delayed type hypersensitivity (DTH) skin testing, 17% of patients were shown to have a cellular immune response to the adjuvant rhGM-CSF alone. Thymidine incorporation assays also showed a peripheral blood T-cell response to rhGM-CSF in at least 17% of the patients. The generation of rhGM-CSF-specific T-cell immune responses, elicited in this fashion, is an important observation because rhGM-CSF is being used as a vaccine adjuvant in various vaccine strategies. rhGM-CSF-specific immune responses may be incorrectly interpreted as antigen-specific immunity, particularly when local DTH responses to vaccination are the primary means of immunologic evaluation. We found no evidence of hematologic or infectious complications as a result of the development of rhGM-CSF-specific immune responses.

Adjuvants, Immunologic↗

Capillary density in developing and healing tuberculous lesions produced by BCG in rabbits. A quantitative study.

Dermal tuberculous lesions were produced in rabbits by the intradermal injection of BCG. At various times after infection, anesthetized animals were perfused with a gelatin-colloidal carbon medium via the abdominal aorta. The capillary density of the nonnecrotic granulation tissue in the lesions was determined quantitatively by counting the capillaries under an ocular grid of a microscope. The capillary density in normal skin near the lesions was 3.8 plus or minus 0.5 in millimetersof capillary lengths per square millimeter in 250-mu tissue sections. The capillary density of the nonnecrotic tissue in BCGlesions averaged 6.1 plus or minus 0.6 mm/sq mm, an increase of 60%. The capillary density remained more or less constant as the BCG lesions grew and then regressed. The development of delayed hypersensitivity seemed to increase the capillary density, but this increase may have been a response to an extension of the necrosis at the time delayed hypersensitivity developed. Capillary densities in tuberculin reactions resembled those in BCG lesions. In the early stages, the increaseed capillary network of dermal BCG lesions was derived mainly from the subpapillary vascular plexus of the deep dermis supplied branches that surrounded the lower half of the caseous necrotic center and anastomosed with capillaries from the subpapillary plexus supplying the upper half. When the necrotic center extended, nearby capillaries thrombosed and in turn became necrotic. Peripherally, new capillaries formed and anastomosed with existing capillaries. From these vessels, mononuclear phagocytes emigrated, destroyed the tubercle bacilli, and enabled the lesion to heal. In the BCG lesions at all stages of development and healing, the capillary network in the nonnecrotic areas seemed adequate to supply and nourish the defense cells controlling the infection.

Animals↗

Serial nerve conduction and electromyographic studies in experimental allergic neuritis.

Experimental allergic neuritis (EAN) was produced in ten guinea pigs by intradermal injection of peripheral nerve antigen and complete Freund's adjuvant. Six additional animals were injected with adjuvant only, and three control animals received saline. Slowing of motor nerve conduction velocity occurred in all animals ijected with antigen. Velocities progressively decreased through the first six weeks, at which time they started increasing, returning to the normal range in the third month. Six of the animals--generally those having received the greatest amount of antigen and adjuvant--developed severe encephalomyelitis and died early in the study. These animals also developed more severe peripheral nerve involvement, and conduction velocities decreased more than in mildly affected animals. Abnormal electromyographic findings were observed in all EAN animals surviving through the third week. Two of the six animals injected with complete adjuvant without antigen showed some minimal electromyographic changes. Several developed slight slowing of nerve conduction velocity during the first few weeks. Saline control animals had normal nerve conductions and electromyographic studies throughout the course of observation.

Animals↗

BCG-vaccination campaign in Aden Colony.

A mass BCG-vaccination campaign was undertaken in Aden Colony during February-May 1952 by WHO/UNICEF in co-operation with the Directorate of Medical Services. Over 31,000 persons (about one-fourth of the total population) were given an intradermal 5 TU test, and 22,000 returned for the reaction to be read. Of these, about one-third were classified as negative and all but a very few of them were given an intradermal injection of BCG vaccine. Of those vaccinated, over half were children of school-age. The results obtained in this campaign are described with particular reference to the number and size of tuberculin reactions, and the results of follow-up examinations in nearly 2,000 schoolchildren.

BCG Vaccine↗

Effect of intradermal tuberculin tests on BCG-induced allergy.

