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Intradermal anesthesia and comparison of intravenous catheter gauge.

A double-blinded randomized prospective study was performed to determine whether alkalinization of lidocaine decreases the pain of intradermal injection and if a larger intravenous catheter (16 gauge) causes more discomfort on insertion than a smaller (20 gauge) catheter when intradermal anesthesia has been used. In a random manner, 100 patients received skin wheals with commercially prepared lidocaine or lidocaine with the addition of sodium bicarbonate before the insertion of a 16- or 20-gauge intravenous catheter. Visual analogue pain scores were obtained after the skin wheal was placed and after the intravenous catheter was inserted. There was no statistically significant difference in pain scores between the two local anesthetic solutions. However, the catheter insertions pain scores were slightly, but statistically significantly larger in the 16-gauge group regardless of local anesthetic solution used. The addition of sodium bicarbonate to commercially prepared lidocaine does not decrease the pain associated with an intradermal skin wheal. There is a slight increase in patient discomfort upon insertion of a large-bore intravenous catheter, even with the prior use of local anesthetic.

Anesthesia, Local↗

[Botulinum toxin in the treatment of focal hyperhidrosis].

INTRODUCTION: Botulinum A toxin (BTX-A) acts primarily at peripheral cholinergic synapses, inhibiting the release of acetylcholine. Initially it has been used to block the neuromuscular junction in focal dystonic and spastic syndromes. Recently there has been suggestions for potential clinical indications in non-muscular diseases where cholinergic terminals play a role. GUSTATORY SWEATING: In 1995 physicians reported a long-lasting anhidrotic effect of intracutaneous BTX-A injections in patients suffering from gustatory sweating (Frey's syndrome). Consequently, a number of clinical studies demonstrated good efficacy of intradermal injections of botulinumtoxin in patients with focal hyperhidrosis. FOCAL HYPERHIDROSIS OF THE PALMS AND AXILLAE: Focal hyperhidrosis is usually confined to the palms and axillae. Excessive sweating may be a social handicap and an occupational hazard. The management of focal hyperhidrosis remains controversial. Topical antiperspirants are only effective in very mild cases. Iontophoresis with tap water or anticholinergic drugs is messy and time consuming with only short-lived effect. Sympathectomy, the cornerstone of surgical management, is usually effective in palmar hyperhidrosis. Complications of this technique include surgical risks, postoperative and cosmetic problems and compensatory hyperhidrosis. AXILLARY HYPERHIDROSIS: Several studies confirmed that intracutaneous injections of botulinum toxin are useful in the majority of patients with axillary hyperhidrosis resistant to conventional treatment. In axillary hyperhidrosis total doses are ranging from 200-400 mU Dysport or from 80 to 130 mU Botox to reach a good clinical response. Injections are usually well tolerated and no serious side-effects have been observed. The mean duration of anhidrotic effect ranges between 3 and 9 weeks. PALMAR HYPERHIDROSIS: The use of botulinumtoxin in patients with palmar hyperhidrosis is rather difficult. The therapeutic window is smaller because injections are complicated by transient weakness of the small hand-muscles. Furthermore the injections at the palms are painful which can be overcomed by application of local anaesthetics or the blockade of the ulnar and median nerves. The duration of anhidrotic effect ranges from 20 to 50 weeks. CONCLUSION: Intracutaneous injections of botulinum-toxin should be offered to patients with focal hyperhidrosis of the palms and axillae causing serious social, psychologic and occupational problems, resistant to other conventional treatment options.

Axilla↗

Treatment of dyshidrotic hand dermatitis with intradermal botulinum toxin.

BACKGROUND: Botulinum toxin (Btx A) has recently been used in the treatment of focal hyperhidrosis. Hyperhidrosis is also an aggravating factor in nearly 40% of patients with dyshidrotic hand eczema. OBJECTIVE: The objective of this study was to evaluate the effect of intradermal injections of Btx A on dermatitis in patients with vesicular hand dermatitis. METHODS: Ten patients with vesicular dermatitis were treated on one hand with intradermal Btx A (mean, 162 U BOTOX, Allergan Pharmaceuticals, Irvine, Calif) with the untreated side as a control. RESULTS: Self-assessment at follow-up 5 to 6 weeks after injection on a 5-point scale (none, slight, moderate, good, or very good effect) showed that 7 of 10 patients experienced good or very good effect. A decrease in itching was shown with a visual linear analogue scale (VAS) for itching, with mean 39% on the treated side compared with an increase by 52% on the untreated side. These findings were supported by the evaluation of clinical signs. Six of 7 patients who experienced good or very good effect also had aggravating hand sweating or worsening during the summer. CONCLUSION: Btx A can be a valuable alternative for patients with treatment-refractory hand eczema of the vesicular type, especially with hyperhidrosis or worsening during the summer.

