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Radiation dose to the operator during vertebroplasty: prospective comparison of the use of 1-cc syringes versus an injection device.

BACKGROUND AND PURPOSE: Percutaneous vertebroplasty procedures require relatively long durations of fluoroscopic guidance, which might lead to substantial radiation dose to operators. Specialized injection devices have been proposed to limit operator exposure. Our purpose was to compare the radiation dose to the operator's hands during vertebroplasty when using 1-cc syringes versus that when using an injection device. METHODS: Radiation dosimeters were worn on the left wrist during 39 vertebroplasty injection procedures in 25 patients. Cases were alternated between the use of 1-cc syringes (19 procedures) and the use of an injection device (20 procedures). For each procedure, one dosimeter was worn throughout the procedure, both during needle placement and injection, and a second dosimeter was worn during the injection phase only. Mean doses for the whole case and mean doses for the injection procedure alone were compared between groups. RESULTS: Mean whole case dose was 128 +/- 161 mrem (range, 0-660 mrem) for the 1-cc syringe group versus 98 +/- 90 mrem (range, 0-340 mrem) for the injection device group (P =.23). Mean dose during injection was 100 +/- 145 mrem (range, 0-660 mrem) for the 1-cc syringe group versus 55 +/- 43 mrem (range, 0-130 mrem) for the injection device group (P =.09). Three of 19 1-cc syringe cases yielded zero dose, compared with four of 20 injection device cases. Duration of injection was markedly different between groups, with mean injection times of 4.2 and 7.5 min for 1-cc syringe and injection device cases, respectively (P <.00002). Mean injection dose per minute of lateral fluoroscopy was 23.6 and 7.3 mrem for the 1-cc syringe and injection device groups, respectively (P =.002). CONCLUSION: The use of an injection device significantly decreased the radiation dose to the operator's extremity per unit time of injection. However, total dose per injection was equivalent between groups because of significantly longer injection duration for the injection device cohort.

Bone Cements↗

Incomplete retention after direct myocardial injection.

Direct intramyocardial injection may permit local delivery of protein and gene therapy agents for myocardial and coronary artery disease. Little is known about the immediate fate of materials administered via percutaneous endomyocardial catheters or via surgical epicardial injection. In this study, we use a novel method to evaluate the acute retention of agents injected directly into the myocardium, compare epicardial with the percutaneous endocardial and postmortem delivery, and evaluate the influence of injectate volume on myocardial retention. Fifteen 40-50 kg pigs underwent overlapping myocardial injections using a percutaneous endomyocardial catheter, an epicardial needle via an open chest, and epicardial needle postmortem. Multiple distinct 15 micro neutron-activated microsphere species were used as tracers. Two or three myocardial walls were injected in each animal using 3.5 mm, 27-28 gauge needles at varying injectate volumes. Animals were sacrificed immediately. Myocardial walls were divided and multiple microsphere species were quantified. In an additional study, nine 70 kg pigs underwent percutaneous endomyocardial injections with replication-deficient adenovirus encoding for the production of lac-Z. The injectate volume was varied, while the viral particle number remained constant. The animals were sacrificed 5 days after the percutaneous injections; the heart, liver, and spleen were collected for beta-galactosidase activity. Endomyocardial injection was associated with 43% +/- 15% microsphere retention, compared with 15% +/- 21% (P < 0.01) retention of open chest epicardial injection and 89% +/- 60% (P < 0.01) for postmortem injection. Reducing the injectate volume from 100 to 10 microL improved microsphere retention (P = 0.01). There was a trend toward improved viral transfection associated with smaller injection volumes. Despite direct intramyocardial administration, a significant fraction of injectate is not retained locally. Catheter-based needle endomyocardial injection is associated with equivalent or superior injectate retention compared with open chest epicardial injection. Proportionately, more injectate may be retained at lower volumes. Loss may involve a combination of channel leakage, venous, and lymphatic return.

Adenoviridae↗

Neurologic and histologic outcome after intraneural injections of lidocaine in canine sciatic nerves.

