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PubMed1977

Fibrous contracture of muscles following intramuscular injections in adults.

Periarticular fibrous muscle contractures in adults from repeated injections in the same site is predictable. The causes of joint contracture in children are many and complex, but in adults it seems certain that this phenomenon is the result of repeated injections of analgesics or other agents into 1 muscle area. Any drug if repeatedly injected locally may cause fibrosis of the muscle and subsequent joint contracture. Five cases of bilateral abduction contracture of the shoulder in adults including the first case of bilateral abduction contractures of shoulder and hip plus bilateral flexion contracture of elbow and extension contracture of a knee are reported. No underlying disease which might predispose to this fibrosis of muscles was noted. The frequency and period of injections were variable over several years. In all patients the interference in activtities of daily living were serious, but the deformities were corrected by release of the fibrous band with relief of discomfort and restoration of joint motion without recurrence. Noting the potential complication of repeated intramuscular injections in one area, this practice should be avoided whenever possible in adults, as well as in children.

Adult↗

PubMed1982

Termination of second trimester pregnancy by intramuscular injection of 16-phenoxy-omega-17,18,19,20-tetranor-PGE2 methyl sulphonylamide.

Two doses of the prostaglandin analogue 16-phenoxy-omega-17,18,19,20,-tetranor-PGE2 methyl sulphonylamide were compared in a randomized multicentre trial in 6 centres for the termination of second trimester pregnancy. A total of 295 patients were treated with either 0.5 mg or 1.0 mg given by intramuscular injection every 4 h or 8 h, respectively. The 1-mg dose was more effective in inducing an abortion than the lower dose but the difference was not statistically significant. Eighty-four per cent of the patients aborted within 30 h from the onset of treatment. The induction-abortion interval was approximately 15 h in both groups. The incidence of incomplete abortion, heavy blood loss and blood transfusion was similar for both treatments. Cervical lacerations occurred in 1.3% of patients given the smaller dose and 2.1% of the larger dose. In one patient belonging to the latter group an anterior rupture of the lower uterine segment was diagnosed necessitating hysterectomy. Fifty per cent of the patients had no vomiting and 90% no diarrhea. The frequency of gastrointestinal side effects was slightly higher with the 1-mg dose. The major advantages of this treatment are the simplicity of administration and the low frequency of gastrointestinal side effects in comparison with prostaglandin F analogues.

Abortifacient Agents↗

PubMed1995

Quantification of IgG anti-D bound to D-positive red cells infused into D-negative subjects after intramuscular injection of monoclonal anti-D.

A flow-cytometric method was developed to determine the number of molecules of IgG bound to D-positive red blood cells (RBC) when sensitized with low plasma concentrations of IgG anti-D in the presence of an excess of D-negative RBC. D-positive RBC were infused into 12 D-negative male volunteers 2 days after intramuscular injection of monoclonal anti-D (BRAD-3, IgG3 or BRAD-5, IgG1). Blood samples were taken immediately before, 3 min and 3 h after injection of the RBC, incubated for 1 h at 37 degrees C, washed, then incubated sequentially with FITC-conjugated anti-IgG, IgM monoclonal anti-D, biotin-conjugated anti-IgM, and R-phycoerythrin-conjugated streptavidin. To prepare a standard curve, O R1R2 RBC were incubated in duplicate with varying dilutions of BRAD-3 or BRAD-5, and RBC from one set were mixed with an excess of D-negative RBC (1:100) and labelled as above, while cell-bound IgG on the other set was quantified by ELISA. The test samples and standards were analyzed by flow cytometry and the mean channel (FITC) fluorescence was plotted against molecules IgG/cell, from which the sensitization level of D-positive RBC in the test samples was determined. The use of IgM anti-D enhanced the discrimination between D-positive and D-negative RBC, especially when fewer than about 3000 molecules IgG/cell were bound. The assay was sensitive to about 1000 molecules IgG/cell. The sensitization levels of the D-positive RBC in samples taken 3 h after injection were found to be in the range 1500-10,000 molecules IgG anti-D per cell.

Antibodies, Monoclonal↗

PubMed2004

Degeneration and regeneration of murine skeletal neuromuscular junctions after intramuscular injection with a sublethal dose of Clostridium sordellii lethal toxin.

