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Complete seroconversion by low-dose intradermal injection of recombinant hepatitis B vaccine in hemodialysis patients.

The present study was undertaken to find out if the seroconversion rate of hemodialysis (HD) patients was enhanced by the intradermal (i.d.) inoculation of recombinant hepatitis B (HB) vaccine. Thirty-five HBs-Ag, HBs-Ab and HBc-Ag, HBc-Ab negative HD patients were divided into three groups: 14 patients in group I received 5 micrograms HBs Ag i.d. every 2 weeks, 13 patients in group II were given 2.5 micrograms HBs vaccine i.d. every 2 weeks, 5 times, then every week. The remaining 8 patients in group III were immunised with 10 micrograms HBs Ag every 4 weeks 5 times intramuscularly (i.m.), then 5 micrograms i.d., every 2 weeks until complete seroconversion. Antibody response to i.m. injection was poor and only 37.5% of patients developed anti-HBs at a titer of 10 mIU/ml or more at 16 weeks after the start of immunisation. However, this poor response was improved by i.d. injection. The time of seroconversion was significantly earlier and the rate of response was higher in group I. The poor response in group II was markedly improved by doubling the inoculation rate. Overall, 100% of seroconversion was finally obtained by multiple i.d. immunisation. However, the anti-HBs titers were lower in all patients and declined in some patients after the immunisation was stopped. The last seroconverted patient in each group lost protective antibody levels at the 39th week. These patients became antibody positive again at the 52nd week with a booster dose. We feel that the i.d. route remains a useful and cheaper method of obtaining prophylaxis against HBs in high-risk HD patients but it would seem to be prudent to monitor these patients serially to assess the persistence of anti-HBs in the serum.

Adult↗

Pain and hyperalgesia after intradermal injection of bradykinin in humans.

Pain and hyperalgesia, the perceptual campanions of tissue injury and inflammation, are thought to be in part attributable to the sensitization of primary afferent nociceptors by endogenously released chemicals, such as bradykinin. Bradykinin (0.1 to 10 nmol in 10 microliters) evoked a dose-dependent pain, hyperalgesia to heat stimuli, and wheal and flare when injected in a double-blind manner into the volar forearm intradermally. Though hyperalgesia to mechanical stimuli is a conspicuous feature of inflammatory pain, none was measurable for any of the bradykinin doses in response to graded nylon monofilament probes. A second injection of bradykinin (5- or 30-minute intervals) at the same site produced markedly less pain and hyperalgesia to heat stimuli, indicating that the algesic and hyperalgesic effects of bradykinin undergo tachyphylaxis. These findings suggest that bradykinin alone cannot account for all aspects of the hyperalgesia that occurs after inflammation.

Adolescent↗

Lidocaine intradermal injection--a new approach in tinnitus therapy: preliminary report.

The efficacy of lidocaine in controlling tinnitus is well documented. It can be administered intravenously or by transtympanic injection. The first method of delivery can produce cardiovascular and central nervous system adverse reactions. The transtympanic injection can bring about slight sensorineural hearing loss, vertigo, vomiting, and taste disturbances. To improve on results obtained in persons with tinnitus, the vasoactive drug lidocaine was delivered by a novel intradermal route in 68 patients. The control group, which received intradermal saline injection, included 20 patients with tinnitus. As parameters of evaluation, the self-evaluation scale of subjective disturbance and tinnitus loudness were considered. Significant improvement in level of disturbance and tinnitus loudness was observed both in patients with tinnitus intensity less than 10 dB and in those with tinnitus intensity greater than 10 dB. No significant results were observed in the control group. Of particular interest was the complete absence of unpleasant complications with intradermal lidocaine.

Adult↗

Intradermal injection of norepinephrine evokes pain in patients with sympathetically maintained pain.

Tissue injuries, with or without involvement of nerves, may lead to ongoing pain and hyperalgesia to external stimuli. In a subset of patients, the pain is maintained by sympathetic efferent activity (SMP). We investigated if the peripheral administration of the alpha-adrenergic agonist, norepinephrine (NE), in physiologically relevant doses resulted in pain in patients with SMP. To establish the dose of intradermal NE required to induce cutaneous vasoconstriction, NE (1 nM-10 microM, 30 microl) was injected under a laser Doppler probe on the volar forearm of seven normal subjects. A decrease in blood flow was evident at a dose of 10 microM. Twelve patients (five male, seven female) diagnosed to have SMP based on the decrease in pain by a local anesthetic sympathetic blockade (70+/-6%) were enrolled in the study. Pain ratings were obtained continuously for 5 min after intradermal injections of saline and NE (0.1-10 microM) into their hyperalgesic zone and the mirror-image contralateral side. Injections were done during the period of pain relief following a local anesthetic sympathetic blockade. Similar injections were made in eight control subjects. On the affected side of the patients, the two highest concentrations of NE (1 and 10 microM) caused significantly more pain than saline (P<0.05, ANOVA). In contrast, there was no significant pain induced by the NE injections in the unaffected side and in control subjects. Six of nine patients tested reported a marked decrease in pain and hyperalgesia following infusion of phentolamine (1 mg/kg over 10 min). Two of the three patients who did not receive pain relief following phentolamine infusion also did not report pain to the NE injections. We conclude that NE injections produce pain in SMP patients at doses that are at the threshold for producing vasoconstriction. These studies support a role for cutaneous adrenoceptors in the mechanisms of sympathetically maintained pain.