Adult↗

Oxygen intermediates are involved in ultraviolet radiation-induced damage of Langerhans cells.

Experiments were conducted to determine whether ultraviolet (UV) radiation exerts its effect through the generation of oxygen intermediates on Langerhans cells (LC). Guinea pigs were exposed to one single dose of UVB (0.9-2.7J/cm2), and biopsy specimens were taken 5 days after the irradiation. The population of LC was evaluated using ATPase-stained epidermal sheets. These exposures reduced the number of LC to 20-25% of the original density. On the other hand, superoxide dismutase (SOD) (0.02-0.2 mg), a scavenger of superoxide anion, which had been injected intradermally just before UV radiation, significantly prevented the depletion of LC, although not completely (37-40% of the original density). The injection immediately after the exposure was still significantly effective, but less so. Other scavengers of oxygen intermediates including catalase, D-mannitol, and L-histidine revealed no detectable effect. A single exposure of UVB at doses of 0.3-0.6 J/cm2 did not deplete the ATPase-positive LC. However, the same dose of UVB reduced the number of LC to 70%, when exposed after the injection of an SOD inactivator, diethyldithiocarbamate, possibly due to inactivation of physiologically existing SOD. These observations indicate that oxygen intermediates such as superoxide anion or its subsequent species are generated by UV radiation exposure and damage the epidermal LC.

Animals↗

A histologic study on the fate of intradermally implanted epidermal cells in guinea pigs: a new method for evaluation of skin allograft survival.

The fate of allogeneic (strains 13, 2, and JY-1) and autologous epidermal cell (EC) suspensions injected intradermally was investigated histologically in JY-1 strain guinea pigs. Epidermal cells were found to proliferate actively in the dermis and form EC nests with central keratinization. The significant reject reaction associated with necrosis of the epidermal structures was seen in due time in the animals implanted with allogeneic ECs. We attempted to assess the effect of cyclosporin A (CYA) on skin allograft survival by observing the fate of strain 13 ECs implanted intradermally into the CYA-treated JY-1. Successful prolongation of allograft survival with CYA was clearly demonstrated by this method. This is considered to be a useful experimental way for evaluation of skin allograft survival and to be suitable for routine use.

Animals↗

Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical phase I/II trial.

PURPOSE: To investigate the safety and the immunologic and clinical responses of dendritic cell therapy for patients with recurrent malignant glioma. EXPERIMENTAL DESIGN: Twenty-four patients with recurrent malignant glioma (6 grade 3 and 18 grade 4 patients) were evaluated in a phase I/II clinical study of dendritic cell therapy. All patients were resistant to the standard maximum therapy. The patient's peripheral blood dendritic cells were generated with granulocyte macrophage colony-stimulating factor, plus interleukin 4 with or without OK-432, and pulsed with an autologous tumor lysate. Dendritic cells were injected intradermally, or both intratumorally and intradermally every 3 weeks. RESULTS: The protocols were well tolerated with only local redness and swelling at the injection site in several cases. Clinical responses were as follows: 1 patient with partial response, 3 patients with minor response, 10 patients with stable disease, and 10 patients with progressive disease. The patients whose dendritic cells were matured with OK-432 had longer survival times than the dendritic cells from patients without OK-432 maturation. The patients with both intratumoral and intradermal administrations had a longer survival time than the patients with intradermal administration only. Increased ELISPOT and delayed-type hypersensitivity responses after vaccination could provide good laboratory markers to predict the clinical outcome of patients receiving dendritic cell vaccination. The overall survival of patients with grade 4 glioma was 480 days, which was significantly better than that in the control group. CONCLUSIONS: This study showed the safety and clinical response of autologous tumor lysate-pulsed dendritic cell therapy for patients with malignant glioma. Dendritic cell therapy is recommended for further clinical studies in malignant glioma patients.

Adult↗

Some cutaneous responses to mitogen injection in sheep, with special reference to eosinophil leucocytes.

Research in laboratory animals suggests that eosinophil numbers in some cutaneous reactions may reveal inherent differences in resistance to parasite infection. An intradermal injection with 10 microgram of the mitogen phytohaemagglutinin, followed by counting eosinophils in the deep dermis of skin biopsies removed 24 hours later, appears to be a practical and reproducible way of comparing the ability of individual sheep to marshal eosinophils in a tissue. This procedure will allow study of the relationship between eosinophil response and resistance to parasite infection in sheep.

