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Psychological responses to the needle-free Medi-Jector or the multidose Disetronic injection pen in human growth hormone therapy.

The aim of the study was to test the hypothesis that daily administration of growth hormone using the Medi-Jector results in fewer adverse psychological responses than needle injection with a multidose injection pen. The Medi-Jector is a needle-free injection device that can deliver growth hormone subcutaneously through jet injection. The group studied consisted of 18 children aged 10 y or over who were participating in a study of the bioequivalence and bioequipotence of the administration of growth hormone through jet injection or needle injection. Previously, all subjects had received growth hormone therapy with commercially available multidose injection pens. The study was designed as a prospective, randomized, two-period cross-over trial. A questionnaire was used to assess psychological responses such as non-compliance, opinion on ease of preparation, affective responses to administration and local side-effects, as well as overall preference. In addition, the subjects kept a diary during the study. The subjects found the Medi-Jector less offputting (p < 0.01), less painful with respect to both frequency (p < 0.04) and intensity (p < 0.01) and less unpleasant (p < 0.05) than a multidose injection pen with a 28G needle (p < 0.01). No difference in compliance was detected. Most subjects preferred the Medi-Jector for future use (p < 0.05). The mean score on a 1-10 point scale (10 is excellent) was 7.9 (SD 1.4) for the Medi-Jector and 6.8 (SD 2.3) for the multidose injection pen (p < 0.08). The prevalence of visible bruises each day was higher (p < 0.01) with the Medi-Jector (2.5, SD 2.1) than with the multidose injection pen (0.7, SD 1.1), but children showed indifferent affective responses to bruising. Thirteen out of 18 subjects decided to continue therapy with the Medi-Jector (p < 0.06). It is concluded that use of the Medi-Jector in growth hormone therapy tends to lead to fewer adverse psychological responses than a multidose injection pen with 28G needles.

Adolescent↗

Adjuncts to local anesthesia: separating fact from fiction.

Adjunctive local anesthetic techniques and their armamentaria, such as intraosseous injection, computer-controlled delivery systems, periodontal ligament injection and needleless jet injection, have been proposed to hold particular advantages over conventional means of achieving local anesthesia. This article describes the use of each technique and proprietary armamentarium and reviews the literature appraising their use.

Alveolar Process↗

Intradermal immunization with novel plasmid DNA-coated nanoparticles via a needle-free injection device.

A high population of dendritic cells in the skin makes intradermal (ID) immunization an attractive route. We sought to further enhance immune responses from a previously reported novel nanoparticle-based DNA vaccine delivery system by administering the system intradermally into mouse skin using Biojector 2000, a needle-free jet injection device. Two mouse studies were carried out. Balb/C mice (n=5-6) were immunized on day 0, 7, and 14 by subcutaneous injection or via the Biojector 2000 with pDNA alone (CMV-beta-galactosidase, 5 micro g), pDNA-coated nanoparticles, or beta-galactosidase protein (10 micro g) adjuvanted with 'Alum' (15 micro g). On day 28, mice were sacrificed and specific serum IgG and IgA titer, in vitro cytokine release, and cell proliferation of isolated splenocytes were determined. Similar to previous reports, in both mouse studies, SC immunization with pDNA-coated nanoparticles led to over a log increase in specific serum IgG titer as compared to immunization with pDNA alone. For pDNA alone, jet and SC injection did not result in significant differences in IgG titer. In contrast, for pDNA-coated nanoparticles, jet injection led to as high as a 20-fold enhancement in IgG titer over SC injection. In addition, jet injection of pDNA-coated nanoparticles enhanced the IgG titer by more than 200-fold over jet injection of pDNA alone. Also, jet injection of pDNA-coated nanoparticles resulted in significantly enhanced specific serum IgA titer. For in vitro cytokine release, immunization with pDNA-coated nanoparticles by jet injection enhanced IFN-gamma and IL-4 release over pDNA alone by 6- and 5-fold, respectively. SC injection of pDNA-coated nanoparticles also resulted in enhanced IFN-gamma and IL-4 release over pDNA alone although with less magnitude. Finally, immunization with pDNA-coated nanoparticles, by both jet injection and SC injection, led to improved splenocyte proliferation over pDNA alone. In conclusion, a combination of a novel cationic nanoparticle-based DNA delivery system with ID jet injection led to enhanced antibody production, Th-1/Th-2 balanced cytokine release, and enhanced splenocyte proliferation.

