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Comparison of the changes in plasma human growth hormone (HGH) and immuno-reactive glucagon (IRG) after intravenous and subcutaneous injection of glucagon.

Ten healthy male volunteers were studied to compare the effectiveness of intravenous and subcutaneous injections of 1 mg of glucagon on HG secretion. Plasma HGH level rose to a peak of 6 ng/ml or greater 120 minutes after the subcutaneous injection of glucagon (sc glucagon) in all subjects, whereas the intravenous injection of glucagon (iv glucagon) caused comparable increments in plasma HGH in only six out of ten subjects. Furthermore, in comparison to those in sc glucagon the periods required to show maximum responses were less consistent in iv glucagon. Plasma IRG levels reached a peak of 102.4+/-22.6 ng/ml at two minutes following iv glucagon, and a peak of 3.33+/-1.08 ng/ml at 15 minutes following sc glucagon. These fell to initial levels at 60 minutes and at 180 minutes, respectively. There was no definite correlation either between the magnitudes of changes in plasma IRG and HGH levels or between the velocities of decrement in blood sugar and HGH responsiveness. Judging from its simplicity and reproducibility it may be concluded that sc glucagon is more suitable for a clinical provocative test of HGH release than is iv glucagon. In regards to the mechanism of glucagon-induced HGH release, neither glucagon per se nor the fall of blood sugar after hyperglycemia was assumed to play any major role. The sustained elevation of plasma IRG for a certain period might be responsible for the glucagon-induced HGH release.

Adult↗

[Analgesic effects of Emla cream and saccharose solution for subcutaneous injections in preterm newborns: a prospective study of 265 injections].

OBJECTIVE: To compare the analgesic effects of non nutritive pacifier sucking, oral administration of a 30% saccharose solution, local application of Emla and their association for subcutaneous injection of erythropoietin (EPO) in preterm infants. METHODS: Our study was a randomised, prospective study conducted over 5 months. Neonates with a gestational age below 33 weeks of gestation and older than 8 days of life were included if they were treated with EPO (three subcutaneous injections per week during 6 weeks). For each consecutive EPO injection, patients were randomised between four groups of intervention: non nutritive pacifier sucking (T), oral administration of 0.2-0.5 ml of a 30% saccharose solution with non nutritive pacifier sucking (S), local application of Emla with non nutritive pacifier sucking (E), and oral administration of 0.2-0.5 ml of a 30% saccharose solution with local application of Emla and with non nutritive pacifier sucking (S + E). Each child was its own control. Pain was assessed with the Newborn Acute Pain scale (DAN) and with the Neonatal Facial Coding System (NFCS). RESULTS: Thirty-three neonates were included, representing 265 injections. Distribution was: 41 in group T, 71 in group E, 86 in group S and 67 in group E + S. Mean DAN and NFCS scores were statistically different between groups T, E and S. Analgesic effect of saccharose (-1.05) was greater than Emla (-0.56). Used together, effects were adding up without potentialisation. CONCLUSION: This study shows that the association of non nutritive pacifier sucking with oral administration of saccharose and local application of Emla has a better analgesic effect than each of these three interventions alone for subcutaneous injection of EPO.

Administration, Cutaneous↗

Recombinant human interleukin-3 induces extramedullary hematopoiesis at subcutaneous injection sites in cynomolgus monkeys.

