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Effects of atropine, injected into a lateral cerebral ventricle of the rabbit, on fevers due to intravenous leucocyte pyrogen and hypothalamic and intraventricular injections of prostaglandin E1.

1. Cholinergic synapses in the hypothalamus may transmit information in those thermoregulatory pathways which function to raise body temperature. The effect of atropine, administered intracranially, on the febrile response to intravenous leucocyte pyrogen or intracranial prostaglandin E1 was therefore examined in conscious rabbits. 2. In rabbits exposed to a thermoneutral environment, micro-injections of PGE1, into the anterior hypothalamus, intraventricular injections of PGE1, and intravenous injection so leucocyte pyrogen all caused fever accompanied by vasoconstriction in the ears and reduced respiratory rate. Intraventricular injection of 200 mug atropine during such fevers attenuated their development. This was due to the activation of heat loss mechanisms through vasodilatation in the ears and an increase in the frequency of respiration. This suggests a similarity in the pattern of neuronal activity evoked by PGE1 and leucocyte pyrogen, at least at the site(s) where atropine directly or indirectly exerted its effect and in the efferent pathways from this site. 3. In rabbits exposed to a cold environment, intraventricular injection of PGE1 caused fever through the activation of shivering accompanied by increased O2 consumption. Intraventricular injection of atropine during the development of fever caused an inhibition of shivering accompanied by increased O2 consumption. Intraventricular injection of atropine during the development of fever caused an inhibition of shievering and a decrease in O2 consumption so that temperature ceased to rise and returned to normal. 4. During fever, reversal by atropine of the increased heat conservation of rabbits in a neutral environment, and of their increased heat production in a cold environment adds further support to the concept that cholinergic synapses provide an important link in central temperature-rasising pathways.

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

Neurological dysfunction after intrathecal injection of dynorphin A (1-13) in the rat. I. Injection procedures modify pharmacological responses.

In rats, the spinal subarachnoid injection of the kappa opioid agonist Dynorphin A (Dyn A)(1-13) and the delta opioid receptor antagonist ICI 174864 produced dose-related flaccid paralysis of hindlimbs and tail that were influenced appreciably by injection procedures. When injected through indwelling intrathecal (i.t.) catheters terminating at L1 to L2, both peptides were significantly more potent producing paralysis 1 day, rather than 10 to 14 days, after i.t. catheterization. Other rats received direct subarachnoid injections of these peptides through 30-gauge needles placed in the L4 to L5 intervertebral space. In naive, uncatheterized and acutely catheterized rats, direct intervertebral injection of these peptides, as well as D-Ala2-Dyn A (1-13) amide (a metabolically stable analog of Dyn A (1-13), produced hindlimb paralysis with potencies comparable to those recorded after injections through acutely implanted catheters. In contrast, chronically catheterized rats showed significantly reduced responsivity to direct intervertebral injections of all three of these peptides. Loss of hindlimb motor function was associated with loss of nociceptive responsiveness. Elevations in tail-flick latencies were only seen with doses of Dyn A (1-13) which produced motor dysfunction, and were not blocked or reversed by high doses of the opioid antagonist naloxone. These results indicate that: 1) indwelling i.t. catheters induce spinal cord alterations which complicate their experimental usefulness, 2) Dyn A (1-13) does not alter responsiveness to thermal nociceptive stimuli through opioid mechanism and 3) Dyn A (1-13) causes parallel disruptions of spinal cord motor and nociceptive function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Same day injections of Tc-99m methoxy isobutyl isonitrile (hexamibi) for myocardial tomographic imaging: comparison between rest-stress and stress-rest injection sequences.

It has been shown that both rest and stress 99mTc-hexamibi myocardial perfusion imaging can be performed on the same day using two different doses injected within few hours (the first one at rest followed by a second at stress). In order to evaluate and compare 2 sequences (rest-stress and stress-rest) of 99mTc-hexamibi injections performed the same day, 18 patients with either abnormal 201Tl myocardial scan or abnormal coronary angiography were studied with 2 99mTc-hexamibi injections protocols. The rest-stress study was performed as follows: 7 mCi 99mTc-hexamibi was injected at rest. Single photon emission computed tomography (SPECT) was performed 60 min later. Immediately after the rest study, patients were injected at peak stress with 25 mCi 99mTc-hexamibi. Tomographic imaging was repeated 1 h later. Patients were submitted to the stress-rest protocol within 3 days. Tomographic imaging was done 1 h after a 7 mCi injection at stress. This study was followed by an injection of 25 mCi 99mTc-hexamibi at rest, a tomographic study was performed 60 min later. Myocardial sections were reconstructed in horizontal long, vertical long, and short axes. Data analysis also included polar map representation. A total of 324 segments were interpreted blind by 3 observers, there was an agreement in 283/324 (87.3%) segments between the 2 protocols. However, 24 segments (7.4%) judged ischemic on rest-stress were called scars on stress-rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Progression of HIV infection in misusers of injected drugs who stop injecting or follow a programme of maintenance treatment with methadone.

