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PubMed1998

Intratumoral injection of rhenium-188 microspheres into an animal model of hepatoma.

UNLABELLED: Intratumoral injection of 90Y microspheres is a potential alternative in the treatment of primary liver tumor. However, complicated preparation and lack of a gamma ray for imaging are the disadvantages of 90Y. In this study, we used 188Re, a generator-produced radioisotope with 155-keV gamma ray emission, to label microspheres. After intratumoral injection of 188Re microspheres into rats with hepatoma, biodistributions and survival times were analyzed. METHODS: Twelve male rats with hepatoma were killed at 1, 24 and 48 hr (4 rats at each time point) after intratumoral injection of approximately 7.4 MBq 188Re microspheres. Samples of various organs were obtained and used to calculate the tissue concentrations. In addition, 30 male rats bearing hepatoma were divided into two groups (15 rats in each group) to evaluate survival time. Group 1 received intratumoral injection of 37 MBq 188Re microspheres, whereas Group 2 served as the control group and received an intratumoral injection of 0.1 ml normal saline only. Survival time was calculated from the day of injection to 2 mo after treatment. RESULTS: Radioactivity in the tumor was very high throughout. Biological half-time was 170.8 hr. Radioactivity in the lung was 1.78% injected dose (i.d.)/g at 1 hr but declined rapidly over time. The concentration in the urine was approximately 6.14% i.d./ml after the first hour and rapidly declined thereafter. The concentrations of radioactivity in other organs, such as normal liver, muscle, spleen, bone, testis and whole blood, were quite low throughout the study. Twelve of 15 (80%) of rats survived over 60 days after intratumoral injection of 188Re microspheres, whereas only 4 of 15 (26.7%) survived more than 60 days after injection of normal saline only. The difference between the groups was significant (p < 0.05). CONCLUSION: Rhenium-188 offers cost-effectiveness, on-site availability, short half-life, energetic beta particle, emission of gamma photons for imaging, easy preparation, easy clinical administration and apparent lack of radiation leakage from the treated tumor. Direct intratumoral injection of 188Re microspheres is extremely attractive as a clinical therapeutic alternative in hepatoma patients.

Animals↗
PubMed1976

Four heparin preparations: anti-Xa potentiating effect of heparin after subcutaneous injection.

Four different heparin preparations--sodium and calcium salts of the same batch of heparin (mean molecular weight 15,000), low molecular weight sodium heparin (mean m.w. 9,000) and high molecular weight sodium heparin (mean m.w. 22,000) were injected subcutaneously on different days each into 6 healthy young volunteers in a randomized trial. Plasma heparin levels were measured using the anti-Xa assay at 1 hour, 3-4 hours and 6-7 hours after the injection. The highest anti-Xa potentiating effect was obtained after the injection of the low molecular weight sodium heparin (mean 0.381 i.u./ml) at 3-4 hours after the injection. With sodium heparin (m.w. 15,000) the highest values (0.135 i.u./ml) were found at 1 hour. Significantly lower anti-Xa potentiating effect was obtained 1 hour after the injection of calcium heparin and in particular after the injection of high molecular weight heparin (mean values 0.072 i. u./ml and 0.043 i. u./ml respectively). Both these preparations showed an increase from 1 hour after injection to 3-4 hours after injection (mean values 0.082 i. u./ml and 0.057 i. u./ml at 3-4 hours after injection). These results indicate that the salt and the molecular weight of the preparation may strongly influence the degree of anticoagulation achieved after subcutaneous injection.

Calcium↗
PubMedDate not supplied

Effect of subcutaneous granulocyte colony-stimulating factor injectate volume on drug efficacy, site complications, and client comfort.

