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Intradermal radioisotope is superior to peritumoral blue dye or radioisotope in identifying breast cancer sentinel nodes.

BACKGROUND: Sentinel lymph node (SLN) mapping and biopsy have emerged as the technique of choice for axillary staging of breast cancer. Several methods have been developed to identify SLNs, including peritumoral or intradermal injection of isosulfan blue dye or technetium sulfur colloid (TSC). We hypothesize that intradermal TSC is the optimal mapping technique and can be used alone to identify SLNs. STUDY DESIGN: From March 1997 through January 2001, 180 women with T1 and T2 invasive breast cancer and clinically negative axilla underwent SLN mapping and biopsy. Peritumoral TSC was injected in 74 patients, 62 of whom also received peritumoral blue dye. Intradermal TSC (above tumor) was performed in 94 patients, 76 of whom also received peritumoral blue dye. Technetium-rich nodes were identified intraoperatively using a hand-held gamma probe and blue nodes were identified visually. Hematoxylin- and eosin-stained SLN sections were examined by light microscopy for breast cancer metastases. RESULTS: Overall, the SLN mapping procedures were successful in 91% of patients. Peritumoral and intradermal TSC were successful in identifying SLNs in 78% and 97% of patients, respectively. Peritumorally injected isosulfan blue was successful in identifying 83% of SLNs. Intradermal TSC was found to be superior to peritumoral TSC and peritumoral blue dye in identifying SLNs (p = 0.00094, chi-squared, and p = 0.020, ANOVA). CONCLUSIONS: SLN mapping by intradermal TSC has a significantly higher success rate than peritumoral TSC or blue dye. There was minimal benefit in identifying additional SLNs with addition of peritumoral blue dye to intradermal TSC. So, SLN mapping and biopsy using intradermal-injected TSC can be used alone to effectively stage the axilla for breast cancer.

Breast Neoplasms↗

Locally injected bleomycin in the treatment of warts.

To evaluate the clinical effectiveness of intradermally injected bleomycin in saline and oil versus placebo, a double-blind study of 62 patients with 108 warts was made. Although bleomycin has been recommended in previous reports, we found no difference between the group treated with bleomycin and the placebo group.

Bleomycin↗

Specific immunological and bronchopulmonary responses following intradermal sensitization to free trimellitic anhydride in guinea pigs.

We have developed a guinea pig model of trimellitic anhydride-induced airway hypersensitivity responses. In one group of guinea pigs, injected intradermally with 0.1 ml 30% trimellitic anhydride (TMA), we examined the specificity of the bronchopulmonary response to TMA comparing the effect of intravenous TMA conjugated to guinea pig serum albumin (GPSA) with a control hapten (procion dye) protein conjugate (PD-GPSA). A significant increase in pulmonary inflation pressure (PIP) was provoked in sensitized animals following intravenous injection with TMA-GPSA (20%; 0-400, median; range) as compared to intravenous injection of PD-GPSA. In the second group we compared three different methods of sensitization: single injection of 0.1 ml of 0.3% TMA; four injections of 0.1 ml of 0.1% TMA; and a single high dose injection of 30% TMA. Following intravenous TMA-GPSA guinea pigs sensitized with a single injection 0.3% TMA had an increase in PIP of 395%; 220-600, while those given four repeat injections of 0.1% TMA had an increase in PIP of 343%; 315-490. These results were significantly higher than the increase in PIP (160%; 0-220) which occurred in guinea pigs sensitized with a single dose of 30% TMA. Four of 11 guinea pigs given low dose injections of TMA had bronchopulmonary responses to inhaled TMA-GPSA. All sensitized guinea pigs had specific IgG1 antibodies demonstrated by enzyme linked immunosorbent assay (ELISA) and confirmed by ELISA inhibition. Four guinea pigs sensitized by low dose injections of TMA had IgE antibodies demonstrated by passive cutaneous anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Normal human skin lymphocytic and Langerhans' cell responses to intradermal interferon alpha-2 beta injections.

The effects of intradermal injection of interferon alpha-2 beta on normal human skin were studied in 12 healthy adult volunteers using 500,000 international units recombinant human interferon alpha-2 beta, 3 times a week for five injections (n = 6) and nine injections (n = 6). Saline injections served as control sites. Lymphocytic infiltrates and the population of epidermal Langerhans' cells in the injection areas were observed. The results showed that epidermal Langerhans' cells (both adenosine triphosphatase positive and CD-1+) decreased significantly whereas human leukocyte antigen-DR expression in keratinocytes was enhanced. Dermal CD-3+ (Pan T cells), CD-4+ (T helper cells) and human leukocyte antigen DR+ cells increased. No significant differences in the number of CD-19+ (B cells) and CD-57+ (NK cells) were observed. There were no significant differences between the five-injection and nine-injection groups.