Adrenergic alpha-Agonists↗

The cell-mediated immune response induced by plasmid encoding bovine herpesvirus 1 glycoprotein B is enhanced by plasmid encoding IL-12 when delivered intramuscularly or by gene gun, but not after intradermal injection.

Bovine herpesvirus 1 (BHV-1) causes respiratory and genital infections in cattle. Previously we demonstrated that a DNA vaccine encoding a truncated, secreted form of BHV-1 glycoprotein B (tgB) induces cytotoxic T lymphocyte (CTL) responses in C3H mice. In this study we investigated the potential of interleukin 12 (IL-12) to further enhance the CTL response. C3H mice were immunized with a plasmid encoding tgB or with plasmids encoding tgB and murine IL-12. When the plasmid encoding tgB was delivered intramuscularly or epidermally by a gene gun, co-administration with IL-12 plasmid stimulated the synthesis of more IgG2a, the production of higher levels of IFN-gamma, and more effective killing by CTLs. In contrast, after intradermal delivery no effect of co-administration of IL-12 encoding plasmid was observed. Further investigation suggested that antigen and IL-12 need to be expressed in the draining lymph nodes, where IL-12 can have a direct effect on T cells.

Animals↗

Factors affecting the quantitative response of human eccrine sweat glands to intradermal injections of acetylcholine and methacholine.

1. Using a ventilated capsule in conjunction with an infra-red water vapour analyser, and an indwelling intradermal needle, quantitative studies were made relating the magnitude of the sweat responses to the doses of acetylcholine or methacholine.2. Acetylcholine dose-response curves were constructed, and from these curves the threshold dose was defined. The threshold was similar in all subjects (10(-3) +/- S.E. 10(-4) mug/0.1 ml.).3. Factors affecting the acetylcholine dose-response curves were studied. Optimum conditions for stimulation in all subjects occurred using a capsule of 0.63 cm diameter, injection volume of 0.1 ml. and a solution temperature of 37 degrees C. When the skin temperature was 36 degrees C the maximal acetylcholine response was then the same as the maximal thermal response.4. No change in the acetylcholine dose-response curves occurred with repeated determinations at the same site on the same occasion.5. The dose-response relationship for methacholine was similar to that for acetylcholine. The methacholine response was, however, more prolonged and so the volumes secreted were greater.

Acetylcholine↗

Induction of humoral and cellular anti-idiotypic immunity by intradermal injection of naked DNA encoding a human variable region gene sequence of an immunoglobulin heavy chain in a B cell malignancy.

The idiotypic determinants of a B cell neoplasia could provide a tumor-specific target for vaccinating patients against their B cell tumors. Several approaches for inducing idiotype-specific immunization have been reported, but their major theoretical focus was related to the induction of humoral immunity. We have investigated an immunization procedure with naked DNA encoding human variable region gene sequences of an immunoglobulin heavy chain (VH), which may generate both humoral and cellular immune responses against the idiotype of a B cell acute lymphoblastic leukemia (ALL). Using polymerase chain reaction (PCR) amplification, we investigated heavy chain variable region genes obtained from an ALL patient and whether they could induce humoral and cellular immune responses in DBA/2 mice. The VH sequence was cloned into a mammalian expression vector for intradermal DNA vaccination and into a bacterial expression vector to obtain VH protein for Western blotting. The mammalian expression vector encoding the VH gene was injected into mice three times at 7-day intervals and was transduced into P1HTR which is a syngeneic tumor of DBA/2, to serve as target cells to detect cellular immunity. Spleen cells from the inoculated mice exhibited a significant cytotoxic T lymphocyte response to the target cells. By Western blotting, we could also detect trace levels of anti-VH antibodies in all mice serum. This approach for the induction of cellular immunity by intradermal injection is easy and variable region-specific, and may be used as vaccines after chemotherapy treatment of B cell malignancies.

Amino Acid Sequence↗

Comparison of the effect of various antisera and cobra venom factor on inflammatory reactions in guinea-pig skin. I. Non-specific inflammation due to the intradermal injection of turpentine.

