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Induction of CD4(+) T cell-dependent CD8(+) type 1 responses in humans by a malaria DNA vaccine.

We assessed immunogenicity of a malaria DNA vaccine administered by needle i.m. or needleless jet injection [i.m. or i.m./intradermally (i.d.)] in 14 volunteers. Antigen-specific IFN-gamma responses were detected by enzyme-linked immunospot (ELISPOT) assays in all subjects to multiple 9- to 23-aa peptides containing class I and/or class II restricted epitopes, and were dependent on both CD8(+) and CD4(+) T cells. Overall, frequency of response was significantly greater after i.m. jet injection. CD8(+)-dependent cytotoxic T lymphocytes (CTL) were detected in 8/14 volunteers. Demonstration in humans of elicitation of the class I restricted IFN-gamma responses we believe necessary for protection against the liver stage of malaria parasites brings us closer to an effective malaria vaccine.

Adolescent↗

The penetration of a soft solid by a liquid jet, with application to the administration of a needle-free injection.

Liquid jet injections have been performed on human skin in vivo and silicone rubber using Intraject needle-free injectors. The discharge characteristics of the liquid jet were measured using a custom-built test instrument. The experiments reveal that a high-speed liquid jet penetrates a soft solid by the formation and opening of a planar crack. The fluid stagnation pressure required for skin penetration decreases with increasing diameter of the liquid jet. These findings are consistent with the slow-speed penetration of a soft solid by a sharp-tipped punch. It is demonstrated that the Shergold-Fleck sharp-tipped punch penetration model [Shergold, O.A., Fleck, N.A., 2004. Mechanisms of deep penetration of soft solids. Proc. Roy. Soc. Lond. A 460, 3037-3058.] gives adequate predictions for the pressure required to penetrate a soft solid by a high-speed liquid jet.

Biomechanical Phenomena↗

Preanesthetic medication of children with midazolam using the Biojector jet injector.

BACKGROUND: A rapid, dependable, and economical technique to atraumatically sedate children before anesthesia that does not prolong postanesthesia care unit time remains elusive. The Biojector jet injection system uses carbon dioxide rather than a needle to deliver an intramuscular injection. The dose-response relationship when midazolam is administered was studied using this jet injector. METHODS: Forty children (2.3 +/- 1.3 yr old) undergoing elective myringotomy and tube placement were randomly assigned to receive 0.05, 0.1, 0.15, 0.2, or 0.3 mg.kg-1 midazolam injected intramuscularly using the Biojector disposable syringe (0.006-inch orifice). Assessment of each child before, during, and 10 min after injection, on application of the anesthesia face mask, and every 15 min for 1 h after arrival to the postanesthesia care unit was made by an observer blinded to drug dosage. RESULTS: Face mask tolerance using doses > or = 0.1 mg.kg-1 midazolam was acceptable and statistically different from 0.05 mg/kg. Crying on injection tended to increase with increasing dose. All children were awake and arousable, meeting discharge criteria, after 30 min from arrival in the postanesthesia care unit. CONCLUSIONS: Midazolam (0.1-0.15 mg.kg-1) administered using jet injection effectively and rapidly produces sedation, in a manner acceptable to parents, without delaying postanesthesia care unit discharge.

Child, Preschool↗

Mitigation of tokamak disruptions using high-pressure gas injection.

High-pressure gas-jet injection of neon and argon is shown to be a simple and robust method to mitigate the deleterious effects of disruptions on the DIII-D tokamak. The gas jet penetrates to the central plasma at its sonic velocity. The deposited species dissipates >95% of the plasma by radiation and substantially reduces mechanical stresses on the vessel caused by poloidal halo currents. The gas-jet species-charge distribution can include >50% fraction neutral species which inhibits runaway electrons. The favorable scaling of this technique to burning fusion plasmas is discussed.

Journal Article↗

The surgical approach to Peyronie's disease.