Animals↗

Subcutaneous administration of midazolam: a comparison of the Bioject jet injector with the conventional syringe and needle.

PURPOSE: The purpose of this study was to compare jet injection to a syringe and needle in terms of the difference in discomfort and pharmacokinetics after the subcutaneous administration of midazolam. PATIENTS AND METHODS: Using a prospective, randomized, double-blinded study design, 14 subjects were administered midazolam on two separate occasions (at least 2 weeks apart). The subjects were randomly distributed into two groups: syringe and needle (saline)/jet injector (midazolam) or syringe and needle (midazolam)/jet injector (saline). The subjects were randomly assigned to receive either EMLA (eutectic mixture of local anesthetics) or a placebo at the injection site for the first administration and the other topical agent on the second visit. Each subject received one subcutaneous injection in the deltoid region per arm per day. Each injection contained the same volume of solution. Subjects completed visual analog scale (VAS) questionnaires assessing the discomfort of the injection. Blood samples were taken at specified intervals over 2 hours for determination of midazolam levels. RESULTS: The discomfort associated with the injection was less with the Biojector 2000 (Bioject Inc, Portland, OR) although this was not statistically significant. However, persistent discomfort was significantly greater at the needle site. The mean peak plasma level of midazolam was achieved more rapidly with the Biojector 2000 than with the syringe and needle (P < .05). However, the peak plasma level after jet injection or injection with a syringe and needle was not statistically different. CONCLUSION: The results of the study show that the Biojector 2000 is a needle-free injection system that can be used for the administration of a premedicant before induction of anesthesia. It has several advantages, including the potential reduction of anxiety associated with the "fear of needles" and occupational injuries.

Adolescent↗

Treatment of keloids and hypertrophic scars with dermojet injections of bleomycin: a preliminary study.

BACKGROUND: Numerous treatment modalities have been used to treat keloids and hypertrophic scars, but the optimal treatment has not been established. OBJECTIVE: The aim of this study was to determine the efficacy and safety of intralesional jet injection of bleomycin as therapy for keloids and hypertrophic scars that are unresponsive to intralesional steroid injection. METHODS: The study included 14 patients with 15 keloids or hypertrophic scars that had not responded to a minimum of three intralesional injections of triamcinolone acetonide. Multiple jet injections of 0.1 ml of bleomycin (1.5 IU/ml) were administered to each lesion, with injection sites spaced 0.5 mm apart. Injections were repeated each month. Scar height was measured, and scar pliability and erythema were scored at baseline and then monthly during the treatment and follow-up periods. Patients' self-assessments of subjective symptoms (pruritus and pain) were also scored. Clinical improvement was defined primarily on the basis of scar height reduction (percentage reduction from baseline), and was classified using the following scale: complete flattening (100%), highly significant flattening (> 90%), significant flattening (75-90%), moderate flattening (50-75%), and minimal flattening (< 50%). Pre- and post-treatment mean values for scar height, scar pliability, erythema, pruritus and pain were statistically compared. RESULTS: The number of sessions required to successfully treat the lesions ranged from two to six. Eleven lesions (73.3%) showed complete flattening, one (6.7%) showed highly significant flattening, two (13.3%) showed significant flattening, and one scar (6.7%) showed moderate flattening. The mean scar height was significantly lower, and the mean scores for scar pliability and erythema were significantly better at the end of treatment (P < 0.001, P < 0.001 and P < 0.001, respectively). The mean scores for pruritus and pain also improved significantly (P < 0.001 and P = 0.01, respectively). The observed side-effects were hyperpigmentation (four lesions) and skin atrophy (three lesions). No recurrences were noted during follow up (mean duration of 19 months). CONCLUSIONS: Intralesional jet injection of bleomycin is an effective and safe method of treating keloids and hypertrophic scars that are unresponsive to intralesional steroid therapy.

Adolescent↗

Evaluation of the insulin jet injector as a potential source of infection.

