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Pharmacokinetics of heparin after a single intravenous or subcutaneous injection.

In 2 groups of 4 probands the pharmacokinetics of heparin were investigated by a physiologic method (factor Xa inhibition) and an isotope method (35S-heparin) following a single intravenous injection of 5000 IU heparin and a single subcutaneous injection of 10000 IU heparin respectively. Following intravenous administration the anticoagulant effect and radioactivity fall exponentially. The half-life is about 50 min and the distribution volume 3000 ml (factor Xa inhibition) and 3800 ml (radioactivity). With subcutaneous injection peak concentrations above 0.2 IR heparin/ml were measured by both methods 2-4 h after administration; 9 h after administration, no further factor Xa inhibition was detectable in 2 probands. In the light of these and previously published results, some practical aspects of the conduct of therapy and prophylaxis of thromboembolism with heparin are discussed.

Antithrombin III↗

[Factors that enable the patients to live their life till death at home by controlling cancer-pains with continuous subcutaneous injection of opioids-case reports of 3 patients with a terminal cancer].

Recently, it is gradually getting easier to change a life-style of the patients with cancer-pains from the conventional hospitalized way to the home healthcare system, because of the progress in technique of reducing pains and symptoms and because of prevalence of visiting nurse system. Home healthcare system or hospice is aimed at the improvement of the quality of life (QOL) of the patients. We had 3 patients who died at home after home healthcare service and whose cancer-pains were well controlled till their death at home by continuous subcutaneous injections of opioids (painkiller) when these patients could not take oral medications any more. Therefore, in order to determine the factors that enable the patients to live the terminal stage of their life at home until death by controlling their cancer-pain with continuous subcutaneous injections of opioid, we examined 3 patients who died of cancer at home under a good pain control. The subjects of the present study were 3 patients, who initially had oral or rectal medication of opioid for their pain control, eventually switched to subcutaneous injection of opioid and then died at home under a good pain control between April 1998 and December 2000. We collected all the information through nursing diaries, regarding painkiller care, and interaction of the patients, their family members and other people, and discussed the factors which enabled to maintain a good pain control in these patients at home by continuous subcutaneous injection of painkiller (opioid). As a result, the following 7 items were notified as the factors common in these 3 patients. 1) The patients themselves understood the diagnosis of their diseases and symptoms and could openly discuss the issues such as "how the patient and his/her family would like to live his/her life from now on" among family members, and also between family and medical associates. 2). The patients received detailed explanation of continuous subcutaneous injection at the time of admission to the hospital and chose to receive the continuous subcutaneous injection with their own will. 3) The patients had no other painful symptoms except cancer pains or had them well controlled if they had any, and had much stronger desire to live their life at home than above all. The family member agreed with the patients and respected their choice. 4) The family members had enough nursing capability, so they could properly handle medications and medical equipment as well as they could take care of the patients. 5) Both primary care physicians and visiting nurses had enough knowledge of home healthcare service for painkiller, and were able to frequently interact with the patients and their family in order to reduce their pains. 6) Visiting nurses supported the family by 24 hr-system and assisted the family in nursing the patients at home without worry. 7) Pharmacists also participated in the home healthcare system, thus, they could smoothly provide and manage opioids without any trouble.

Aged↗

Transport of colloidal particles in lymphatics and vasculature after subcutaneous injection.

This study was designed to determine the transport of subcutaneously injected viral-size colloid particles into the lymph and the vascular system in the hind leg of the dog. Transport of two colloid particles, with average size approximately 1 and 0.41 microm, respectively, and with and without leg rotation, was tested. Leg rotation serves to enhance the lymph flow rates. The right femoral vein, lymph vessel, and left femoral artery were cannulated while the animal was under anesthesia, and samples were collected at regular intervals after subcutaneous injection of the particles at the right knee level. The number of particles in the samples were counted under fluorescence microscopy by using a hemocytometer. With and without leg rotation, both particle sets were rapidly taken up into the venous blood and into the lymph fluid. The number of particles carried away from the injection site within the first 5 min was <5% of the injected pool. Particles were also seen in arterial blood samples; this suggests reflow and a prolonged residence time in the blood. These results show that particles the size of viruses are rapidly taken up into the lymphatics and blood vessels after subcutaneous deposition.

