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[Effects of radiotherapy combined with daily intramuscular injection of bleomycin for uterine cervical cancer].

A total of 103 cases of cancer of the uterine cervix, untreated previously, were treated with radiotherapy combined with daily intramuscular injection of Bleomycin 30 minutes before irradiation (BR therapy) in 12 institutions. Result showed that especially in cases of stage III, BR therapy was superior in primary local control rate (89.6%), recurrence rate (20.8%) and crude 5-year survival rate (56.5%) to that of nationwide statistics. No severe side effects were found. It was concluded that external radiotherapy could control advanced cancers of uterine cervix combining with intramuscular injection of Bleomycin.

Bleomycin↗

Transdermal delivery and intramuscular injection of trimethoprim/sulphadiazine in sucking piglets.

The pharmacokinetics of a combination of trimethoprim (TMP) and sulphadiazine (SDZ) after topical application to sucking piglets was compared with the pharmacokinetics after intramuscular injection. A long-lasting and fairly constant SDZ/TMP concentration ratio in plasma was obtained after topical application. The mean plasma concentration of TMP ranged from 0.091 to 0.17 micrograms/ml and that of SDZ from 0.72 to 1.1 micrograms/ml for at least 24 h. TMP and SDZ had different half-lives after intramuscular injection. Transdermal delivery of a combined preparation of TMP/SDZ may be usable for colibacillosis of sucking piglets, although the bioavailability of the drugs is poor.

Administration, Cutaneous↗

Worm establishment and egg production of Schistosoma japonicum in pigs infected by percutaneous methods or intramuscular injection.

Worm establishment and egg production were compared in Landrace/Yorkshire crossbred pigs infected with Schistosoma japonicum using 3 different infection techniques. S. japonicum worm establishment and overall egg production following intramuscular injection of cercariae suspended in Iscove's medium exceeded that in pigs infected by the leg immersion or the coverslip percutaneous technique. However, the egg production per mature female was similar for all three infection methods. The results support the use of intramuscular injection of medium-suspended cercariae as an effective, safe, rapid and convenient infection method for studies on the population biology of S. japonicum in pigs when dermal cercarial penetration is not required.

Animals↗

Passive immunity in transmissible gastroenteritis of swine: intramuscular injection of pregnant swine with a modified live-virus vaccine.

Nine pregnant swine were intramuscularly injected with a modified live-virus transmissible gastroenteritis (TGE) vaccine at approximately 6 and 2 weeks before parturition. The TGE antibody levels in milk whey rapidly decreased within a few days after parturition, and the antibodies were mainly, if not solely, of the immunoglobulin G (IgG) class. Nursing newborn pigs were challenge exposed with virulent TGE virus when 2 to 4 days old. All pigs in 8 of the 9 litters became affected with typical signs of TGE. Of the pigs nursing vaccinated sows, 55% died, and of the 9 vaccinated sows, 8 became affected after challenge exposure of their litters. Subsequently, the antibody titers in serum and milk markedly increased in all 9 sows, with the antibody in milk being predominantly of the immunoglobulin A (IgA) class. Serum samples of prenursing newborn pigs from vaccinated sows did not contain detectable TGE antibodies. The capability of the vaccinated sows to provide only limited passive immunity to their suckling pigs was considered to be due mainly to the low titer and class (IgG) of TGE antibody existing in the milk of the sows at the time the newborn pigs were challenge exposed.

Animals↗

[Circumscribed skin necroses following intramuscular injections. Review and case reports].

In rare instances local hemorrhagic necroses may be observed after intramuscular injection. The clinical features of this side reaction - lividoid dermatitis progressing to hemorrhagic necrosis and prolonged wound healing - are presented in the light of four of our own observations. With regard to the etiology, functional vascular spasm, embolism or/and local thromboses are discussed.

Aged↗

A comparison of the local effects of various intramuscular injections in the rat.

A method is described for the assessment of the local reaction produced by intramuscular injections. This method involves the histological examinations of the injection site after injection of material into the hamstring muscles of the rat. The results obtained with both aqueous and oily materials are described; the correlation of these results with clinical observations in man is discussed.

Animals↗

Ropivacaine myotoxicity after single intramuscular injection in rats.