PURPOSE/OBJECTIVES: To determine the effect of administering 1.6 ml (480 mcg) of granulocyte colony-stimulating factor (G-CSF) in one subcutaneous injection or two injections of 0.8 ml each. DESIGN: Experimental. SETTING: 27-bed bone marrow transplant intensive care unit of a metropolitan, university medical center in the southwestern United States. SAMPLE: Nonprobability; 76 women who received high-dose chemotherapy for breast cancer followed by hemopoietic rescue. METHODS: Subjects were randomized into an experimental group that received one injection per 480 mcg dose and a control group that received two injections per 480 mcg dose administered by research associates using a standardized injection technique. MAIN RESEARCH VARIABLES: Injectate volume. The number of days post-transplant until the absolute neutrophil count (ANC) returned to 1,000/mm3, the incidence and surface area in mm2 of site complications, and scores on Tursky's Quantified Pain Descriptor immediately following the injection(s). FINDINGS: No significant difference existed between the two groups in ANC recovery time, frequency or size of site complications, or intensity, reaction, or sensation of discomfort reported. CONCLUSIONS: Administering 1.6 ml doses of G-CSF in one injection instead of two does not result in slower ANC recovery, induration, more frequent or larger bruises or areas of erythema, or greater client discomfort. IMPLICATIONS FOR NURSING PRACTICE: Administering one injection instead of two may decrease patients' anxiety, the nursing time needed for preparation and administration of injections, patient instruction for self-administration, the potential for contamination of vials or loss of dose, and the cost of supplies.

Adult↗
PubMed1999

Safety of self-injection of gold and methotrexate.

OBJECTIVE: We review our experience with safety, efficacy, and practicality of self-administration of gold and methotrexate (MTX) in 40 patients. METHODS: Between 1992 and 1995, 40 patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) followed in the drug monitoring clinics of the Mary Pack Arthritis Centre were taught to self-administer parenteral gold or MTX. Self-injection education was recommended to patients who were stable and improved taking parenteral gold or MTX, and who had not experienced serious side effects. Charts were reviewed to extract and analyze prospectively collected data regarding safety, efficacy, and compliance. RESULTS: Sixty-five percent of patients performed self-injection and 35% received injections at home from a partner. Side effects in the self-injection patients are similar to those observed in clinic patients receiving drug by nurse administration. One MTX treated patient required treatment for interstitial pneumonitis, which developed after 22 weeks on self-injection. Side effects of self-injection included superficial irritation at the injection site in 2 patients and dosing error in 2 patients with no adverse effects. Seventy percent of gold and MTX treated patients continued self-injection after a mean of 34 months. Patients surveyed for satisfaction identified time saving and convenience as major benefits. CONCLUSION: With basic instruction and close supervision, self-injection of antirheumatic drugs is safe in selected patients. Self-injection reduces utilization of health care services, and is convenient and time and cost-saving to the patient.

Arthritis, Psoriatic↗
PubMed2000

[History of injections. Pictures from the history of otorhinolaryngology highlighted by exhibits of the German History of Medicine Museum in Ingolstadt].

BACKGROUND: Injections are part of the arsenal of all medical disciplines. In addition to this common ground, each specialty has its own particular aspects; the historical development of these are presented here with respect to otorhinolaryngology. INTRAVENOUS INJECTIONS: The first experiments with intravenous injections were carried out in 1642 by a gentleman's hunting servant in eastern Germany. Similar experiments were done in 1656 by Christopher Wren, the astronomer, mathematician, and architect in Oxford, England, and a group of scientists around the physicist Robert Boyle. These experiments were prompted by new knowledge about blood circulation provided by William Harvey in 1628. The first books on the applications of intravenous infusions in humans were published in Germany by Major 1664 (Chirurgia Infusoria) and Elsholtz 1667 (Clysmatica Nova). Bladders of animals or enema syringes were used as instruments. Because of lethal accidents the infusions soon fell from favour. Köhler in Germany in 1776 eliminated a large bolus impacted in a patient's esophagus by an intravenous infusion of tartar emetic thus inducing violent vomiting. After this crucial experiment, foreign bodies in the esophagus were the most important indication for applying intravenous injections until Killian introduced extraction by esophagoscopy in 1990. CALIBRATED SYRINGES AFTER PRAVAZ: The French surgeon C. Pravaz in Lyon in 1853 invented a small syringe, the piston of which could be driven by a screw thus allowing exact dosage. A sharp needle with a pointed trocar could be introduced into the vessel making a dissection unnessessary. Pravaz used his syringe for obliteration of arterial aneurysms by injection of ferric sesquichlorate. Pravaz's syringe initiated the invention of a great number of various calibrated syringes made of glass or metal combined with glass. SUBCUTANEOUS INJECTION AND LOCAL ANAESTHESIA: The calibrated syringes were commonly used in the treatment of syphilis by mercurialization. In otorhinolaryngology, they had and still have their primary application in local anaesthesia, which was introduced by Carl Ludwig Schleich in Berlin in 1892. PARAFFIN-INJECTIONS: Around 1900 the injection of liquid paraffin for closing defects in subcutaneous tissues came into use (Gersuny in Vienna, Delangre in Tournai). This technique was immediately applied to rhinological indications such as a saddle nose (Stein 1901). This gave rise to the invention of special syringes and modifications of paraffin with different hardness and melting points. Around the middle of this century, paraffin was abandoned for this application because of serious complications, and new substances were introduced such like teflon, silicone and collagen. The historical development of these techniques of injections is described in details with many literature citations and figures.