Adenosine Triphosphatases↗

Comparison of peritumoral and subareolar injection of Tc99m sulphur colloid and blue-dye for detection of the sentinel lymph node in breast cancer.

BACKGROUND: The new trend in diagnosis of the lymph node is sentinel node biopsy. This method has become increasingly accepted as a minimally invasive alternative to routine axillary dissection. Although the results of numerous studies have shown that sentinel node biopsy can accurately determine the axillary nodal status, the identification rates and false-negative rates have been variable. The sentinel lymph node is defined as the first node in the lymphatic basin that receives the primary lymphatic flow. MATERIAL AND METHODS: Between September 1998 and August 2002 123 patients with primary operative breast cancer without clinical palpable axillary lymph nodes were enrolled in the study. There were two groups of patients according to sentinel node identification technique: 51 patients (Group I) received parenchymal, peritumoral injection of 1.0 ml of 16 MBq Tc(99m)-radiolabelled sulphur colloid and single intradermal injection of blue-dye over the tumour. The next 72 patients (Group II) received intradermal, periareolar one-site injection of 0.5 ml of 16 MBq Tc(99m)-radiolabelled sulphur colloid and blue-dye. RESULTS: Sentinel lymph node was found in 41 (80.4%) cases in Group I and in 67 (93.0%) cases in Group II (p = 0.028). The localisation of the axillary lymph node as a "hot spot" visualised by lymphoscintigraphy was successful in 39/51 (76.5%) cases in Group I and 67/72 (93.0%) in Group II, p = 0.004). In both groups the success of sentinel node identification in the axillary region by lymphoscintigraphy was connected with sentinel lymph node finding during surgery (Group I: p < 0.001, Group II: p < 0.001). CONCLUSIONS: This study shows that intradermal, periareolar one-site injection of Tc(99m)-radiolabelled sulphur colloid and blue-dye is superior to peritumoral 4-sites injections Tc(99m)-radiolabelled sulphur colloid and single intradermal injection of blue-dye over the tumour in sentinel lymph node identification.

Journal Article↗

Intradermal cholinergic agonists induce itch-associated response via M3 muscarinic acetylcholine receptors in mice.

In the present study, we examined whether cholinergic agonists would elicit an itch-associated response in mice. When mice were given an intradermal injection of carbachol (1-10 nmol) or bethanechol (0.3-100 nmol) into the rostral back, they showed the dose-dependent increase of scratching. Nicotine (1-10 nmol) showed no effect. Pretreatment with naloxone, but not with terfenadine, significantly suppressed the carbachol-induced scratching. When intradermally co-injected with carbachol, atropine and 4-DAMP but neither methoctramine nor pancuronium significantly inhibited the carbachol-induced scratching. Muscarinic agonists are suggested to produce itch through activation of M3 muscarinic receptors in the skin.

Animals↗

Sensitization and testing of guinea pigs with nickel sulfate.

Experiments in passive transfer of nickel allergy require highly sensitive guinea pigs and a reliable and technically usable test method. A comparison was made between two sensitization methods, the guinea pig maximization test of MAGNUSSON and KLIGMAN (MK) and a combined injection and painting method devised by POLAK and TURK (PT). Intradermal injection was chosen as test method. The reactions to the test were greater than those of normal animals and the differences were statistically significant. With testing before the start of sensitization it was found difficult to obtain highly sensitive animals (tolerance). PT painting resulted in rather higher sensitivity with Triton X-100 than with sodium lauryl sulphate. In a comparison between the MK and PT methods, no difference in effectiveness was found provided that the animals had not been pretested. Repeated PT injections and paintings caused a further increase of the sensitivity, but the toxicity of nickel is a limiting factor.

Administration, Topical↗

The prevention of cutaneous necrosis following extravasation of hypertonic saline and sodium tetradecyl sulfate.