BACKGROUND: Inadvertent intraneural injection of local anesthetics may result in neurologic injury. We hypothesized that an intraneural injection may be associated with higher injection pressures and an increase in the risk of neurologic injury. METHODS: The study was conducted in accordance with the principles of laboratory animal care, and was approved by the Laboratory Animal Care and Use Committee. Fifteen dogs of mixed breed (16-21 kg) were studied. After general endotracheal anesthesia, the sciatic nerves (n= 30) were exposed bilaterally. Under direct vision, a 25-gauge, long-beveled needle (30 degrees) was placed either epineurally (n= 10) or intraneurally (n= 20), and 4 ml of preservative-free lidocaine 20 mg/ml was injected using an automated infusion pump (4 ml/min). Injection pressure data were acquired using an in-line manometer coupled to a computer via an analog-to-digital conversion board. After injection, the animals were awakened and subjected to serial neurologic examinations. One week later, the dogs were killed, the sciatic nerves excised and histologic examination was performed by pathologists blind to the purpose of the study. RESULTS: All perineural injections resulted in low pressures (< or = 5 psi). In contrast, eight of 20 intraneural injections resulted in high pressures (20-38 psi) at the beginning of the injection. Twelve intraneural injections, however, resulted in pressures of less than 12 psi. Neurologic function returned to baseline within 3 h after perineural injections and within 24 h after intraneural injections, when the measured injection pressures were less than 12 psi. Neurologic deficits persisted throughout the study period after all eight intraneural injections that resulted in high injection pressures. Histologic examination of the affected nerves revealed fascicular axonolysis and cellular infiltration. CONCLUSIONS: The data in our canine model of intraneural injection suggest that intraneural injections do not always lead to nerve injury. High injection pressures during intraneural injection may be indicative of intrafascicular injection and may predict the development of neurologic injury.

Anesthetics, Local↗

Evaluation of the radiosensitizing effects of RK28 intravenous, intraarterial, and intratumoral injections on the rabbit VX2 tumor system.

PURPOSE: To evaluate the differences in the radiosensitizing effects of intravenous (i.v.) injection, intraarterial (i.a.) injection, and intratumoral (i.t.) injections of the hypoxic cell radiosensitizer RK28 ([1-(4'-hydroxy-2'-butenoxy)methyl-2-nitroimidazole], a 2-nitroimidazole with an acyclic sugar analogue substituted at the N-1 position of the imidazole ring) using an animal experimental system. METHODS AND MATERIALS: Rabbit VX2 tumors, which were implanted in the muscle of left hind legs and grown to 3 cm in diameter, were treated with RK28 (80 mg/kg x b.wt.) before 15 Gy of local x-ray irradiation. The auricular vein and the left saphenous artery were used for systemic injection and regional injection, respectively. For i.t. injection, a 21-gauge needle with three lateral holes was positioned in the central area of the tumor. Tumor regression was precisely evaluated by computed tomograpy (CT), and survival time was also studied. Using high-performance liquid chromatography (HPLC), pharmacokinetic studies for RK28 and its seven major metabolites were performed in tumor and serum at 0, 10, 20, 30, and 60 min after drug injection was completed. RESULTS: Radiosensitizing effects of RK28 were considered present after i.a. injection (p < 0.05) and i.t. injection (p < 0.05) after analyzing tumor volumes on day 21 after treatment. Increased survival was not observed in any group with RK28 injection compared with survival in the group treated by x-ray irradiation alone. Pharmacokinetic studies showed the average concentration of RK28 in the tumor during x-ray irradiation was 1.3 times higher after i.a. injection and 3.5 times higher after i.t. injection than that after i.v. injection. The time modifying factor50 (TMF50: ratio of time for tumor to decrease by 50%, radiation alone vs. radiation plus drug) was calculated to be 1.5 after i.v. injection, 1.7 after i.a. injection, and 2.3 after i.t. injection. The values of TMF50 correlated to the average concentrations of RK28 in the tumor. As to metabolites of RK28, beta-glucuronated compound and cysteine conjugate were highly detected. The concentrations of cysteine conjugate were higher in the tumor than in serum via i.v. injection. CONCLUSIONS: Radiosensitizing effects of RK28 were observed on the rabbit VX-2 tumor system after i.a. or i.t. injection. Pharmacokinetic studies proved that radiosensitizing effects depended on the concentration in the tumor, though the administration routes were different. Combined forms with nonprotein thiols were detected. However, survival benefits were not obtained by RK28. For clinical applications of RK28, i.a. or i.t. injection could facilitate better local control of cancer.

Animals↗

The management of oromandibular motor disorders and facial spasms with injections of botulinum toxin.

