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[Idiopathic Frey's syndrome under the appearance of a recurrent otitis externa].

Frey syndrome has been observed especially in patients who have undergone a parotidectomy operation, but also in zoster herpes, in parotiditis, condilea fractures, obstetric traumatisms with forceps and in surgery of the meningioma of the cerebellopontine angle. It also appears without previous surgery, like in our case. In these circumstances it is believed that a clinical neuritis, primary or secondary to a neighbouring inflammation may cause the start of this disorder. Several treatments have been suggested which highlights the difficulty of them. The most effective one is the intradermic injection of botulinum toxin type A. Its use in Frey's syndrome was initiated by Drobik and Laskawi in 1995. Since then the references to its use are numerous. Nevertheless, it is a treatment which has been introduced very few times in our country.

Aged↗

Roles of mast cells and sensory nerves in cutaneous vascular hyperpermeability and scratching behavior induced by poly-L-arginine in rats.

We investigated whether the polycation poly-L-arginine elicited cutaneous vascular hyperpermeability and scratching behavior and, if so, whether these responses involved mast cells and sensory nerves in rats. Intradermal injections of poly-L-arginine induced vascular hyperpermeability and scratching behavior. Combined treatment with chlorpheniramine and methysergide almost completely suppressed the poly-L-arginine (50 microg/site)-induced plasma leakage. Capsaicin desensitization and the tachykinin NK(1) receptor antagonist LY303870, (R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino]propane, partially inhibited the leakage. In mast cell-deficient rats, poly-L-arginine only minimally induced plasma leakage. On the other hand, capsaicin desensitization and LY303870, but not chlorpheniramine or methysergide, suppressed the poly-L-arginine (200 microg/site)-induced scratching. Moreover, poly-L-arginine elicited the scratching even in mast cell-deficient rats. These results suggest that substance P is at least partly involved in both the cutaneous plasma leakage and the scratching behavior induced by poly-L-arginine. Moreover, mast cell-derived amines are suggested to be involved in the plasma extravasation but scarcely, if any, in the scratching behavior.

Animals↗

Intradermal leukotriene B4, but not prostaglandin E2, induces itch-associated responses in mice.

The itch-associated responses induced by intradermal injection of leukotriene B4 and prostaglandin E2 were studied in mice. Leukotriene B4(0.001-1 nmol/site) elicited scratching of the injected site; the dose-response curve was bell-shaped with a peak effect at 0.03 nmol/site. The effect of leukotriene B4 (0.03 nmol/site) started within 3 min, peaked in the second 10-min period, had almost subsided by 30 min, and was inhibited by the simultaneous injection of the leukotriene B4 receptor antagonist ONO-4057, 5-[2-(2carboxyethyl)-3-(6-( p-methoxyphenyl)-5E-hexenyl) oxyphenyoxy] valeric acid. Prostaglandin E2 (0.003-300 nmol/site) did not significantly elicit scratching. The results raise the possibility that leukotriene B4 is an endogenous itch mediator in the skin.

Animals↗

Topical ondansetron attenuates nociceptive and inflammatory effects of intradermal capsaicin in humans.

Topical application of the 5-HT3 receptor antagonist ondansetron (50-250 microg) delivered in a pluronic lecithin organogel vehicle (PLO, 0.5 ml) produced dose-dependent attenuation of nociceptive and inflammatory effects of intradermally injected capsaicin (10 microg/10 microl) in humans. Significant, dose-dependent analgesic effects were produced by 100 microg and 250 microg doses of ondansetron; these doses also reduced mechanical hyperalgesia produced by capsaicin. However, only 250 microg dose of ondansetron diminished capsaicin-induced inflammatory flare.

Administration, Topical↗

[Correction of facial lipoatrophy with a biodegradable material in HIV-infected patients].

INTRODUCTION: Facial lipoatrophy in HIV-infected patients under tri-therapy occurs frequently and alters their quality of life. No systemic treatment is capable of curing this problem. PATIENTS AND METHODS: Eighty-one patients were included in an open, prospective, compassionate study. A strict intradermal injection of a biodegradable, polyacrylamide cationic copolymer was administered in several sessions. RESULTS: In all the patients, the correction of the facial lipoatrophy was considered satisfactory and stable over a period of 6 months using comparative photographic clichés. The thickness of the dermal skin, assessed by sonography, was doubled. No local or systemic side effect was reported. CONCLUSION: Our study shows that is it possible to durably correct the facial lipoatrophy of HIV-infected patients under tri-therapy by using a biodegradable implant.