OBJECTIVE: To see whether misusers of injected drugs who stop injecting or switch to a programme of maintenance treatment with methadone have a reduced risk of progression of HIV infection when compared with a group of persistent misusers. DESIGN: Observational cohort study in HIV seropositive subjects with a current or past history of misusing injected drugs. SETTING: HIV outpatient clinic at the University Hospital of Zurich, Switzerland. PATIENTS: 297 Current and former parenteral drug misusers (median age 27) with asymptomatic HIV infection. During the observation period 80 subjects adhered to a programme of maintenance treatment with methadone, 124 continued with parenteral drug misuse, and 93 former misusers remained free of illicit drugs. No antiretroviral treatment was given during the study. MAIN OUTCOME MEASURES: Probability of progression of HIV infection from asymptomatic to symptomatic (Centers for Disease Control stage IV) as calculated by life table analysis and compared in the three groups of patients by means of a log rank test, and predictors of disease progression as analysed with a Cox proportional hazards regression model. RESULTS: The 297 patients were followed up for a median of 16 months. The median duration of injecting drug misuse before enrollment was 7.1 years. There were no significant differences among the three groups with respect to CD4+ counts at the beginning of the study (median 0.44 x 10(9)/l). Life table analysis showed a significantly lower probability of progression of HIV disease in both the methadone treated group and former drug misusers than in persistent injecting drug misusers. Multivariate regression analysis showed a relative risk of progression of the disease of 1.78 (95% confidence interval 1.20 to 2.67; p less than 0.01) in persistent injecting drug misusers, 0.48 (0.29 to 0.77; p less than 0.01) in the methadone treated group, and 0.66 (0.41 to 1.06; p = 0.085) in former drug misusers. CONCLUSIONS: Stopping the misuse of injected drugs slows the progression of HIV disease in infected subjects. Drug treatment programmes are effective in secondary prevention of HIV associated morbidity.

Adult

[Percutaneous injection of cisplatin lipiodol suspension (CLS) in rabbit lung, aiming at intratumoral injection therapy for lung cancer].

Cisplatin lipiodol suspension (CLS: cisplatin 20 mg/ml) was percutaneously injected (cisplatin dose, 2, 4 or 6 mg/kg) in normal lungs of 10 rabbits (1.9-2.3 kg) to assess the safety and feasibility of intratumoral injection of CLS for lung cancer. Histological study revealed acute and chronic infiltrates with bronchiolitis and immature fibrosis at the injected lung tissue even at four weeks after injection. Intrathoracic leaks of CLS produced mild and focal fibrinous pleuritis. Intrabronchial leaks of CLS produced peripheral bronchiolitis with regenerative epithelia. However, no noxious parenchymal damage in the lung and surrounding tissues was noted. Neither oil embolism in brain nor renal toxicity was demonstrated. Seven of eight rabbits showed an increase in body weight. Concentration levels of plasma platinum were lower when compared with intravenous injection of cisplatin in the rabbit: highest at 30 minutes and unmeasurable one week after injection. Lipiodol accumulation in mediastinal lymph nodes was demonstrated in two of nine rabbits by X-ray examination, suggesting intralymphatic drainage of CLS. Intratumoral injection of CLS is safe even with CLS leaks in surrounding normal lung tissues and may be a potent therapy for controlling mediastinal lymph nodes metastasized from lung cancer as well as the primary tumor.

Administration, Cutaneous

Grooming induced by intrahypothalamic injection of ACTH in the rat: comparison with grooming induced by intrahypothalamic electrical stimulation and i.c.v. injection of ACTH.