Although much work is yet to be done in this area, nine general conclusions can be derived: 1. Local site-of-injection side effects from botulinum toxin injections are rare, assuming proper technique is used. 2. The two most common medication-related side effects from botulinum toxin orofacial injections are alterations in salivary consistency and inadvertent weakness of the swallowing, speech, and facial muscles. These complications are injection site-specific (eg, more common with lateral pterygoid injections and palatal and tongue muscle injections) and dose-dependent problems. These problems are bothersome but are not contraindications for the therapy if it is needed. 3. The data presented in this article are mostly case series-based and open trial-based information that is promising, but randomized, blinded, controlled trials are needed to establish the true efficacy of this method for the orofacial motor and pain disorders. 4. The novice should begin with injection of muscles he or she can inject with low risk of incorrect placement. The hard-to-find muscles should be avoided when starting out. The novice clinician should inject and dissect a few cadavers to improve injection technique. 5. The general latency for botulinum toxin type A is 1 week, its duration is 2 to 3 months, and it is recommended that injection be done no more than once every 12 weeks to avoid development of antibodies against the toxin. 6. Depending on the target muscle, injection dose is 10 to 50 U of Botox type A per site with a total dose of 200 U in the masticatory system. More than this can be used (400 U maximum) if other sites in the head and neck are included in the injection protocol. 7. Regarding injecting painful muscles that do not exhibit palpable muscle hardness or EMG-determined spasticity or observable involuntary movements but have chronic myofascial trigger points or the patient localizes them as the site of their chronic daily headache pain, botulinum toxin injections might be helpful used in this manner, but conclusive data for this controversial application of botulinum toxin are still missing. 8. Hemifacial spasm has the largest number of open-label, clinical trials, some of which have a 10-year follow-up. The conclusions reached by all of these reports is that treatment of hemifacial spasm with repeated injections of botulinum toxin has been highly successful and that the dose and relative effect of the injections are stable over time. 9. Although EMG-guided injection may be useful, EMG is neither practical nor needed in most situations for orofacial injections because most of the orofacial muscles are easily palpable muscles or have definitive bony landmarks to help with the localization process.

Anti-Dyskinesia Agents↗

Intraarticular corticosteroid injection in the management of children with chronic arthritis.

OBJECTIVE: Intraarticular (IA) corticosteroid injection is a common therapeutic approach in the management of adult rheumatoid arthritis. This study examined the safety and efficacy of IA corticosteroid injection in 71 patients with juvenile arthritis who were being seen at the Sheba Medical Center during the years 1991-1996. METHODS: Sixty-one patients fulfilled the American College of Rheumatology revised criteria for the diagnosis of juvenile rheumatoid arthritis (JRA), 6 patients had reactive arthritis, and 4 patients had various other arthritic conditions. The mean +/- SD age was 9.4 +/- 5.6 years (range 0.5-18 years); 47 were female (mean age 8.1 +/- 5.5 years) and 24 were male (mean age 10.8 +/- 5.4 years). A total of 300 joints were injected with triamcinolone hexacetonide. The most common sites of injection were the knees (124 injections), ankles (71 injections), wrists (46 injections), shoulders (10 injections), and elbows (7 injections). Children under the age of 6 (n = 17), or older children who received more than 4 joint injections at one time (n = 10) were sedated with either ketamine HCI or propofol. All other children received their joint injections under local anesthesia. RESULTS: Full remission of the joint inflammation lasting >6 months following injection was achieved in 246 of the 300 injections (82.0%). In 54 (18.0%) of the injected joints, the inflammation recurred within 6 months of injection. In patients with pauciarticular arthritis, 115 of 141 injections (81.6%) resulted in full remission. Discontinuation of all oral medications was accomplished in 43 patients (60.6%) of the total group of 71 patients and in 32 of the 43 patients with pauciarticular disease (74.4%). Correction of joint contraction was achieved in 42 children (55 joints). In all 11 patients with Baker's cyst and in 12 patients with tenosynovitis, complete remission was achieved following injection. No infection or other serious complications occurred in any of the patients following the procedure. CONCLUSION: IA corticosteroid joint injection in children with juvenile arthritis is a safe and effective mode of therapy. It may be the only therapy needed in patients with pauciarticular JRA, obviating the need for prolonged oral medications, and is effective in correcting joint contractions and deformities.

Adolescent↗

Same-day administration of depot-medroxyprogesterone acetate injection: a retrospective chart review.