Anesthesia, Local↗
PubMed1999

Human insulinlike growth factor 1 gene transfer into paralyzed rat larynx: single vs multiple injection.

OBJECTIVE: To compare the biological effects of single vs multiple treatment of rat denervated laryngeal muscle with human insulinlike growth factor 1 (hIGF1) gene therapy. EXPERIMENTAL METHODS OR DESIGN: A muscle-specific nonviral vector containing the alpha-actin promoter and hIGF1 gene formulated with polyvinyl polymers was injected into denervated adult rat thyroarytenoid muscle. The effects on animals given a single injection (n = 16) vs those given multiple injections (n = 14) vs control groups (n = 18) were evaluated. Twenty-eight days after the first injection, gene expression, muscle fiber size, motor endplate length, and nerve-to-motor endplate contact were evaluated. RESULTS: Gene expression, detected by reverse transcriptase polymerase chain reaction for hIGF1 messenger RNA, occurred in 13 (81%) of 16 animals receiving single injections and 14 (100%) of 14 animals receiving multiple injections. Compared with controls, hIGF1-transfected animals in both single- and multiple-injection groups had a significant increase in the lesser diameter of muscle fiber, a significant decrease in motor endplate length, and a significant increase in the percentage of endplates with nerve contact (P <.05 for all). There was no statistical difference between single- and multiple-injection groups. CONCLUSIONS: Applied to laryngeal paralysis, hIGF1 gene therapy provides an opportunity to augment surgical treatment modalities by the prevention or reversal of muscle atrophy, and enhancement of nerve sprouting and muscle reinnervation. Although the percentage of denervated muscles demonstrating hIGF1 expression was increased following multiple injections, no difference was observed in the biological response compared with that in the single-injection treatment groups. Further investigation will be conducted to assess long-term benefits and physiological responses and to define the limitations of this potentially valuable therapeutic strategy.

Animals↗
PubMed1997

Biodistribution of 111In-labelled SCN-bz-DTPA-BC-2 MAb following loco-regional injection into glioblastomas.

We analyzed the biodistribution of the 111In-labelled murine anti-tenascin-C MAb BC-2 after intralesional injection in 15 glioblastoma patients. The activated ligand DTPA was conjugated via the isothiocyanato-benzyl group onto BC-2. Conjugates were labelled with 111In, displaying immunoreactivity greater than 90% and labelling efficiency of 99 +/- 1%. In contrast to i.v. injections, excellent tumor uptake was obtained by direct intralesional injection of conjugates that showed only slow systemic release. In serum, conjugates were found to be intact; in urine, only low-molecular-weight decay products were detected. In 8 patients, outflow from the site of injection into systemic circulation was low; daily activity in the serum and urine was found to be below 2% of the total injected radioactivity; most of the injected activity was retained within the tumor, resulting in effective half-lives of 58 +/- 5 hr. In contrast, higher outflow up to 10% of regionally injected 111In-DTPA-BC-2 MAb into systemic circulation resulted in considerable shortening of the effective half-lives to 20 to 40 hr in 7 patients. This outflow was found to correlate with tumor size and blood/brain barrier disruption. In one patient, HPLC analysis of tumor cyst fluid 3 and 6 days after intralesional injection revealed conjugates to be intact and allowed the estimate of about 70% of the total injected 111In-DTPA-BC-2 to be confined to tumor tissue. We conclude that different outflow patterns can be observed following locoregional injection of 111In-DTPA-BC-2, leading to considerable variations in the effective half-lives of isotopes within the tumor, requiring adjustment of the radiation dose in therapeutic trials.

