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Effects of intradermally injected and topically applied mouse epidermal growth factor on wool growth, skin and wool follicles of merino sheep.

Twice daily intradermal (ID) injections of mouse epidermal growth factor (mEGF) in sterile saline for 1-4 days into delineated areas of skin of Merino sheep produced dose-dependent changes in wool follicles and fibres, ranging from slight reduction in follicle bulb size and transient disturbance of cuticle formation on some fibres to the induction of catagen of follicles and shedding of fibres with distorted, tapered ends. Regeneration of follicles commenced by day 7. By contrast, ID injections of saline did not affect follicle activity. The epidermis became thicker and more parakeratotic after multiple injections of mEGF than after injection of saline, but was almost normal again by day 14. Persistent small increases in sebaceous gland size, additional to those induced by ID injections of saline, and delayed small increases in sweat gland size also occurred after multiple injections of mEGF. Daily topical applications of mEGF in 50% (v/v) aqueous propylene glycol 5 days each week for 4 weeks did not affect wool growth or the follicles and other skin components. The only effect observed, due to application of the aqueous propylene glycol, was an increase in the number of layers of cornified cells in the stratum corneum of the epidermis, with the cells arranged in clearly discernible stacks. The effects produced by ID injections of mEGF indicate that mEGF acts directly on the pilosebaceous and epidermal components of skin.

Administration, Topical↗

Dose sparing with intradermal injection of influenza vaccine.

BACKGROUND: The loss of half the U.S. supply of influenza vaccine due to contamination has created a critical shortage. Dose-sparing strategies that use intradermal delivery of vaccines may be one approach to consider. METHODS: We conducted a randomized, open-label trial outside the influenza season in 100 healthy adults 18 to 40 years of age to compare the immunogenicity and safety of intradermal immunization with influenza vaccine with standard intramuscular immunization. Subjects were randomly assigned to receive either a single intramuscular dose of 0.5 ml of trivalent influenza vaccine, containing at least 15 microg of hemagglutinin per strain, by means of a prefilled syringe or a single intradermal dose of 0.1 ml, containing at least 3 microg of hemagglutinin per strain, by means of a fine-gauge needle; both injections were in the deltoid region. Changes in the hemagglutination-inhibition (HAI) antibody titer were assessed by comparing geometric mean titers and fold increases relative to baseline values and by comparing changes in the seroconversion and seroprotection rates. Local and systemic adverse events were assessed after both types of vaccination. RESULTS: Subjects who received an intradermal injection with one fifth the standard dose of influenza vaccine had increases in the geometric mean HAI titer by a factor of 15.2 for the H1N1 strain in the vaccine, 19.0 for the H3N2 strain, and 12.4 for the B strain on day 21, as compared with respective increases by a factor of 14.9, 7.1, and 15.3 for the intramuscular injection of the standard dose. Seroconversion and seroprotection rates were similar in the two groups on day 21, ranging from 66 to 82 percent and 84 to 100 percent, respectively. Local reactions were significantly more frequent among recipients of intradermal injections than among recipients of intramuscular injections, but such reactions were mild and transient. CONCLUSIONS: In this study of young adults, intradermal administration of one fifth the standard intramuscular dose of an influenza vaccine elicited immunogenicity that was similar to or better than that elicited by intramuscular injection. Intradermal administration could be used to expand the supplies of influenza vaccine, but further studies are needed before this strategy can be recommended for routine use.

Adolescent↗

The suppressive effect of tape-stripping treatment of guinea-pig skin on the induction of contact sensitivity by intradermal injection of haptenated epidermal cells.