Parenteral administration of recombinant hematopoietic growth factors has been sporadically associated with cutaneous complications, including injection site reactions in humans and nonhuman primates. In this study, subcutaneous injection sites were evaluated from 12 cynomolgus monkeys administered a recombinant human interleukin-3 (rhIL-3) at dose levels of 0, 70, or 700 micrograms/kg daily for 18 days. Monkeys administered rhIL-3 developed small (0.5-1-cm-diameter), firm nodules at the subcutaneous injection sites. Histologically, these nodules from 4 of 8 rhIL-3-treated monkeys contained trilineage extramedullary hematopoiesis (EMH) represented by precursors of myeloid, erythroid, and megakaryocytic series cells. The lineage of hematopoietic cells was confirmed by histochemical and immunohistochemical methods. Hematopoietic cells of myeloid and megakaryocytic lineages were more common than erythroid cells. Of myeloid cells, immature eosinophils were more common, which usually formed small sheets or clusters in the panniculus and deep dermis. This report describes, for the first time, the occurrence of cutaneous EMH at the injection sites of recombinant hematopoietic growth factors, which should be differentiated from inflammation. We believe the cutaneous EMH was the exaggerated pharmacologic effect of rhIL-3.

Animals↗

[Subcutaneous injection of metallic mercury. Report of 4 cases].

4 cases of subcutaneous injection of metallic mercury are reported and compared with those recorded by others. Subcutaneous injection always causes local inflammatory reaction and granuloma formation. Systematic mercury absorption is the rule as it is proved by high mercury levels in blood and urine. Nevertheless this absorption is usually too small to be responsible for toxic manifestations. Surgical excision of all accessible contaminated subcutaneous areas should be performed. When residual mercury is roentgenographically detectable regular monitoring of CNS, renal function and urinary and/or blood mercury levels are necessary.

Accidents↗

Decrease of activated lymphocytes four and nine hours after a subcutaneous injection of a Viscum album L. extract in healthy volunteers.

The immunomodulatory substance, VaQuFrF (an aqueous extract of Viscum album L. of the oak tree) is used as an adjuvant and as monotherapy in the treatment of cancer and AIDS. After subcutaneous injection, there is a local inflammatory reaction at the injection site and systemic elevation of activated lymphocytes. The immunomodulatory effect of VaQuFrF in the first 24 h after subcutaneous injection on blood leukocyte and lymphocyte subpopulation was investigated. Because a significant natural circadian variation of these cellular parameters exist, the influence was studied in regard to this. In two groups of healthy volunteers, one group receiving VaQuFrF, the following parameters were measured every 2-3 h over a period of 24 h: leukocytes, band form, segmented and eosinophilic granulocytes, monocytes, total lymphocytes and CD4-, CD8-, CD3/25- and CD8/38-positive lymphocytes in count and percentage. In regard to the natural circadian variation 24 h after injection of VaQuFrF, a statistically significant fall in the absolute numbers and percentage of CD3/ 25- and CD8/38-positive lymphocytes was observed. Also, monocytes in percent and absolute numbers show a transient fall 6-9 h, lymphocytes only in absolute and CD4-positive lymphocytes only in percentage 2 h after injection. The results demonstrate that there is increased extravasation of (activated) lymphocytes and monocytes after subcutaneous injection of 1 mg VaQuFrF.

Adjuvants, Immunologic↗

Crossover trial of analgesic efficacy of glucose and pacifier in very preterm neonates during subcutaneous injections.

