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Effect of intradermal injection of methionine-enkephalin on human skin.

Methionine-enkephalin (met-enk) detected in monocytes in psoriatic skin can modulate inflammatory processes and keratinocyte differentiation/proliferation in vitro. The purpose of the present study was to determine the effect of intradermal injection of met-enk on normal human skin and on the development of a delayed type skin hypersensitivity reaction. In 6 healthy volunteers, 50 microl of met-enk (16, 30, and 45 nmol) was injected once in the forearm and the reaction was evaluated clinically and by video-optical recording for 120 min. Compared to vehicle (0.9% saline), met-enk induced a time- and dose-dependent flare reaction, but no significant stimulation of a weal reaction. The flare reaction was maximal after 1 min and disappeared within 45 min. Pre-treatment with the antihistamine cetirizine reduced the flare reaction. Furthermore, the effect of met-enk on lymphocyte/monocyte infiltration and epidermal proliferation in normal skin and on a delayed type skin hypersensitivity reaction was assessed. Met-enk (45 nmol/ 50 microl) was injected at 0, 24 and 48 h. In normal skin, met-enk increased the number of dermal lymphocytes/monocytes (CD3/CD68 positive cells) and the degree of epidermal proliferation (MIBI-Ki67). In a delayed type hypersensitivity reaction induced by tuberculin (PPD), the degree of epidermal proliferation and the number of infiltrating lymphocytes/monocytes were reduced compared to PPD alone. Our study suggests that intradermal injection of met-enk in normal human skin induces an inflammatory reaction that may involve the release of histamine. In contrast, met-enk seems to down-regulate the development of a delayed type skin hypersensitivity reaction. These results may indicate that the direction of the effect of the opioid peptide met-enk on human skin depends on the rate of epidermal proliferation and the activity of immunocompetent cells.

Adult↗

Cellular responses to the intradermal injection of recombinant human gamma-interferon in lepromatous leprosy patients.

The local response to a single intradermal injection of 10 micrograms recombinant gamma-interferon (rIFN gamma) has been studied in 17 patients with lepromatous leprosy. Of these, 2 patients additionally received two intradermal injections of 10 micrograms rIFN gamma at another site. The results were compared with those of 3 patients who received three injections of the same dose at a single site in an earlier study. One to 7 days after lymphokine administration 4-mm punch biopsies were obtained and examined for cellular alterations in the dermis and epidermis. This allowed a kinetic analysis of mononuclear cell infiltration, keratinocyte proliferation and differentiation, and Langerhans cell redistribution. At 24 hours, the migration of large numbers of helper T cells and monocytes was already prominent and associated with induration. Mononuclear cell accumulation peaked at 72 hours but then persisted for 5-7 days. Only small numbers (one-third or less of total T cells) of suppressor/cytotoxic T cells were present at any time, and granulocytes were absent. Two daily injections of rIFN gamma led to a more intense accumulation of cells. Ten micrograms of rIFN gamma resulted in enhanced keratinocyte proliferation, Ia expression, and thickening of the epidermis. At 24-48 hours major histocompatibility Class II (Ia) antigen was first noted on the dividing cells of the basal layer. By 72-96 hours the entire epidermis exhibited strong expression of Ia antigen on cell surfaces. Repeated doses of lymphokine accentuated these changes and resulted in a more prompt keratinization and sloughing of this layer. Whereas a single dose of rIFN gamma resulted in the upward movement of T6+ Langerhans cells (LCs) in the epidermis, two injections led to a 50% reduction in their numbers and three doses were associated with an almost total loss of detectable T6+ LCs from the epidermis. These are probably sloughed along with keratinocytes. In contrast to the situation with a delayed immune response in the skin (purified protein derivative), no LCs accumulated in the dermis in association with helper T cells.

Animals↗

Treatment of facial lipoatrophy with intradermal injections of polylactic acid in HIV-infected patients.