A chart review of clients administered depot-medroxyprogesterone acetate (DMPA) injection in September of 2000 was performed to assess implementation of a same-day injection administration protocol irregardless of menstrual cycle day. Women were classified into one of the three categories: (1) routine injection (injection given as specified by the package label), (2) same-day start injection (no injection for more than 6 months, did not meet labeled criteria for administration and received an injection the day of the visit) or (3) same-day restart injection (injection given within 6 months prior to receiving an injection at the visit despite being late for their injection). Of the 228 women receiving an injection, 104 (46%) had a nonroutine same-day injection, meaning almost half of the women receiving a contraceptive injection would have had to return for another visit if this protocol had not been in place. Among these women administered a same-day injection, 23 (22%) were also dispensed emergency contraception. Only 1 of the 104 women was subsequently identified to have become pregnant. Other pregnancies are presented to illustrate the importance of adherence to pregnancy testing at the time of injection and revisit, and the need for backup contraception. Using a same-day injection protocol, women can have increased access to injection contraception, and proper adherence to a protocol can assure few pregnancies.

Adult↗

Endoluminal ultrasonographic and histologic evaluation of periurethral collagen injection.

To determine the acute and chronic ultrasonographic and histologic characteristics of injected glutaraldehyde cross-linked collagen in an animal model in order to enhance the therapeutic efficacy of the delivery of collagen for the treatment of urinary incontinence, three different depths of endoluminal ultrasound-guided injection (submucosal, intramuscular, periadventitial) of collagen into the urethral and bladder walls in two Yucatan mini pigs were investigated. The ultrasonographic characteristics of the injected material were examined 1, 4, 8, and 12 weeks later. A separate set of collagen injections, into the dermis and intramuscular layer of the lateral thigh of the animals, was undertaken with small-parts ultrasound guidance and follow-up. The injected tissues of the bladder, urethra, and thigh were ultrasonographically and histologically examined 3 months post-injection. Acutely injected collagen appeared hypoechoic on ultrasonography, although echogenicity increased over time. Submucosally injected collagen remained contained, forming a discrete collection of the material, whereas periadventitially injected collagen dispersed immediately. The ultrasonographic appearance and size of collagen collections correlated directly with their histologic identification and measurement. Injected collagen generated little inflammatory reaction, although infiltration by histiofibroblasts and neovascularization of the injected collagen occurred. Submucosal collagen injection resulted in superior longevity compared with intramuscular injection. From the results of our study, we hypothesize that durable success with collagen injection for the treatment of urinary incontinence is attributable to histiofibroblast infiltration of the injected collagen. When injected collagen is replaced with a hypertrophic scar, long-lasting clinical success is likely. If the injected collagen is replaced with a contracted scar, however, urethral coaptation may not persist. Endoluminal ultrasonography is helpful in ensuring the accurate submucosal location of collagen injection and in avoiding dispersion of the material and should enhance therapeutic efficacy in the treatment of urinary incontinence.

Animals↗

High-pressure injection injuries to the upper extremity: a review of the literature.

OBJECTIVES: The purpose of this review was to identify the relative impact of injected material, location of injury, time to debridement, injection pressure, infection, and the use of adjuvant steroid medication upon the need for amputation after high-pressure injection injuries to the upper extremity. DATA SOURCES AND STUDY SELECTION: A Medline literature search extending from 1966 to December 2003 was performed, referencing the key words "high-pressure injection injury," "grease gun injury," "paint gun injury," "pressure gun injury," and "high-pressure injection." The results were limited to the English language and to reports involving human subjects. Each abstract was reviewed to confirm that the described injury had occurred in the upper extremity and that it had truly been a high-pressure injection. The reference pages from each of the papers were reviewed to identify additional reports of high-pressure injection injury. Manuscripts describing injuries resulting from hand held syringes or other low-pressure mechanisms were excluded. DATA EXTRACTION: All of the manuscripts were analyzed to identify the clinical outcome, age, hand dominance, site of injection, substance injected, injection pressure, elapsed time to wide debridement, use of steroids, and incidence of infection. These variables were subjected to a Pearson chi test to determine their impact upon the need for amputation. RESULTS: Four hundred thirty-five cases of high-pressure injection injury to the upper extremity were identified. The amputation rate after these injuries was 30%. The location of the injury and the material injected contributed significantly to the need for amputation. For injections of paint, paint thinner, gasoline, oil, or jet fuel (organic solvents), the amputation risk was lower if wide surgical debridement occurred within 6 hours of injury. Steroids did not impact the amputation rate or incidence of infection. The presence of infection did not affect the incidence of amputation. CONCLUSIONS: The risk of amputation after high-pressure injection injury to the upper extremity is highest with organic solvent injection into the fingers. Injections into the thumb or palm result in a much lower frequency of tissue loss. Emergent surgical debridement reduces the amputation risk after injections of organic solvents. From the available data, no conclusions could be reached regarding functional outcomes, other than amputation, after high-pressure injection injury.

