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A comparative study of serum creatine phosphokinase (CPK) activity in rabbits, pigs and humans after intramuscular injection of local damaging drugs.

Serum creatine phosphokinase (CPK) activity has been determined before and after intramuscular injection of lidocaine, diazepam or saline in humans and lidocaine, diazepam, digoxin and saline in pigs and rabbits. Two ml volum of each of the drugs was given to humans as well as to the experimental animals. No changes in CPK activity were found after saline in humans or rabbits but a minor increase was demonstrated in pigs. A marked increase of CPK activity was demonstrated after lidocaine or diazepam in humans and after lidocaine, diazepam or digoxin in pigs and rabbits. Post mortem examination of the injection sites in the animals revealed extensive muscle tissue necrosis after lidocaine, diazepam and digoxin. No damage of the tissue was found after saline. CPK activity was also determined in rabbits receiving 2 ml of dilutions of diazepam in saline. The injection sites were examined post mortem. The CPK activity was increased in animals receiving 1:2 and 1:8 dilutions while a 1:20 dilution did not give rise to changes in the enzyme activity. The necrotic area diminished when diazepam was diluted and no pathological changes were found at the injection sites after the 1:20 dilution. Measuring the CPK activity in rabbits after an intramuscular injection seems to be a sensitive method for the determination of local toxicity.

Animals↗

A case of sudden death after intramuscular injection of butylscopolamine bromide.

A 40-year-old man experienced cardiopulmonary arrest after intramuscular injection of 20 mg of butylscopolamine bromide. No pathological changes were found at autopsy, and 1.19 microg/mL of butylscopolamine bromide was detected in his serum. Since he had taken no other drugs, his severe symptoms were thought to have been caused by an anaphylactic reaction to butylscopolamine bromide. Butylscopolamine bromide has been used for many years worldwide, and is considered to be a safe drug, with no reports of severe side effects following intramuscular injection. Since an anaphylactic reaction may not be related to a particular medication, the possibility of such a severe reaction must be considered, even during administration of an ostensibly safe drug such as butylscopolamine bromide.

Adult↗

Investigation into the pathogenesis of atrophic rhinitis in pigs. II. AR induction and protection after intramuscular injections cell-free filtrates and emulsions containing AR toxin of Pasteurella multocida.

The intramuscular administration of the cell-free culture filtrates of two AR pathogenic Pasteurella multocida (PM) isolates caused Atrophic Rhinitis (AR) in piglets. The culture filtrate of a non-AR-pathogenic PM isolate did not cause AR lesions after intramuscular injection. The severity of the AR lesions appeared to be correlated with the quantity of injected toxin. As the quantity of administered toxin increased, the piglets showed clinical growth retardation, icterus and mortality. Besides lesions typical of AR, severe liver degeneration was observed at necropsy; this liver degeneration was sometimes accompanied by fibrosis. After emulgation of the cell-free culture filtrates in incomplete Freunds adjuvant, AR was caused by administration of the toxin-containing emulsions in piglets of 3 and 6 weeks of age. An experimental water-in-oil emulsion containing the AR toxin of Pasteurella multocida caused AR when intramuscularly injected in 1- to 4-week-old piglets. A PM-AR toxin challenge method is described. After injection of the toxin into piglets born from sows vaccinated against AR, protection was demonstrated. Ten of the 12 piglets (83%) challenged at the age of 3 weeks showed protection. Six animals of the 12 pigs (50%) injected with the toxin at the age of 6 weeks, showed no protection. Differences in protection were noted between and within the litters. After injection with the toxin, all piglets of 3 and 6 weeks of age born from non-vaccinated sows showed deviations typical of AR.

Animals↗

An animal model for aseptic necrosis after intramuscular injections.