Intracerebroventricular (i.c.v.) injection of adrenocorticotropic hormone (ACTH) elicits grooming in the rat, but the neural organization of this response is still obscure. Electrical stimulation (EHS) in an area around the hypothalamic paraventricular nucleus (PVH) also elicits grooming. This hypothalamic area contains many ACTH-immunoreactive fibres. Injection of ACTH1-24 (0.3 microgram/0.3 microliters) in the same area elicits intense grooming responses in the rat. Latency, intensity and precise patterning of the grooming response are dependent upon the exact site of injection. Comparison of grooming responses elicited by EHS, ACTH injected i.c.v. and ACTH injected in the PVH reveals that these are slightly dissimilar. This may provide clues as to the brain mechanisms involved in the organization of the different components of grooming. EHS does not elicits scratching and even reduces 'spontaneous' scratching. Also, EHS-elicited grooming is characterized by short pauses. The time-course of appearance of yawning differs between ACTH-PVH and ACTH-i.c.v. injections. Excited locomotion elicited only by ACTH-i.c.v. is apparently caused by ACTH-sensitive systems outside the PVH. The results suggest that the ACTH-containing part of the hypothalamus around the PVH is crucially involved in the organization of grooming behaviour. We believe that at this level in the brain, the subroutines of grooming, scratching and yawning are integrated into one skin maintenance behaviour.

Adrenocorticotropic Hormone

[Ultrasound-guided renal cyst puncture and 95% ethanol injection. Part 1: Estimation of ethanol levels in the blood and urine following 95% ethanol injection].

Seventeen solitary renal cysts were punctured with the ultrasound-guided procedure and 26-91% of the cyst volume was replaced with 95% ethanol used as a sclerosing agent of the cyst wall. Ethanol was injected through a 7 F pigtail ureteral catheter, allowed to remain in place for 20 minutes and removed through the catheter. Recovery rate of ethanol was 82.4%. The maximum blood level of ethanol was obtained 30 to 60 minutes after injection, while the maximum urinary excretion rate was observed after 60 to 120 minutes. The maximum blood levels of ethanol ranged from 0.015 to 0.339 mg/ml. There was a positive correlation between injected volume of ethanol and the maximum blood level (r = 0.66) or the total amount of urinary excretion during 12 hours (r = 0.72). Residual ethanol concentrations in the body were calculated from injected volume and recovery rate of ethanol. Only 2.3% of the residual ethanol in the body was excreted in the urine during the first 12 hours after injection. However, urine/blood ratio of ethanol 1 hour after injection was tremendously high with a wide variation between 1.6 and 230.5. Therefore, a large part of the ethanol absorbed from the cyst wall seems to be excreted directly from the kidney, not entering general circulation. From the estimation of the blood and urine levels of ethanol, it is concluded that 95% ethanol can be applied to the renal cyst wall as a sclerosing agent through the percutaneous ultrasound-guided procedure in the case of good recovery of ethanol.

Adult

Discrete-trial control of morphine self-injection behaviour in monkeys: effects of injection dose and trials per session.

Responding for intravenous injections of morphine was studied using a discrete-trials procedure in squirrel monkeys. For one group, each session consisted of 10 trials at an inter-trial interval of 15 min; for the second group, each session consisted of 100 trials at an inter-trial interval of 1.5 min. When different injection doses of morphine (1-1000 mug/kg per injection), including saline as a control procedure, were substituted at random for blocks of five consecutive sessions, the frequency of morphine self-administration was found to be an inverted U-shaped function of the injection dose. This relationship was observed in each group of monkeys, despite a 10-fold difference in the total amount of the drug which was available for self-administration per session when a given injection dose was substituted for both groups. The results show that the injection dose of morphine acted as a primary determinant of response probability, even under circumstances in which trial spacing imposed a significant delay between consecutive opportunities for drug self-administration,

Animals

Comparison of serum calcitonin levels after a 1-minute calcium injection and after pentagastrin injection in the diagnosis of medullary thyroid carcinoma.

A 1-min calcium injection was compared with a pentagastrin injection as provocative measures in stimulating calcitonin secretion in 4 patients with medullary thyroid carcinoma. In all cases the calcium injection resulted in a greater rise in serum calcitonin concentration. The patients tolerated the calcium injection well. However, two patients experienced substernal pressure and dyspnea following the pentagastrin injection. It is concluded that a 1-min calcium injection is a safe, rapid and effective procedure in the diagnosis of medullary thyroid carcinoma.

Calcitonin

Stability of ganciclovir sodium in 5% dextrose injection and in 0.9% sodium chloride injection over 35 days.