In recent years jet injection of insulin has been widely used by patients with diabetes mellitus. Jet injectors may become contaminated by bacteria because of repeated use without cleaning; cleansing every 2 weeks is recommended. We investigated the occurrence of bacterial contamination by culturing jet injectors in everyday use by 19 patients with diabetes. Swabs from the interior chambers were cultured on blood agar plates. Only one of 20 cultures yielded bacterial growth, and the organism recovered was a presumed contaminant that could not be identified as any common pathogen. No study patient, nor any of more than 70 patients whom we instructed in jet injection, showed any clinical evidence of infection attributable to jet injector use. Jet injectors are unlikely to become colonized by bacteria or to cause infection in patients using them for insulin administration. The low rate of colonization may be due to the antibacterial preservatives added to commercial preparations of insulin. Additional data based on larger numbers of patients would be useful in further clarifying the risk of infection associated with jet injectors.

Adolescent↗

Induction of mucosal IgA by a novel jet delivery technique for HIV-1 DNA.

Novel ways of delivering plasmid DNA to elicit humoral IgA, IgG and cell-mediated immune responses in mice were investigated. Intraoral administration of DNA in the cheek, using a jet immunization technique, elicited the highest IgA mucosal responses. Intranasal immunization gave strong mucosal IgA responses and persistent systemic IgG. Immunoglobulin isotype analysis revealed an IgG1 profile for intramuscular tongue and gene gun immunizations and an IgG2a profile following oral jet injection and intranasal application. The route of delivery was of importance for the characteristics and quality of the mucosal immune response following DNA immunization. For DNA vaccine delivery, the intraoral jet injection technique has the advantages of being a simple and rapid way of administering the DNA in solution and of provoking specific mucosal IgA when administered in the mucosal associated lymphoid tissue.

Administration, Intranasal↗

The efficacy and acceptability of using a jet injector in performing digital blocks.

This prospective, nonblinded study, comparing jet injection with needle-syringe injection of lidocaine in performing digital blocks, tested the hypothesis that jet injection can be used effectively as a less painful way to perform digital blocks. Twenty-four adult patients with injuries of the middle or distal phalanges of the fingers received digital blocks using a jet injector on one side of the finger and a needle-syringe on the other side; pain was assessed at 0, 1, 3, 6, 12, and 24 hours using visual analog scales. Differences in pain scores for the two procedures (jet injector vs needle) were tested at each time period using nonparametric statistical procedures for paired or matched data (paired Wilcoxon). At the time of injection (time 0) and at 12 hours, the jet had a significantly lower pain score than the needle. Comparisons made at the other points were statistically nonsignificant at .05. The anesthesia achieved using the jet injector was considered adequate in 23 of 24 patients. We conclude that the jet injector can be used effectively in performing digital blocks and is less painful than standard needle-syringe methods.

Adult↗

A safer method for paracervical block in therapeutic abortions.

Adverse reactions to paracervical block, including death, are believed to be dose related. By using a modified jet injector instead of the standard syringe-and-needle technique, we obtained equal analgesia with one fifth of the standard milligram dosage of lidocaine in patients undergoing therapeutic abortion. Blood lidocaine levels as determined by gas chromatography were reduced by two thirds with jet injection. These results led us to conclude that jet injection for paracervical block is safer than the syringe-and-needle technique.

Abortion, Therapeutic↗

Tracheobronchial and pulmonary histopathology following conventional and high-frequency jet ventilation.

The advent of high-frequency jet ventilation (HFJV) as an alternative method of respiratory support for newborns has been implicated as a causative agent of necrotizing tracheobronchitis (NTB). We conducted a controlled trial of prolonged HFJV and conventional mechanical ventilation (CMV) in adult cats to determine effects on airway injury related to mode of ventilation and placement of the jet injector (proximal vs distal trachea). Fifteen cats were randomly assigned to either high-frequency positive pressure ventilation, proximal injection jet ventilation, or distal injection jet ventilation. The animals were ventilated for more than 33 hours. Post mortem, the trachea and respiratory tree were removed en bloc and fixed in formalin. A pathologist, unaware of the mode of ventilation, examined tracheobronchial histology and assigned scores using a technique previously described. Lung parenchymal tissue was also assessed using a similar grading system. Statistical analysis (Kruskal-Wallis analysis of variance) demonstrated no significant differences between tracheobronchial or lung parenchymal histopathology regardless of the mode of ventilation. We conclude that (1) the adult cat serves as a useful model for evaluating histopathologic effects of prolonged ventilation, (2) the etiology and pathogenesis of airway injury appears to be multifactorial, and the mode of ventilation is only one of many contributing variables, and (3) previously demonstrated differences between CMV and HFJV may be related to a much shorter duration of ventilation.