Animals↗

The absorption of subcutaneously injected short-acting soluble insulin: influence of injection technique and concentration.

The effect of injection technique on the absorption of subcutaneously injected short-acting insulin [125I-labeled Actrapid (MC), Novo, Copenhagen, Denmark] was investigated in insulin-dependent diabetic patients. In one side of the abdomen insulin was given with a fixed standard technique. In the other side of the abdomen the temperature of the injected insulin, the depth of injection, and the duration of injection were varied. Furthermore, we compared the absorption of U40 and U100 insulin by giving either 8 U of the two insulins or 0.1 ml of both insulins simultaneously to the patients in either side of the abdomen. With regard to the injection technique the only significant finding was a faster absorption rate with deep (12 mm) than with superficial (3 mm) injection. The absorption of U100 insulin was significantly slower than of U40 insulin, when given in the same amount (8 U) as well as in the same volume (0.1 ml).

Absorption↗

Immunization of mice against Leishmania donovani by subcutaneous injections of dead promastigotes.

Mice immunized by a series of intravenous, intraperitoneal or subcutaneous injections of formalin-killed Leishmania donovani promastigotes with glucan, a beta 1, 3 polyglucose, exhibited a significant degree of resistance against subsequent infection with viable promastigotes. Intramuscular immunization was not effective. Immunization via subcutaneous injections of dead promastigotes simultaneously with glucan elicited protective resistance, positive skin test responsiveness before and after challenge and increased antipromastigote antibody levels. Injections of glucan alone induced a lesser degree of resistance against infection without significant skin test or humoral responsiveness. Injections of dead promastigotes alone elicited increased antibody levels but no skin test responsiveness or resistance against infection.

Adjuvants, Immunologic↗

The effects of subcutaneous injections of glucocorticoids on amoeboid microglia in postnatal rats.

Subcutaneous injections of glucocorticoids into postnatal rats resulted in a drastic reduction in the number of amoeboid microglial cells in the corpus callosum as shown by their labelling with the monoclonal antibodies of the OX-series, ED1, lectin and rhodamine isothiocynate (RhIc). In rats receiving 2 or 3 injections of glucocorticoids and killed at the age of 4 or 7 days, between 40 to 60% of the callosal amoeboid microglial cells were depleted when compared with the corresponding control animals. The cells that survived the glucocorticoid treatments became ramified, while those in the controls of the same age group remained round or amoeboidic. In rats killed at 2 or 3 weeks of age, the microglia became extremely ramified with a concomitant diminution in their immunostaining, particularly in the glucocorticoid-injected rats. In rats receiving glucocorticoid injections along with RhIc, the RhIc-laden amoeboid microglia appeared round and amoeboidic and were intensely stained with OX-42, suggesting their activation and upregulation of complement type 3 receptors when compared with rats receiving only glucocorticoids. Compared with the control, cellular proliferation continued in rats given glucocorticoid injection as indicated by the occurrence of many bromodeoxyuridine-labelled cells in the corpus callosum at the age of 6 days. Ultrastructural studies confirmed the presence of mitotic cells identified as amoeboid microglia because of their labelling with isolectin. A striking ultrastructural feature in glucocorticoids-injected rats was the wide occurrence of amoeboid microglial cells that had ingested a variable number of lectin-labelled cells. It is concluded from this study that the drastic reduction of amoeboid microglia after glucocorticoid injections can be attributed to the suppression of their precursor cells, monocytes. Another possible explanation is the acceleration of their degeneration process, probably greatly enhanced by glucocorticoids; the degenerating amoeboid microglia were readily eliminated by the surviving amoeboid microglial cells through endocytosis. Glucocorticoids also accelerated the maturation process of the persisting amoeboid microglia to become ramified in form.

Animals↗

Enhanced bioavailability of subcutaneously injected insulin by pretreatment with ointment containing protease inhibitors.