OBJECTIVE: Very preterm newborns undergo multiple invasive procedures. Nonpharmacological interventions are valuable alternatives for pain relief during minor procedures in neonates. Oral sucrose analgesia has been widely studied in term and preterm neonates during painful procedures. The analgesic effect of oral glucose in very preterm infants has not yet been reported. The objectives of this study were to assess the analgesic effect of orally administered glucose and to determine the synergetic analgesic effect of glucose and pacifiers during subcutaneous injections in very preterm neonates using a validated behavioral acute pain rating scale. DESIGN: Two crossover trials. SETTING: One neonatal intensive care unit in a community-based general hospital. METHODS: A prospective study was conducted in 40 very preterm neonates. Each infant received 2 treatments in a crossover manner during 2 consecutive subcutaneous injections of erythropoietin. The first trial (25 infants) was intended to compare oral 30% glucose (0.3 mL) versus placebo (0.3 mL of sterile water); the second trial (15 infants) compared oral 30% glucose (0.3 mL) versus oral 30% glucose (0.3 mL) followed by sucking a pacifier. The primary outcome measure was the evaluation of pain induced by a subcutaneous injection of erythropoietin, using Douleur Aiguë Nouveau-né scale (0 no pain, 10 maximum pain). RESULTS: Twenty-four infants completed the study in the first trial and 15 in the second one. Mean (95% confidence interval [CI]) gestational age, birth weight, postnatal age, and weight at inclusion for neonates in the first and second trial were, respectively, 28.1 (95% CI: 27.3-29.0) and 29.1 (95% CI: 27.8-30.4) weeks, 1036 (95% CI: 944-1128) and 995 (95% CI: 848-1141) g, 26.4 (95% CI: 22.4-30.3) and 26 (95% CI: 22.0-29.9) days, and 1234 (95% CI: 1120-1348) and 1209 (95% CI: 1059-1359) g. In the first trial, median (interquartile) pain scores for placebo and 30% glucose, respectively, were 7 (2.5-9.75) and 4.5 (1-6). In the second trial, median (interquartile) pain scores for 30% glucose and for 30% glucose plus pacifier, respectively, were 4 (2-7) and 4 (1-6). CONCLUSIONS: A small dose of 0.3 mL of 30% oral glucose has an analgesic effect in very preterm neonates during subcutaneous injections. This effect is clinically evident because it can be detected by a behavioral pain rating scale. The synergetic analgesic effect of glucose plus sucking a pacifier is less obvious in very preterm neonates as opposed to what other studies have showed in full-term infants.

Administration, Oral↗

[A four year follow-up study of recombinant HB vaccine--comparisons between three doses of subcutaneous injections and additional low dose intradermal injection].

To determine the efficacy of an additional low dose of intradermal injection of recombinant HB vaccine administered to nonresponders in addition to the standard three injections, we investigated the anti-HBs positive rate and titer of anti-HBs after four years among 58 subjects who did not develop antibodies after three doses of subcutaneous injections and who did develop the antibody after an additional low dose intradermal injection (Nonresponders), and compared them with 150 subjects who developed anti-HBs after three doses of subcutaneous injections (Responders). Fifty four subjects who were negative after four years were revaccinated with one or three doses of the subcutaneous injection. Anti-HBs positive rates after four years were 56.0 percent in Responders and 56.9 percent in Nonresponders, showing no differences. Eighty eight percent of 54 subjects who were given one or three doses of the vaccine developed anti-HBs. There were no differences in the antibody rates or titer of the antibody between the one and three doses groups. The decrease in titer of antibody was related to the levels initially having the most marked decrease in the level four years later. From these findings, we concluded that there were no differences of anti-HBs positive rates or antibody titer after four years in Responders and Nonresponders, and that one additional dose of the vaccine may be effective four years after initial administration among both groups.

Adult↗

Lack of lymph node reaction to subcutaneously injected silicone gel: histological and computer aided morphometric study in rats.

The gel of silicone implants may bleed through the elastomeric envelope or may come into contact with the body because of rupture of the implant. We have studied the effects of free silicone gel injected into the subcutaneous space in rats and analysed the morphological features of the axillary and inguinal lymph nodes. Ninety six Wistar rats had 3 cm3 of silicone gel injected into their subcutaneous space and 96 Wistar rats (the control group) had distilled water injected into their subcutaneous space. The animals were killed on days 1,3,7,9,15, 30,60,90,120,180,270, and 365 after the injection. There was no detectable silicone and no damage to the lymph nodes on routine histopathological analysis. Small amounts of silicone that could migrate to lymph nodes could result in hyperplasia. To evaluate this possibility, a morphometric study based on a computer aided system compared the area of lymph node sections between treated and control animals, and showed no difference between treated and control groups. If silicone did migrate, it did not provoke morphological signs or hyperplasia in the lymph nodes.

Animals↗

A new method to reduce pin-prick pain of intra-muscular and subcutaneous injections.