Acrylic Resins↗

Quantitative assessment of directed hind limb scratching behavior as a rodent itch model.

Hind limb scratching is used increasingly as an itch model in rodents. Scratching is usually quantified as the number of scratching bouts over a 60 min period. Since the antipruritic effect of scratching should depend on the total time of skin contact, then the duration of scratching bouts and within-bout scratching frequency may also be important factors. Therefore, we measured these parameters during episodes of scratching directed toward the site (nape of neck) of intradermal injection of serotonin in Sprague-Dawley rats. Serotonin elicited significantly more scratching bouts than saline. There was a biphasic pattern of scratching over time, with peaks at 10-20 and 40-50 min. Although cumulative bout duration (2-min intervals) had a similar biphasic distribution, the mean individual bout duration (2.1 s) did not change significantly over time. Within-bout scratching frequency remained constant over time at 8 Hz. The number of scratching bouts was suppressed in a dose dependent manner by naltrexone (3 and 5 mg/kg), while the individual bout duration and the within-bout frequency were not significantly different compared with serotonin-evoked scratching without naltrexone. These results validate the total number of scratching bouts as an indicator of the magnitude of itch-related scratching.

Animals↗

Analysis of reporter gene expression in ovine dermis and afferent lymph dendritic cells in vitro and in vivo.

Plasmid DNA administration has revolutionised approaches to vaccination, and many studies have demonstrated the generation of both humoral and cytotoxic T cell responses which confer protection against live pathogen challenge. However, the mechanisms underlying DNA vaccination are poorly understood. Several studies have suggested the involvement of professional antigen presenting cells such as dendritic cells (DC), but direct evidence for this is lacking. We have used the pseudoafferent lymphatic cannulation model in sheep to study the expression of a plasmid encoding enhanced green fluorescent protein (EGFP) by afferent lymph DC following administration to skin. The cells were analysed by flow cytometry. Preliminary studies were carried out to determine if the pEGFP would function in sheep cells in vitro. The results showed that electroporation of sheep skin fibroblasts, primary macrophages, and afferent lymph DC with 30 microg pEGFP resulted in varying degrees of fluorescence in these cells e.g. 35% of skin cells examined at 48 h, and 7% of afferent lymph DC examined after 4 h. Following intradermal injection of 120 microg of pEGFP, small numbers of fluorescent DC (1-5%) were evident by flow cytometry after 1-4 h. The fluorescent DC continued to drain into the lymphatics over a period of 24 h. Analysis by PCR showed that free pEGFP appeared in the afferent lymph plasma within 1 h of injection, peaking at 2 h and becoming undetectable after 6 h. The results suggest that primary immune responses may be initiated by uptake of soluble protein antigen by afferent lymph DC and by free plasmid rapidly draining to the lymphatics where it may be taken up by DC in the lymph plasma and the local lymph node.

Animals↗

Buffered lidocaine as a local anesthetic: an investigation of shelf life.

STUDY OBJECTIVE: To determine whether buffered lidocaine must be prepared just before use. DESIGN: Randomized, double-blind, prospective trial. SETTING: University hospital. PARTICIPANTS: Twenty-four adult volunteers. INTERVENTIONS: Three buffered lidocaine solutions prepared seven days, one day, and just before use were compared with a control solution. Subjects received 0.5 mL intradermal injections of each solution. Pain of infiltration and extent and duration of anesthesia were measured. MEASUREMENTS AND MAIN RESULTS: Pain of infiltration was less with all buffered solutions than control (P less than .0001). Mean maximum diameter of anesthesia ranged from 29 to 33 mm for the buffered solutions compared with 31 mm for control. Mean duration of anesthesia was 33 minutes for control and 30 minutes for all of the buffered solutions. There was no statistically significant difference in extent or duration of anesthesia for any of the solutions (P greater than .5, beta = .15 for delta = 10%). CONCLUSION: Buffered lidocaine stays effective for up to one week after preparation. It is therefore convenient to use in emergency settings.

Adult↗

Pain reduction in local anesthetic administration through pH buffering.