Guinea-pigs were treated with agents which lowered the serum complement levels and the effect on the inflammatory reaction to intradermal turpentine was studied. A comparison was made between two antisera to beta1C/beta1A globulin which had been prepared in different ways. One was made using C3 fixed to zymosan particles as the antigen, and the other using chemically extracted beta 1C/beta1A globulin. The antisera to beta1C/beta1A globulin (zymosan) was found to have the greater anti-inflammatory activity. The effect of each on the parameters of complement studied, and on the circulating platelet count, was much the same. An antiserum to serum factors fixed to zymosan during C3 activication was prepared free of anti-beta1C/beta1A globulin antibodies. This was found to have some of the anti-inflammatory activity of the anti-beta1C/beta1A globulin (zymosan), as well as lowering total complement levels. Anti-gamma globulin andheterologous immune complexes also lowered serum complement levels and were antiinflammatory. However, all the above agents were also found to reduce the number of circulating platelets. This was in contrast to CVF which reduced complement levels by 90 per cent. but had no effect on platelet numbers. CVF also reduced the inflammatory response but was no more effective than the other agents. In view of these findings a role for the participation of the complement system, possibly involving the alternate pathway of activation of C3, is discussed as well as the participation of platelets in the reaction.

Animals↗

[Local reaction to the intradermal injection of PHA in healthy persons and in chronic lympholeukosis patients].

Phytohemagglutinin (PHA) that stimulates the lymphocytes to blast transformation in conditions of cellular cultures provokes local skin reaction, when applied intradermally. At the beginning that reaction is manifested with hypermia at the place of the application and later an infiltration is formed. In healthy subjects the infliltration reaches maximal dimensions on the 48th to the 72nd hour post PHA injection. The presence of lymphocytes was established with the cytologic examination of the material from that infilitration at the 24th hour, lymphoblasts and hyperbasophilic blast cells at the 48th and 72nd hour and single reactive lymphocytes were observed at the 96th hour. The infiltration appears later in patients with quiet development of chronic leukosis, only after the 96th hour and is with smaller demensions. Negligible infiltration is observed in malignant leukosis, its progress in time does not differ from that in healthy subjects. However, skin reaction in intraderma injection of PHA gives a certain orientation about the immune organism reactivity and in case of 1 chronic leaukosis--about the form and severity of the disease.

Adult↗

The role of nitric oxide in the phosphorylation of cyclic adenosine monophosphate-responsive element-binding protein in the spinal cord after intradermal injection of capsaicin.

We investigated the involvement of nitric oxide (NO) in the phosphorylation of cyclic adenosine monophosphate-responsive element-binding protein (CREB) in the spinal cord of rats during central sensitization after intradermal capsaicin injection. CREB and phosphorylated CREB (p-CREB) were measured by immunoblotting. The level of p-CREB increased by 20 minutes, peaked between 20 and 60 minutes after capsaicin injection, and started to decrease after 150 minutes. CREB itself did not show an obvious change after capsaicin injection. The p-CREB expression on the ipsilateral side of the spinal dorsal horn, but not on the contralateral side, increased significantly after capsaicin injection. The increase in p-CREB induced by capsaicin injection was partially blocked by pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, administered through a microdialysis fiber placed across the spinal cord. D-NAME, an inactive form of L-NAME, had no effect. CREB phosphorylation, not the level of CREB, was induced within 20 minutes by microdialysis administration of SIN-1, an NO donor. These results indicate that CREB phosphorylation in the spinal cord results from both endogenous and exogenous NO release and that p-CREB may play a role in central sensitization or in longer-term changes in gene expression induced by strong peripheral noxious stimulation.

Journal Article↗

Codeine-induced histamine release in intact human skin monitored by skin microdialysis technique: comparison of intradermal injections with an atraumatic intraprobe drug delivery system.