The present study was undertaken to develop an ointment preparation containing a protease inhibitor for stabilizing subcutaneously injected insulin. The ointment containing the protease inhibitor, gabexate mesilate or nafamostat mesilate, was applied to the skin around the insulin injection site. Three results were obtained. First, gabexate and nafamostat inhibited insulin degradation in subcutaneous tissue homogenates in vitro. Second, after application of gabexate or nafamostat ointment, an appreciable amount of gabexate or nafamostat appeared in the subcutaneous tissue of rats or hairless mice and their concentrations were comparable to those seen in the in vitro experiment. Third, insulin degradation at the subcutaneous injection site in the rat was depressed after pretreatment with gabexate or nafamostat ointment. Pretreatment with gabexate or nafamostat ointment increased the plasma immunoreactive insulin (IRI) levels and the hypoglycermic effect of insulin in healthy volunteers. These results indicate that gabexate or nafamostat ointments stabilize subcutaneously injected insulin.

Administration, Topical↗

Subareolar subcutaneous injection of blue dye versus peritumoral injection of technetium-labeled human albumin to identify sentinel lymph nodes in breast cancer patients.

Lymphatic mapping in breast cancer patients is a widely used technique for axillary staging, though the optimal technique is not yet established. The purpose of this study was to show that subareolar and subcutaneous injection of blue dye drains to the same sentinel lymph node (SLN) in the axillary basin as does peritumoral injection of technetium (Tc)-labeled albumin. Two injection methods were compared in 154 consecutive patients with newly diagnosed pT1 or pT2 breast cancers (tumor size 5-45 mm). The diagnosis of invasive breast cancer was confirmed by core needle biopsy. Peritumoral injection of 40 to 60 MBq 99Tc-labeled colloidal albumin was performed 18 to 20 hours prior to surgery. In addition, 2 ml of blue dye was injected subcutaneously into the subareolar plexus of the same patients exactly 5 minutes prior to incision and dissection of the SLNs. The blue and hot SLNs were identified by searching for the blue lymphatic vessel and the blue lymph node and by counting the radioactivity with a gamma probe. The correlation between the blue nodes and the hot nodes was examined. Altogether, 154 patients were enrolled in the study. Three patients had bilateral breast cancer, and a total of 157 sentinel lymph node biopsies (SLNBs) were performed. The SLNs could be identified in 155 of the 157 SLNBs (98.7%), and the hot node clearly corresponded to the blue node in 151 of the 155 SLNBs (97.4%). Neither a hot node nor a blue node could be identified in 2 of the 157 SLNBs (1.3%). No concordance between the blue node and the hot node could be achieved in 4 of the 155 SLNBs (2.6%). Injection of blue dye into the subareolar lymphatic plexus shows excellent correlation with peritumoral injection of technetium-labeled albumin concerning the identification of SLNs. Our results support the hypothesis that the lymphatic drainage of the breast parenchyma and the subareolar plexus leads to the same sentinel lymph node. It is a rapid, reliable method for identifying SLNs in breast cancer patients. It is easy to perform, especially in nonpalpable tumors, and it does not disturb surgery by discoloring peritumoral tissue.

Adult↗

Pain assessment of subcutaneous injections.