Aged↗
PubMed1998

Microtubule and chromatin organization during the first cell-cycle following intracytoplasmic injection of round spermatid into porcine oocytes.

The objective of this study was to determine microtubule assembly and chromatin configuration in porcine oocytes during the first cell cycle following round spermatid injection into matured porcine oocytes in the presence or absence of electrical stimulation. The oocytes with two large pronuclei and two polar bodies were classified as normal fertilization at 6 to 8 h following injection. The incidence of normal fertilization following round spermatid injection with electrical stimulation was significantly higher (21/45, 47%) than that following injection alone (6/39, 15%). Although a small microtubular aster was organized near the decondensed spermatid chromatin in some oocytes (2/6, 33%, spermatid injection alone; 9/21, 29%, spermatid injection and electrical stimulation), it did not enlarge nor fill the cytoplasm. Instead, a dense network of microtubules in the cytoplasm was organized from cortex. At 12 to 15 h after injection, we classified the oocytes with closely apposed pronuclei as normal fertilization. The electrical stimulation following spermatid injection enhanced (P < 0.05) the incidence of normal fertilization (18/54, 33%) compared with spermatid injection alone (7/52, 13%). During pronuclear movement, the maternally derived microtubules filled the whole cytoplasm, which appeared to move male and female chromatin. Mitosis and two-cell division were observed at 20 to 24 h after spermatid injection with electrical stimulation (12/41, 29%). At mitotic metaphase, the microtubular spindle had focused astral poles, and chromosomes were aligned on the spindle equator. During mitosis, asters were assembled at each spindle pole, and they filled the cytoplasm. These results suggested that round spermatid nuclei of the pig can develop into a morphologically normal pronucleus in matured porcine oocytes and are competent to participate in syngamy with the ootid chromatin. In addition, functional microtubules for complete fertilization with spermatid were not associated with male-derived centrosome but were organized solely from maternal stores.

Animals↗
PubMed2005

Medicinal and injection therapies for mechanical neck disorders.

BACKGROUND: Medicinal therapies and injections are commonly recommended for neck pain, yet controversy persists over their effectiveness. OBJECTIVES: To determine the effect of medicines and injections on pain, function/disability, patient satisfaction and range of motion in participants with mechanical neck disorders (MND). SEARCH STRATEGY: We searched CENTRAL (Issue 4, 2002), and MEDLINE, EMBASE, MANTIS, CINHAL from their start to March 2003. We scrutinized reference lists for other trials. SELECTION CRITERIA: We included randomized controlled trials with adults with MND, with or without associated headache or radicular findings. We considered medicinal and injection therapies, regardless of route of administration. DATA COLLECTION AND ANALYSIS: Two authors independently selected articles, abstracted data and assessed methodological quality using the Jadad criteria. Consensus was used to resolve disagreements. When clinical heterogeneity was absent, we combined studies using random-effects meta-analysis models. MAIN RESULTS: We found 32 trials that examined the effects of oral NSAIDs, psychotropic agents, injections of steroids, and anaesthetic agents. Overall, methodological quality had a mean of 3.2/5 on the Jadad Scale. For acute whiplash, administering intravenous methylprednisolone within eight hours reduced pain at one week, and sick leave but not pain at six months compared to placebo. For chronic MND at short-term follow-up, intramuscular injection of lidocaine was superior to placebo or dry needling, but similar to ultrasound. In chronic MND with radicular findings, epidural methylprednisolone and lidocaine reduced neck pain and improved function at one-year follow-up compared to the intramuscular route. In subacute/chronic MND, we found conflicting evidence of pain reduction for oral psychotropic agents compared to placebo or control. Single trials of eperison hydrochloride and tetrazepam showed positive results. Results for cyclobenzaprine were mixed. Diazepam did not show benefit. Other treatments including NSAIDS and nerve blocks had unclear or limited evidence of benefit. In participants with chronic MND with or without radicular findings or headache, there was moderate evidence from five high quality trials showing that Botox A intramuscular injections were not better than saline in improving pain (pooled SMD: -0.39 (95%CI: -1.25 to 0.47), disability or global perceived effect. AUTHORS' CONCLUSIONS: Intra-muscular injection of lidocaine for chronic MND and intravenous injection of methylprednisolone for acute whiplash were effective treatments. There was limited evidence of effectiveness of epidural injection of methylprednisolone and lidocaine for chronic MND with radicular findings. Oral psychotropic agents had mixed results. There was moderate evidence that Botox A intramuscular injections for chronic MND were no better than saline. Other medications, including NSAIDs, had contradictory or limited evidence of effectiveness.