Seven patients with Peyronie's disease were treated by surgical exposure of the fibrous plaque and dermo-jet injection of steroids into the plaque under direct vision. Relief of pain was obtained in 2 of 3 patients and curvature was only moderately improved i 2 of 7 patients. One of 4 patients who were unable to perform coitus because of the curvature noted improvement after the injections. The low rate of response in this small series of patients would suggest that there is no additional benefit in the use of the dermo-jet over percutaneous injection of the plaques. The latter procedure can be performed more easily on a repeated basis over a longer period. Two patients whose plaques were excised and repalced by a dermal inlay graft have had a good response to treatment and it would appear that this technique is useful for the patient who has failed to respond to conservative measures and who is significantly disabled by the disease.

Adult↗

Pharmacokinetics of human growth hormone administered subcutaneously with two different injection systems.

The bioavailability of recombinant human growth hormone (somatropin, CAS 12629-01-5) was compared between a transcutaneous jet injection device and subcutaneous cannula injection. Thirteen healthy male subjects received 8.64 IU somatropin once with jet and once with cannula injection in a randomized cross-over study. Baseline-corrected somatropin serum concentrations were evaluated with non-compartmental and compartmental methods. The 90% confidence intervals with two one-sided t-tests around the ratios of injection devices were 91-120% for maximum concentration, 94-110% for area-under-curve until 14 h, and 92-103% for area-under-curve to infinity. Somatropin has a known metabolic half-life of ca. 20-30 min while the observed terminal half-lives were 2-4 h. Absorption and elimination rate constants were similar. Times of maximum concentrations, terminal half-lives and lag times to start of absorption appeared to be shorter and the absorption rate constant appeared to be larger for jet than for cannula injection. In conclusion, the kinetics of somatropin from subcutaneous tissue had a "flip-flop" characteristic. Bioavailability of somatropin after jet injection was equivalent to cannula injection.

Adult↗

[The safety of the jet (needle-free) injection].

The analysis of literature doesn't give strong confirmation that jet injection could provoke the transmission of the infection. Nevertheless such infection is possible because of retrograde flow of vaccine preparation which just has mixed with tissue liquid of a previous patient or taking into account a continuous contact of an injector head with patient's skin during injection. The design of the injector head has a certain significance on this matter. These risk factors can be eliminated by strict observation of rules for handling these instruments. It's necessary to conduct additional experimental researches to prove or refute the safety of jet injections.

Animals↗

Optimization of a jet-propelled particle injection system for the uniform transdermal delivery of drug/vaccine.

A jet-propelled particle injection system, the biolistics, has been developed and employed to accelerate micro-particles for transdermal drug delivery. We have examined a prototype biolistic device employing a converging-diverging supersonic nozzle (CDSN), and found that the micro-particles were delivered with a wide velocity range (200-800 m/s) and spatial distribution. To provide a controllable system for transdermal drug delivery, we present a contoured shock-tube (CST) concept and its embodiment device. The CST configuration utilizes a quasi-steady, quasi-one dimensional and shock-free supersonic flow to deliver the micro-particles with an almost uniform velocity (the mean velocity and the standard deviation, 699 +/- 4.7 m/s) and spatial distribution. The transient gas and particle dynamics in both prototype devices are interrogated with the validated computational fluid dynamics (CFD) approach. The predicted results for static pressure and Mach number histories, gas flow structures, particle velocity distributions and gas-particle interactions are presented and interpreted. The implications for clinical uses are discussed.

Computer-Aided Design↗

An in vitro study of the hemodynamic effects of catheter injections.

The injection jet from a catheter has been shown to elevate distal pressure and flow. These disturbances in flow present a problem for the application of digital arteriography to measure physiologic flow. The authors used an in vitro model to determine the primary factors responsible for the increases in distal flow with the goal that these disturbances might be estimated and minimized. Experiments were performed to evaluate the importance of the cross-sectional area of the catheter and vessel, the importance of absolute vessel flow, and the importance of distal resistance. A lumped resistance model predicted the flow changes to within 3% of the preinjection vessel flow. In the model system the elevation of distal flow in percent was equal to (the injection rate divided by the tube flow rate) multiplied by (the proximal resistance divided by the total resistance) multiplied by 100. Because the resistance ratio generally is small, injections at physiologic flow rates should produce acceptably small increases in distal flow. The use of a large diameter catheter or the presence of a proximal stenotic lesion would increase the ratio.