AIM: Although about 10% of the normal population is thought to be needle-phobic, no method to reduce pin-prick pain is currently available for large scale application. We describe a new simple and easy-to-do method to reduce pin-prick pain through the pressure of multiple blunt pins at the injection site. METHODS: Two-hundred and twelve patients were randomly assigned to 2 groups. The treated group (n= 106) received intramuscular and subcutaneous injections with the application of the blunt pins and the control group (n= 106) with a placebo device. Pain was tested with the visual analogue scale on a 0 (no pain)-10 (maximum pain) scale. RESULTS: After intramuscular injections a significant (P< 0.0001) pain reduction in the treated group compared to placebo was observed: 1.90+/-1.27 versus 5.16+/-1.37 (mean pain reduction: 63.2%); 88.5% of the patients in the treated group and 11.4% in placebo group rated the pain as = or < 3. After subcutaneous injections mean reported pain in the treated group compared to placebo was: 0.32+/-0.51 versus 2.61+/-0.77 (mean pain reduction: 87.7%) (P< 0.0001); 95.1% of the patients in the treated group and 9.8% in the placebo rated the pain as = or <1. No side effects were observed. CONCLUSIONS: Multiple blunt pins pressure on the skin, at the time of intramuscular or subcutaneous injection is able to significantly reduce pin-prick pain. The underlying physiological mechanisms are briefly discussed.

Adult↗

Studies on the toxic effect of cadmium in the rat. I. Testicular changes induced by a single subcutaneous injection of cadmium chloride.

Adult male rats of Wistar strain were subcutaneously injected with a single dose of 0.025 mM CdCl2/kg body weight. The autopsies were performed 2 and 12 weeks post cadmium injection. Experimental animals showed a normal gain of body weight while a marked lowering of the testes weight was observed. The lowering of testes weight of cadmium treated rats occured mainly due to the necrosis of seminiferous tubules, volume of which is markedly lower if compared to intact control rats. After 2 weeks of experiment a marked enlargement of the interstitial gland of the testis occured while after 12 weeks the gland is markedly lower if compared to control rats and to rats studied 2 weeks post cadmium injection. Histochemical reactions for lactic, succinic, alpha-glycerophosphate and 3beta-hydroxy steroid dehydrogenases, NADH tetrazolium reductase, acid phosphatase and nonspecific esterases showed for irreversible necrotic changes of seminiferous tubules of cadmium treated rats while the damage to interstitial gland is only temporary.

Animals↗

Potential treatment of fatty liver with 14-day subcutaneous injections of glucagon.

Fatty liver is a major metabolic disease of dairy cows in early lactation that can be treated with 14-d continuous, intravenous infusions of 10 mg/d of glucagon. The objective was to test whether similar effects can be obtained with 14-d subcutaneous 7.5- or 15-mg daily dosages of glucagon beginning at d 8 postpartum. Multiparous Holstein cows (n = 32) were grouped on the basis of their liver triacylglycerol concentration at d 8 postpartum into "normal" (n = 8; triacylglycerol < 1% liver wet wt) and "susceptible" (n = 24; triacylglycerol > 1% liver wet wt) cows. Susceptible cows were assigned randomly to three groups and beginning at d 8 postpartum received 0, 2.5, or 5 mg of glucagon in 60 ml of saline by subcutaneous injections every 8 h for 14 d. Beginning at d 8 postpartum, normal cows received 60 ml of saline by subcutaneous injections every 8 h for 14 d. Both dosages of glucagon increased concentrations of plasma glucose and insulin and decreased concentrations of plasma nonesterfied fatty acids. Glucagon injections of 15 mg/d decreased concentrations of liver triacylglycerol in cows older than 3.5 yr, but not in younger multiparous cows. Our results document that subcutaneous injections of glucagon have the potential to decrease the degree of fatty liver in older dairy cows in early lactation.

Animals↗