Anesthetics, Local↗
PubMed2002

Oral versus injectable ovulation induction agents for unexplained subfertility.

BACKGROUND: Oral (anti-oestrogens) and injectable (gonadotrophins) ovulation induction agents have been used to increase the number of eggs produced by a woman per cycle in treatment for unexplained subfertility. It is unclear whether there are significant advantages of one type of treatment over the other in this context or in terms of fertility. OBJECTIVES: To assess the efficacy of oral versus injectable ovulation induction agents for unexplained subfertility. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Group was used for the identification of relevant randomised controlled trials. SELECTION CRITERIA: All trials where oral ovulation induction agents were compared with injectable ovulation induction agents in treatment groups generated by randomisation, from couples with unexplained subfertility, were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Five randomised controlled trials, including a total of 231 identified couples with unexplained subfertility, were found and included in this review. All trials were assessed for quality criteria. The studied outcomes were pregnancy, live birth, miscarriage, multiple birth, occurrence of ovarian hyperstimulation syndrome and cycle cancellation. MAIN RESULTS: Where trials with important co-interventions were excluded, there was no significant difference in the odds of beneficial outcomes for oral versus injectable ovulation induction agents - live birth per couple (OR 0.06, 95%CI 0.00-1.15), pregnancy per woman (OR 0.33, 95%CI 0.09-1.20); nor of detrimental outcomes for injectable versus oral agents - miscarriage (OR 0.11, 95%CI 0.00-2.84); there were no reported cases of multiple births, cases of ovarian hyperstimulation or discontinued cycles consequent upon overstimulation. Where trials with the co-intervention of a human chorionic gonadotrophin trigger injection (given only in the injectable ovulation induction agent treatment arm) were not excluded there was no significant difference in the odds of live birth per couple (OR 0.40, 95%CI 0.15-1.08). However oral ovulation induction agents had significantly reduced odds of pregnancy per woman compared to injectable ovulation induction agents (OR 0.41, 95%CI 0.17-0.80). For detrimental outcomes, there were no significant differences in the odds of miscarriage (OR 0.61, 95%CI 0.09-4.01) and multiple birth (OR 1.08, 95%CI 0.16-7.03) for injectable versus oral agents. No data were available concerning the occurrence of ovarian hyperstimulation syndrome nor cycle cancellation. REVIEWER'S CONCLUSIONS: There is insufficient evidence to suggest that oral agents are inferior or superior to injectable agents in the treatment of unexplained subfertility. Information on harms is sketchy, and remains compatible with large differences in either direction. Much larger trials than have previously been undertaken are required to provide information on relative harms as well as benefits.

Administration, Oral↗
PubMed1989

Rigid endoscopy under general anaesthesia is safe for chronic injection sclerotherapy.