Animals↗

The use of an endotracheal ventilation catheter for jet ventilation during a difficult intubation.

This case report describes the use of an endotracheal ventilation catheter (ETVC) to provide prolonged intraoperative jet ventilation, reintubation and the maintenance of tracheal access following extubation. It emphasizes that excellent oxygenation and ventilation can be achieved but such management can be complicated by a pneumothorax even when the risks are minimized. A 43-yr-old man presented for possible pulmonary sleeve resection. Placement of a double lumen endotracheal tube (DLT) by direct laryngoscopy was unsuccessful due to the inability to visualize the glottis. A 7.5 mm endotracheal tube (ETT) was successfully introduced over a fibreoptic bronchoscope (FOB). An ETVC was passed, permitting manually cycled jet ventilation while general intravenous anaesthesia and muscle relaxation were maintained. The ETT was then withdrawn over the ETVC and jet ventilation continued for approximately 90 min, while attempts at placing a DLT over a now malfunctioning FOB continued. These attempts were eventually abandoned and the patient was returned to the post-anaesthesia care unit (PACU) haemodynamically stable. The trachea was extubated over the ETVC, which remained in situ. A pneumothorax was noted on the postoperative chest x-ray. This case illustrates prolonged intraoperative jet injection via a "jet stylet" with satisfactory ventilation and oxygenation but complicated by a pneumothorax. Also it illustrates a strategy for the management of a "difficult extubation."

Adult↗

Phase I trial of a recombinant vaccinia virus encoding carcinoembryonic antigen in metastatic adenocarcinoma: comparison of intradermal versus subcutaneous administration.

The principal objectives of this trial were twofold: (a) to examine the safety and relative efficacy of intradermal needle injection versus s.c. jet administration of a carcinoembryonic antigen (CEA)-encoding recombinant vaccinia virus (rV-CEA) over a limited dose range and (b) to evaluate CEA-specific immune responses or antitumor effects induced by rV-CEA vaccination. Patients were randomly assigned to one of two groups, depending upon the technique of vaccine administration. All 20 patients received two doses of 10(7) or 10(8) pfu of rV-CEA at a 4-week interval. Toxicity was limited to modest local inflammation at the inoculation site as well as low-grade fever and increased fatigue, each affecting fewer than 20% of the patients. No evidence of CEA-specific lymphoproliferation, interleukin 2 release, delayed-type hypersensitivity, or antibody response was observed. Thus, the efficacy comparison between the two administration techniques was based upon the induction of immune responses to the vaccinia virus vector. Both techniques induced vaccinia-specific lymphoproliferation, interleukin 2 release, and antibody responses of comparable magnitude and frequency as well as protected 80% of patients against pustule formation following vaccinia scarification. Thus, there is no compelling reason to recommend one administration technique over the other based upon toxicity or efficacy. We have selected s.c. jet injection for subsequent trials of rV-CEA based on the ability to accommodate larger injection volumes, enhanced standardization between clinicians, and avoidance of needles that could transmit the vaccine or blood-borne pathogens to health care workers. We recommend use of 10(8) pfu doses for subsequent trials of recombinant vaccinia virus vaccines based upon the favorable toxicity profile and more consistent local pustule formation indicative of an adequate inoculation of live virus. No objective clinical responses to the rV-CEA vaccine were observed among this population of patients with widely metastatic adenocarcinoma.

Adenocarcinoma↗

The use of jet-injectors in BCG vaccination.

In mass vaccination programmes, the jet-injection of vaccine may have considerable operational advantages over the classical techniques. The technical performance of two models of jet-injector, the Dermo-Jet and the Ped-O-Jet, in BCG vaccination was assessed in a number of studies which are reviewed by the authors. It is shown that the jet-injectors do not administer the full dose for which they are calibrated and that the size of the vaccination lesion varies more than after vaccination by syringe.By increasing the dosage considerably, the results of vaccination by jet-injection may be improved to a certain extent but the risk of unpleasant reactions is also increased.