Ten drugs or vaccines commonly given to patients by intramuscular injection were injected into the femoral artery of normal young anaesthetized pigs, in order to establish an animal model for macroscopically identifiable aseptic tissue necrosis (Nicolau syndrome). Despite the wide range of constituents and chemical groupings in the drugs which had caused Nicolau syndrome in patients, when injected into the pigs a typical pattern of reactions could be observed for many of them, as follows: the leg contracted rapidly, the skin area supplied by this artery initially became pale and then bluish-red with an irregular reticular appearance before finally tissue necrosis developed. These reactions are comparable to the symptoms of Nicolau syndrome in man. However, no reactions were seen when drugs or vaccines which have not been known to cause aseptic necrosis in man, e.g. tetanus toxoid, influenza vaccine or triamcinolon, were injected i.a.

Animals↗

[Induction for termination of pregnancy in the second trimester and for delivery of babies dead in utero using intramuscular injections of 15-methyl-PGF2 alpha (author's transl)].

Intramuscular injection of 15-methyl-PGF2 alpha was used to induce 48 terminations of pregnancy in the second trimester as well as to deliver 8 cases of death in utero and one hydatidiform mole. It is an effective method of treatment with a failure rate of 1.9%. As compared to the administration of pain-relieving drugs intravenously, continuous epidural analgesia has shown itself to be the only method which will allow the best possible conditions for the maintenance and control of prostaglandin induction to be carried out, suppressing effectively even the pains which are associated with uterine contractions brought on by prostaglandin. Although this method of systemic administration of prostaglandin does avoid any intervention through the cervicovaginal route, it does not completely do away with rare infections which are found to complicate matters when PGF2 alpha gel is administered by the extra-amniotic route. All the same, the acceptability and use of this method as a routine method must be limited by the high incidence of episodes of diarrhoea which are made worse by paralysis of the sphincters that is inseparable from epidural analgesia.

Abortifacient Agents↗

Development of a novel dosage form for intramuscular injection of titrated extract of Centella asiatica in a mixed micellar system.

Titrated extract of Centella asiatica (TECA), a drug used in treating systemic scleroderma, is poorly water-soluble. A conventional dosage form for the intramuscular injection of TECA, propylene glycol (PG)-based TECA solution, causes severe pain after intramuscular injection. To improve the solubility of TECA and reduce pain after injection, mixed micellar systems composed of 10% surfactant mixture (Tween 20 and Tween 85) and 90% phosphate-buffered saline, pH 7.0 (PBS) were prepared. As the ratio of Tween 20 to Tween 85 increased from 0:10 to 10:0, the solubility of TECA in the mixed micellar systems increased from 7- to 26-fold compared to that in PBS (pH 7.0). The droplet size of micelles gradually decreased with the increasing ratio of Tween 20 to Tween 85 from 0:10 to 4:6, followed by an abrupt decrease in size above the ratio of 6:4. Furthermore, the micellar systems prepared with Tween 20 and Tween 85 at the ratio of 6:4, 8:2 or 10:0 could solubilize TECA more than 10 mg/ml and the resultant droplet sizes were less than 2 microm. No significant changes were observed in the droplet sizes and asiaticoside contents in these micellar formulations during storage, indicating these systems are stable for at least 60 days. Their osmotic pressures were remarkably lower than those of PG-based TECA solution and similar to that of saline solution, irrespective of dilution ratios. Most importantly, they markedly reduced the number of writhes compared with PG-based TECA solution after injection to mice. All of these results suggest that these three TECA micellar formulations prepared with Tween 20 and Tween 85 improved the solubility of TECA and reduced pain following injection, possibly due to the decrease in osmotic pressure. Thus, these micellar formulations composed of optimum ratios of Tween 20 and Tween 85 may have a potential as dosage forms for the intramuscular injection of a poorly water-soluble TECA.

Animals↗

Fibrous myopathy as a complication of repeated intramuscular injections for chronic headache.