The stability of ganciclovir 1 and 5 mg/mL in 5% dextrose injection and in 0.9% sodium chloride injection was studied at 25 degrees C and 5 degrees C over 35 days. Ganciclovir (as the sodium salt) was added to 120 polyvinyl chloride bags containing either 5% dextrose injection or 0.9% sodium chloride injection to attain ganciclovir concentrations of 1 and 5 mg/mL. Thirty bags were prepared for each combination of drug concentration and i.v. solution. Half of the bags in each group were stored at 25 degrees C; the other half were stored at 5 degrees C. Samples withdrawn from all 120 bags immediately after preparation were frozen for later determination of initial concentration. At 7, 14, 21, 28, and 35 days after preparation, approximately 5-mL samples representing each test condition were withdrawn for analysis. The samples were visually examined, tested for pH, and assayed by high-performance liquid chromatography. There was no significant loss of ganciclovir under any of the study conditions over 35 days. All solutions were clear throughout the study period. The pH decreased slightly in both diluents at both ganciclovir concentrations but did not deviate from the manufacturer's range (9-11). Admixtures containing ganciclovir 1 and 5 mg/mL (as the sodium salt) in 5% dextrose injection and 0.9% sodium chloride injection were stable in polyvinyl chloride bags stored at 25 degrees C and 5 degrees C for 35 days.

Chromatography, High Pressure Liquid

Stability of zidovudine in 5% dextrose injection and 0.9% sodium chloride injection.

The stability of zidovudine at a concentration of 4 mg/mL in 5% dextrose injection and 0.9% sodium chloride injection in polyvinyl chloride infusion bags stored at room and refrigerated temperatures for up to eight days was studied. Zidovudine was diluted in 5% dextrose injection and in 0.9% sodium chloride injection to a concentration of 4 mg/mL. Six admixtures were prepared with each diluent; three were stored at room temperature (25 +/- 1 degree C) and three were refrigerated (4 +/- 1 degree C). At 0, 3, 6, 24, 48, 72, and 192 hours, 2-mL aliquots were removed. One milliliter of each aliquot was diluted to a zidovudine concentration of approximately 40 micrograms/mL and assayed in duplicate by a stability-indicating high-performance liquid chromatographic method. Visual inspection was performed at each sampling time for precipitation, turbidity, color change, and gas formation. Sample pH was recorded at 0 and 192 hours. In all admixtures, more than 97% of the initial zidovudine concentration remained throughout the study period. No visual or pH changes were observed. Zidovudine 4 mg/mL in admixtures with 5% dextrose injection or 0.9% sodium chloride injection stored in polyvinyl chloride infusion bags was stable for up to 192 hours (eight days) at room temperature and under refrigeration.

Chromatography, High Pressure Liquid

Percutaneous procedures for the diagnosis and treatment of lower back pain: diskography, facet-joint injection, and epidural injection.

This review discusses the indications, techniques, complications, and results of three percutaneous procedures used to evaluate and treat lower back pain: diskography, facet-joint injection, and epidural injection. Diskography, performed by injection of contrast medium into the nucleus pulposus, is a technique used to determine the cause of lower back pain in patients in whom findings on other imaging studies are normal or conflicting. Injection of steroids and anesthetic into the facet joints of the lumbar spine is useful to diagnose or treat patients with facet syndrome (back pain caused by abnormalities of the facet joints). Injection of steroids and anesthetic agents into the epidural space provides short-term relief, and can sometimes provide permanent relief, of lower back pain.

Anesthesia, Spinal

Absorption kinetics of subcutaneously injected insulin. Evidence for degradation at the injection site.

The absorption of subcutaneously injected insulin was examined by injecting semisynthetic [3H] insulin in anaesthetized pigs and subsequently analysing the tissue excised from the injection site. Contrary to previously accepted views, a significant proportion of insulin was degraded at the injection site. The disappearance of intact [3H] insulin from the injection site followed a monoexponential function with a half-time of 59 min.

Absorption

Anal submucosal injection: a new route for drug administration in pelvic malignancies. IV. Submucosal anal injection in the treatment of cancer of uterine cervix--preliminary study.

Seven patients with advanced cancer of the uterine cervix were treated by anal submucosal injection of methotrexate. Each course consists of five injections, one every 5 days; each injection contains 100 mg of methotrexate. The course was repeated at 3-week intervals and was given on an outpatient basis. Investigations were performed before, during, and after treatment. Methotrexate blood level was measured 4 and 24 hours after administration. Complete response occurred in all seven patients. Relapse occurred in four but could be controlled by further methotrexate administration. Average duration of survival is 46 1/2 months. No side effects were encountered as a result of a low methotrexate serum level that was recorded 4 hours after administration, 0.82 mumol after anal injection compared with 2.8 mumol for the intravenous route. The beneficial effect seems to be the result of the high methotrexate concentration in uterine and tumor tissue. The route adopted by the drug to reach the uterus from the anal submucosa is through the hemorrhoidogenital communicating veins. This preliminary study demonstrates that anal injection of methotrexate is effective in the treatment of advanced cancer. It is safe, well tolerated, and can be used as an outpatient treatment.

Aged