Contact sensitivity (CS) to 2,4-dinitrochlorobenzene (DNCB) was produced in inbred JY1-strain guinea pigs by the intradermal injection of epidermal cells (ECs) prepared from DNCB-painted skin (DNP-ECs). When the site of DNP-EC-induced CS was pretreated by tape stripping, the rate and intensity of the challenge reactions to DNCB were diminished. The ability of DNP-ECs to induce CS returned to normal when normal peritoneal macrophages together with DNP-ECs were administered into the stripped skin. Normal ECs had a similar effect. Using either anti-Ia antiserum and complement or allogeneic ECs (strains 2 and 13), Ia-positive cells among the ECs (presumably Langerhans cells) were found to be essential for the recovery of CS. Tape-stripping treatment also resulted in the development of immunological tolerance, as assessed by subsequent painting with a sensitizing dose of DNCB. These findings suggest that the immunological function of the mononuclear-phagocyte system in the dermis may be impaired when the epidermal surface is markedly disturbed by tape-stripping treatment.

Adenosine Triphosphatases↗

Fine structures of the basophil infiltration in regional lymph nodes of the guinea-pig after the intradermal injection of T cell mitogens.

Basophil-rich infiltrates in regional lymph nodes of guinea-pigs were demonstrated by electron microscopy after the intradermal injection of T cell mitogens (PHA and Con A). Basophils infiltrated the stroma of the lymph node via the postcapillary venules (PCV) and migrated to the paracortex. Prior to infiltration of the lymph nodes a cutaneous basophil hypersensitivity reaction was seen in the mitogen-injected skin. B cell mitogen (LPS) injection did not induce this response.

Animals↗

Intradermal injection vs. oral treatment of tinnitus.

Local pharmacological intradermal infiltration is a therapy being used more and more thanks to the positive results achieved, particularly for all those therapies acting on the microcirculation. In trying to better the results obtained with medical therapy for tinnitus sufferers, to assess the effect of a vasoactive drug, the method of administration by the intradermal route, which allows a strengthening of the pharmacological effect, has been added. The present study comprised 120 tinnitus sufferers who underwent intradermal auricle infiltration with a vasoactive drug. The control group includes 115 tinnitus sufferers who underwent systemic vasoactive therapy with the same drug. Forty-five days after beginning intradermal treatment the symptom improved and continued to do so following further infiltrations which patients underwent every 15 days. In the control group we noticed a moderate improvement 45 days after the beginning of oral therapy; thereafter the results reached a plateau by the 60th day. Intradermal vasoactive therapy for idiopathic tinnitus seems to be a new success, which will be an interesting progression in the therapy of this kind of symptom.

Administration, Oral↗

Effect of repeated intradermal injections of bovine herpesvirus type 1 antigen on seronegative cattle.

Forty-three cattle seronegative to bovine herpesvirus-1 (BHV-1) were given from one to five intradermal injections of BHV-1 inactivated antigen at four-week intervals. This delayed hypersensitivity test was assessed by the increase in skin thickness. The activity of the antigen was assessed in five animals which had a previous natural BHV-1 infection with clinical signs and seroconversion. Anti-BHV-1 antibodies were detected by seroneutralisation and an enzyme-linked immunoassay. Only one animal showed a significant but slight increase in skin thickness after the first test, but it was negative after a second test. The animals remained seronegative after the first test. Seroconversion was identified in 11 of the 43 animals (25 per cent) submitted to repeated delayed hypersensitivity tests. Five of 37 animals seroconverted after only two tests. The serological response was transient in seven of 11 seroconverted calves. Repeated hypersensitivity tests were therefore able to induce a serological response in seronegative calves but the response was weak and often transient. The test must therefore be applied cautiously to seronegative animals.

Animals↗

Effect of intradermal injection of saline or a local anaesthetic agent on skin blood flow--a methodological study in man.