BACKGROUND: Most authors have recommended treating extravasation during sclerotherapy by infiltrating the area with 0.9% sodium chloride and/or procaine. OBJECTIVE: To evaluate interventions in the prevention of necrosis following intradermal injection of 23.4% sodium chloride and 3% sodium tetradecyl sulfate. METHODS: Following intradermal 23.4% sodium chloride (Study I) or 3% sodium tetradecyl sulfate (Study II), subjects (Sprague-Dawley rats) received either no treatment or injections of 0.9% sodium chloride, sterile water, 1% procaine, or hyaluronidase. Groups were compared regarding incidence and size of necrosis. RESULTS: In study I, hyaluronidase treated groups had significantly fewer and smaller areas of necrosis than other groups. In study II, the hyaluronidase group developed significantly fewer ulcers than the 0.9% sodium chloride group. The 0.9% sodium chloride group had significantly larger ulcers than other groups. CONCLUSION: In the model studied, hyaluronidase was the only effective treatment in the prevention of necrosis. Following 3% sodium tetradecyl sulfate, 0.9% sodium chloride was associated with larger ulcers than other groups.

Animals↗

The sensitization potential of D & C Yellow No. 11 in guinea pigs.

The certified drug and cosmetic dye substance known as D & C Yellow No. 11 [2-(2-quinolyl)-1,3 indandione] was tested for its dermal sensitization potential in guinea pigs. An induction regimen consisting of a single footpad injection of Complete Freund's Adjuvant diluted with antigen, and an intradermal injection of antigen, produced delayed-type hypersensitivity reactions. A high sensitization frequency was observed with 50 micrograms D & C Yellow No. 11 and the positive control 2,4-dinitrochlorobenzene (DNCB). The reaction severities of both DNCB and 50 micrograms D & C Yellow No. 11 were comparable. A dose-response profile was obtained with D & C Yellow No. 11 employing several concentrations (50, 250 and 500 micrograms/ml). Histologic examination of selected skin sites demonstrated a cellular inflammatory response which was consistent with delayed-type hypersensitivity.

Animals↗

Pain during insertion of peripheral intravenous catheters with and without intradermal lidocaine.

Phase 1 of this study evaluated the perception of pain in 50 patients undergoing peripheral venous catheter insertion without the use of a local anesthetic. Phase 2 evaluated perceived pain in 50 patients who received intradermal lidocaine before the i.v. catheter was inserted. The researchers found that lidocaine injected intradermally before placement of an i.v. catheter resulted in significantly lower self-reported pain perceptions (p < 0.01). No additional time (determined in intervals of 15 minutes) was required for the study group. Based on these findings, the hospital policy was modified so that intradermal lidocaine would be offered to all patients requiring peripherally inserted i.v. catheters.

Anesthetics, Local↗

Role of kinins in pain and hyperalgesia: psychophysical studies in a patient with kininogen deficiency.

1. Bradykinin is considered to be an important mediator of pain and hyperalgesia associated with injury and inflammation. Psychophysical studies were conducted in a patient with complete kininogen deficiency to determine whether the absence of bradykinin was associated with abnormalities in pain sensibility. Pain evoked by heat stimuli to the thenar eminence was tested before and after a localized burn, which has been shown to cause hyperalgesia in normal subjects. In addition, pain evoked by intradermal administration of bradykinin (0.1-10 micrograms) to the forearm and the effects of bradykinin on pain induced by heat stimuli were studied. The patient rated the intensity of pain evoked by all heat stimuli relative to the pain induced by a 3 s 45 degrees C stimulus. 2. The patient's heat pain threshold (45 degrees C) in the glabrous skin was similar to that of age-matched control subjects (n = 5) and to that previously observed in younger control subjects. 3. The burn resulted in a decrease in pain threshold and an increase in pain induced by suprathreshold stimuli. The magnitude of hyperalgesia was within the range observed in the age-matched control subjects and in younger control subjects. Thus, kinins are not essential for the development of hyperalgesia after heat injury. 4. In control subjects, intradermal injections of bradykinin produced pain and hyperalgesia to heat stimuli. In the patient, intradermal bradykinin injections induced minimal pain and no hyperalgesia to heat stimuli. Thus, congenital absence of kininogens may be associated with a deficiency in bradykinin receptors.

Aged↗

Intradermal vaccination against hepatitis B in Immanuel Hospital personnel--a preliminary report.