Forearm Injuries↗

[Induced tolerance to cardiac allografts with multiple intravenous injection of donor spleen cells].

OBJECTIVE: To study the methods and mechanisms of immune tolerance in cardiac transplantation. METHODS: Male DA rat hearts were transplanted to male Lewis rats using Ono's model and randomly divided into five groups: untreated, intravenous injection of 1 x 10(8) DA splenocytes to Lewis rat, intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat, intravenous injection of 1 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat, multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide, 11 days later heart transplantation was performed. Mean survival time (MST), histological changes, mixed lymphocyte reaction (MLR), the role of interleukin-2 (IL-2) to MLR and the role of tolerant rat splenocytes to MLR were measured after operation. RESULTS: The survival time of heart allografts in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide [MST: (85.3 +/- 7.5) d, t = 0, P < 0.01] was significantly longer than in the groups of untreated [MST: (7.3 +/- 1.0) d], intravenous injection of 1 x 10(8) DA splenocytes to Lewis rat [MST: (7.9 +/- 0.9) d], intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat [MST: (8.1 +/- 1.2) d], intravenous injection of 1 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat [MST: (25.8 +/- 3.5) d]. Only a few inflammatory cells infiltrated in cardiac allografts in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide. MLR in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide were significantly decreased compared with those of normal control (t = 0, P < 0.01). IL-2 could partly reversed the hyporesponsiveness of MLR in tolerant rats, the tolerance could be transferred in vitro. CONCLUSIONS: Multiple injection of donor splenocytes combined with intraperitoneal injection of cyclophosphamide to recipients could induce immune tolerance to cardiac allografts.

Adoptive Transfer↗

Are diagnostic lumbar facet injections influenced by pain of muscular origin?

INTRODUCTION: Nonradicular low back pain can be a difficult entity to accurately diagnose and treat. Facet joints, muscle, ligaments, and fascia have all been reported to be etiologies of acute and chronic low back pain. However, the facet joint as a source of low back pain is controversial. The diagnosis of facet joint pain is made by diagnostic facet joint or median nerve branch injections with a local anesthetic. The purpose of this study was to determine if the results of diagnostic facet joint injections are influenced by the technique used to perform these injections. METHODS: Seventy-five male patients aged 45 years or younger and 18 years or older who were injured while performing heavy work with nonradicular low back pain were included in this study. Diagnostic injection therapy was performed following Institutional Review Board approval and the patient's informed consent. Patients were assigned to one of five groups to receive diagnostic injections in a double-blinded fashion as follows: Group I: facet joint injection with continuous lidocaine administration from the skin to the facet joint as the needle was advanced; Group II: facet joint injection with saline administration from the skin to the facet joint as the needle was advanced; Group III: median nerve branch injection with a lidocaine advancing needle technique; Group IV: median nerve branch injection with saline advancing needle technique; and Group V: injection of the paraspinous muscles with local anesthetic and steroid following noted areas of pain diagnosed with saline injection and radiopaque contrast. After one week, the patients in Groups I to IV who had no pain relief with facet joint or median nerve block injections subsequently received paraspinous muscle injections, while the patients in Group V who had no long-term relief with muscle injections were given facet joint injections. The appropriate parametric and nonparametric tests were performed with statistical significance defined as P < or = 0.05. RESULTS: There were no differences among the groups demographically. The incidence of pain relief was significantly higher in subjects who had a continuous injection of local anesthetic into their musculature than in those individuals who received continuous saline followed by an injection of local anesthetic into their facet joint or median nerve branch. DISCUSSION: The results of this study demonstrated that local anesthetic injections are useful for the diagnosis of nonradicular low back pain but may yield false positive results with respect to lumbar facet pain depending upon the technique utilized.

Journal Article↗

The effects of injection of calcium ions and calcium chelators on calcium channel inactivation in Helix neurones.