The effects of pH buffering on the pain of administration and efficacy of three local anesthetics (1% lidocaine, 1% lidocaine with 1:100,000 epinephrine, and 1% mepivacaine) were investigated in a randomized, prospective, double-blind study of 25 adult volunteers. Plain and buffered solutions of the three local anesthetics were prepared, and a 0.5 intradermal injection of each was administered. Pain of anesthetic infiltration was rated from zero to ten. The area of anesthetized skin surrounding each injection site was measured at time intervals following each injection. Buffering the local anesthetics significantly reduced the mean quantitative pain estimates compared to the nonbuffered controls: 1) 1% lidocaine compared with buffered 1% lidocaine, 4.9 +/- 0.4 versus 1.1 +/- 0.2 (P less than 10(-6)); 2) 1% lidocaine with epinephrine compared with buffered 1% lidocaine with epinephrine, 5.1 +/- 0.4 versus 1.8 +/- 0.4 (P less than 10(-6)); and 3) 1% mepivacaine compared with buffered 1% mepivacaine, 5.1 +/- 0.4 versus 0.9 +/- 0.2 (P less than 10(-6)). Onset, extent, and duration of skin anesthesia were not statistically altered by pH buffering. The pain of local anesthetic administration can be dramatically reduced by buffering the local anesthetic prior to its infiltration. Anesthetic efficacy is not compromised, and patient acceptance may be significantly increased.

Adult↗

Benzyl alcohol as an alternative local anesthetic.

STUDY OBJECTIVES: Benzyl alcohol has been used as a local anesthetic for brief superficial skin procedures; however, its efficacy for long-term cutaneous anesthesia has not been established. We sought to compare the cutaneous anesthetic effects of benzyl alcohol with epinephrine with the effects of lidocaine with epinephrine and with placebo. METHODS: This study was a prospective, randomized, double-blind, placebo-controlled clinical trial of 30 healthy paid adult volunteers. Subjects received 1-mL intradermal injections of benzyl alcohol.9% with 1:100,000 epinephrine, lidocaine 1% with 1:100,000 epinephrine, and physiologic saline solution without benzyl alcohol as placebo in a randomized, double-blind fashion. Pain on injection and degree of anesthesia at 5, 15, 30, and 45 minutes was assessed with a 10-cm graded visual analog scale (VAS). Statistical significance was determined by repeated measures ANOVA between groups with a Neuman-Keuls test for post hoc comparison of means and Student's t test for paired means. RESULTS: Benzyl alcohol was 48% less painful on injection than placebo (P <.008) and 42% less painful on injection than lidocaine with epinephrine (P <.05). Lidocaine with epinephrine and placebo were equally painful on injection. After the 5-minute measurement, benzyl alcohol provided significantly better anesthesia than placebo during the remaining observation period (VAS score 48%, 49%, and 51% decreased from baseline at 15, 30, and 45 minutes, respectively, all P <.02 versus placebo). However, benzyl alcohol provided less effective anesthesia than lidocaine with epinephrine (VAS score 72%, 76%, 84%, and 88% decreased from baseline at 5, 15, 30, and 45 minutes, respectively, all P <.001 versus placebo) throughout most of the observation period. CONCLUSION: Benzyl alcohol with epinephrine provides prolonged cutaneous anesthesia, although it is not as effective as lidocaine with epinephrine. However, benzyl alcohol is significantly less painful on injection than lidocaine with epinephrine, and it may offer an alternative for local anesthesia.

Adult↗

In vivo antigen loading and activation of dendritic cells via a liposomal peptide vaccine mediates protective antiviral and anti-tumour immunity.

Initiation of antiviral and anti-tumour T cell responses is probably achieved mainly by dendritic cells (DC) transporting antigen from the periphery into organised lymphoid tissues. To develop T cell vaccines it is, therefore, important to understand the accessibility of the antigen to DC in vivo and whether DC are activated by vaccination. Here we have evaluated the immunogenicity of a liposomal vaccine formulation with antigenic peptides derived from the glycoprotein of the lymphocytic choriomeningitis virus. Liposome-encapsulated peptides were highly immunogenic when administered intradermally and elicited protective antiviral immunity. After intradermal injection, liposomes formed antigen depots which facilitated long-lasting in vivo antigen loading of dendritic cells almost exclusively in the local draining lymph nodes. The immunogenicity of the liposomal peptide vaccine was further enhanced by incorporation of immunostimulatory oligonucleotides leading to activation of DC. This optimised liposomal peptide vaccine elicited also anti-tumour immunity and induced CTL responses comparable to adoptively transferred, peptide-presenting DC. Thus, our data show that liposomal formulations of peptide vaccines are highly effective at direct in vivo antigen loading and activation of DC leading to protective antiviral and anti-tumour immune responses.