BACKGROUND: This study assessed the safety and efficacy of intradermal injections of polylactic acid (PLA) in patients with facial lipoatrophy under antiretroviral therapy. METHODS: In a prospective open-label study, PLA was injected in both cheeks every 2 weeks. The primary efficacy endpoint was the patient's self-perception of improvement as assessed by a visual analogue scale (VAS). Secondary endpoints included 3-dimensional photographs (3DP) to measure dermal thickness, quality of life (QoL) scores, and adverse events. RESULTS: Ninety-four patients received a median of 5 sets of injection in both cheeks. Median age was 43 years, and median CD4 cell count was 500/mm3. Median VAS score significantly increased from 3.4/10 at baseline to 6.8/10 at the end of the treatment procedure and was sustained at 7/10 at the end of follow-up (P < 0.0001 vs. baseline). Median dermal thickness increase was 2.3 mm at the end of follow-up. QoL scores remained unchanged. Seventeen patients needed further injections of PLA during a median follow-up of 12 months. Injections were well tolerated with only 1 serious adverse event (anaphylactic reaction) that necessitated treatment interruption. CONCLUSIONS: Injections of PLA improved patients' self-perception of facial lipoatrophy, with a good safety profile. The benefit of the procedure, however, decreased with time.

Adult↗

Lymphoscintigraphy in patients with lymphedema. A new approach using intradermal injections of technetium-99m human serum albumin.

Forty cases were examined by a new lymphoscintigraphic approach using intradermal injections of Tc-99m human serum albumin (HSA). Thirty-three patients had lymphedema due to the metastases of a malignant tumor and/or the dissection of lymph nodes. The others were control patients without lymphedema. With the assistance of a computer, sequential images and time-activity curves of tracer activity in the lymph nodes and the soft tissue were obtained at 30 minutes after injection. An image of the axillary or inguinal lymph nodes was identified 2-6 minutes after injection in control cases. Four main abnormal findings, the delayed appearance of radioactivity and interruption of the lymphatic system, the collateral pathways, and the retrograde lymphatic flow were observed clearly, as was the nonvisualization of the lymph nodes. These abnormalities were observed in a high percentage of patients with moderate lymphedema, as compared with a low percentage of patients with slight lymphedema. The collateral pathways could not be observed in patients with severe lymphedema. Imaging with Tc-99m HSA was considered to be more useful than other techniques, including radiocolloid lymphoscintigraphy, for examining patients with lymphedema.

Adult↗

[Assessment of autonomic nervous function in impotence using sweat response induced by intradermal injection of acetylcholine].

It is important to evaluate the autonomic nervous function which controls penile erection. One method utilizes intradermal injection of acetylcholine to produce localized sweat response. The sweat response depends on the peripheral autonomic nervous supply. Therefore, the response can be used to detect peripheral autonomic nervous dysfunction. We tried to evaluate the peripheral autonomic dysfunction in 29 impotence using a sweat spots test. We classified the 29 impotence into 6 groups with standard tests such as the papaverine test, nocturnal penile tumescence monitoring, recordings of bulbocavernous reflex, etc. The results were as follows: psychogenic IMP; 8, neurogenic IMP; 8, arterial insufficiency; 5, corporeal veno-occlusive insufficiency; 6 neurogenic with arterial insufficiency; 1, and neurogenic with corporeal veno-occlusive insufficiency; 1. The score of sweat spots test was 25.3 +/- 10.9, being in normal, nineteen severe in 3 and slightly abnormal in 7. Many cases of severe and slightly abnormal patients were DM patients classified into neurogenic IMP. We found 2 cases that were not detected by bulbocavernous reflex but found to be abnormal by sweat spots test. Therefore we conclude that this test effective to detect the autonomic nervous dysfunction in impotence.

Acetylcholine↗

Comparison of intradermal injections of bromodeoxyuridine and tritiated thymidine in the in vivo measurement of epidermal cell turnover time in goats.

Study of keratinisation defects such as seborrhoea may require investigation of epidermal cell kinetics in clinical cases. For this to be practically useful a safe, reliable and quick method is essential. This study compared epidermal cell kinetics in the goat following the use of intradermal injection of tritiated thymidine ([3H]TdR) and bromodeoxyuridine (BURD) to label S phase nuclei. Turnover time for goat epithelial cells was not significantly different for the two agents; 26.3 +/- 6.0 days for thymidine and 21.8 +/- 5.2 days for BURD. It was concluded that intradermal injection of BURD will be a suitable technique for investigating epidermal cell kinetics in vivo and could have applications in a clinical situation because it is quicker and safer than [3H]TdR.

Animals↗

Laser Doppler flowmetry for determining changes in cutaneous blood flow following intradermal injection of histamine.