Animals↗

Nonanimal stabilized hyaluronic acid for lip augmentation and facial rhytid ablation.

OBJECTIVE: To evaluate the effectiveness of nonanimal stabilized hyaluronic acid as an injectable filling agent. DESIGN: Nonrandomized, retrospective, interventional case series. RESULTS: A total of 1446 consecutive patients (1029 women and 417 men) underwent intradermal injection of commercially available nonanimal stabilized hyaluronic acid (2242 treatments) for the enhancement of lip volume and contour and the reduction of visible facial rhytids. Almost 61% of all patients remained satisfied with their results after 9 months. The effect was longest in the glabellar and nasolabial fold areas. Minimal transient sequelae were noted. CONCLUSIONS: Nonanimal stabilized hyaluronic acid is an effective and safe facial soft tissue expander. Its duration varies with each facial area treated.

Female↗

Antiinflammatory effects of second-generation leukotriene B4 receptor antagonist, SC-53228: impact upon leukotriene B4- and 12(R)-HETE-mediated events.

Leukotriene B4 (LTB4) and 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE] are proinflammatory products of arachidonic acid metabolism that have been implicated as mediators in a number of inflammatory diseases. When injected intradermally into the guinea pig. LTB4 and 12(R)-HETE elicit a dose-dependent migration (chemotaxis) of neutrophils (PMNs) into the injection sites as assessed by the presence of a neutrophil marker enzyme myeloperoxidase. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxyl]-3,4-dihy dro-8-propyl-2H - 1-benzopyran-2-carboxylic acid), a first-generation LTB4 receptor antagonist, inhibited the chemotactic actions of LTB4 when given orally with an ED50 value of 1.7 mg/kg. The second-generation LTB4 receptor antagonist, SC-53228 [(+)-(S)-7-(3-(2-(cyclopropylmethyl)-3-methoxy-4- [(methylamino)carbonyl]phenoxy)propoxy)-3,4-dihydro-8-propyl-2H-1- benzopyran-2-propanoic acid], inhibited LTB4-induced chemotaxis when given intragastrically with an ED50 value of 0.07 mg/kg. Furthermore, SC-53228 inhibited 12(R)-HETE-induced granulocyte chemotaxis with an oral ED50 value of 5.8 mg/kg. When dosed orally over a range of 0.03-100 mg/kg, SC-53228 gave Cmax plasma concentrations of 0.015-41.1 micrograms/ml. SC-53228 inhibited LTB4-primed membrane depolarization of human neutrophils with an IC50 value of 34 nM. As a potent LTB4 receptor antagonist, SC-53228 may well have application in the medical management of disease states such as asthma, rheumatoid arthritis, inflammatory bowel disease, contact dermatitis, and psoriasis, in which LTB4 and/or 12(R)-HETE are implicated as inflammatory mediators.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Secondary heat hyperalgesia induced by melittin in humans.

Melittin, which is a principal protein of honeybee venom, can induce mechanical hyperalgesia in humans. The characteristics of the melittin induced mechanical hyperalgesia are quantitatively and qualitatively different from those evoked by capsaicin. The aim of the present study was to investigate in detail secondary heat hyperalgesia induced by melittin in humans. In six healthy volunteers, 10 microg of melittin was injected intradermally on the volar forearm, and VAS score to radiant heat stimuli (focused light from a xenon lamp) was assessed around the injection site 5, 30, and 60 min after injection. For normalization purposes, a pain rating index was calculated as the individual heat evoked VAS scores obtained after melittin divided by the individual baseline VAS scores. A two-way ANOVA revealed a significant increase of the pain rating index over time (F=3.6; P=0.03). The pain rating index at 60 min was significantly larger than at 5 min (P=0.04) and at 30 min (P=0.03). These results demonstrated slowly developing secondary heat hyperalgesia after injection of melittin. A possible contribution of peripheral inflammatory responses to the manifestation of secondary heat hyperalgesia is suggested, which in reality render the distinction between the primary and secondary area of heat hyperalgesia unnecessary.

Adult↗

Comparative trial of administration of half (0.05 mg) and quarter (0.025 mg) dose of intradermal Pasteur BCG on 291 infants from birth to 1 year in French Guyana.