The influence of intradermal needle insertion and fluid injection on skin blood flow was investigated using laser Doppler flowmetry. Seventeen healthy, young male volunteers participated. Four test sites on each forearm (volar surface) were used in a randomized, double-blind study. Recordings were made at 20, 40, 60 and in Group III also at 90 min after needle insertion or intradermal injection. In Group I (n = 6) different volumes of saline (0.05, 0.1, 0.2, 0.3 and 0.5 ml) were injected, producing an increase in flow, there being no differences between the various volumes. In Group II (n = 4) needle insertions were made using different needle sizes (20 G, 23 G and 30 G), the larger ones being impractical to use. Increases in flow were seen, and were somewhat higher for the larger needles. Group III (n = 12) was studied regarding the effects of three local anaesthetic agents on skin blood flow (0.1 ml, 30 G needle). Injection of bupivacaine 0.75% produced a marked increase in flow, similar to lidocaine 1% but apparently longer lasting. Bupivacaine 0.25% caused less increase in flow, similar to the flow seen with saline. Injections of ropivacaine 0.75% and 0.25%, i.e. in clinical concentrations, caused a decrease in blood flow, this being most marked after 0.25%, indicating a unique flow-decreasing effect of this new local anaesthetic drug.

Adult↗

The effects of repeated dermal application of capsaicin to the human skin on pain and vasodilatation induced by intradermal injection of acid and hypertonic solutions.

1. The effect of repeated capsaicin application on the skin of the volar surface of the forearm on the pain sensation and on the increase in blood flow induced by intradermal injection of low pH media or hypertonic solutions was investigated in 13 healthy volunteers. 2. Low pH media (4, and 2.5) were obtained by adding HCl to 0.9% saline. Hypertonic solutions (300 and 600 mM) were obtained by adding NaCl to pH 7.4, 0.9% saline. Capsaicin (1% in 50% ethanol) was painted on the volar skin of one forearm, chosen at random, for 7 days. The contralateral forearm was treated with the capsaicin vehicle. Pain was assessed by a visual analogue scale and skin blood flow by a laser doppler flowmeter. 3. Pain sensation and increase in blood flow (both peak and area under the curve) induced by low pH media were markedly reduced in the capsaicin pretreated side. Capsaicin pretreatment also reduced the increase in blood flow, but did not affect the pain response induced by hypertonic saline solutions. 4. Repeated application of capsaicin to the human skin inhibits both the sensory (pain) and 'efferent' (vasodilatation) responses induced by low pH media, whereas it reduces the vasodilatation, but not the pain caused by hypertonic media. 5. Repeated application of capsaicin to the human skin, a therapy used in various diseases, discriminates between sensory, but not 'efferent' responses induced by different stimuli.

Acids↗

Intradermal injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with metastatic melanoma recruits dendritic cells.

Dendritic cells (DCs) are the main antigen-presenting cells in the skin. We hypothesized that intradermal (i.d.) injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) would recruit DCs into melanoma skin metastases and enhance autologous melanoma antigen presentation to host T cells. Sixteen patients with cutaneous or subcutaneous melanoma metastases were treated with GM-CSF injected i.d. into a single dermal metastasis and into a normal skin site for 10 consecutive days at one of four dose levels (10, 20, 40, or 80 microg/injection). Pretreatment and post-treatment skin and tumor biopsies were stained for a panel of T-cell, B-cell, macrophage, and DC immunohistochemical markers. Positive cells were quantitated in a blinded fashion. There was a significant increase in the number of DCs (HLA-DR+, S100+, factor XIIIa+) and CD45R0+ T cells in the skin and in the tumors Injected with GM-CSF at all dose levels. Uninjected control tumors showed no increase in HLA-DR+ cells or T-cell infiltrate, but did show an Increase in S100+ and factor XIIIa+ cells, suggesting a non-DC population. ID GM-CSF administered in this manner recruited DCs into melanoma tumors and normal skin. Although no antitumor effects were seen, this represents a potential method of preparing skin sites for vaccine delivery.

Antigen Presentation↗

What happens if intradermal injections of rabies vaccine are partially or entirely injected subcutaneously?