Two cases of fibrous myopathy associated with repeated, long-term intramuscular injections for treatment of chronic temporomandibular joint pain and chronic headache, respectively, are described. Both patients developed severe, function-limiting contractures in upper and lower extremity muscles used as injection sites. In one of the cases, the contractures were painful. Electrophysiological testing, magnetic resonance imaging and muscle biopsy results were all consistent with myopathy and replacement of skeletal muscle with noncontractile fibrous tissue. These cases are presented to increase awareness of fibrous myopathy and to promote surveillance for this serious potential complication of long-term intramuscular injections in chronic headache and other pain patients.

Adult↗

[The behaviour of creatine phosphokinase in serum after the intramuscular injection of a Tetracyclin preparation (author's transl)].

The single intramuscular injection of 275 mg Rolitetracyclin (Reverin) led to a rise in serum creatine phosphokinase in 11 out of 20 heart healthy patients, 7 cases with values over 100 mU/ml. In sane cases the initial values had still not been reached 72 hours after injection. With Rolitetracyclin given intravenously the creatine phosphokinase values do not alter, as with an isotonic Na-Cl solution given intramuscularly. A rise in the serum creatine phosphokinase was seen in 2 out of 6 cases after an intramuscular injection of Oxytetracyclin (Terramycin -Depot). One is not dealing with a reaction which is typical only to Rolitetracyclin. The cause is thought to be the setting free of enzymes through the musclelesions. The results underline the sensitivity of and problems involved with creatine phosphokinase in the diagnosis of heart-infarction.

Adult↗

[Tibial nerve and fibular nerve paresis in pigs after intramuscular injection in the caudal thigh muscle (case report)].

Paresis of the hindlimb in piglets after intramuscular injection of various therapeutics in the caudal thigh muscles were observed. The injection was followed by inflammatory changes of the muscle tissue at the injection site. The tibial and fibular nerve were enclosed in the alterations and showed a distinct to complete loss of nerve fibers resulting in clinical signs of paresis. The affected hindlimb was dragged on the dorsal digital surface. The piglet showed an extended consecutive swelling and ulceration below the hock and loss of the claws. These findings strongly demonstrate the necessity of a correct intramuscular injection in piglets, which should be done in the lateral neck muscles.

Animals↗

The loss of creatine phosphokinase (CK) from intramuscular injection sites in rabbits. A predictive tool for local toxicity.

The CK activity was measured in muscle tissue taken from the injected area (dorsal longissimus muscle) and the contralateral side of the injection site 72 hours after intramuscular injection into rabbits of 1 ml of different dilutions of propylene glycol or glycerol formal in distilled water or 0.9% saline. The total loss of CK activity from the injection site was calculated as the difference between the CK concentration in the normal muscle tissue and that of the injection site from the same animal. From the results the arbitrary amount of muscle tissue depleted of CK activity was further calculated and compared with the severity of the gross pathological findings. A large necrotic area at the injection site was present in all samples with more than 1 g of muscle tissue depleted of CK activity. Minor and probably acceptable pathological changes were found in samples with less than 1 g of muscle tissue depleted of CK activity. The local damaging effect of drug preparations for intramuscular use can thus be evaluated from the calculated amount of muscle tissue depleted of CK activity.

Animals↗

Detection of integration of plasmid DNA into host genomic DNA following intramuscular injection and electroporation.

Plasmid vectors have been widely used for DNA vaccines and gene therapy. Following intramuscular injection, the plasmid that persists is extrachromosomal and integration into host DNA, if it occurs at all, is negligible. However, new technologies for improving DNA delivery could increase the frequency of integration. In the present study, we tested the effect of electroporation on plasmid uptake and potential integration following intramuscular injection in mice, using a plasmid containing the mouse erythropoietin gene. Electroporation increased plasmid tissue levels by approximately six- to 34-fold. Using a quantitative gel-purification assay for integration, electroporation was found to markedly increase the level of plasmid associated with high-molecular-weight genomic DNA. To confirm integration and identify the insertion sites, we developed a new assay - referred to as repeat-anchored integration capture (RAIC) PCR - that is capable of detecting rare integration events in a complex mixture in vivo. Using this assay, we identified four independent integration events. Sequencing of the insertion sites suggested a random integration process, but with short segments of homology between the vector breakpoint and the insertion site in three of the four cases. This is the first definitive demonstration of integration of plasmid DNA into genomic DNA following injection in vivo.