Clostridium sordellii lethal toxin (LT), a 250-kDa protein which is the bacteria's major virulence factor, belongs to a family of large clostridial cytotoxins which glucosylate small GTP-binding proteins. Here, we report the results of our ex vivo analysis of the structure and function of skeletal neuromuscular tissue obtained from mice at various times after intramuscular injection of a sublethal dose of LT (0.25 ng/g of body wt). The toxin caused, within 24 h, pronounced localized edema, inflammation, myofibril disassembly, and degeneration of skeletal muscle fibers in the injected area, and it glucosylated the muscle tissue's small GTPases. Regeneration of the damaged fibers was evident 6 to 9 days postinjury and was completed by 60 days. The expression of dystrophin, laminin, and fast and neonatal myosin in regenerating fibers, detected by immunofluorescence microscopy, confirmed that LT does not impair the high regenerative capacity of murine skeletal muscle fibers. Functional studies revealed that LT affects muscle contractility and neuromuscular transmission. However, partial recovery of nerve-evoked muscle twitches and tetanic contractions was observed by day 15 postinjection, and extensive remodeling of the neuromuscular junction's nerve terminals and clusters of muscle acetylcholine receptors was still evident 30 days postinjection. In conclusion, to the best of our knowledge, this is the first report to characterize the degeneration and regeneration of skeletal neuromuscular tissue after in vivo exposure to a large clostridial cytotoxin. In addition, our data may provide an explanation for the severe neuromuscular alterations accompanying wound infections caused by C. sordellii.

Animals↗

PubMed2004

Autonomic dysreflexia after intramuscular injection in traumatic tetraplegia: a case report.

Autonomic dysreflexia is a syndrome of massive imbalance of reflex sympathetic discharge occurring in patients with spinal cord lesion above the splanchnic outflow (T6). It is characterized by a sudden onset and severe increase in blood pressure and is potentially life threatening. The most common causes are bladder and rectum distention. In this case study, we report an autonomic dysreflexia case that developed after intramuscular injection in a 29-yr-old tetraplegic patient with C5 American Spinal Injury Association grade A lesion. After careful scrutiny of English literature, this clinical manifestation seems to be an unusual event.

Adult↗

PubMed1998

Systemic delivery of interleukin 10 by intramuscular injection of expression plasmid DNA prevents autoimmune diabetes in nonobese diabetic mice.

We previously demonstrated that intramuscular plasmid injection serves as a useful method of long-term systemic delivery of cytokines. In the present study, we assess intramuscular DNA injection as a means of systemically delivering interleukin 10 (IL-10), a cytokine with immunosuppressive properties, and preventing the progression of autoimmune diabetes in the nonobese diabetic (NOD) mouse, an excellent model for human insulin-dependent diabetes mellitus (IDDM). We injected IL-10 expression plasmid (pCAGGS-IL10) or a control pCAGGS plasmid into the muscles of NOD mice twice at 3 and 5 weeks of age. IL-10 was detectable by ELISA in the sera of mice injected with pCAGGS-IL10 for more than 2 weeks after the injection. Although the severity of insulitis at 13 weeks of age was not improved by the intramuscular injection of pCAGGS-IL10, the incidence of diabetes was markedly reduced in NOD mice injected with pCAGGS-IL10 as compared with those injected with pCAGGS or as compared with nontreated NOD mice. These results show that the progression of autoimmune diseases in mice can effectively be suppressed by intramuscular DNA injection, and suggest that this method is potentially applicable to the treatment of human autoimmune diseases.

Animals↗

PubMed2001

Efficient induction of antigen-specific, T helper type 1-mediated immune responses by intramuscular injection with ovalbumin/interleukin-18 fusion DNA.

The balance of two types of T helper (Th) cells, Th1 and Th2 subsets, is important with respect to susceptibility or resistance to particular infections, or to autoimmune diseases and allergic diseases. To effectively induce Th1 immune responses in an antigen-specific manner, we constructed a mammalian expression plasmid (pOVA/IL-18) carrying a fusion gene in which the ovalbumin (OVA; a model antigen) cDNA was covalently linked to mature interleukin-18 (IL-18) cDNA. Intramuscular injection of C57BL/6 mice with the pOVA/IL-18 DNA efficiently increased the production of both OVA-specific IFN-gamma and anti-OVA IgG2a isotype, compared with the injection with the pOVA DNA. In addition, the pOVA/IL-18 was more efficient than a simple mixture of pOVA and pIL-18 in inducing antigen-specific, Th1 immune responses and in inhibiting OVA-specific, IL-4 production. These studies indicate that vaccination with the OVA/IL-18 fusion DNA efficiently induces Th1 immune response in an antigen-specific manner.