Trials are going forward to determine whether intradermal tuberculin testing with 10 TU at yearly intervals after BCG vaccination may prevent waning of BCG-induced allergy in schoolchildren. Meanwhile, two experiments to the same purpose, carried out in guinea-pigs, are described. They show that waning allergy in guinea-pigs can be sustantially enhanced by intradermal injection of either purified tuberculin or Old Tuberculin, the effect lasting for at least 8 weeks, even with so small a dose as 5 TU. It is pointed out that this enhancing effect has been demonstrated only in BCG-vaccinated guinea-pigs and that it is not known whether the same phenomenon would occur in guinea-pigs infected with living human tubercle bacilli.

BCG Vaccine↗

Antihistaminic efficacy of Ranitidine with & without Dimethendine maleate on histamine-induced cutaneous reactions.

The effect of Ranitidine, the H2-receptor antagonist, was investigated on cutaneous response to intradermal injection of histamine in healthy volunteers in a controlled, randomized, cross over study. The response was compared with that of the H1-receptor blocker; Dimethendine maleate used alone and in combination with the two antagonists. Reduction in the wheal area was significant in subjects pretreated with Ranitidine alone (P less than 0.05), and Dimethendine maleate alone (P less than 0.05); the combination of the two antagonists, did not produce additional reduction. Reduction in erythema area was not significant with Dimethendine maleate alone, but significant with Ranitidine alone (P less than 0.01). With the combination of the two antagonists the reduction was not more significant than with Ranitidine alone. The flare response scoring on visual analogue scale was not reduced significantly by Dimethendine maleate alone but reduced significantly by Ranitidine alone (P less than 0.10), and by combination of Ranitidine and Dimethendine maleate (P less than 0.05). Thus, Ranitidine appears to be more effective than Dimethendine maleate in reducing the erythema area and intensity of flare response and equieffective in reducing wheal response to histamine injection.

Adult↗

Treatment of hyperhidrosis with botulinum toxin A.

Focal hyperhidrosis of axillae, palms or soles is a frequent, socially debilitating condition triggered by various emotional stimuli. There are several treatment options such as local application of metal sales (aluminum chloride) or tap water iontophoresis, which provide temporary relief for some patients. More recently, local intradermal injections of botulinum toxin A (BTX-A), a neurotoxin blocking the cholinergic stimulus of eccrine sweat glands, offers an effective treatment option with few side-effects. Patient satisfaction rates are high, although treatment effects only last a few months. For definite care, surgical procedures have to be considered.

Algorithms↗

Intradermal BCG: partial protection against tuberculosis in children: unproven efficacy of multipuncture administration.

(1) In France the annual incidence of tuberculosis is currently about 11 cases per 100 000 population; fewer than two of the 11 cases are children under 15. (2) The incidence of tuberculosis is higher among sub-Saharan African immigrants living in France, and also among their children. (3) The protection afforded by bacillus Calmette Guerin (BCG) must be evaluated clinically. A positive tuberculin test after BCG vaccination does not necessarily indicate protection against tuberculosis. (4) Intradermal BCG vaccination protects about 80% of young children from extrapulmonary tuberculosis (especially tuberculosis meningitis). It seems far less effective against pulmonary tuberculosis, the most frequent and most contagious form. (5) Efficacy of BCG vaccination in adults is uncertain. Protection is moderate at best. (6) Multipuncture BCG vaccination has not been assessed using clinical outcomes, and may be less effective than intradermal injection. Yet it remains the most frequent mode of BCG delivery in France. (7) In some European countries, interruption of BCG mass vaccination was followed by a few extra cases of tuberculous meningitis per year. (8) In countries with low endemicity there are no reliable clinical evaluation or epidemiological data to support revaccination after a negative postvaccination tuberculin skin-test.

Adult↗

[Tuberculin intradermal reaction (IDR) or tuberculin test].