Injection sclerotherapy for acutely bleeding oesophageal varices has been used in Belfast since 1958. However, a chronic injection sclerotherapy programme with rigid oesophagoscopy under general anaesthesia commenced only in 1979. So far, 82 patients have entered the programme; 57 patients had already received 73 acute injections before commencing chronic sclerotherapy. Subsequently, the 82 patients received 221 chronic injections plus a further 29 acute injections for rebleeding episodes which occurred during the programme. There were 24 Child's grade A patients, 23 B and 35 C; 48 per cent had alcoholic cirrhosis. Forty-eight patients achieved variceal obliteration with a mean of four injections. During the programme 24 patients experienced 42 acute bleeds. There were only two bleeding episodes within 1 week of a chronic injection and eight within 4 weeks. In the 8-year period there have been four early deaths. One occurred 17 days after a chronic injection and three followed acute injections required for rebleeding during the programme. There were 21 late deaths, mostly due to progressive liver failure, and none from rebleeding. We conclude that chronic injection sclerotherapy using rigid oesophagoscopy under general anaesthesia is both safe and effective.

Adolescent↗
PubMedDate not supplied

Feline immunodeficiency virus vectors. Gene transfer to mouse retina following intravitreal injection.

BACKGROUND: Transduction of the murine retinal pigmented epithelium (RPE) with adenovirus vectors requires technically difficult and invasive subretinal injections. This study tested the hypothesis that recombinant vectors based on feline immunodeficiency virus (FIV) could access the retina following intravitreal injection. METHODS: FIV vectors expressing E. coli beta-galactosidase (FIVbetagal) were injected alone, or in combination with adenovirus vectors expressing eGFP, into the vitreous of normal mice and eyes evaluated for transgene expression. In further studies, the utility of FIV-mediated gene transfer to correct lysosomal storage defects in the anterior and posterior chambers of eyes was tested using recombinant FIV vectors expressing beta-glucuronidase. FIVbetagluc vectors were injected into beta-glucuronidase-deficient mice, an animal model of mucopolysacharridoses type VII. RESULTS: The results of this study show that similar to adenovirus, both corneal endothelium and cells of the iris could be transduced following intravitreal injection of FIVbetagal. However, in contrast to adenovirus, intravitreal injection of FIVbetagal also resulted in transduction of the RPE. Immunohistochemistry following an intravitreal injection of an AdeGFP (adenovirus expressing green fluorescent protein) and FIVbetagal mixture confirmed that both viruses mediated transduction of corneal endothelium and cells of the iris, while only FIVbetagal transduced cells in the retina. Using the beta-glucuronidase-deficient mouse, the therapeutic efficacy of intravitreal injection of FIVbetagluc (FIV expressing beta-glucuronidase) was tested. Intravitreal injection of FIVbetagluc to the eyes of beta-glucuronidase-deficient mice resulted in rapid reduction (within 2 weeks) of the lysosomal storage defect within the RPE, corneal endothelium, and the non-pigmented epithelium of the ciliary process. Transgene expression and correction of the lysosomal storage defect remained for at least 12 weeks, the latest time point tested. CONCLUSION: These studies demonstrate that intravitreal injection of FIV-based vectors can mediate efficient and lasting transduction of cells in the cornea, iris, and retina.

Animals↗
PubMed1989

Delayed response deficits produced by local injection of bicuculline into the dorsolateral prefrontal cortex in Japanese macaque monkeys.