BACKGROUND: The skin microdialysis technique makes it possible to measure histamine release in intact human skin in vivo directly. In this study we have used the microdialysis technique to characterize histamine release by codeine after intracutaneous injections and following skin challenge by a novel atraumatic delivery technique. OBJECTIVE: The purpose of the study was to compare histamine release in human skin by codeine, delivered by an intraprobe drug delivery system (IPD) and intracutaneous injections (ICT), with respect to dose-response relations, kinetics of histamine appearance and decay, correlations between histamine release and skin responses, and reproducibility. METHODS: Hollow dialysis fibres were inserted intradermally in 12 healthy subjects. Twelve fibres were inserted in each subject, six fibres in each arm. Each fibre was perfused at a rate of 3 microM/min, and samples were collected in 2 min fractions. By the IPD technique, codeine was administered to the skin by adding codeine to the perfusion medium. Sequential IPD challenges were performed in one arm, and ICTs were done on the other arm. RESULTS: Sixfold serial dilutions of codeine (0.01-3 mg/mL) caused a significant dose-related histamine release by ICT and IPD. Peak histamine release was found within the first 4 min after skin challenge by ICT and IPD, followed by a fast decline with a dialysate histamine half life of approximately 2-3 min. Peak histamine release was linearly correlated with cumulative release of the 20 min sampling period, and histamine release correlated with weal size. The coefficient of variation on peak histamine release was 18.9% and 4.8% for codeine ICT and IPD, respectively. CONCLUSION: We have described in detail codeine-induced histamine release in intact human skin in vivo by the microdialysis technique. It was possible to administer codeine atraumatically to the skin by intraprobe delivery. The skin microdialysis technique opens up possibilities for measurement of inflammatory mediators release in normal and diseased skin, and it will be possible to deliver immunopharmacologically active drugs to the skin by intraprobe delivery.

Adult↗

Prospective immunogenicity study of multiple intradermal injections of rabies vaccine in an effort to obtain an early immune response without the use of immunoglobulin.

The present study sought to determine whether increasing and accelerating rabies vaccine administration would result in earlier protective levels of neutralizing antibody. Results indicated that the 8-site and double-dose Thai Red Cross intradermal regimens produced higher antibody titers by day 14 but not significantly higher titers by days 5 and 7. Administration of rabies immunoglobulin into and around bite wounds on the first day of rabies prophylaxis should remain the optimal postexposure treatment.

Adult↗

Therapeutic effect of intradermal injections with difucosyl lactosamine (dimeric Lex) on patients with rheumatoid arthritis.

As reported by us, a new myeloid cell population with an oncofetal membrane marker, dimeric Lex (di-Lex; III3FucV3 FucnLc6), was found in the epiphyseal bone marrow adjacent to the involved joints of patients with severe rheumatoid arthritis (RA). Patients with RA received intradermal (id) injections of di-Lex incorporated in liposome or of high molecular weight glycoprotein, or tumor associated carbohydrate antigen (TCA), containing the same carbohydrate epitope as di-Lex. The epiphyseal myeloid cells were reduced or sometimes eliminated during id injection. In random trials of id injection, observation under clinical and laboratory conditions showed improvement in 63% (17/27) of the patients treated for 6 months with appropriate doses of di-Lex (III3FucnLc4), and in 72% (31/43) of those treated with an identical protocol for TCA. However, id injection with monomeric Lex had no effect.

Adult↗

Sensitization of naive beagles by intradermal injection of an ascaris antigen: induction of a model of skin allergy.

Ascaris suum-hypersensitive beagles represent a unique model of skin allergy. Despite its suitability, the need to test numerous dogs prior to the selection of natural positive responders causes many complications. We hypothesized that the model could be induced in adult beagles by primary sensitization. Ten dogs were included in an intradermal sensitization program using ascaris antigen and were thereafter tested for cutaneous reaction. After 2 weeks, 60% developed a positive reaction that lasted for months. We therefore present a straightforward method to establish the Ascaris canine model of allergy that will extend its availability for research in cutaneous allergy immunomodulation.

Animals↗

Analysis of the wheal-and-flare reactions that follow the intradermal injection of histamine and morphine in adults with recurrent, unexplained anaphylaxis and systemic mastocytosis.

It has been suggested that patients with recurrent, unexplained anaphylaxis may be more responsive, and patients with systemic mastocytosis, less responsive, to mast cell-derived mediators, including histamine, compared to normal subjects. This would help explain why patients with recurrent, unexplained anaphylaxis have an anaphylactic response and, conversely, why patients with systemic mastocytosis can tolerate high levels of plasma histamine. To test this hypothesis, intradermal titrations (0.02 ml of solution from 1 ng/ml to 2 micrograms/ml) of histamine and morphine sulfate (MS) (10 ng/ml to 10 micrograms/ml) were administered to normal volunteers (N = 15), patients with recurrent, unexplained anaphylaxis (N = 10), and patients with systemic mastocytosis (N = 18). Antihistamines were stopped at least 72 hours before the study. Resultant areas of wheal and flare were determined with a computerized morphometric system. Comparison of any two given means at each dose of histamine or morphine with the two-sample Student's t test with Bonferroni inequality demonstrated no significant differences (p greater than 0.05) among the three groups. The median amount of MS or histamine required to produce a half-maximal response was compared for equality. None of the differences observed reached statistical significance, in agreement with the similarity of the dose-response curves. An analysis of the correlation between response to MS and to histamine in individual subjects revealed the responses to be significantly correlated in all cases, with the exception of wheal in patients with recurrent, unexplained anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