Intradermal vaccination of HB-VAX vaccine (Merck Sharp & Dohme) was administered to hospital personnel to immunise them against Hepatitis-B infection. The intradermal route was chosen to reduce vaccination cost. Seronegative personnel (141) were given a series of three intradermal injections of 0.1 ml-2.0 micrograms HB-VAX (Merck Sharp & Dohme) after the initial injection. The second was given one month later, and the third six months later. Blood samples drawn one month after the third vaccination were tested for levels of antibody to Hepatitis-B Surface antigen (Anti-HBs) by Enzyme Immuno Assay. Seroconversion (greater than 10 IU/L) was detected in 127 individuals (90.1%), which was similar to other intradermal vaccinations (83.3-100%) or other intramuscular studies (89-100%). The Geometric Mean Titre (GMT) was 426 IU/L, which was significantly lower than intramuscular vaccinations (11 138-14 532 IU/L). The percentage of seroconversion in women was significantly higher than that in men. Side effects of the vaccine were minor and limited to local reactions at the site of administration. Intradermal vaccination using 2 micrograms HB-VAX offers a means of reducing vaccination cost by 32%, 63% and 79% respectively when compared with 3 doses of 5 micrograms, 10 micrograms and 20 micrograms given intramuscularly. This study provides preliminary data that suggests three 2.0 micrograms intradermal doses of vaccine may effectively immunise healthy individuals against Hepatitis-B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sensory neuron-specific receptor activation elicits central and peripheral nociceptive effects in rats.

The sensory neuron-specific G protein coupled receptors (SNSRs) have been described as a family of receptors whose expression in small diameter sensory neurons in the trigeminal and dorsal root ganglia suggests an implication in nociception. To date, the physiological function(s) of SNSRs remain unknown. Hence, the aim of the present study was to determine the effects of rat SNSR1 activation on nociception in rats. The pharmacological characterization of rat SNSR1 was initially performed in vitro to identify a specific ligand, which could be used subsequently in the rat for physiological testing. Among all ligands tested, gamma2-MSH was the most potent at activating rat SNSR1. Structure-activity relationship studies revealed that the active moiety recognized by rat SNSR1 was the C-terminal part of gamma2-MSH. The radiolabeled C-terminal part of gamma2-MSH, gamma2-MSH-6-12, bound with high affinity to membranes derived from rat skin and spinal cord, demonstrating the presence of receptor protein at both the proximal and distal terminals of dorsal root ganglia. To investigate the physiological role of SNSR, specific ligands to rat SNSR1 were tested in behavioral assays of pain sensitivity in rats. Selective rat SNSR1 agonists produced spontaneous pain behavior, enhanced heat and mechanical sensitivity when injected intradermally, and heat hypersensitivity when injected centrally, consistent with the localization of rat SNSR1 protein at central and peripheral sites. Together, these results clearly indicate that the SNSR1 plays a role in nociception and may provide novel therapeutic opportunities for analgesia.

Animals↗

Late phase allergic reaction to a CT contrast medium (iotrolan).

A 46-year-old male developed wide-spread erythema and edema after intravenous injection of a CT contrast medium (iotrolan). The skin eruption appeared at 6 h, reached a maximum at 9 to 12 h, and faded within 36 h after injection. A challenge with an intradermal injection of the agent provoked the same reaction where the eruption had originally appeared, but had no effect on previously unaffected regions. Histopathologic examination revealed a perivascular infiltration of small round cells, and a few neutrophils, and eosinophils in the dermis and focal spongiosis in the epidermis. This is the first report of a late phase allergic skin reaction induced by iotrolan.

Contrast Media↗

Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels.

Although T-type Ca(2+) channels are implicated in nociception, the function of specific subtypes has not been well defined. Here, we compared pain susceptibility in mice lacking Ca(V)3.2 subtype of T-type Ca(2+) channels (Ca(V)3.2(-/-)) with wild-type littermates in various behavioral models of pain to explore the roles of Ca(V)3.2 in the processing of noxious stimuli in vivo. In acute mechanical, thermal and chemical pain tests, Ca(V)3.2(-/-) mice showed decreased pain responses compared to wild-type mice. Ca(V)3.2(-/-) mice also displayed attenuated pain responses to tonic noxious stimuli such as intraperitoneal injections of irritant agents and intradermal injections of formalin. In spinal nerve ligation-induced neuropathic pain, however, behavioral responses of Ca(V)3.2(-/-) mice were not different from those of wild-type mice. The present study reveals that the Ca(V)3.2 subtype of T-type Ca(2+) channels are important in the peripheral processing of noxious signals, regardless of modality, duration or affected tissue type.

Animals↗

Homozygous human C3 deficiency. The role of C3 in antibody production, C-1s-induced vasopermeability, and cobra venom-induced passive hemolysis.