BCG Vaccine↗

[Elaboration of the combination of antitumor preparations bleomycetin + 5-fluorouracil + cisplatin].

Clinical trials on efficacy and toxicity of combined use of bleomycetin, 5-fluorouracil and cisplatin in patients with disseminated tumor processes were conducted. Two regimens were applied. Regimen I included intravenous administration of cisplatin in a dose of 100-150 mg/m2 on day 1, intramuscular administration of bleomycetin in a dose of 10 mg on days 2-4 and intravenous jet injection of 5-fluorouracil in a dose of 400 mg/m2 on days 2-4. Regimen II consisted of intramuscular administration of bleomycetin in a dose of 10 mg on days 1-3, intravenous jet injection of 5-fluorouracil in a dose of 400 mg/m2 on the same days and intravenous administration of cisplatin in a dose of 100-150 mg/m2 on day 4. The intervals between the courses amounted to 4 weeks. Complete regression of cervical carcinoma relapsing was observed in 1 patient. In 5 patients i.e. 1 with small-cell lung cancer, 3 with squamous cell lung cancer and 1 with metastases of low-differentiated cancer from an undetected focus to supraclavicular lymph nodes the effect was partial. Long-term stabilization of the disease at the background of the treatment for 6-7 months was stated in 3 patients. On the whole the objective response was in 6 out of 22 patients or in 27 per cent. 7 of them were treated with cisplatin in a dose of 150 mg/m2. The regimens of the combined use of 5-fluorouracil, bleomycetin and cisplatin were low toxic. The therapeutic effect showed that the combination was of practical value.

Antineoplastic Combined Chemotherapy Protocols↗

Optimization of DNA-based vaccination in cows using green fluorescent protein and protein A as a prelude to immunization against staphylococcal mastitis.

Staphylococcus aureus is a contagious pathogen that often results in chronic intramammary infections in dairy cows. Current vaccine formulations are ineffective in preventing this infection. The objective of this study was to stimulate an immune response in dairy cows through injection of plasmid DNA designed to express staphylococcal Protein A in transfected cells. Intramuscular and intradermal vaccination sites were evaluated using a plasmid containing the human cytomegalovirus (CMV) promoter/enhancer directing expression of green fluorescent protein (pcDNA3/GFP). DNA was delivered by needle and syringe, or by high-, intermediate-, or low-pressure jet injections (Ped-o-Jet and LectraJet). Five cows per treatment were injected with 0.5 mg of plasmid DNA at 6, 4, and 2 wk prepartum. Serum antibody levels determined by ELISA indicated that intradermal high-pressure jet injection elicited a greater immune response compared to needle and syringe injection. Differences in antibody production among low-pressure and needle and syringe treatment groups were not significant. An expression plasmid containing the CMV promoter/enhancer driving expression of the Fc-binding domain of S. aureus Protein A was coinjected into cows by vulvamucosal vaccination using the high-pressure Ped-o-Jet. Beginning 6 wk prepartum, groups of cows (n = 5) were injected three times at 2-wk intervals with DNA in saline, DNA in aluminum phosphate adjuvant, or served as noninjected controls. A cellular immune response to Protein A was detected in 4 of 10 animals, while cellular responses to GFP were not detected. Humoral responses to Protein A were observed in 6 of 10 animals and to GFP in 2 of 10 animals. Aluminum phosphate adjuvant appeared to enhance antibody production in response to Protein A. In experiment 3, a protein boost injection of Protein A was given to six animals approximately 5 mo postpartum. Three animals were nonvaccinated controls, and three were among those stimulated to produce antibody in response to the DNA-based vaccine. These results showed that Protein A specific antibodies remained elevated as compared to nonvaccinated controls and were stimulated in response to the protein boost. However, the magnitude of the response in animals previously vaccinated with DNA was not different than that observed in the nonvaccinated controls. We have shown that a humoral and cellular immune response to abbreviated Protein A can be raised in dairy cows using intravulvamucosal jet injection of a DNA-based vaccine.

Animals↗