Bicuculline (10-30 micrograms, but usually 30 micrograms) was injected locally into 20 different sites in the dorsolateral prefrontal cortex (PFC) of 2 Japanese macaque monkeys, while they were performing a delayed response task. The task was initiated by the rotation of a handle to a central zone by the wrist joint and consisted of seven periods: an initial waiting period of 0.3 s, a pre-cue period (central green lamp of 1.0 s), a cue period (left or right green cue of 0.3 s), a delay period of 4.0 s (occasionally 1 s), a go period (central red lamp; rotation of the handle to either the left or right zone within 1.0 s), a hold period (holding of the handle in either the left or the right zone), and a final reward period. The parameters of the task performance, such as the frequency of correct trials, the frequency of directional error trials in which the monkeys rotated the handle in an incorrect direction during the go period, and the frequency of omission error trials, in which the monkeys did not rotate the handle during the go period, were examined before and after the injection of bicuculline. The injections of bicuculline induced a burst of multi-neuronal activity around the sites of injection. Within 5 min of an injection into one of 7 different sites in the PFC, three different kinds of performance deficit were observed: 1) an increase in the frequency of error responses during the go period in both left-cue and right-cue trials, after injection into the dorso-caudal portion of the principal sulcus (2 sites); 2) an increase in the frequency of directional error responses during the go period in either left-cue or right-cue trials, after injection into the bottom of the middle principal sulcus (3 sites), and 3) an increase in the frequency of omission of responses during the go period, after injection into the dorsal region of the caudal principal sulcus (2 sites). Injections at the remaining 13 sites did not induce any deficits, although injections into the dorsal bank of the principal sulcus (3 sites) induced a decrease in the frequency of the task trials as a result of prolonged intertrial intervals (ITIs). Our results suggest that locally disturbed neuronal activity in different small areas of the PFC induces different deficits in the performance of the delayed response task.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Self-injection of d,1-3,4-methylenedioxymethamphetamine (MDMA) in the baboon.

MDMA (d,1-3,4-Methylenedioxymethamphetamine HCl; "ecstasy") self-injection (0.1-3.2 mg/kg/injection) was examined in baboons under conditions in which baseline responding was maintained by intravenous injections of cocaine HCl (0.32 mg/kg/injection). Drug was available under a FR 160-response schedule of intravenous injection. Each drug injection was followed by a 3-h time out allowing a maximum of eight injections per day. MDMA or MDMA vehicle (saline) was substituted for cocaine for a period of 14 or more days followed by a return to the cocaine baseline. MDMA (0.32-3.2 mg/kg/inj) maintained more injections and higher responses rates than were maintained by saline. The maximal number of injections maintained by MDMA and the maximal response rate maintained by MDMA were less than those maintained under baseline conditions with cocaine. The highest dose of MDMA tested maintained a cyclic pattern of self-injection, i.e., days of high numbers of injections intermixed with days of low numbers of injections. At the highest dose of MDMA tested, concurrent food maintained behavior was suppressed to an extent that food intake was also decreased.

3,4-Methylenedioxyamphetamine↗
PubMed2005

Biodistribution of radiolabelled human dendritic cells injected by various routes.

PURPOSE: The purpose of this study was to investigate the biodistribution of mature dendritic cells (DCs) injected by various routes, during a cell therapy protocol. METHODS: In the context of a vaccine therapy protocol for melanoma, DCs matured with Ribomunyl and interferon-gamma were labelled with( 111)In-oxine and injected into eight patients along various routes: afferent lymphatic vessel (IL) (4 times), lymph node (IN) (5 times) and intradermally (ID) (6 times). RESULTS: Scintigraphic investigations showed that the IL route allowed localisation of 80% of injected radioactivity in eight to ten nodes. In three cases of IN injection, the entire radioactivity stagnated in the injected nodes, while in two cases, migration to adjacent nodes was observed. This migration was detected rapidly after injection, as with IL injections, suggesting that passive transport occurred along the physiological lymphatic pathways. In two of the six ID injections, 1-2% of injected radioactivity reached a proximal lymph node. Migration was detectable in the first hour, but increased considerably after 24 h, suggesting an active migration mechanism. In both of the aforementioned cases, DCs were strongly CCR7-positive, but this feature was not a sufficient condition for effective migration. In comparison with DCs matured with TNF-alpha, IL-1beta, IL-6 and PGE2, our DCs showed a weaker in vitro migratory response to CCL21, despite comparable CCR7 expression, and higher allostimulatory and TH1 polarisation capacities. CONCLUSION: The IL route allowed reproducible administration of specified numbers of DCs. The IN route sometimes yielded fairly similar results, but not reproducibly. Lastly, we showed that DCs matured without PGE2 that have in vitro TH1 polarisation capacities can migrate to lymph nodes after ID injection.

Antigens, Bacterial↗
PubMed2000

Reinforcement of spinal anesthesia by epidural injection of saline: a comparison of hyperbaric and isobaric tetracaine.