1. The effects of intracellular injection of Ca, EGTA and EGTA/Ca buffers on inward currents flowing through the Ca channel in Helix aspersa neurones were studied under voltage clamp. 2. Inward currents were reversibly reduced by Ca injection. The extent of the reduction was dependent on the size and duration of the injection. Recovery from injection was exponential with a time constant around 18 s at 18-20 degrees C. 3. In our salines, which contained tetraethylammonium chloride and 4-aminopyridine, no outward current was activated by Ca injection at the holding potential. A given Ca injection reduced the inward current by the same fraction in 25 mM- and 2 . 5 mM-Sr and also at different test potentials. We conclude that Ca injection does not activate an outward current. 4. Mean resting ionized internal Ca concentration, [Ca]i, measured with a Ca-sensitive electrode was 1.9 X 10(-7) M. Our injections increased this by less than 10(-5) M, as expected if most of the injected Ca is bound. Constant-field or Eyring rate theory considerations suggest that this rise in [Ca]i would not significantly affect the inward current through open Ca channels and we conclude, therefore, that Ca injection causes Ca channel inactivation. 5. The effect of Ca injection was blocked by prior injection of EGTA. Extracellular application of carbonyl cyanide m-chlorophenylhydrazone increased the effect of Ca injection. 6. Ca injection does not inactivate Ca channels by lowering pHi since large H+ injections only caused small irreversible decreases in inward current. 7. EGTA injection increased peak Ca current (ICa) by around 30% and decreased the rate and extent of inactivation. Some inactivation remained, however, even after maximal EGTA injections. 8. Injection of EGTA/Ca buffers with free [Ca] less than 1.8 X 10(-7) M increased peak ICa, while buffers with free [Ca] greater than 8.9 X 10(-7) M decreased ICa. 9. Our results support the suggestion that Ca ions cause Ca inactivation by binding to a site which is accessible from the inside of the cell, and also suggest that there is some steady-state inactivation present at physiological [Ca]i. A simple model is presented which describes the decline of Ca current in terms of Ca binding to a site accessible from the cytoplasm.

Animals↗

Low-volume jet injection for intradermal immunization in rabbits.

BACKGROUND: This study tested a low-volume (20-30 microl/20-30 microg DNA) jet injection method for intradermal delivery of a DNA vaccine. Jet injection offers the advantages of a needle-less system, low-cost, rapid preparation of the injected DNA solution, and a simple delivery system. More than one construct can be injected simultaneously and the method may be combined with adjuvants. RESULTS: Low-volume jet injection targeted delivery of a DNA solution exclusively to the dermis and epidermis of rabbits. A three injection series of plasmid DNA, encoding the Hepatitis B Surface Antigen stimulated a humoral immune response in 2/5 rabbits. One rabbit developed a significant rise in antibody titer after 1 injection and one following 2 injections. There were no significant differences between jet injection and particle bombardment in the maximal antibody titers or number of injections before response. A three injection series of the same plasmid DNA by particle bombardment elicited a significant rise in antibody titer in 3/5 rabbits. One rabbit developed antibody after 1 injection and two after 3 injections. In contrast, 0/5 rabbits receiving DNA by needle and syringe injection responded. In the jet injection and particle bombardment groups, gene expression levels in the skin did not predict response. While immune responses were similar, luciferase gene expression levels in the skin following particle bombardment were 10-100 times higher than jet injection. CONCLUSION: Low-volume jet injection is a simple, effective methodology for intradermal DNA immunization.

Animals↗

Intratesticular injection as a method to assess the potential toxicity of various agents and to study mechanisms of normal spermatogenesis.