Animals↗

PubMedDate not supplied

Plasma concentrations and acceptability of mexiletine given by intramuscular injection in patients admitted to a coronary care unit.

We measured the plasma concentrations of mexiletine in patients admitted to a hospital coronary care unit after the intramuscular injection (IMI) of 200, 300, 400, and 500 mg mexiletine. Mexiletine was rapidly absorbed and concentrations greater than 0.75 microgram/ml were achieved in some patients within 5 min of the injection. The maximum mean plasma concentration increased with 200, 300, and 400 mg but was lower after 500 mg than after 400 mg. After 400 mg mexiletine, plasma concentrations greater than 0.75 microgram/ml were achieved in at least seven of nine patients from 15 min to 2 h after administration. There were no local reactions to 200, 300, or 400 mg mexiletine, but local pain and tenderness occurred in three of nine patients after 500 mg. It was decided that 400 mg mexiletine would probably be the desired dose for intramuscular administration. In 14 patients given mexiletine 400 mg by IMI followed at 2 and 12 h by 360 mg by mouth the plasma concentration was in the therapeutic range (0.75-2.0 micrograms/ml) from 15 min to 24 h in at least 64% of patients. In 12 healthy volunteers the IMI of 400 mg mexiletine increased total creatinine kinase (CK), aspartate amino-transferase, and lactate dehydrogenase enzymes but CK-MB, LDi, and LDii concentration or LDi/LDii ratio were not outside the normal range. These studies indicate that mexiletine can be safely given to patients by IMI and that therapeutic plasma concentrations are achieved.

Adult↗

PubMed1976

Effect of formulation of intramuscular injections of phenothiazines on duration of activity.

Trifluoperazine and pericyazine were formulated using both the hydrochloride and embonate salts, and some comparisons were made with the activity of fluphenazine salt and ester formulations. Simple solutions in polyethylene glycol, gelled aqueous solutions, nonaqueous suspensions, multiple emulsions, and microencapsulated preparations were formulated, and their duration of activity was tested in dogs. While the multiple emulsion system showed some promise, a nylon microcapsule system produced significant prolonged activity of the drug after deep intramuscular injection.

Animals↗

PubMedDate not supplied

[Using the preparation "human immunoglobulin against herpes simplex virus type 1 for intramuscular injections" in the complex therapy of nervous system diseases].

The technology of obtaining of specific immunoglobulin for serotherapy of neuroinfection caused by virus herpes simplex 1 type was developed. The patients presented with the following diseases: arachnoencephalitis, encephalopolyradiculoneuritis, encephalomyelitis, encephalitis, arachnoiditis, polyneuropathy, encephalomyelopolyradiculoneuritis, meningoencephalitis. The study showed good tolerance and safety of the medicine, no adverse effects registered during the study. The assessed median score of the efficacy was 2.8 from 3. The obtained results suggest using the liquid form preparation for intramuscular injection "Immunoglobulin for treatment of neuroinfection caused by virus herpes simplex type 1". The Close corporation "Biofarma" located in Kyiv produces this medicine.

Central Nervous System Viral Diseases↗

PubMed2006

Induction of dystrophin expression by exon skipping in mdx mice following intramuscular injection of antisense oligonucleotides complexed with PEG-PEI copolymers.

Antisense oligonucleotides (AOs) with 2-O-methyl modifications can circumvent dystrophin mutations via exon skipping and, it is hoped, can become drugs for treatment of Duchenne muscular dystrophy (DMD). However, AO-based approaches are hindered by a lack of effective carriers to facilitate delivery of AOs to myonuclei. We examined whether copolymers composed of cationic poly(ethylene imine) (PEI) and polyethylene glycol (PEG) can enhance AO transfection in skeletal muscle of mdx mice. Single intramuscular injections of AO complexed with low Mw PEI2000(PEG550) copolymers into TA muscles of mdx mice resulted in widespread distribution of dystrophin-positive fibers at 3 weeks after injection, with no apparent cytotoxicity. Overall, injections of these low Mw polyplexes, which formed 250-nm aggregate particles, resulted in about sixfold more dystrophin-positive fibers than AO alone. Western analysis confirmed the dystrophin expression in these muscles. Surprisingly, injections of AO complexed with high Mw PEI25000(PEG5000) copolymers, which formed smaller nonaggregated particles, produced about threefold fewer dystrophin-positive fibers than injections of the low Mw polyplexes. We conclude that low Mw PEI2000(PEG550) copolymers function as high-capacity, nontoxic AO carriers suitable for in vivo transfection of skeletal muscle and are promising compounds for potential use in molecular therapy of DMD.