Reported are the results of a study with the Thai Red Cross two-site intradermal purified Vero-cell rabies vaccine (PVRV) schedule that was deliberately injected into subcutaneous tissue. The 44 healthy nonimmune Thai adults who were enrolled in the study were randomly assigned to the following groups and given PVRV as shown: group A (two intradermal injections on days 0, 3, and 7); group B (one intradermal and one subcutaneous injection on days 0, 3, and 7); and group C (two subcutaneous injections on days 0, 3, and 7). Neutralizing antirabies antibody titres were determined on day 14 using the rapid fluorescent focus inhibition test. High rabies antibody titres were obtained for all three groups. These results suggest that the economical and safe Thai Red Cross intradermal PVRV regimen could be used in selected general health care facilities.

Adolescent↗

Nitric oxide synthase in spinal cord central sensitization following intradermal injection of capsaicin.

Nitric oxide (NO) is believed to be an important messenger molecule in signal transduction pathways that enhance nociceptive transmission in the central nervous system (CNS). The role of nitric oxide synthase (NOS) I and II, which synthesize NO, in central sensitization induced by an intradermal capsaicin injection was investigated. To elucidate whether changes in NOS I and NOS II activities caused by capsaicin injection contribute to behavioral changes, responses to von Frey filaments with two different innocuous bending forces applied on the rat foot were tested. The allodynic responses induced by capsaicin injection in the foot were partially reversed by the administration of either the selective NOS I inhibitor, 7-nitroindazole (7-NINA), or the selective NOS II inhibitor, 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT). To confirm changes at the level of single nociceptive neurons, extracellular recordings were made from rat dorsal horn neurons. The electrophysiological results showed that increased responses to noxious and innocuous stimuli caused by capsaicin injection were blocked by either 7-NINA or AMT delivered through a microdialysis fiber inserted through the dorsal horn. Finally, the expression of both NOS I and NOS II in the spinal cord as demonstrated by Western blots was increased by 20 min following intradermal capsaicin injection in the rat foot. These results suggest that both NOS I and NOS II are upregulated following intradermal capsaicin injection and that both cause NO release that contributes to the secondary hyperalgesia and allodynia following this noxious chemical stimulus.

Animals↗

Protection of cattle against experimentally induced salmonellosis by intradermal injection of heat-killed Salmonella dublin.

A single intradermal dose (7.5 mg) of heat-killed Salmonella dublin protected two out of three cattle against intravenous challenge with live S dublin. A second dose of 8 mg increased the protection rate to six out of seven. Four of the survivors had transient diarrhoea and S dublin was recovered from the carcases of four killed at four to 21 weeks after infection. Protected animals had elevated serum antibody titres and their serum passively protected rats against intraperitoneal challenge. The resistance of vaccinated cattle, presumably immunological in character, was not associated with leucocyte migration inhibition by salmonella antigen, depression of serum iron levels or haematological changes.

Animals↗

Late asthmatic reactions provoked by intradermal injection of T-cell peptide epitopes are not associated with bronchial mucosal infiltration of eosinophils or T(H)2-type cells or with elevated concentrations of histamine or eicosanoids in bronchoalveolar fluid.

BACKGROUND: Isolated late asthmatic reactions can be provoked by intradermal challenge of allergen-derived T-cell peptide epitopes. OBJECTIVE: The purpose of this study was to determine whether the isolated LAR is associated with the local accumulation of inflammatory cells, the expression of T(H)2 cytokines, and the production of pharmacologic mediators. METHODS: A randomized, placebo-controlled, crossover study design was used. The investigation involved bronchial and skin biopsies and bronchoalveolar lavage (BAL) fluids from 8 cat-allergic subjects who developed significant late asthmatic reactions 6 hours after intradermal injection of Fel d 1 chain 1-derived peptides (FC1Ps). RESULTS: Immunostaining of bronchial biopsy specimens showed no changes in the numbers of eosinophils, neutrophils, basophils, mast cells, CD3(+), CD4(+) or CD8(+) T cells, CD25(+) cells or macrophages, or cells mRNA(+) for IL-4, IL-5, or IL-13 when the FC1P day was compared with the diluent control day. There were also no significant differences in eosinophil numbers, either in BAL fluids or in peripheral blood after FC1P challenge. Furthermore, there were no significant alterations in the concentrations of histamine, histamine-releasing factors, or eicosanoids (LTC(4)/D(4)/E(4), PGD(2), PGE(2), TXB(2), PGF(2alpha)) in BAL fluids. FC1Ps induced a significant (P <.05) elevation in CD8(+) cells in the skin and an unexpected decrease in IL-5 in BAL fluids (P =.043). CONCLUSION: Part of the asthma process might involve T cell-dependent airway narrowing with no requirement for IgE, mast cells, or infiltrating inflammatory cells.