BACKGROUND AND OBJECTIVE: We conducted this study in order to evaluate the potential myotoxic effects of ropivacaine after single injection in rats and the time-course of the possible damage. METHODS: One hundred and twenty-eight male Wistar rats were allocated to four different groups. The first three groups received intramuscular injections with ropivacaine 0.75%, ropivacaine 0.5% and normal saline, respectively, into the right tibialis anterior muscle. The fourth group received needle puncture without injection. Eight rats from each group were sacrificed 2, 4, 7 and 30 days after injection. Samples were blindly examined under light microscope for evidence of myotoxicity, scored as 0 = no damage to 3 = myonecrosis and statistically analysed. Samples obtained 7 days after injection were also examined under transmission electron microscope. RESULTS: Ropivacaine 0.75% and ropivacaine 0.5% caused extensive destruction to muscles fibres, compared to saline or needle on days 2, 4 and 7. Statistically significant differences were found in muscle damage by drug injections among all groups except for saline vs. needle groups. Thirty days after injections all sample appearances had returned to normal. CONCLUSIONS: Ropivacaine after single intramuscular injection caused reversible muscle damage in a dose-dependent manner.

Amides↗

Luteolytic and abortifacient effects of serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha in early pregnancy.

Pregnancy was successfully terminated in 8 of 9 patients 5 to 6 weeks after the last menstrual period by serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha (15-ME-PGF2alpha). In one patient the treatment induced vaginal bleeding and a drop in hormone levels, but the patient did not completely abort and the uterus had to be evacuated. Serial intramuscular injections of 15-ME-PGF2alpha appeared to have some luteolytic effect, resulting in a significant drop in progesterone and estradiol levels. However, it is uncertain if the luteolytic effect of the prostaglandin was the precipitating factor in the abortion since the administration of 15-ME-PFG2alpha was accompanied by strong uterine activity which played a role in the abortion.

Abortifacient Agents↗

In vivo non-invasive quantification of muscle damage following a single intramuscular injection of phenylbutazone in sheep.

Intramuscular drug administration can lead to more or less extensive muscle damage. The aim of the present study was to show the possibility of quantitating, in vivo and non-invasively, the equivalence of muscle destroyed by the administration of a test drug (phenylbutazone) known for its injurious properties. Creatine kinase (CK) kinetic parameters (clearance, volume of distribution) were measured in 6 sheep after an iv administration of muscle CK homogenate. In the same 6 sheep, CK release after iv and im 8 mg phenylbutazone/kg was measured. The calculated total CK released, based on the CK plasma clearance (0.28 mL/kg/min) and area under the curve of CK activity after im phenylbutazone administration was 191 +/- 140 U/kg. By relating this quantity to that of CK gluteal muscle (5114 +/- 891 U/g), it was calculated that im phenylbutazone administration was able to destroy an equivalence of 2.4 +/- 2.1 g of muscle. For the 2 main sites of im administration (neck and gluteal muscle), general equations are proposed to calculate the equivalence of muscle destroyed in sheep when only plasma CK activity following a test drug administration is available.

Animals↗

An in vitro model to evaluate muscle damage following intramuscular injections.

An isolated rat muscle preparation was developed to screen for muscle damage (myotoxic potential) following intramuscular injections. Myotoxicity is evaluated by the total cumulative efflux of the enzyme creatine kinase from the extensor digitorum longus muscle into the incubation medium over a 2-hr period or by the slope of the cumulative creatine kinase efflux curve. The system allows for rapid screening of compounds and/or formulations regarding their myotoxic potential and is not sensitive to fluctuations of in vivo creatine kinase levels caused by animal handling or patient conditions. A good rank-order correlation was obtained between this in vitro technique and the in vivo myotoxicity of a number of pharmaceutical formulations, as indicated by circulating creatine kinase levels and histological observations.

Animals↗

Anaphylactic reaction after intramuscular injection of cyanocobalamin (vitamin B12): a case report.

We report a case of anaphylactic reaction to intramuscular injection of cyanocobalamin. This 52-year-old lady was diagnosed as a case of megaloblastic anemia secondary to dietary vitamin B12 deficiency. She had severe anaphylactic reaction after the parenteral administration of cyanocobalamine. Later she received oral vitamin B12 with no adverse effects. The purpose of this case report is to draw attention to the hypersensitive reaction to injectable vitamin B12, which is rarely seen. This could be due to sensitization to the vitamin B12 molecule itself or an IgE mediated reaction. We concluded that anaphylactic reaction to vitamin B12 is a rare but serious side effect and it should be kept in mind while the drug is being administered to the patient, especially via the parenteral route.

Anaphylaxis↗

Iatrogenic staphylococcus aureus septicaemia following intravenous and intramuscular injections: clinical course and pathomorphological findings.

