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PubMed1989

Availability of amino acids supplied by constant intravenous infusion of synthetic dipeptides in healthy man.

1. A commercial amino acid solution supplemented with two synthetic dipeptides, L-alanyl-L-glutamine (Ala-Gln) and glycyl-L-tyrosine (Gly-Tyr), or alternatively with isonitrogenous amounts of free alanine and glycine has been continuously infused over 4 h in six apparently healthy volunteers. 2. The infusion of the solutions was not accompanied by any side effects and the volunteers reported no complaints. 3. Infusion of the alanine- and glycine-supplemented control solution resulted in an increase of the concentration of these amino acids, while no appreciable change in free glutamine concentration was observed and free tyrosine revealed a steady decrease throughout the infusion. 4. Infusion of the peptide-supplemented solution resulted in a prompt equimolar liberation of the constituent free amino acids (glutamine, alanine, tyrosine and glycine), approaching steady state after about 30 min infusion, while only trace but stable concentrations of the two dipeptides were measured throughout the infusion. No peptides were detectable in urine. The findings suggest a nearly quantitative extracellular hydrolysis of the infused dipeptides and indicate a subsequent utilization of the liberated free amino acids. 5. The estimated metabolic clearance rates and total body plasma clearances were very similar for the two dipeptides (Ala-Gln 35.9 +/- 9.5 ml min-1 kg-1 and 2.9 +/- 0.9 l/min, respectively; Gly-Tyr 33.7 +/- 9.5 ml min-1 kg-1 and 2.7 +/- 0.9 l/min, respectively); thus there is little difference in the metabolic handling of these dipeptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Intravenous infusion of tridihomo-gamma-linolenoyl-glycerol reduces leukotriene B4 production in the rat and rabbit.

1. We have formulated an infusible emulsion of 10% tridihomo-gamma-linolenoyl-glycerol (94% pure) and investigated the effects of its infusion on leukotriene B4 production. 2. We infused the emulsion into the ear veins of two rabbits in a dose of 0.8g of tridihomo-gamma-linolenoyl-glycerol/kg. Polymorphonuclear leucocytes were obtained from rabbits before the infusion, and 6, 24, 72 and 168 h after. The ionophore-stimulated leukotriene B4 production by polymorphonuclear leucocytes was reduced to about 50% of baseline as early as 6 h after the infusion and remained reduced until 24 h after the infusion. 3. To closely investigate the changes in leukotriene B4 production at 6 h after the infusion, we infused 1.0 g of tridihomo-gamma-linolenoyl-glycerol/kg into the tail veins of eight male Wistar rats. Six hours later, peritoneal macrophages were obtained from four rats for the analysis of ionophore-stimulated leukotriene B4 production. Peritoneal cells and blood samples were also obtained from the remaining rats for fatty acid analysis. Another eight rats were used without prior infusion for baseline determination. 4. The production of leukotriene B4 by macrophages was significantly reduced to 42% of baseline, and the plasma free dihomo-gamma-linolenic acid was markedly increased from 0.26 to 4.82 mol%, in 6 h. 5. We conclude that the infusion of a tridihomo-gamma-linolenoyl-glycerol emulsion is able to decrease leukotriene B4 production and to increase the dihomo-gamma-linolenic acid concentrations in the plasma and peritoneal cells of rats in 6 h.

8,11,14-Eicosatrienoic Acid↗
PubMed2001

The immunomodulatory effects of prolonged intravenous infusion of propofol versus midazolam in critically ill surgical patients.

Both propofol and midazolam are known to inhibit immune function. The aim of this study was to investigate cytokine production in critically ill surgical patients as early markers of immune response to prolonged infusion of propofol and midazolam. The study enrolled 40 elective patients who were to receive long-term sedation for more than 2 days. Patients were randomly allocated to one of two equally sized groups. Central venous blood samples for measurement of interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were drawn prior to the start and after 48 h of infusion. After 48 h, propofol caused significant increases in IL-1beta (24%), IL-6 (23%) and TNF-alpha (4.8 times) levels, while midazolam caused significant decreases in IL-1beta (21%), IL-6 (21%) and TNF-alpha (19%). Both agents caused significant decreases in IL-8 levels (propofol: 30%, midazolam: 48%, p < 0.05). Propofol caused significant decreases in IL-2 levels (68%, p < 0.001) but increases in IFN-gamma (30%, p < 0.05), whereas there was no significant change with midazolam compared with the pre-infusion level. In conclusion, during 48 h of continuous infusion, propofol stimulated, while midazolam suppressed, the production of the pro-inflammatory cytokines IL-1beta, IL-6 and TNF-alpha, and both caused suppression of IL-8 production. Propofol inhibited IL-2 production and stimulated IFN-gamma production, whereas midazolam failed to do so. Therefore, sedative agents may have clinical implications in high-risk and immunocompromised patients.