PURPOSE: An epidural injection of saline was reported to extend spinal anesthesia because of a volume effect. The aim of this study was to evaluate the influence of the baricity of spinal local anesthetics upon the extension of spinal anesthesia by epidural injection of saline. METHODS: Forty patients undergoing elective lower-limb surgery were randomly allocated to four groups of 10 patients each. Group A received no epidural injection after the spinal administration of hyperbaric tetracaine (dissolved in 10% glucose). Group B received an epidural injection of 8 ml of physiological saline 20 min after spinal hyperbaric tetracaine. Group C received no epidural injection after spinal isobaric tetracaine (dissolved in physiological saline). Group D received an epidural injection of 8 ml of saline 20 min after spinal isobaric tetracaine. The level of analgesia was examined by the pinprick method at 5-min intervals. RESULTS: The levels of analgesia 20 min after spinal anesthesia were significantly higher in hyperbaric groups than in isobaric groups [T5 (T2-L2) vs. T7 (T3-12)]. After epidural injection of saline, the levels of analgesia in groups B and D were significantly higher than in groups A and C. The segmental increases after epidural saline injection were 2 (0-3) in group B and 2 (1-7) in group D. Sensation in the sacral area remained 20 min after spinal block in one patient in group D; however, it disappeared after epidural saline injection. CONCLUSION: In this study, 8 ml of epidural saline extended spinal analgesia. However, there was no difference between the augmenting effect in isobaric and hyperbaric spinal anesthesia. We conclude that the reinforcement of spinal anesthesia by epidural injection of saline is not affected by the baricity of the spinal anesthetic solution used.

Clinical Trial↗
PubMed2000

Intradiscal pressure after intradiscal injection of hypertonic saline: an experimental study.

Although chemonucleolysis with chymopapain is a long-established treatment for lumbar intervertebral disc herniation, serious complications have been reported. Accordingly, alternative substances for chemonucleolysis have been sought. The main beneficial effect of chemonucleolysis derives from the decrease in intradiscal pressure. Several previous studies have investigated the relationship between physiological saline injection and disc mechanics in cadaveric specimens [2, 5, 16]. However, no previous study has assessed the intradiscal pressure after intradiscal injection of "hypertonic saline" in living animals. The present study compared the changes in intradiscal pressure after intradiscal injection of hypertonic saline with those after chymopapain injection. The lumbar intervertebral discs of 26 living rabbits were examined: 10% hypertonic saline was injected in ten rabbits, and chymopapain (10 pikokatal units) was injected intradiscally in another ten, with the remaining six being used as controls. The intradiscal pressure was measured at 1, 4, and 12 weeks after injection. The intradiscal pressure of the hypertonic saline-injected group at 4 weeks was significantly lower than that of the control group, but by 12 weeks it had recovered. On the other hand, that of the chymopapain-injected group remained significantly lower than that of the control group at 12 weeks. The results of this study found that hypertonic saline injected into the intervertebral discs temporarily decreased the intradiscal pressure.

Animals↗
PubMed1979

Observations of HRP labeling following injection through a chronically implanted cannula--a method to avoid diffusion of HRP into injured fibers.

One of the limitations of the horseradish peroxidase (HRP) tracer method is the diffusion of HRP into injured axons resulting in unintended labeling of neurons not terminating in the injection area. To overcome this limitation, an experiment was designed to inject the HRP through an implanted cannula after degeneration and healing had taken place. It was shown that implantation of a cannula into the internal capsule significantly decreased the number of labeled axons in the injection site, thus limiting the unintended labeling of neurons from that injection. When injections followed implantation of the cannula by 24 h or more, fibers damaged by the cannula had healed or degenerated sufficiently that intraaxonal diffusion of HRP into those injured fibers did not occur. A significant difference between control (without the cannula) and experimental (with the cannula) injections was observed. Extensive axonal and neuronal labeling following the control injections was seen at the injection site and caudate nucleus, and in the thalamus and parietal cortex, respectively. Experimental injections resulted in sparse axonal and neuronal labeling evident mostly with the larger injections of HRP.

Amygdala↗