The use of laser Doppler flowmetry (LDF) in determining changes in cutaneous blood flow following intradermal injection of histamine has been investigated in this double-blind study. In eight subjects blood flow (LDF) and weal-and-flare area (planimetry) were measured at regular intervals for 1 hr following 50-microliter injections of different concentrations of histamine (6.5 X 10(-5)-6.5 X 10(-3)M) and saline. The mean maximum increase in LDF values over the flare was at least nine-fold greater than the baseline values for all three concentrations of histamine injected. When the LDF values observed at different sites were integrated to obtain the 'LDF response' it was possible to demonstrate concentration-related increases in blood flow and to differentiate clearly between the different concentrations of histamine and saline for up to 30 min after injection. During this period, the repeatability and the time course of the LDF response was comparable with that of the flare area. These studies suggest that the noninvasive technique of LDF is a sensitive and reproducible method for quantifying the changes in cutaneous blood flow that occurs for the first 30 min after intradermal injection of histamine.

Administration, Cutaneous↗

Intradermal injection of transforming growth factor-beta1 gene enhances wound healing in genetically diabetic mice.

PURPOSE: To evaluate the biologic effect of direct cutaneous TGF-beta1 gene delivery on impaired wound healing models using genetically diabetic mice. METHODS: Diabetic mice (C57BKS.Cg-m +/+ Leprdb female mice) with 1 cm x 1 cm excisional wounds were intradermally injected with 60 microg of plasmid DNA encoding TGF-beta1 gene. The wound closure was measured up to 14 days postwounding. At days 7 and 14 postwounding, sections of skin were taken for hematoxylin and eosin and Masson's trichome staining to examine the morphology and collagen deposition. The cell proliferation and TGF-beta1 gene expression were studied using immunohistochemical stainings for 5-bromo-2-deoxyuridine and for TGF-beta1. RESULTS: A higher cell proliferation rate and a denser and more organized new extracellular matrix were observed in the treated wound site. Complete wound closure was detected as early as 7 days for TGF-beta1-treated group in comparison with 11-14 days for the untreated, control plasmid DNA- and PBS-treated groups. CONCLUSION: A single intradermal injection of TGF-beta1 plasmid DNA was sufficient to enhance wound healing. This approach represents a new strategy that may be applied to the treatment of excisional wounds in human diabetic patients.

Animals↗

Pathological changes in calves injected intradermally with Mycobacterium intracellulare serotype Davis and M. avium serotype 2.

Three strains of the M. intracellulare-M. avium complex were injected intradermally into 12 calves. M. intracellulare serotype Davis (M. avium complex serotype 8) was injected into five calves. One calf died with disseminated caseous granulomas at 79 days; three calves killed between 56 and 82 days after inoculation had widely disseminated caseous or caseous or caseocalcareous granulomas. One calf killed at 173 days had only encapsulated granulomas at the injection site and its regional lymph node. Two strains of M. avium serotype 2 (M. avium complex serotype 2) were injected intradermally into seven calves. Six had disseminated granulomas when killed 54-170 days after inoculation. One calf killed at 55 days had granulomas confined to the inoculation sites and their regional lymph nodes. Lesions induced by both M. avium serotype 2 and M. intracellulare serotype Davis were initially caseocalcareous granulomas which became encapsulated and nonprogressive after about 112 days. Two calves inoculated with similar doses of M. bovis and killed in extremis at 37 and 65 days after inoculation had disseminated progressive lesions without encapsulation.

Animals↗

Inflammatory responses to intradermal injection of platelet activating factor, histamine and prostaglandin E2 in healthy volunteers: a double blind investigation.

1. The local responses to intradermal injection of PAF, histamine and PGE2 were investigated in eight healthy male volunteers. Acute effects were monitored by weal and flare measurement; delayed effects were investigated by pain threshold testing and skinfold thickness measurements. 2. PAF and PGE2 were found to induce weal and flare responses which were clearly distinguishable from vehicle and dose related. 3. PAF was approximately 50 times as potent as PGE2 at inducing weal on a molar basis. 4. A dose related hyperalgesia was recorded in response to PGE2. No hyperalgesia could be demonstrated following PAF injection compared with vehicle. 5. PAF and histamine elicited an increase in skinfold thickness up to 2 h after injection which was distinguishable from vehicle.