Adult↗

Dermal cellular responses of helminth-free and Ostertagia ostertagi-infected calves to intradermal injections of soluble extracts from O. ostertagi L3 larvae.

Twelve calves were raised helminth-free until 9 weeks of age when six were orally inoculated with 100,000 Ostertagia ostertagi infective stage larvae (L3). Three uninfected and three experimentally infected calves received intradermal injections of sterile saline and soluble larval extract (SLE) from O. ostertagi L3 with a protein concentration ranging from 1 to 200 micrograms ml-1. Biopsies were performed 48 h post-injection. A kinetic study was performed on the remaining six calves, three infected and three uninfected, using a 100 micrograms ml-1 concentration of SLE and taking biopsies 1, 4, 8, 12, 24, and 72 h post-injection at both the saline and SLE-injected sites. All calves had an immediate wheal and increase in skin thickness at the SLE-injected sites. The numbers of eosinophils infiltrating SLE-injected sites as compared to saline-injected sites were significant in both uninfected and infected calves, but the infected calves had significant numbers to a wider range of SLE concentrations and had significantly higher numbers than uninfected calves in the kinetic study. Infected calves also had significant numbers of basophils in the dose response study at concentrations of 5 and 100 micrograms ml-1 SLE. Neutrophil infiltration was similar in both groups and was significant at SLE-injected sites early in the kinetic study. Detectable mast cells were decreased in SLE-injected sites of infected animals and perivascular accumulation of mononuclear and some polymorphonuclear cells was observed in the deep dermis of infected animals.

Animals↗

An anatomo-clinical study of delayed skin allergic reactions to nickel following intradermal injections of lidocaïne with a Dermo-jet.

10 women allergic to nickel developed skin reactions at injection sites with a Dermo-Jet (Krantz model) of (a) 2% lidocaine solution and (b) 0.9% saline solution. 10 women (age-matched) not allergic to nickel were selected as controls and submitted to the same injections; they had no positive reactions. Various controls (including injections with a needle and patch tests) were made in both groups. Nickel was leached into fluids from the metallic internal parts of the Dermo-Jet. The positive reactions were allergic and due to nickel. Histology showed changes of an allergic contact dermatitis with particular features, probably due to the intradermal injection of nickel. Some practical implications regarding the quality of medical instruments are discussed.

Biopsy↗

Prevention of tumor growth after intradermal injection of BCG extracts: a comparison of results in strain-2 guinea pigs from the National Institutes of Health and from the National Jewish Hospital and Research Center.

Line 10, a transplantable hepatocellular carcinoma, was obtained originally from an NIH strain-2 male guinea pig fed diethylnitrosamine. The antitumor activity of BCG and BCG extracts was evaluated in strain-2 guinea pigs obtained both from NIH and the National Jewish Hospital and Research Center (NJH). Animals were immunized with these materials and then tested for their capacity to resist the growth of intradermally injected line-10 tumor cells. Tumor growth was not prevented in 18 NIH animals immunized with living BCG. No tumor growth occurred in 1 of 22 NIH animals immunized with a residue that remained after exhaustive methanol extraction of BCG and in 1 of 44 NIH guinea pigs immunized with BCG extracts. In contrast, tumor growth was prevented in 13 of 22 similarly immunized NJH guinea pigs.

Animals↗