OBJECTIVE: To compare injection pain after subcutaneous administration of four different solution volumes. DESIGN: Double-blind, randomized, prospective, multiple crossover study. SETTING: Steno Diabetes Center, Gentofte, Denmark. PARTICIPANTS: Eighteen healthy volunteers, 9 women and 9 men, aged 21-30 years. METHODS: The subjects were injected with four different volumes (0.2, 0.5, 1.0, 1.5 mL) of NaCl 0.9%. The study was performed on 2 days with a 1-week washout period between the study days. On each study day the subjects received four injections in each thigh. To evaluate the validity of our pain assessing model the subjects received eight injections of 0.5% mL on one of the study days. Pain assessment was done immediately after each injection using both a 10-cm visual analog scale (VAS) and a six-item verbal rating scale (VRS). RESULTS: A significant difference in pain score on both the VAS (p < 0.05) and the VRS (p < 0.01) was seen between the four injection volumes. The pain was significantly increased with volumes of 1.0 and 1.5 mL. No significant difference in injection pain could be detected between 0.2 and 0.5 mL and between 1.0 and 1.5 mL. No significant period or carryover effect could be detected in the study. A significant correlation between the pain score on the VAS and the pain score on the VRS was found (r = 0.79, p < 0.0001). CONCLUSIONS: The pain of a subcutaneous injection is related to injection volume in the thigh. The results show that increasing the volume from 0.5 to 1.0 mL increases the pain significantly. The findings from this study should be considered when injection preparations for subcutaneous administration are formulated. The volume should generally be less than 1.0 mL if injected into the thigh.

Adult↗

Subcutaneous injections of 2-chlorodeoxyadenosine for symptomatic hairy cell leukemia.

PURPOSE: To evaluate the clinical efficacy and safety of 2-chlorodeoxyadenosine (CdA) when administered by subcutaneous injection to patients with symptomatic hairy cell leukemia (HCL), and to evaluate predictive factors for response. PATIENTS AND METHODS: Seventy-three patients were given CdA as a subcutaneous injection once daily for 7 days. Complete remission (CR) required normalized blood counts and the absence of B-ly 7-positive bone marrow cells by flow cytometry. CdA concentrations in plasma following the first injection were analyzed by high-pressure liquid chromatography. RESULTS: Fifty-nine patients (81%) achieved a durable CR after one (n = 55) or two courses, and 10 had a partial remission (PR). With a median follow-up duration of 20 months, no patient had a clinical relapse. Neutropenic fever that required intravenous antibiotics occurred in 28 patients (38%). No toxicity at injection sites was observed. Incomplete response was predicted by an elevated lymphocyte count and serum beta 2-microglobulin level, and by a high percentage of hairy cells in the bone marrow. Plasma CdA levels were similar to those achieved from intravenous administration. CONCLUSION: Subcutaneous injection of CdA is safe and as effective as continuous infusion without problems associated with the mode of administration. Our schedule simplifies CdA treatment and can be generally recommended.

Adult↗

Multiple subcutaneous injections of somatostatin induce tachyphylaxis of the suppression of plasma insulin, but not glucagon, in the rat.

The time course of pancreatic effects of somatostatin was studied over a period of 2 h in unanesthetized unrestrained rats after administration of the peptide by intravenous infusion and by single and multiple subcutaneous injections. During infusion of 10 and 30 micrograms/kg per min, somatostatin continuously suppressed plasma insulin and plasma glucagon. Plasma glucose was significantly increased at the lower dose, but not affected at the higher dose. Single subcutaneous injections of 0.3 and 3 mg/kg decreased plasma insulin and glucagon dose-dependently for 20-60 min without affecting plasma glucose. Multiple subcutaneous injections of somatostatin (one to four doses of 3 mg/kg, administered at intervals of 30 min) caused an initial decrease of plasma insulin (at 30 min), a rebound-increase at 60 and 90 min, and a final return to control values by 120 min. Plasma glucagon remained continuously suppressed. Plasma glucose increased significantly at 60 and 90 min and tended to return towards control values thereafter. In conclusion, pancreatic B cells - but not A cells - of the rat develop tachyphylaxis to somatostatin within 2 h after multiple subcutaneous injections of the peptide. By this mode of administration, 'selective' suppression of plasma glucagon can be achieved with somatostatin in the rat.

Animals↗

Analysis for loss of heterozygosity (LOH) of p53 allele in tumors derived from p53+/- and CD-1 mice following repeated subcutaneous injections of solutions containing antioxidants.