To better understand, to optimize, and to validate the technique of intratesticular (i.t.) injection, several parameters related to i.t. injection were examined. Volumes exceeding 50 microliters could be injected i.t.; however, testes frequently became excessively turgid and backflow of injected fluids occurred. Thus, a volume of 50 microliters or less was deemed optimal for injection. To determine the rate of distribution of substances throughout the testis, trypan blue was injected i.t. near the caudal pole of the testis, and the movement of dye was monitored. Within 2 min, the dye had spread approximately 1 cm from the site of injection, and in 5 min it had spread twice that distance. In 2 h, the dye had become distributed throughout the testis except at its extreme cranial pole. Seminiferous tubules did not take up dye, indicating that the spread of dye was via peritubular lymphatics. Seminiferous tubule histology appeared virtually unaffected by i.t. injection, even at regions adjacent to the site of injection, when a sterile 26-gauge or smaller bore needle was utilized. To determine disappearance from the testis, radiolabeled inulin was injected i.t. Half time for absorption was achieved at 1.75 h. Potential vehicles were explored in which compounds with a variety of physical properties could be injected. Gum tragacanth, normal saline, ethylene glycol, dimethyl sulfoxide (DMSO) mixed 1:1 with normal saline, sesame oil, and propylene glycol were found to be suitable injection vehicles, whereas ethanol, dissolved in normal saline in concentrations as low as 0.5% was found unsuitable. To assess vehicle efficiency, various vehicles were utilized with a known testicular toxin (taxol) and injected into one testis, and the histology was compared with the contralateral testis injected with vehicle alone. All vehicles, found suitable above, allowed dispersion of taxol to influence areas distant from the site of injection. Intratesticular injection assesses the potential of agents to directly affect the testis, and systemic metabolism is avoided. Their rapid spread throughout the lymphatics of the testes allows seminiferous tubules to be exposed to agents in innocuous vehicles more rapidly and in higher concentration than is often possible when using systemic injections.

Alkaloids↗

Effect of intratesticular injection of sodium fluoride on spermatogenesis.

The potential of sodium fluoride to affect spermatogenesis in the rat was assessed by intratesticular injection. Experimental rats' left testis was injected with sodium fluoride (50, 175 and 250 ppm) in vehicle (0.9% physiological saline); control testes were injected with vehicle. The right testis served as a non-injected control. Testicular tissues collected 'at' and 'distal to' the injection site and from the non-injected control testes were evaluated microscopically 24 hr and 1, 2 and 3 wk post-injection. Testicular tissues obtained at and distal to the injection site in all fluoride-injected groups resembled tissues collected from corresponding areas in the controls. Seminiferous tubule damage observed in both the vehicle-injected control testes and the fluoride-injected testes but not in the non-injected testes was attributed to injection trauma. Polymorphonuclear leucocyte infiltration was observed 24 hr post injection only at the injection site in the vehicle- and fluoride-injected groups. Leydig cells were unaffected. Leucocyte infiltration with seminiferous tubule damage was not considered to be a fluoride treatment-related effect because it was observed in both vehicle- and fluoride-injected testes. The results demonstrate that the rat is not adversely affected by direct exposure to fluoride at levels 200 times greater than those under normal conditions.

Animals↗

Accurate localization of tissue layers in the esophagus by using a double-lumen injection catheter: implications for the Enteryx procedure.

BACKGROUND: Enteryx (Boston Scientific Corp, Natick, Mass) is an injectable polymer used for the treatment of GERD. Current use of Enteryx requires fluoroscopy for accurate placement into the deep esophageal wall (ie, the deep submucosa or muscularis propria). In this study, we assessed the use of a new double-lumen, double-needle injection catheter for accurate placement of Enteryx into the deep esophageal wall, without fluoroscopy, in a porcine model. METHODS: All procedures were performed by using a new injection catheter (GZ Medical, LLC, Minnetonka, Minn), which allows for tissue depth assessment via the flow of gas through one lumen and the injection of a therapeutic substance (Enteryx) via a second lumen. Endoscopy was performed on 5 consecutive pigs by using the new catheter alone, without fluoroscopy, and attempting deep injections. Four injections of Enteryx were made at the gastroesophageal junction, 10 cm above the junction, and 15 cm above the junction. A total of 60 sites (12 per animal) were injected. The animals were sacrificed and each esophagus was harvested. The mediastinal cavity was searched for extravasated Enteryx material, and the esophagus was examined grossly for Enteryx adherent to the outside wall. Injection sites then were classified morphologically as superficial (mucosa or submucosa), deep (muscularis propria or deep submucosa contiguous to muscularis), subadventitial (between muscle and adventitia), or transmural. Only deep injections were considered adequate. RESULTS: No extravasated Enteryx was found in the mediastinum in 60 injected sites. One area of transmural injection had Enteryx adherent to the outside esophageal wall (1.7%). Fifty-one injected sites (85%) were adequate deep injections, 4 injections (6.7%) were subadventitial, 1 injection (1.7%) was superficial, and 3 injections (5%) could not be assessed. There were no complications observed in any animal. CONCLUSIONS: By using a new injection device without fluoroscopy, Enteryx can be deposited consistently into the deep esophageal wall with a high degree of accuracy, avoiding mediastinal extravasation. Additional clinical trials are necessary to determine the relative accuracy and role of the new technique compared to standard radiographically guided placement.