Tuberculinic switch is defined as an increase of the intradermal reaction diameter in two tests carried out within three months of each other. The tuberculinic skin reaction proves the presence of a delayed hypersensitivity induced by mycobacterial antigens (Mycobacterium tuberculosis, BCG, some atypical mycobacteria). However, this reaction does not always prove an effective protection against the BK. The intradermal injection of a purified Purified Protein Derivative (PPD) resulting from a culture of M. tuberculosis is the only method validated for the diagnosis of tuberculosis infection (latent infection) and screening for hypersensitivity and post-vaccine BCG (Official French decree No 96-775 of September 5, 1996 and its decree relating to vaccination by BCG and tuberculin tests). The guidelines concerning tuberculin testing are: investigating on a case of tuberculosis; tracking or surveillance of people frequently exposed to tuberculosis (examination on recruitment and follow-up of exposed professionals); prevaccine testing in children over four weeks of age.

France↗

Leukocyte immunotherapy improves live delivery rates following embryo transfer in women with at least two previous failures: a retrospective review.

PURPOSE: To determine whether leukocyte immunotherapy (LIT) could improve live delivery rate following embryo transfer (ET) in women who were not successful in prior attempts. METHODS: Paternal leukocytes were intradermally injected in some women who had failed to have a successful pregnancy following at least two prior ETs approximately two weeks prior to fresh or frozen ET and repeated at the time of the 3rd rising serum beta human chorionic gonadotropin level and at eight weeks if a pregnancy occurred. Clinical pregnancy and live pregnancy rates (PRs) were compared to those women having ETs during the same time period not receiving LIT. RESULTS: Thirty-six of 94 (38.3%) patients receiving LIT (group 1) conceived following fresh or frozen ET vs 98 of 341 (28.7%) for women not receiving LIT (group 2) (p = NS). The live delivery rate per ET cycle was 30.8% (39/94) vs 19.7% for group 2 (p = .02). For the subset of women failing despite five previous ETs 17 of 37 (45.9%) group 1 women had a clinical pregnancy vs 18 of 64 (28.1%) group 2 women (p = .07%) and live delivery rates were 35.1% (13/37) vs 15.6% (10/64) (p = .024). CONCLUSIONS: These retrospective data encourage a prospective study of LIT combined with progesterone vs controls receiving progesterone only for recalcitrant patients having ETs.

Adult↗

Gardner-Diamond syndrome with multiple glomus tumors.

The case of a patient with two unusual dermatologic entities, multiple glomus tumors and the painful purpura of Gardner-Diamond syndrome, is reported. The diagnosis of multiple glomus tumors was confirmed by biopsy, and the Gardner-Diamond syndrome was confirmed by reproduction of the painful purpura with the intradermal injection of the patient's sonicated erythrocytes.

Adult↗

Bacillus Calmette-Guerin vaccination in preterm infants.

OBJECTIVE: To evaluate the tuberculin response after bacille Calmette-Guérin (BCG) vaccination in preterm infants. METHODS: Thirty-five infants born at <35 weeks gestation were included in the study. An intradermal injection of 0.05 ml BCG vaccine was given to each infant at postnatal months 2-3. Tuberculin skin tests (TSTs) were done 8-12 weeks after vaccination using 0.1 ml of 5 TU purified protein derivative (PPD). The diameter of induration was measured 72 h later and > or =5 mm induration was taken as a positive response. RESULTS: The babies had a mean birth weight (SD) of 1650 (424) g, and a gestational age of 32.4 (2.1) weeks. The TST was positive in 20 (57%) of the infants. The mean body weight of the tuberculin-positive babies was significantly higher than the others at both vaccination and TST. No difference was found between groups concerning sex, birth weight, gestational age, intrauterine growth and postnatal age at BCG vaccination and TST. CONCLUSION: BCG vaccination in preterm infants at months 2-3 of postnatal life results in a high percentage of BCG scarring and 57% TST conversion. A positive tuberculin response was significantly related to the postnatal weight gain of the preterm infants.

BCG Vaccine↗

Metabolism of linoleic acid in porcine epidermis.

The time course of linoleic acid metabolism in porcine epidermis has been studied in order to better evaluate the lipid transformations that accompany differentiation in this tissue. One day after intradermal injection of [U-14C]linoleic acid, most of the radioactivity in the epidermis was associated with phospholipids, triglycerides, and free fatty acids. Within 3-7 days, a portion of the radiolabel was selectively transferred to acylglucosylceramide and acylceramide fractions, after which the specific activities of all lipids fractions decreased. The results suggest that neither the lipoxygenation of linoleate nor the hydrolysis of acylceramide to form acylacid and free sphingosine are major routes of linoleate metabolism in normal epidermis. The principal pathway of linoleate metabolism in normal epidermis appears to be transfer from phospholipids to acylglucosylceramide to acylceramide. The triglyceride fraction, although minor in amount, attains an initially high specific activity, and may serve as an intermediate in linoleate transfer.