Studies of the family of a patient with marked deficiency of the third component of complement (C3) demonstrated that the patient was homozygous for a blank allele at the C3 locus, C3-. Metabolic studies with purified radiolabeled C3 in the patient revealed a mildly elevated fractional catabolic rate and a markedly reduced synthesis rate, consistent with a lack of C3 synthesis as the patient's primary defect. There was also a mild increase in the rate of conversion of purified C3 added to her serum and incubated at 37 degrees C in vitro. Major blood group-compatible erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria had the same shortened survival in the C3-deficient patient as in a normal control. Although no leukocytosis developed in the patient in spontaneous infection by pyogenic organisms, there was a normal leukocytosis in response to the injection of thyphoid vaccine. The intradermal injection of C-1s, which produces a marked increase in vasopermeability in the skin of normal subjects, produced no definite change in the patient, possibly implicating C3 or a protein in the alternative pathway as the normal mediator of this response. The patient's serum exhibited near-normal immune adherence activity, confirming the lack of requirement of C3 for this function. C5 inactivation and passive hemolysis of unsensitized guinea pig erythrocytes occurred normally in C3-deficient serum on incubation with cobra venom factor, indicating that C3 is not required for these reactions. The patient's humoral antibody response to both protein and carbohydrate antigens was entirely normal, making it unlikely that C3 is required for antigen processing.

Alleles↗

Recombinant neutral endopeptidase attenuates substance P-induced plasma extravasation in the guinea pig skin.

To determine whether exogenously administered neutral endopeptidase (NEP; enkephalinase, EC 3.4.24.11) inhibits the substance P-induced increase in vascular permeability in the skin, we examined the effects of recombinant human NEP on plasma extravasation induced by intradermal injection of substance P in guinea pig skin. Injection of substance P (2.5 X 10(-8) M) induced significant plasma extravasation in the skin (53 +/- 4 mm2 of Evans blue extravasation; mean +/- 1 SEM). In vitro incubation of substance P with recombinant human NEP prior to injection prevented the substance P-induced plasma extravasation in the skin in a dose-dependent fashion. Intradermal preinjection of recombinant human NEP partially inhibited plasma extravasation induced by subsequent injection of substance P (52 +/- 9% of the control without NEP). The H1 and H2 histamine antagonists pyrilamine and cimetidine, and a muscarinic antagonist, atropine, had no effects on substance P-induced responses. Two products of substance P degradation by NEP containing the carboxy-terminal portion, substance P7-11 and substance P8-11, were also without effect. These findings suggest that recombinant human NEP can attenuate substance P-induced increases in vascular permeability in guinea pig skin and, therefore, may be useful in treating dermatologic disorders in which abnormal responses to substance P or other neuropeptides cleaved by NEP may occur.

Animals↗

Experimental non-transmissible marker vaccines for classical swine fever (CSF) by trans-complementation of E(rns) or E2 of CSFV.

Three mutants with deletions in the E2 gene of the infectious DNA copy of the classical swine fever virus (CSFV) strain-C were constructed: one missing the B/C domain of CSFV-E2 between amino acids (aa) 693 and 746, one missing the A domain between aa 800 and 864, and one missing the complete E2 between aa 689 and 1062. All three CSFV-E2 deletion mutants were unable to generate viable virus, indicating that each of the antigenic domains of E2 is essential for viability of CSFV. To rescue the CSFV-E2 deletion mutants SK6 cell lines constitutively expressing glycoprotein E2 of CSFV were generated. The rescued viruses infected and replicated in SK6 cells as demonstrated by expression of viral proteins, but this primary infection did not result in reproduction of infectious virus. Thus, these E2 complemented viruses are considered non-transmissible. In previous experiments, we showed that simultaneous injection of E(rns) complemented virus (Flc23) via intradermal (ID), intramuscular (IM) or intranasal (IN) routes conferred protection to pigs against a lethal challenge with CSFV [J. Virol. 74 (2000) 2973]. Here, we evaluate different routes of application (ID, IM or IN) with E(rns) complemented virus Flc23 in order to find the best route for complemented CSFVs. Intradermal injection with Flc23 protected pigs against a lethal CSFV challenge, whereas intramuscular injection induced partial protection, and intranasal injection did not mediate a protective immune response in pigs at all. We used the intradermal route of vaccination to test the E2 complemented viruses. Vaccination of pigs via the intradermal route with the E2 complemented CSFVs also resulted in the induction of antibodies and in (partial) protection against CSFV challenge. Pigs vaccinated with E2 complemented virus Flc4 (deletion B/C domain) survived a lethal CSFV challenge, whereas partial protection was induced in pigs vaccinated with Flc47 (deletion E2) or Flc48 (deletion A domain) E2 complemented viruses. Serological data demonstrate that these E2 complemented mutant viruses are, in combination with well known diagnostic tests based on E2, potential marker vaccines for CSF.

Animals↗