Alternative Splicing↗

PubMed1995

An explanation of the differences between expert and novice performance in the administration of an intramuscular injection of an analgesic agent to a patient in pain.

It has been stated that nurse education in the United Kingdom (UK) currently draws upon Schön's concept of the reflective practitioner, and Benner's concept of the expert. Studies have explored the claim that experienced expert practitioners are unable to articulate all they know, and that their theoretical knowledge and clinical skills are of a qualitatively different type from that of novice practitioners. This paper aims to explain the differences between expert and novice performance using the example of administering an intramuscular injection of an analgesic agent to a patient in pain. Theoretical concepts concerning the nature of expertise are used to evaluate novice/expert performance in nursing. Criticisms of Benner's theory are developed in relationship to her methodology and the interpretation and assessment of nursing practice.

Clinical Competence↗

PubMed1999

[Direct intramuscular injection of pSV-VEGF(165) augments capillaries formation in a rabbit model of hindlimb ischemia].

OBJECTIVE: To investigate an easier and safer clinical method of gene therapy for treating arterial ischemic diseases in the lower extremity. METHODS: Recombinant plasmid pSV-VEGF(165) constructed in vitro was directly injected into the ischemic hindlimb muscles in rabbit models. 30 days after gene transfer, the capillary density and the capillary to muscle fiber ratio were determined histochemically in the resected samples. RESULTS: The capillary density and the capillary to muscle fiber ratio were significantly higher for pSV-VEGF(165) transfected group than for control group, particularly increased in the shank of the hindlimbs. CONCLUSIONS: Direct intramuscular injection of pSV-VEGF(165) was an easier and efficient gene therapy method, and it significantly augmented the capillary formation in ischemic limbs.

Animals↗

PubMed1983

[Drug concentrations in blood, synovial fluid, synovial membrane, periarticular bone, muscle and adipose tissue in patients with rheumatoid polyarthritis receiving a single intramuscular injection of ketoprofen or acetylsalicylic acid (3 hours after the injection)].

The therapeutic activity of antiinflammatory agents in rheumatic joint disease is related to their presence at the target site of action, i.e. the joints. Tissue concentrations of such agents have been previously determined in patients with rheumatic disorders under long-term treatment with acemetacin and indomethacin (Köhler et al., 1981). The purpose of the present study was to determine concentrations of ketoprofen and acetylsalicylic acid in blood as well as synovial fluid, synovial membrane and periarticular bone and adipose tissue, three hours after administration of a single dose. Drug concentrations found in each of these tissues following a single intramuscular injection were sufficient to ensure therapeutic efficiency.

Adipose Tissue↗

PubMed2000

Immunization of rabbits with cottontail rabbit papillomavirus E1 and E2 genes: protective immunity induced by gene gun-mediated intracutaneous delivery but not by intramuscular injection.

We previously demonstrated that gene gun-based intracutaneous vaccination of rabbits with a combination of, but not with individual papillomavirus E1, E2, E6 and E7 genes provided complete protection against cottontail rabbit papillomavirus (CRPV) infection. In the present study, we tested whether vaccination of inbred and outbred rabbits with a combination of CRPV E1 and E2 genes could provide complete protection against virus infection. In the first experiment, gene gun-based intracutaneous vaccination with E1 and E2 genes prevented papilloma formation in the majority of inbred rabbits and promoted systemic papilloma regression in one non-protected rabbit. In contrast, needle-mediated intramuscular injection of E1 and E2 genes did not prevent papilloma formation nor promoted systemic papilloma regression, indicating an absence of strong protective immunity. In the second experiment, six outbred rabbits were immunized by gene gun-based intracutaneous administration of the E1 and E2 genes. Prevention of papilloma formation or systemic papilloma regression was observed in three vaccinated rabbits. Papillomas persisted on the remaining three rabbits, but were significantly smaller than that on control rabbits. These results suggested that gene gun-based intracutaneous vaccination with the combination of papillomavirus E1 and E2 genes induced strong protective antivirus immunity but may be insufficient for complete protection in an outbred population.