Catheterization, Peripheral↗

Making vaccines more acceptable--methods to prevent and minimize pain and other common adverse events associated with vaccines.

The growing abundance of highly immunogenic vaccines has arrived with a burden of pain, distress, and common adverse reactions that in turn may interfere with parental compliance and aggravate anti-vaccine sentiment. In a study of 150 children in each of 2 age-groups, we found that approximately 20% of the subjects suffered serious distress or worse. During the procedural phase, approximately 90% of the 15-to-18 month old children and 45% of the 4-to-6 year old children showed serious distress or worse. To address non-adherence with pediatric vaccine schedules, we must consider all of the possible issues that might prevent a parent from taking a child to a health care provider for vaccination. In that same study we identified useful predictors for both preparatory and procedural distress - predictors that might be used in identifying children who might benefit from preventive interventions. Vaccine providers might consider a variety of interventions. Attitude, empathy, instruction, and practice have all been shown to have a salutatory effect upon pain and anxiety with medical procedures in general and specifically with vaccinations. Distraction has also been found to be an effective method for distress and pain prevention in children. More formal methods of clinical hypnosis which combine a deep state of relaxation with focused imagery and suggestion have also been found to be effective in helping children and adolescents prepare for, cope with, and tolerate the pain and anxiety associated with medical procedures. So-called 'sugar nipples' delivering small amounts of sucrose orally at the time of a painful procedure in an infant has been not been shown to decrease vaccination pain and studies on refrigerant topical anesthetics are mixed. Studies have found a eutectic mixture of 2.5% lidocaine and 2.5% prilocaine (EMLA) effective in providing adequate local anesthesia in children, but it suffers from problems in practical application. Studies with various injection techniques have not identified ready solutions, and although jet injection appears to provoke less anxiety and cause less immediate pain, studies also indicate a somewhat greater incidence of delayed local reactogenicity including soreness and edema. Other measures to prevent or rapidly treat other common adverse events have been shown effective and should be considered as well.

Administration, Intranasal↗

Fluid mechanics analysis of a spring-loaded jet injector.

A syringe jet injector is a device designed to administer a drug quickly and painlessly through the skin. Though syringe jet injectors have been in use for almost 50 years, current designs still suffer from inconsistent performance. To better understand the fluid mechanics of jet injection and gain insight into how the design might influence performance, two theoretical analyses to determine the fluid pressure profile at the exit orifice were conducted. The first was a continuum analysis assuming static incompressibility. Results demonstrated that the maximum jet pressure was highly sensitive to the spring constant, initial piston velocity, and piston cross-sectional area while the time to achieve the maximum pressure was most sensitive to the injection chamber length, initial piston velocity, bulk modulus of the injectant, and the piston cross-sectional area. The second analysis was a shock wave analysis. Results demonstrated a stepwise pressure-time plot that was similar in magnitude to that for the continuum analysis assuming static incompressibility. Results from these two investigations are useful for design modification of the jet injector to achieve desired pressure-time profiles at the orifice. Control of pressure-time profiles may help to achieve a more consistent and effective injection process.

Equipment Design↗

Pharmacokinetics and pharmacodynamics of recombinant human growth hormone by subcutaneous jet- or needle-injection in patients with growth hormone deficiency.

Eighteen growth hormone (GH) deficient children and adolescents (11 6/12-20 9/12 y) participated in a randomized open, two-period (4 weeks) cross-over study to evaluate the pharmacokinetics and pharmacodynamics of recombinant human growth hormone (rhGH) administered daily, either by subcutaneous jet-injection or conventional needle-injection. Plasma growth hormone (GH), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), glucose, insulin, HbAlc and serum-free fatty acids (FFA) levels were analysed repeatedly. GH absorption characteristics, expressed as AUC(0-infinity), Cmax and Tmax ratio (%) jet-injected over needle-injected were similar in both groups. IGF-I and IGFBP-3 plasma levels were identical in both groups. Serum FFA concentrations were comparable after GH administration with either injection device. Surprisingly nocturnal blood glucose decreased to asymptomatic hypoglycaemic levels in all patients. The results of this study showed equal responses concerning absorption and bioavailability of growth hormone administered daily for 4 weeks by either a jet- or a needle-injection device in GH-deficient children and adolescents.