Adjuvants, Immunologic↗

Effects of intradermal administration of streptococcal preparation OK-432 on interferon and natural killer cell activities in patients with oral cancer.

The streptococcal preparation OK-432 was used by intradermal administration as an immunotherapy in 18 patients with oral cancer, and the sera from patients during OK-432 treatment were serially assayed for interferon (IFN) activity by the plaque-reduction method with vesicular stomatitis virus in FL cells derived from human amniotic membrane. The type of serum IFN was characterized by acid-treatment and neutralization test with anti-IFN-alpha and anti-IFN-beta antisera. IFN-gamma was expressed for its titer as the residual IFN activity after neutralization with both antisera. An intradermal injection of OK-432 transiently induced IFN activity and 3 patterns in the type and level of the produced IFN were observed. Although most of the patients induced IFN-gamma and acid-stable IFN or only IFN-gamma, 2 patients seemed to be unresponsive to OK-432. When we examined the relationship between natural killer (NK) activity and IFN titer, a sharply declined NK activity was found immediately post OK-432 administration, and then NK activity stayed around the pretreatment level. Most of the tested patients' induced IFN-gamma, preceding the step toward the gradual increase in NK activity, decreased with OK-432. However, even in the patients showing no IFN induction with OK-432, a significant decrease of NK activity occurred.

Aged↗

Topographic effects of tonic cutaneous nociceptive stimulation on human electroencephalograph.

To examine the specific effects of cutaneous pain on electroencephalographic (EEG) activities, tonic painful and non-painful sensations in left forearm were induced by intradermal injection of capsaicin 100 microg/20microl and the same volume of vehicle, respectively, in 15 healthy males. The EEG data acquired in five experimental conditions: (i) baseline A; (ii) non-painful vehicle injection; (iii) baseline B; (iv) painful capsaicin injection and (v) waning pain, were analyzed and compared with analysis of variance. Only the painful capsaicin injection evoked significant decreases of theta, alpha-1 and alpha-2 powers over the centro-parieto-occipital regions compared with baseline B. No significant difference in EEG activation between the non-painful vehicle injection and painful capsaicin injection was found. This implicates that the observed topographic EEG activation is not specific for pain but probably related to the cutaneous stimulation.

Adult↗

Deletion of the preprotachykinin A gene in mice does not reduce scratching behavior elicited by intradermal serotonin.

Itch is thought to be signaled by a sub-population of pruritogen-selective C-fiber primary afferents. To assess a possible role of the neuropeptide, substance P (SP), in the central neurotransmission of itch, we investigated itch-related scratching behavior elicited by intradermal injection of serotonin (5-HT; 0.03-0.3%) in normal mice (wildtype, WT) and knockout mice (KO) with deletion of the preprotachykinin A gene. Both KO and WT groups showed dose-related increases in the number of 5-HT-evoked scratching bouts over the 44 min observation period. There were no significant differences in the numbers or durations of scratching bouts between WT and KO groups, although KO mice exhibited numerically more spontaneous and 5-HT-evoked scratching. It is concluded that either SP is not involved in the central neurotransmission of itch-related scratching behavior in this strain of mouse, or that compensatory developmental changes in the KO mice allow itch-related signaling.

Animals↗

Low density lipoprotein oxidized in xanthoma tissue induces the formation and infiltration of foam cells.

Human low density lipoprotein (LDL) was incubated with rabbit xanthoma tissue or non-lesional dermis. The xanthoma tissue-modified LDL (x-LDL) was oxidized showing a 12-fold higher level of thiobarbituric acid-reactive substances (TBARSs) and a faster anodic electrophoretic mobility than native LDL (n-LDL). The LDL treated with non-lesional dermis (d-LDL) had a twofold higher TBARS level compared with n-LDL, but the electrophoretic mobility of d-LDL and n-LDL was similar. Cholesterol esterifying activity in mouse peritoneal macrophages, an indicator of LDL uptake, was up-regulated 5-fold and 1.8-fold by incubation with x-LDL and d-LDL, respectively, compared with n-LDL. Macrophages transformed into foam cells in incubation with x-LDL, and intradermal injections of x-LDL induced infiltration of great many foam cells in the normolipemic rabbit dermis. d-LDL had much less effects on the foam cell formation and foam cell infiltration than x-LDL. Cholesterol:protein ratio was higher in x-LDL than in n-LDL and d-LDL, suggesting that x-LDL-induced foam cells accumulated the lipids by incorporating the cholesterol-rich x-LDL. In conclusion, extravasated LDL receives oxidation and contributes to foam cell recruitment in xanthoma lesions. On the other hand, extravasated LDL in non-lesional dermis receives limited oxidation and additional promoting factors are necessary for initiation of xanthoma development.