The study concerns 291 newborns and infants aged 0 to 1 year placed randomly in two groups which respectively received 0.025 and 0.05 mg Pasteur BCG by intradermal injection, between 1 December 1988 and 28 February 1989. This random test aimed to determine if the administration of one quarter dose (0.025 mg) of intradermal BCG conferred immunity comparable to that of one half (0.05 mg) while diminishing the risk of complications, in particular suppurative adenopathy, in infants of ages 0-1 year. Statistical analysis of the results showed that the 0.025 mg dose of intradermal BCG entails an immunoresponse as satisfactory as that entailed by the 0.05 mg dose, while the rate of suppurative adenitis is significantly higher in the group that received the 0.05 mg dose. It is therefore well justified to recommend a dose of 0.025 mg of intradermal Pasteur BCG for infants aged 1 year and less.

BCG Vaccine↗

The sensitizing effect of a Brucella abortus antigen in cattle after repeated intradermal inoculations.

An antigen prepared from a mucoid strain of B. abortus was repeatedly injected intradermally into cattle to determine whether it sensitizes cattle so that they test false positive with the skin delayed-type hypersensitivity (SDTH) test. Cattle (n = 14) that were experimentally inoculated. with microorganisms that serologically cross-react with B. abortus, and uninfected cattle (n = 15) were tested with the antigen 2 to 5 times over a period of 16 to 17 weeks. An increase in skinfold thickness of > or = 2.0 mm on the injection site was considered a reaction elicited by the antigen. The sera from the cattle were tested with the serum agglutination test, complement fixation test, and an enzyme-linked immunosorbent assay for antibodies against B. abortus. Results showed that none of the animals had an increase in skinfold thickness of > or = 2.0 mm on the injection site of the antigen, which is considered a positive reaction. However, cattle experimentally inoculated with microorganisms other than B. abortus tested seropositive for brucellosis after one SDHT test only. We conclude that the B. abortus antigen inoculated intradermally does not sensitize cattle after repeated inculations, and therefore does not interfere with the subsequent use of the SDTH test in the diagnosis of brucellosis.

Animals↗

Intradermal irritation of dental bleaching agents in rats.

AIM: To evaluate the irritative potential of three dental bleaching agents (hydrogen oxide, carbopol, and carbamide peroxide). METHODS: In rats, Evans blue (2.5%, 1 mL.L-1) was injected i.v. and later each test solution was injected intradermally on the back. After the concentration of the dye in the stained skin area was determined by spectrophotometric analysis. RESULTS: All the dental bleaching agents caused increase of vascular permeability and the intensity varied with the time. CONCLUSION: Dental bleach agents had a great potential for irritating soft tissues.

Acrylic Resins↗

Successful treatment of granulomatous reactions secondary to injection of esthetic implants.

BACKGROUND: In recent years, various injectable materials have come into use to improve esthetic appearance. OBJECTIVE: We describe the clinical and histopathologic aspects of two patients who received intradermal injections of an unknown dermal filler and the different diagnostic tools used to identify the unknown injected material (reflexion electron microscopy, electron dispersing x-ray) and discuss the possibility of a metastatic granulomatous reaction in one patient. We also describe two treatments for this complication and evaluate the legal considerations of the use of materials that have been adulterated and/or whose composition is unknown to the patient. METHODS: We present two patients who developed a granulomatous foreign-body reaction after the subcutaneous injection of an esthetic implant. We treated patient 1 with isotretinoin and 2 months later with doxycycline. We administered isotretinoin to patient 2. RESULTS: We observed a partial improvement in patient 1 after isotretinoin treatment and a remarkable improvement after administration of doxycycline. In patient 2, we observed an excellent response to isotretinoin. CONCLUSION: Isotretinoin and doxycycline, when administered separately, seem to offer effective treatment for reactions resulting from silicone implants. However, further studies that include a larger number of patients and those with reactions secondary to other fillers are clearly needed before the effectiveness of this treatment can be confirmed.

Aged↗

Anti-macrophage antiserum in the treatment of experimentally induced incontinentia pigmenti histologica.

To facilitate the removal of dermal melanin which is located in melanophages of the skin, we studied the effect of anti-macrophage antiserum on the elimination of dermal melanin in incontinentia pigmenti histologica. Although a pronounced inflammatory reaction was produced at the sites injected with the antiserum, no significant decrease in the amounts of radioactive melanosomes was observed at the injected sites. The failure of the intradermal injection of the antiserum to remove melanin pigment could have been due to the very low mobility of the newly recruited macrophages.

Animals↗

Penile lymphoscintigraphy for sentinel node identification.