Animals↗

Ultraviolet B light-induced alterations in epidermal Langerhans cells are mediated in part by tumor necrosis factor-alpha.

Acute, low-dose treatment of murine skin with ultraviolet B light (UVB) impairs the induction of contact hypersensitivity to dinitrofluorobenzene, and depletes the epidermis of normally appearing class II MHC positive Langerhans cells. Recent studies with inbred strains of mice have revealed that impairment of contact hypersensitivity by UVB is a polymorphic trait that is polygenically dictated by susceptibility alleles at the Lps and Tnf alpha loci. Since impairment of contact hypersensitivity by UVB has been associated with deleterious effects on Langerhans cells, we have tested the hypotheses that UVB and TNF alpha have similar effects on epidermal Langerhans cells and that TNF alpha is an important mediator of this UVB-induced effect. Our results confirm that both UVB and TNF alpha reduce the density of class II MHC-bearing epidermal cells and alter the morphology (shortened or absent dendrites, rounded shape) of the cells that remain. UVB- and TNF alpha-induced changes are prevented by systemic administration of neutralizing anti-TNF alpha antibodies. Circumstantial evidence, based on time of onset of numerical and morphologic changes among Langerhans cells following epidermal treatment, suggests that TNF alpha is the mediator of UVB-induced changes. Moreover, the ability of intradermally injected TNF alpha to alter Langerhans cells depends, in part, on whether the strain of mouse is of the UVB-susceptible or UVB-resistant phenotype as it pertains to the effect of UVB on contact hypersensitivity.

Animals↗

Acute inflammatory effects of a monocyte-derived neutrophil-activating peptide in rabbit skin.

The inflammatory effects of a monocyte-derived neutrophil-activating peptide (MONAP), purified to homogeneity from lipopolysaccharide-stimulated human peripheral blood monocytes, have been evaluated in rabbit skin. Intradermal injection of MONAP alone caused a mild infiltration of polymorphonuclear leucocytes (PMNL) but did not induce any change in plasma extravasation. When combined with prostaglandin E2(PGE2), MONAP caused a marked and synergistic increase in PMNL infiltration and plasma extravasation into the injected skin sites. The increase in vascular permeability induced by MONAP depended on the presence of circulating PMNL. MONAP is a novel cytokine with pro-inflammatory properties and may have physiological and pathophysiological roles in health and disease.

Animals↗

Variable reduction in beta-adrenergic sweat secretion in cystic fibrosis heterozygotes.

Because patients with cystic fibrosis (CF) consistently lack sweating response to isoproterenol (ISO) in vivo and in vitro, we studied to what extent beta-adrenergic defect is expressed in CF heterozygotes. To improve the sensitivity and accuracy of determining the sweating response to intradermal ISO (also containing theophylline and atropine), a water vapor analyzer was used, and the peak sweat rates attained after intradermal injection in the forearm of optimal concentrations of ISO and methacholine (MCH) were determined. The peak ISO sweat rate was further normalized by the peak MCH sweat rate in each individual and expressed as the relative ISO sweat ratemax (in percent). The relative ISO sweat ratemax was determined independent of age and sex and was unchanged after brief acclimatization. The mean relative ISO sweat ratemax of CF heterozygotes was significantly lower than that of controls (10.1% vs 19.5%); however, 21 of the 54 CF heterozygotes overlapped with controls, and the remainder of the CF heterozygotes fell below the arbitrary demarcation line drawn at the relative sweat rate of around 10%. Thus, although the ISO sweat test may not be a practical discrimination test for CF heterozygotes, knowledge of the diversity of beta-adrenergic sweating responses in CF heterozygotes will provide a useful data base for further understanding the possible linkage (or its absence) between the abnormal CF gene(s) (which may be identified by molecular biologists in the near future) and the abnormal intracellular process(es) that takes place during beta-adrenergic stimulation of the CF eccrine sweat gland.

Acclimatization↗