The clinical course, autopsy and histological findings are presented from three (one 33-year-old female and two males aged 26 and 56) fatalities resulting from injection therapy which has produced Staphylococcus aureus septicaemia. The autopsies were performed within 2-4 days postmortem. No primary focus other than the insertion site of the peripheral venous catheters or the intramuscular injections, representing the initial entry site of Staphylococcus aureus, could be identified. Death was attributed directly to the staphylococcal infection as a result of iatrogenic injection therapy for the treatment of a non-severe underlying illness (premature labour pains, acute loss of hearing, lumbago). The forensic diagnosis of Staphylococcus aureus septicaemia following iatrogenic injections has to be critically evaluated and can be established routinely in cases with delayed autopsy only when no other cause of death is revealed by autopsy, no apparent source of infection other than the insertion site can be detected and careful attention is paid to histological and bacteriological findings. All doubtful cases of nosocomial bloodstream infections with fatal outcome should undergo an immediate autopsy. In cases of very early forensic involvement microbiological investigations, including phagotyping, molecular biological characterization and identification of bacterial toxins from micro-organisms out of appropriate specimens obtained postmortem, could be efforts of potential evidential value regarding the aetiological proof. To optimize aetiopathogenetic conclusions concerning a causal relationship between iatrogenic injections and septic complications, the medicolegal investigation should also include an interdisciplinary co-operation with consultants from other relevant fields (e.g. microbiology and hygienics).

Adult↗

Norethisterone levels in maternal serum and milk after intramuscular injection of norethisterone oenanthate as a contraceptive.

There is concern that the breast-fed infant whose mother is receiving intra-muscular progestogens for contraception will be exposed to significant quantities of the steroid. Norethisterone levels in maternal serum and milk were studied throughout an injection interval after intramuscular administration of 200mg norethisterone oenanthate. Milk samples were taken at the beginning and at the end of the feed. Norethisterone concentrations in milk were very much lower, but declined more slowly, than serum concentrations. Post-suckling concentrations were higher than pre-suckling concentrations. Experiments in adults receiving an oral dose of norethisterone in cow's milk comparable to that ingested by an infant in a day resulted in low serum levels. It is concluded that only very low concentrations of norethisterone would be present in the infant's circulation.

Breast Feeding↗

Aspects of the pharmacokinetics of doxycycline given to healthy and pneumonic East African dwarf goats by intramuscular injection.

The effect of experimentally induced Pasteurella haemolytica pneumonia on the pharmacokinetics of doxycycline (Doxycen Retard) administered intramuscularly was studied in seven East African dwarf goats. The study was conducted in two consecutive phases, separated by a washout period of four weeks. The experimental infection, induced by intratracheal administration of 5 ml of 10(7) to 10(9) cfu/ml of Pasteurella haemolytica, produced a temperature rise, depression and laboured breathing within 6-12 days after inoculation. The concentrations of doxycycline in the serum were determined by a quantitative microbiological assay using an agar-gel diffusion method employing Bacillus cereus var mycoides (ATCC 11778) as the test organism, with a level of detectability of approximately 0.05 micrograms/ml. The concentration-time curve of doxycycline in the serum after intramuscular injection of 20 mg/kg bodyweight of the long-acting formulation before and after experimental infection was adequately described by a one-compartment open model. The maximum serum concentrations (Cmax) of doxycycline were lower in pneumonic goats than in healthy goats (3.87 +/- 0.52 and 5.56 +/- 0.213 micrograms/ml, respectively), suggesting an increased distribution volume in the peripheral compartment. The mean +/- SEM absorption rate (ka) before infection (1.13 +/- 0.02 h-1) was smaller than the after infection (8.23 +/- 3.81 h-1), but the difference was not significant. The apparent elimination half-life (t 1/2 beta) (24.51 +/- 0.02 h) after infection was significantly increased (p < 0.05), while the corresponding rate constant (beta) was decreased (p < 0.01). The absorption half-life (t 1/2(alpha)) (0.137 +/- 0.03 h) was significantly decreased (p < 0.01) after infection. The distribution volume (Vd(beta)) was significantly increased after infection (p < 0.05). It is concluded that, although experimental infection had an effect on the disposition kinetics of doxycycline, this was not sufficiently pronounced to require alteration of the dosage during disease.

Africa, Eastern↗

Enhanced therapeutic angiogenesis by cotransfection of prostacyclin synthase gene or optimization of intramuscular injection of naked plasmid DNA.