Lymphoscintigraphy for sentinel node (SN) identification has been extensively validated in breast cancer and melanoma. The aim of this study was to evaluate the findings of lymphoscintigraphy for SN identification in carcinoma of the penis. Lymphoscintigraphy was performed in 74 consecutive patients (mean age 62.2 years, range 28-87 years) with clinically lymph node-negative squamous cell carcinoma of the penis (stage T2 or greater). Following local anaesthesia by xylocaine 10% spray, technetium-99m nanocolloid (mean dose 64.8 MBq, range 40-131 MBq) in a volume of 0.3-0.4 ml was injected intradermally around the tumour. Shortly after injection, a 20-min dynamic study was performed with a dual-head gamma camera; subsequently, static anterior and lateral images were obtained at 30 min and 2 h using simultaneous cobalt-57 flood source transmission scanning. 57Co-assisted skin marking defined SN location for gamma probe/blue dye-guided biopsy, which was performed the next day. The SN visualization rate was 97% (72/74). Lymphatic drainage was bilateral in 81% of the cases (58/72), exclusively to the left groin in 13% (9/72) and only to the right groin in 6%. Bilateral lymph node drainage was synchronous in 38% (22/58) and asynchronous in 62% (in 18 patients the initial route was the left groin, and in the other 18, the right groin). Visualization before 30 min occurred in 66 patients (93%), in 64 of them (88%) already during the dynamic study. A total of 173 SNs were visualized (85 in the right groin, 88 in the left groin). Pitfalls were caused by inguinal skin contamination during injection (four patients) and intracavernous administration (one patient). At surgery, a total of 161 SNs were identified and removed. Sixteen patients (22%) had a tumour-positive SN and underwent standard regional lymph node dissection subsequently. During follow-up (median 28 months, range 3-74 months), two patients with a negative SN developed lymph node metastases in the mapped basin. It is concluded that penile lymphoscintigraphy is a valid and well-tolerated method for lymphatic mapping and SN identification. Although bilateral early inguinal drainage is the most frequent pattern, late imaging is recommended principally in patients with initial unilateral drainage in order to exclude delayed lymph node filling in the contralateral groin. SN identification may lead to a more accurate staging and avoid extensive lymph node dissection in the majority of patients with penile carcinoma.

Adult↗

Vesiculo-vacuolar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine, and serotonin.

In contrast to normal microvessels, those that supply tumors are strikingly hyperpermeable to circulating macromolecules such as plasma proteins. This leakiness is largely attributable to a tumor-secreted cytokine, vascular permeability factor (VPF). Tracer studies have shown that macromolecules cross tumor vascular endothelium by way of a recently described cytoplasmic organelle, the vesiculo-vacuolar organelle or VVO (VVOs are grapelike clusters of interconnected, uncoated vesicles and vacuoles). However, equivalent VVOs are also present in the cytoplasm of normal venules that do not leak substantial amounts of plasma protein. To explain these findings, we hypothesized that VPF increased the permeability of tumor blood vessels by increasing VVO function and that the VVOs of normal venules were relatively impermeable in the absence of VPF stimulation. To test this hypothesis, VPF was injected intradermally in normal animals after intravenous injection of a soluble macromolecular tracer, ferritin, whose extravasation could be followed by electron microscopy. VPF caused normal venules to leak ferritin, and, as predicted by our hypothesis, ferritin extravasated by way of VVOs, just as in hyperpermeable tumor microvessels. Ultrathin (14-nm) serial electron microscopic sections and computer-aided three-dimensional reconstructions better defined VVO structure. VVOs occupied 16-18% of endothelial cytoplasm in normal venules. Individual VVOs were clusters of numerous (median, 124) interconnected vesicles and vacuoles that formed complex pathways across venular endothelium with multiple openings to both luminal and abluminal surfaces. Like VPF, histamine and serotonin also stimulated ferritin extravasation across venules by way of VVOs. Together, these data establish VVOs as the major pathway by which soluble plasma proteins exit venules in response to several mediators that increase venular hyperpermeability. These same mediators also increased the extravasation of colloidal carbon, but this large particulate nonphysiological tracer exited venules primarily through endothelial gaps.

Animals↗

The effects of histamine in malaria.

1. Extracts of the blood of monkeys (Macaca mulatta) infected with Plasmodium knowlesi contain histamine. A mean total concentration of 0.15 mug/ml was present in the circulating blood.2. No histamine was detected in the blood of healthy monkeys.3. Vasodilatation and increased vascular permeability was observed at the site of injection of the extract into the skin and brain of guinea-pigs.4. Infiltration of the dermal layer by leucocytes was observed after intradermal injection of the histamine extract. A similar response was obtained in the brain.5. The extract of the blood from the infected animal produced hypotension in rabbits when administered intravenously.6. The pathophysiological significance of histamine in malaria is discussed.

Animals↗