Absorption↗

Plasma free insulin profiles after administration of insulin by jet and conventional syringe injection.

Plasma free insulin profiles in insulin-dependent diabetic subjects were compared after jet and syringe injection of insulin. Jet injection of insulin resulted in a shift of the free insulin profile to the left. Thus higher plasma free insulin levels were found over the first 30 min after injection (P less than 0.05), while after 240 min plasma free insulin levels were lower than those seen following syringe injection (P less than 0.05). Significant differences in the response of blood glucose and 3-hydroxybutyrate levels reflected the differences in plasma free insulin levels. Jet administration results in more rapid absorption of insulin and could be useful in providing a more physiologic postprandial insulin profile than that seen after conventional injection.

Adult↗

Hepatitis A vaccine administration: comparison between jet-injector and needle injection.

INTRODUCTION: Type A hepatitis virus (HAV) is a serious health problem throughout the world and can be spread via fecal-oral contact. Both immune globulin and an HAV vaccine provide protection, but the vaccine gives complete protection. Efficacy of methods of vaccination in relation to the formation of anti-HAV antibodies is unclear; thus, this study seeks to determine if significant differences exist between the syringe as compared to the jet injection technique. The purpose of this study was to compare in a randomized trial Biojet jet-injection system to a needle-syringe method. To determine if a significant difference between these two methods in seroconversion rates or geometric mean titers of anti HAV antibody occurs at day 15, 30, and 210 days after vaccination. METHOD: Anti-HAV IgG(-) adult hospital employees were randomized to receive 1440 EL.U of hepatitis a vaccine (HAVRIX(R)) in 2 doses by either needle or jet-injector (Biojector(R)) system at month 0 and 6. HAV seroconversion titer results were measured by the Boehringer-Mannheim method. RESULTS/DISCUSSION: A higher proportion of persons who received HAV vaccine via the Biojector(R) seroconverted with anti-HAV level >/=20 mIU at day 15, 30, and month 7 when compared with a needle injection.Side-effect profiles reported by participants in both methods were below those identified in current published and insert information, but the Biojector(R) had greater local reactivity in all categories when compared to the needle method.

Adult↗

[Pharmacokinetics of the new Soviet anti-arrhythmia preparation etacizin].

Ten patients without marked abnormalities on the part of the liver and kidneys were examined for the pharmacokinetics of a new Soviet antiarrhythmic drug etacizin. The drug was injected intravenously at a rate of 0.5-0.8 mg/kg bw. The blood required for determining drug concentrations was taken 1, 2, 3 and 4 hours after drug jet injection. It was demonstrated that the drug half-life was on the average 164 +/- 24.7 min, exceeding 2 times the half-life of etmozine, a drug of the same series applied to the treatment of some forms of heart rhythm abnormalities.

Anti-Arrhythmia Agents↗

[Euthyroid Graves' disease (problems of diagnosis and treatment)].

Twenty-six patients with endocrine ophthalmopathy without signs of thyroid disease (according to ultrasonic scanning, measurements of free thyroxin and thyrotropic hormone-TTH) were examined. Edematous exophthalmos in the compensated stage was diagnosed in 13 patients, subclinical stage of this condition in 10, and endocrine myopathy in 3 patients. Russian drug thyroliberin was used for accurate diagnosis of thyroid dysfunction; injection of this drugs to normal subjects leads to a drastic (3.5-5-fold) increase of TTH level. After measurement of TTH, the drug was infused intravenously by jet injection in a dose of 500 micrograms. Ten normal subjects were controls. 30 min after thyroliberin injection, TTH was measured. It was sharply increased in half of patients and in the control group. In one-third of cases (mainly with edematous exophthalmos) TTH level increased negligibly or even decreased after the test. After 1.5-2 years, signs of hyperthyrosis manifested in one-third of this group of patients. The authors consider that patients with the so-called Graves' disease are at a high risk of thyroid abnormalities and should be regularly consulted by both ophthalmologist and endocrinologist.

Adult↗