BACKGROUND: Although clinical trials of therapeutic angiogenesis by angiogenic growth factors with intramuscular injection of naked plasmid DNA have been successful, there are still unresolved problems such as low transfection efficiency. From this viewpoint, we performed the following modifications: (1) combination with vasodilation using prostacyclin and (2) changing the agents or volume of naked plasmid DNA in vivo. METHODS AND RESULTS: First, we examined cotransfection of the VEGF gene with the prostacyclin synthase gene in a mouse hindlimb ischemia model. Cotransfection of the VEGF gene with the prostacyclin synthase gene resulted in a further increase in blood flow and capillary density compared with single VEGF gene. Similar results were obtained with other angiogenic growth factors, such as hepatocyte growth factor (HGF). Alternatively, we changed the injection volume of the solution of plasmid DNA. Luciferase activity was increased in a volume-dependent manner. An increase in injection volume at 1 site rather than separate injections at multiple sites resulted in high transfection efficiency, which suggests that transfection of naked plasmid DNA is mediated by pressure. Interestingly, treatment with hyperbaric oxygen increased the transfection efficiency. Finally, we also examined the effects of different solutions. Saline and PBS, but not water, achieved high transfection efficiency. In addition, sucrose solution but not glucose solution resulted in high luciferase activity. CONCLUSIONS: Overall, angiogenesis might be enhanced by cotransfection of prostacyclin synthase gene or an increase in injection volume and osmotic pressure. These data provide important information for the clinical application of therapeutic angiogenesis to treat peripheral arterial disease.

Animals↗

Tissue damage caused by the intramuscular injection of long-acting penicillin.

In order to elucidate whether tissue damage produced on occasion by intramuscular injection of long-acting penicillin is due to accidental intra-arterial injection or vasospasm, two types of experiments were carried out in rabbits. In the first set of experiments, six New Zealand White rabbits were given intra-arterial injections of 0.4 mL of a mixture containing 300,000 U of penicillin G benzathine and 300,000 units of penicillin procaine per milliliter (Bicillin C-R) into the left femoral artery and 0.4 mL of normal saline into the right femoral artery as autocontrol. In a second set of experiments, 0.4 mL of the same penicillin preparation was injected in the space surrounding the left femoral artery in five New Zealand rabbits, and 0.4 mL of normal saline was injected in a similar fashion around the right femoral artery as control. The legs of the rabbits that received the intra-arterial injection of penicillin invariably developed ischemic manifestations. None of the legs of rabbits given intra-arterial injections of normal saline had pathologic manifestations. None of the rabbits that received the periarterial penicillin preparation or normal saline developed abnormalities. These results strongly suggest that the tissue damage produced by penicillin is secondary to the intra-arterial administration of the drug.

Animals↗

Efficient gene transfer into zebrafish skeletal muscle by intramuscular injection of plasmid DNA.

The ability of zebrafish skeletal muscles to internalize and express plasmid DNA was demonstrated using pCMVCAT1, a chloramphenicol acetyltransferase (CAT) construct driven by the human cytomegalovirus immediate early (CMV-IE) promoter. We found that CAT activity was correlated to the amount of plasmid DNA injected, with maximal expression at 5 micrograms of pCMVCAT1. CAT activity was also shown to increase steadily over the first seven days after injection, with high levels of CAT expression persisting up to one year. Intramuscular injection of CAT constructs driven by other viral promoters also resulted in high levels of CAT activity. Histochemical localization using a CMV beta-galactosidase construct confirmed that only myofibers at the site of injection expressed beta-galactosidase enzyme. The persistence and strong expression of injected plasmid constructs suggest that zebrafish may be a simple and readily accessible system for direct muscle injection studies.

Animals↗

No influence of tumor growth by intramuscular injection of hepatocyte growth factor plasmid DNA: safety evaluation of therapeutic angiogenesis gene therapy in mice.

Recently, a novel therapeutic treatment for ischemic diseases using angiogenic growth factors to augment collateral artery development has been proposed. As intramuscular injection of naked human hepatocyte growth factor (HGF) plasmid DNA induced therapeutic angiogenesis in several animal test subjects, we have started a clinical trial to treat peripheral arterial disease. However, one might assume that over-expression of angiogenic growth factors could enhance tumor growth. To resolve this issue, we examined the over-expression of HGF in tumor bearing mice. Tumors on their backs were prepared with an intradermal inoculation of A431, human epidermoid cancer cells expressing c-Met. These mice were intramuscularly injected with human HGF plasmid or control plasmid into the femoral muscle. Human HGF concentration was increased only in the femoral muscle, but not in blood. Although recombinant HGF stimulated the growth of A431 cells in vitro, temporally and locally HGF elevation in hindlimb had no effect on tumor growth in mice.

Animals↗