Genomic DNA was isolated from subcutaneous masses observed in CD-1 and p53+/- heterozygous mice during the course of carcinogenicity studies in the vehicle control groups. These masses resulted after daily subcutaneous injection of an antioxidant vehicle with a pH adjusted to 3-4. The vehicle was 1.0% ascorbic acid plus 0.05% sodium metabisulfite in 0.75% saline in a dosing volume of 10 ml/kg/day. These masses were first palpable after 13 and 37 weeks of dosing among p53+/- and CD-1 mice, respectively. By week 26, the incidence of these masses was 89% and 80% in male and female p53+/- mice, respectively (n = 15 mice/sex) and was 0% in both male and female CD-1 mice (n = 60 mice/sex). These masses originated from panniculus carnosus muscle. Histopathological examination of the p53+/- mouse masses indicated the tumors to be sarcomas of spindle-cell origin. The histopathological examination of the masses in the CD-1 mice revealed fibrosarcomas. Five mice/sex/strain were randomly selected from a pool of mice that developed these masses in the course of the two studies. Frozen tissues from these masses were used to examine the DNA for loss of the functional p53 allele in the p53+/- mice (i.e., loss of heterozygosity, or LOH) or for loss of one of the alleles in the wild type (p53+/+) CD-1 mice by the polymerase chain reaction (PCR) technique. Loss of the functional allele was observed only in the tumor from one p53+/- male mouse. These results support a nongenotoxic mechanism for these injection site masses.

Alleles↗

Radionuclide venography of lower limbs by subcutaneous injection: a clinical evaluation.

SC-RNV, radionuclide venography by subcutaneous injection of Tc-99m pertechnetate at acupuncture points K-3, a new alternative of lower limb venography, was recently developed in our clinical laboratory. In some of the previous studies, we have proved its superiority to radionuclide venography by intravenous injection. The current investigation was conducted to understand the reliability of SC-RNV in the diagnosis of deep vein thrombosis (DVT). Fifty-seven cases with lower leg edema, from Nov., 1989 through Oct., 1990, received both SC-RNV and duplex US for causative evaluation. As a result of duplex US, 26 were considered normal (non-DVT), 19 were classified as unilateral DVT, and 12 as bilateral DVT. In nineteen cases (61%, 19/31) with DVT also a XCT and/or a CV (contrast venography) was taken, that showed compatible results. All of the non-DVT had a normal pattern of SC-RNV, all of the unilateral DVT had unilateral impairment of deep vein drainage in SC-RNV, and all of the bilateral DVT had impaired deep venous drainage bilaterally in SC-RNV. It is therefore concluded that SC-RNV is one of the best choices among available non-invasive lower-limb venographic methods.

Acupuncture Points↗

[Secretion of radioactively labeled amino acids into the digestive tract. 2. 14C labeling and amount of 14C leucine in the intestinal contents after subcutaneous injection of 14C leucine in rats].

Experimental rats received a subcutaneous injection of 14C of varying activity. The rats were then killed in groups within a period of from 2 mins to 30 mins after the injection. A certain amount of 14C activity was detected in the intestinal contents as early as 2 mins after the injection, both as free 14C leucine and in the TCE soluble portion of the intestinal contents (TCE=trichloroacetic acid). A comparison of the degree of labelling in the TCE soluble and the TCE precipitable fractions of the intestinal contents showed that the most likely way for free 14C leucine to get into the lumen of the intestine is via the pancreatic juice while that for protein-bound 14C leucine is through the proteins in the pancreatic gland. The degree of labelling in both fractions decreased very steeply from the first to the third third of the intestine. This may be caused either by absorption of the secreted 14C leucine or may be brought about by a delay in food passage through the intestine.

Amino Acids↗

[Surgical management of inflammatory granuloma which developed following subcutaneous injection of leuprorelin acetate: a case report].

A case of granuloma which developed following a subcutaneous injection of leuprorelin acetate is presented. A prominent induration developed at the site of injection with a three-month type preparation, and radical retropubic prostatectomy and simultaneous excision of the granulomas were requested by the patient since they were large, infectious and painful. Our experience may indicate the necessity of conversion from leuprorelin acetate to other drugs (e.g., goserelin acetate, castration) if a local induration, caused by a subcutaneous injection of leuprorelin acetate, has developed to a large granuloma.

Aged↗