Animals↗

Immunization with DNA through the skin.

The skin has evolved as a barrier to prevent external agents, including pathogens, from entering the body. It has a complex and efficient immune surveillance system, which includes Langerhans cells and dendritic cells. By targeting the body's natural defense system, skin-DNA immunization attempts to produce an efficient immune response. Nucleic acid vaccines provide DNA for protein expression in a variety of cells, including keratinocytes, Langerhans cells, and dendritic cells, which are located in the two main areas of the skin, the epidermis (the most superficial layer) and the dermis. After maturation, Langerhans cells and dermal dendritic cells can migrate to local lymph nodes where presentation of antigens to T cells can occur and thus start a variety of immunologic responses. Dermal immunization methods described in this article target the epidermis, the dermis, or both and include: (a) stripping; (b) chemical modification; (c) trans-epidermal immunization (transcutaneous immunization or non-invasive vaccination of the skin); (d) gene gun technology; (e) electroporation; (f) intradermal injections; and (g) microseeding. These techniques all require the removal of hair, the circumvention or modification of the stratum corneum layer of the epidermis, and the addition of DNA or amplification of DNA signal. As the biology of the skin and the mechanisms of DNA vaccination are elucidated, these skin immunization techniques will be optimized. With refinement, skin-DNA immunization will achieve the goal of producing a reliable and efficacious immune response to a variety of pathogens.

Administration, Cutaneous↗

Neutralized lidocaine: use in pain reduction in local anesthesia.

The effect of pH neutralization on the pain experienced during intradermal lidocaine administration was investigated in a prospective blind study of 20 adult volunteers. A plain solution (pH congruent to 6.1) and three different buffered solutions of 1% lidocaine (pH values of 6.8, 7.0, and 7.2) were prepared, and a 0.5-mL intradermal injection of each was administered to the volar aspect of the forearm. Pain associated with lidocaine infiltration was rated with a linear visual analogue scale. Solutions with a pH of less than 6.8 (unbuffered lidocaine in this study) predictably produced a burning pain sensation on injection. However, buffering of 1% lidocaine above a pH of 6.8 significantly (P less than .05) reduced the mean quantitative pain estimates compared with the nonbuffered controls.

Adult↗

A single intradermal administration of soluble leishmanial antigen and plasmid expressing interleukin-12 protects BALB/c mice from Leishmania major infection.

In murine leishmaniasis, the induction of the T-helper type 1 (Th1) response contributes to infection resistance, whereas the establishment of the Th2 response makes the mice susceptible to infection. Interleukin-12 (IL-12) plays a pivotal role in the diversification of immune responses to the Th1 type. In this study, we tested whether the co-administration of IL-12 expression plasmid which compose p35 and p40 subunits and soluble leishmanial antigen (SLA) will skew the susceptible BALB/c mice to Th1 response and protect from leishmaniasis. When the mice were intradermally injected with the combination of IL-12 plasmid and SLA 7 days prior to the challenge with 1x10(6) promastigotes of Leishmania major, the local lesions completely healed and the parasite burden in the local lymph nodes significantly decreased. The cured mice attained long-term immunity, and were resistant to any subsequent rechallenge of the lethal dose of the parasite. The protective effect was associated with the development of a Th1 response, as demonstrated by the enhanced level of antigen-specific interferon-gamma (IFN-gamma) and dominant production of IgG2a in the serum. In contrast, the administration of empty plasmid plus SLA or IL-12 plasmid alone failed to protect the disease and shape the Th1 response. Furthermore, the protective efficiency induced by the vaccination was clearly prevented by the injection of either neutralizing anti-IL-12 mAb or anti-IFN-gamma mAb. The IL-12 expression plasmid is thus an effective adjuvant for the elicitation of a protective Th1 response against leishmaniasis and is therefore, considered to be appropriate for vaccinations that require the induction of Th1 type immunity.

Animals↗