Dinoprostone↗

Reactions to intradermally injected substance P and topically applied mustard oil in atopic dermatitis patients.

Skin reactions and itch or burning pain sensations following intradermal injection of the neuropeptide substance P and topical application of the substance P releasing agent mustard oil were studied in 20 atopic dermatitis patients and 20 healthy controls. Changes in skin blood flow were measured with a Laser Doppler flowmeter. Areas of wheal and flare reactions were evaluated planimetrically. Simultaneous with Laser Doppler flowmeter measurements, subjective itch and burning pain ratings were verbally reported on a category partitioning scale at 10-second intervals. Substance P evoked dose-dependent wheal, flare, and itch reactions in both patients and controls. However, substance P doses of 10(-9) -10(-11) mol elicited smaller flares in patients than in the controls whereas the wheal sizes were similar in both groups. Substance P-induced itch ratings were lower in patients at a dose of 10(-10) mol, and the onset of itching was delayed at all substance P levels applied. Mustard oil elicited similar neurogenic inflammatory reactions in both groups, although pain sensations were significantly delayed in atopic dermatitis patients at two mustard oil concentrations, which is further indication of a desensitization of afferent nerve endings contributing to the neurogenic inflammatory reactions in the skin of these patients.

Acute Disease↗

Reactivity to intradermal injections of extracts of house dust and housedust mite in healthy dogs and dogs suspected of being atopic.

Fifty dogs underwent intradermal allergy testing with housedust mite and house dust extracts, using concentrations recommended by the manufacturer. Twelve dogs (group I) were healthy dogs obtained from a pound; 12 dogs (group II) were healthy, privately owned dogs; 15 dogs (group III) were suspected of being atopic and had had multiple positive reactions to intradermal injections of allergens of specific trees, weeds, grasses, or molds; and 11 dogs (group IV) were suspected of being atopic, but only had had positive reactions to intradermal injections of housedust mite, house dust, and flea antigen extracts. Use of the concentrations of housedust mite and house dust extracts currently recommended for intradermal allergy testing resulted in false-positive reactions in 14 of 24 (58%) and 12 of 24 (50%) healthy dogs tested, respectively. Differences in number of dogs with positive reactions or grade of reaction to housedust mite or house dust allergens were not detected between groups of healthy dogs (groups I vs II), between groups of suspected atopic dogs (groups III vs IV), or between healthy dogs and dogs suspected of being atopic (groups I and II vs III and IV). Therefore, clinical importance of positive results of intradermal allergy testing of house dust or housedust mite allergens was equivocal for dogs suspected of being atopic. Threshold concentrations for intradermal allergy testing were determined in 24 healthy dogs (group I and II) by intradermal administration of 5 dilutions each of housedust mite extract and house dust extract.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Analysis of technical and clinical variables affecting sentinel node localization in patients with breast cancer after a single intradermal injection of 99mTc nanocolloidal albumin.

AIM: To investigate the technical, clinical and pathological findings that can, potentially, affect pre-operative lymphoscintigraphy in visualizing sentinel lymph node (SLN) and intra-operative probe detection of SLN in patients with breast cancer. METHODS: One hundred and forty-two consecutive female patients with, clinically, a solitary, small breast cancer and clinically N0 axilla were enrolled. Preoperative lymphoscintigraphy was performed by a single intradermal injection of 99mTc nacolloidal albumin (Nanocoll) the day before surgery. For radioguided surgery two gamma probes with diameters of 11 mm and 15 mm, and set up with a count rate ranging from 1 to 4 s were used. The following variables were evaluated: patient's age, radiotracer dose, volume of injectate, primary tumour location, primary tumour size, and presence and extension of axillary nodal metastases. RESULTS: Lymphoscintigraphy showed high sensitivity in visualizing the SLN (98% success rate) and it resulted in a rapid technique since SLN was visualized within 30 min from injection in 85.21% of cases for the whole series. The probe detection rate was also very high (97.8% success rate): the mean per cent uptake in the SLN was 0.98. Statistical analysis showed that no parameter was found to have significantly influenced either SLN visualization at lymphoscintigraphy or SLN probe detection at surgery. CONCLUSION: In our experience, lymphoscintigraphy performed by a single intradermal injection of Nanocoll was an effective and rapid technique for visualizing axilla SLNs in breast cancer patients. Moreover, this technique appeared to be independent of any technical, clinical and pathological findings.