Animals↗

Short-term course of intraocular pressure after intravitreal injection of triamcinolone acetonide.

OBJECTIVE: To describe the natural history of intraocular pressure (IOP) within the first 30 minutes after intravitreal injection of triamcinolone acetonide (TA). DESIGN: Prospective, interventional, consecutive case series. PARTICIPANTS: Thirty-eight consecutive patients who met inclusion and exclusion criteria and underwent intravitreal injection of 0.1 ml (4 mg) of TA were studied. METHODS: Intraocular pressure was measured by Goldmann applanation tonometry at baseline; immediately after injection; and at 2, 5, 10, 20, and 30 minutes after injection. MAIN OUTCOME MEASURES: Intraocular pressure measurements at baseline; immediately after intravitreal injection; and 2, 5, 10, 20, and 30 minutes after injection, and percentage of patients with IOP < or = 24 mmHg at 30 minutes. RESULTS: Patients who did not experience vitreous reflux (30/38 [78.9%]) at the site of injection had a significant initial elevation of IOP that rapidly normalized. Patients who experienced vitreous reflux (8/38 [21.1%]) at the site of injection had either no change in IOP or a small drop in IOP that rapidly normalized. The IOP measured in millimeters of mercury immediately after injection (45.9 [no reflux], 12.6 [reflux]), 2 minutes after injection (39.9 [no reflux], 13.5 [reflux]), 5 minutes after injection (33.3 [no reflux], 13.8 [reflux]), 10 minutes after injection (26.4 [no reflux], 15.1 [reflux]), and 20 minutes after injection (21.8 [no reflux], 15.0 [reflux]) showed a statistically significant difference between the 2 groups. The difference in IOP between the 2 groups was not significant at baseline or 30 minutes after injection. At 30 minutes, 90% (95% confidence interval, 85.8%-95.2%) of patients without vitreous reflux had an IOP < 24 mmHg. CONCLUSIONS: Patients undergoing intravitreal injection of TA with no vitreous reflux have a risk of short-term elevation of IOP that rapidly normalizes over 30 minutes. In patients with vitreous reflux after the injection, the IOP declines immediately after injection and rapidly normalizes over 10 minutes.

Aged↗

Repeated intravitreal high-dosage injections of triamcinolone acetonide for diffuse diabetic macular edema.

OBJECTIVE: To report the results of repeated intravitreal injections of triamcinolone acetonide for treatment of diffuse diabetic macular edema. DESIGN: Retrospective interventional comparative study. PARTICIPANTS: The investigation included a study group (the responders) of 19 patients (22 eyes) with diffuse diabetic macular edema, who showed an improvement in visual acuity after an intravitreal injection of approximately 20 mg triamcinolone acetonide, and who received a second intravitreal injection 10.0+/-3.8 months after the first injection. A control group consisted of 31 patients with diffuse diabetic macular edema without treatment during follow-up. METHODS: Intravitreal injection of approximately 20 mg triamcinolone acetonide. MAIN OUTCOME MEASURES: Visual acuity and intraocular pressure. RESULTS: Follow-up after the second injection was 9.1+/-4.9 months. Four patients received a third injection at 9.7+/-3.7 months after the second injection, with a follow-up after the third injection that was at 7.9+/-11.5 months. After the second and third injections, visual acuity increased significantly (P = 0.002 and P = 0.068, respectively) by 1.8+/-2.1 and 4.0+/-2.6 Snellen lines, respectively. Eleven eyes (50%) showed an improvement in visual acuity by at least 2 Snellen lines after the second injection, and 3 patients (75%) experienced a gain in visual acuity by at least 2 Snellen lines after the third injection. Intraocular pressure increased significantly (P<0.01) after each injection, and returned to baseline values before each reinjection. Visual acuity improvement (P>0.05) and intraocular pressure rise did not differ significantly (P>0.55) between the various injections. Improvement in visual acuity and rise of intraocular pressure lasted approximately 6 to 8 months after each injection. CONCLUSIONS: Intravitreal injection of approximately 20 mg triamcinolone acetonide may repeatedly lead to an improvement in visual acuity and a rise of intraocular pressure in patients with diffuse diabetic macular edema. The duration of the effect after each injection is approximately 6 to 8 months. Tachyphylaxis in visual acuity or intraocular pressure outcomes were not observed.

Adult↗