Animals↗

Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after a stroke.

BACKGROUND: Spasticity is a disabling complication of stroke, and it is uncertain whether intramuscular injections of botulinum toxin type A reduce disability in persons with spasticity of the wrist and fingers after a stroke. METHODS: We performed a randomized, double-blind, placebo-controlled, multicenter trial to assess the efficacy and safety of one-time injections of botulinum toxin A (200 to 240 units) in 126 subjects with increased flexor tone in the wrist and fingers after a stroke. The primary outcome measure was self-reported disability in four areas: personal hygiene, dressing, pain, and limb position (on a four-point scale ranging from no disability to severe disability) at six weeks; at base line, each subject selected one of these areas in which there was moderate-to-severe disability as the principal target of treatment. RESULTS: Subjects who received botulinum toxin A had greater improvement in flexor tone in the wrist and fingers at all follow-up visits through 12 weeks than did subjects who received placebo (P<0.001 for all comparisons). Subjects treated with botulinum toxin A had greater improvement in the principal target of treatment at weeks 4, 6, 8, and 12 (P<0.001, P<0.001, P=0.03, and P=0.02, respectively); at week 6, 40 of the 64 subjects in the botulinum-toxin group (62 percent), as compared with 17 of the 62 in the placebo group (27 percent), reported improvement of at least one point on the Disability Assessment Scale in the principal target of treatment (P<0.001). There were no major adverse events associated with injection of botulinum toxin A. CONCLUSIONS: Intramuscular injections of botulinum toxin A reduce spasticity of the wrist and finger muscles and associated disability in patients who have had a stroke.

Adult↗

Immunization of mice with gamma-irradiated intramuscularly injected schistosomula of Schistosoma mansoni.

The parameters involved in the induction of resistance against Schistosoma mansoni by injection of irradiated, artificially transformed schistosomula were studied in mice. Single intramuscular injections of 500 schistosomula exposed to radiation doses in the range 2.3 to 160 krad. resulted in significant protection (in the range 20 to 50% as assessed by reduced worm burdens) against a challenge infection administered at intervals from 3 to 24 weeks post-vaccination. However, schistosomula irradiated with 20 krad. consistently resulted in better protection than those exposed to either higher or lower radiation doses despite the persistence of stunted adults from the infections irradiated with 2.3 krad. Vaccination with 40 krad. schistosomula resulted in significant protection in terms of reduced worm and tissue egg burdens and increased survival following lethal challenge. Varying the number of irradiated schistosomula, the frequency and route of their administration, the site of challenge and the strain of host all failed to enhance the level of resistance. However, percutaneously applied, irradiated cercariae were found to be more effective in stimulating resistance (60%) than intramuscularly injected, irradiated schistosomula (40%).

Animals↗

Pain on intramuscular injection of bupivacaine, ropivacaine, with and without dexamethasone.