Aged↗

[Efficiency of lymphatic mapping by intradermal injection of vital blue dye for sentinel node identification in T1-2 N0-1 M0 stage breast cancer patients].

The lymphatic mapping and sentinel lymphadenectomy procedure is a highly accurate method of axillary staging in breast cancer. Because no other method accurately predicts axillary node status without complete axillary dissection, this technique has a potential to become the standard method of axillary staging for breast cancer in near future. The aim of the study was to evaluate efficiency of lymphatic mapping by intradermal injection of vital blue dye for sentinel node identification in T(1-2) N(0-1) M(0) stage breast cancer patients. The sentinel lymph node biopsy with total axillary dissection was performed in 36 patients. The efficiency of lymphatic mapping by intradermal injection of vital blue dye (identification rate) was 97,2%, specificity--100% and the false-negative rate was 2,8%.

Adult↗

Histological study on the fate of haptenated epidermal cells injected intradermally in guinea pigs.

The percutaneous administration of in vitro haptenated epidermal cells (EC) has become established as a procedure to produce contact sensitivity (CS) in experimental animals for routine use. The cells have also been found to elicit a significant delayed-type skin reaction by intradermal test in the animals sensitized by painting the skin with the hapten. The fate of 2,4-dinitrophenylated (DNP) isogeneic epidermal cell suspensions (EC) injected intradermally was investigated histologically in intact or 2,4-dinitrochlorobenzene (DNCB)-sensitized strain 13 guinea pigs to study the role of the cells in CS. DNP-EC were found to proliferate actively in the dermis and formed EC nests with central keratinization and then elicited inflammatory reaction associated with necrosis of the epidermal structures 7 days after injection in the intact animals. DNP-EC injected intradermally into the animals which had received and reacted against DNCB underwent a suppression of EC proliferation. These findings are discussed in relation to the role of the haptenated EC in CS.

Animals↗

Side-controlled intradermal injection of botulinum toxin A in recalcitrant axillary hyperhidrosis.

BACKGROUND: Although topical application of aluminium chloride is the most common measure against axillary sweating, severely affected patients often undergo surgical procedures that are expensive and may have considerable side effects. Recently botulinum toxin A (BT-A) has been reported as a potentially effective antihyperhidrotic agent. OBJECTIVE: Our purpose was to determine the therapeutic strength, safety, and mode of application of BT-A in severe axillary hyperhidrosis. METHODS: Intradermal injection of BT-A (Dysport) was given in an open left-versus-right side trial with each patient being his own control for initial efficacy, followed by treatment of the contralateral side. RESULTS: Seven days after initial treatment sweat production fell to below 10% of the untreated contralateral axilla as determined by gravimetry. Satisfaction was rated unanimously as "very good," the highest of 5 rankings. No side effects such as skin irritation or muscle weakness were noted in any patient. CONCLUSION: Intradermal injection of BT-A is a potent and well-accepted therapeutic option in patients with recalcitrant axillary hyperhidrosis.

Adult↗

Local anesthetic effect of tramadol, metoclopramide, and lidocaine following intradermal injection.

BACKGROUND AND OBJECTIVES: We observed clinically that tramadol and metoclopramide appear to have local anesthetic action. Tramadol is a central-acting analgesic. Metoclopramide is a commonly used antiemetic. The local anesthetic effect of tramadol in reducing propofol injection pain has never been mentioned, although it was speculated with metoclopramide. METHODS: We conducted a double-blind, placebo-controlled study by injecting tramadol or metoclopramide intradermally in 10 healthy volunteers (5 men, 5 women; age 25-56 years). Each subject received 0.5 mL of four solutions in random order on the volar side of the forearm. These solutions were 25 mg tramadol, 5 mg metoclopramide, 5 mg lidocaine, and 0.5 mL normal saline. Pain on injections and the degree of local anesthesia (tested by pinprick, light touch, and cold) at each site was reported on a 0-3 scale at designed time intervals. RESULTS: Like 1% lidocaine, tramadol and metoclopramide demonstrated loss of sensation for pinprick, light touch, and cold for 15 minutes after intradermal injection (P < .01 ). CONCLUSIONS: Intradermal tramadol or metoclopramide can produce local anesthetic effect.

Adult↗