Administration, Cutaneous↗

PubMed1999

Evidence for subnucleus interpolaris in craniofacial muscle pain mechanisms demonstrated by intramuscular injections with hypertonic saline.

The subnucleus interpolaris (Vi) has been identified as a major recipient for trigeminal ganglionic input from jaw muscles, and contains neurons with nociceptive properties similar to those in the subnucleus caudalis (Vc). Therefore, Vi may be another important site for processing craniofacial muscle nociception. The aims of present study were to define functional properties of Vi neurons that receive input from masseter muscle afferents by characterizing their responses to electrical, mechanical, and to chemical stimulation of the muscle. Ninety cells were identified as masseter muscle units in 11 adult cats. Most of these units (79%) received additional inputs from orofacial skin. Following the intramuscular injection of 5% hypertonic saline, 49% of the cells showed a significant modulation of either the resting discharge and/or responses to innocuous mechanical stimulation on their cutaneous receptive fields (RFs). The most common response to saline injection was an induction or facilitation of resting discharge which declined as an exponential decay function, returning to pre-injection level within 3-4 min. Forty-five percent of the muscle units that were tested with mechanical stimulation (13/29) showed a prolonged inhibition of mechanically-evoked responses. In most cases (8/13), the inhibitory response was accompanied by initial facilitation. The observations that Vi contained a population of neurons that receive small diameter muscle afferent inputs, responded to noxious mechanical stimulation on the muscle and to a chemical irritant that is known to produce pain in humans provide compelling evidence for the involvement of Vi in craniofacial muscle pain mechanisms.

Animals↗

PubMed2013

Delivery of recombinant adeno-associated virus vectors to rat diaphragm muscle via direct intramuscular injection.

The diaphragm is the most important inspiratory muscle in all mammals, and ventilatory insufficiency caused by diaphragm dysfunction is the leading cause of morbidity and mortality in many genetic and acquired diseases affecting skeletal muscle. Currently, pharmacological inhibitors, genetically modified animals, and invasive procedures are used to study disorders affecting the diaphragm. However, these methodologies can be problematic because of off-target drug effects and the possible nonphysiological consequences of lifelong genetic alterations. Therefore, alternative methods to study this important respiratory muscle are needed. To resolve this, we have developed a methodology to deliver recombinant adeno-associated virus (rAAV) vectors to the rat diaphragm via direct intramuscular injection. We hypothesized that by direct injection of rAAV into the muscle we can selectively target the diaphragm and establish a novel experimental method for studying signaling pathways and also provide a strategy for effectively using rAAV to protect the diaphragm against disease. This report describes the methods and evidence to support the use of rAAV as a therapeutic intervention to study rat diaphragm biology during conditions that promote diaphragm dysfunction.

Animals↗

PubMed1999

Distribution of camptothecin after delivery as a liposome aerosol or following intramuscular injection in mice.

PURPOSE: The plant alkaloid camptothecin (CPT) has shown significant antitumor activity against a wide variety of human tumors xenografted in nude mice. In previous studies we have found that administration of dilauroylphosphatidylcholine (DLPC) liposome aerosols containing 9-nitrocamptothecin (9-NC) inhibits the growth of human breast, colon and lung cancer xenografts. The purpose of this study was to analyze the pharmacokinetics and tissue distribution of inhaled CPT formulated in DLPC liposomes. METHODS: C57BL/6 mice with subcutaneous Lewis lung carcinoma, Swiss nu/nu mice with human lung carcinoma xenografts and BALB/c mice without tumors were used for pharmacokinetic studies of CPT administered as a liposome aerosol and BALB/c mice were given CPT intramuscularly. RESULTS: After 30 min inhalation of CPT liposome aerosol, drug was deposited in the lungs (310 ng/g) and was followed promptly by the appearance of high concentrations in the liver (192 ng/g) and with lesser amounts appearing in other organs. Drug concentration in the brain was 61 ng/g. After intramuscular injection of CPT dissolved in DMSO, drug was released from the site of injection very slowly and accumulated mainly in the liver (136 ng/g). Only trace amounts appeared in the lungs (2-4 ng/g). These results demonstrate a prompt pulmonary and later systemic distribution of CPT following liposome aerosol administration. CONCLUSIONS: The substantial concentrations of CPT in lungs and other organs following inhalation of liposome aerosol suggest the possible benefit of it and of its more active derivative, 9-NC, in the treatment of lung, liver, kidney and brain cancer in humans.

Aerosols↗