BACKGROUND AND OBJECTIVES: We wished to determine which long-acting local anesthetic would produce the least pain on injection for treatment of myofascial pain disorders. We compared the pain on intramuscular injection of bupivacaine, ropivacaine, bupivacaine with dexamethasone, ropivacaine with dexamethasone, and needle placement alone. METHODS: Thirty volunteers received 5 injections each: (1) needle only, (2) bupivacaine 0.5%, (3) ropivacaine 0.5%, (4) bupivacaine 0.5% with dexamethasone 0.13 mg/mL, and (5) ropivacaine 0.5% with dexamethasone 0.13 mg/mL. The injections were made in the volunteers' upper trapezius muscles; there was a 15-minute interval between injections. The sequence of injections was randomized by Latin square design. The intensity of pain was rated on a 0 to 10 cm visual analogue scale (VAS) score. Neither the investigator nor the volunteer was aware of the nature of the injectate. The pH of the injected solutions was checked to determine if differences in the intensity of pain on injection were due to differences in the pH of the solutions. RESULTS: The VAS pain scores were 3.1 +/- 2.4 for needle only, 4.4 +/- 2.8 for bupivacaine, 2.5 +/- 2.0 for ropivacaine, 4.7 +/- 2.7 for bupivacaine/dexamethasone, and 3.7 +/- 2.2 for ropivacaine/dexamethasone. The pain on injection of ropivacaine was significantly less than the pain on injection of bupivacaine or bupivacaine/dexamethasone. The pH values of the solutions were as follows: (1) bupivacaine, 5.50; (2) ropivacaine, 5.57; (3) bupivacaine/dexamethasone, 6.64; and (4) ropivacaine/dexamethasone, 6.60. CONCLUSIONS: The pain on intramuscular injection of bupivacaine is significantly more intense than with ropivacaine. The difference in the intensity of the pain on injection between bupivacaine and ropivacaine does not appear to be related to differences in pH. The results of our study have implications on the choice of the local anesthetic used in trigger point injections.

Adult↗

Tissue reaction after intramuscular injection of liposomes in mice.

Liposomes are effective carrier systems for prolonged drug release. As all other drug formulations for parenteral use, the safety of liposomal formulations should be established before clinical application. In this study, some safety aspects of intramuscularly injected (single dose) "gel-state" type liposomes and the ability of liposome encapsulation to diminish irritating effects of intramuscularly applied drugs were studied by histopathological analysis over a period of 14 days in mice. Injection of saline solution showed no tissue reaction at the injection site. Intramuscular injection of liposomes alone showed an infiltrative reaction consisting of a population of macrophages. Within this population fat cells were present. In time, the population of macrophages present at the injection site was largely replaced by loose connective tissue. Novaminsulfon (NS) injected intramuscularly in "free" form is a strongly irritating drug, causing hemorrhage, cell necrosis, inflammatory reactions and eventually fibrosis. However, NS being encapsulated in liposomes was hardly more irritating than liposomes alone. The same was true for liposome-encapsulated chloroquine and free chloroquine. When sustained-release of a drug is therapeutically desirable, the parenteral application of a liposome-encapsulated formulation can be considered for drugs, in particular for those drugs causing tissue injury at the injection site.

Animals↗

Local skin necroses after intramuscular injection -Experimental animal studies-.

The pathogenesis of local skin necroses after intramuscular injection of various drugs such as phenylbutazone (Embolia cutis medicamentosa, Nicolau's syndrome) is not clear. In an attempt to simulate this clinical feature experiments were performed on the rabbit ear lobe. A 20% phenylbutazone solution was injected paraarterial, intraarterial and paraarterial after perforation of the vessel. The drug produced a violent inflammation with all kinds of application. The local inflammation induced by paraarterial injection resulted in a fine scarring. Both other kinds of application produced necroses or even perforations. The histological examinations in these cases revealed massive destructions of the inner arterial wall. In control-experiments necroses or perforations were nerve observed. From these data the following conclusions on the etiology of Nicolau's syndrome can be drawn: Phenylbutazone injected into the vascular or perivascular tissue causes an obligatory inflammation. After lesion of an artery complete destruction of the vessel followed by necrosis of the skin may occur. It seems obvious that this secondary effect can not completely be avoided.

Animals↗

The effects of inadvertent intramuscular injection of BCG vaccine.

We report on a case of inadvertent intramuscular injection of BCG vaccine into an already tuberculin-sensitive individual which resulted in a severe and prolonged local reaction. There is no consensus on the best management of this complication, although in this case healing appeared to be hastened by anti-tuberculous chemotherapy.

Abscess↗