APACHE↗
PubMed2000

Pharmacokinetics and tolerability of intravenous infusion of adenosine (SUNY4001) in healthy volunteers.

AIMS: To examine the tolerability and disposition of i.v. adenosine (SUNY4001) in healthy male Japanese volunteers. METHODS: SUNY4001 was infused i.v. for 6 min at 0 (placebo), 60, 100, 120 and 140 microg kg-1 min-1 in a dose-escalating manner in 30 healthy subjects. Adenosine and its metabolites were determined in the plasma and urine. RESULTS: Only plasma hypoxanthine was increased from 3 min during until 5-10 min after SUNY4001 infusion at the higher rates without any significant dose-related changes in plasma adenosine, inosine, xanthine or uric acid, or in urinary adenosine and all metabolites compared with the placebo. There was a dose-related increase in the incidence of subjective symptoms such as heat sensation, flushed face, dyspnoea, chest discomfort, etc. Transient and self-subsiding episodes of second-degree atrioventricular block were found in two subjects each at the higher doses. CONCLUSIONS: Adenosine infusion at < or = 140 microg kg-1 min-1 was concluded to be generally well tolerated.

Adenosine↗
PubMed2003

Relevance and complications of intravenous infusion at the emergency unit at Nice university hospital.

OBJECTIVE: Insertion of peripheral venous catheters (PVCs) is current practice within the hospital environment and particularly in the emergency department (ED). This simple yet invasive technique may result in venous thrombosis, infection or mechanical complications. We conducted a prospective study at the Nice University Hospital ED in order to determine the frequency, relevance and complications of peripheral venous cannulation. PATIENTS AND METHODS: Fourteen 24 h periods were surveyed over the months of May and June 2000, during which 2515 patients over 16 years of age attended the unit. Demographic and medical data were recorded for every patient who received a PVC. These patients were followed at 12 h intervals until the catheter was removed. Reasons for PVC, time left in place, and eventual complications were recorded. Justification for PVC was evaluated upon arrival at the ED, upon exiting the ED and in some cases within the hospital ward. RESULTS: Six hundred and thirty of 2515 patients (25%) received a PVC (290 women (46%) and 340 men (54%); meanage 58 years). Indication for the PVC was considered unjustified in 24.8% of cases upon arrival at the ED, and 33.8% upon leaving the ED. Upon admission in a hospital ward after passing through the ED, out of 318 patients, the PVC was left in place for no reason in 63 (20%). Overall, 390 PVCs were followed until the time of their removal. Mean duration of IV infusion was 28 h. Among these 390 patients, 62 (15.9%) developed complications, of which 54 (13.6%) had thrombophlebitis and 9 (2.3%) developed local infection. Mean duration of PVC left in place for patients with complications was 50 h vs 25 h for patients with no complications (P<0.001). CONCLUSION: Insertion of a PVC is common practice especially in EDs. The excessive use of this procedure leads to extra cost and iatrogenic complications. A renewed definition of its indication and raised awareness among hospital staff concerning the risks involved with this standard procedure should result in less use of PVC and fewer complications.

Catheterization, Peripheral↗
PubMed2002

The local vascular tolerance to an intravenous infusion of a concentrated glutamine solution in ICU patients.

BACKGROUND AND AIMS: The beneficial effects of glutamine is well-documented in ICU patients. However, the documentation and control of enteral administration of glutamine is still insufficient. As an adjunct to enteral nutrition, a concentrated dipeptide solution may be given in a central venous line, but administration via a peripheral vein would be preferable. Therefore, we systematically evaluated local vascular tolerance following a concentrated dipeptide infusion in ICU-patients. METHODS: ICU-patients (n=20) were randomized to receive a 20% alanyl-glutamine infusion of 0.5 g/kg or placebo during 4 h in a peripheral vein on 3 consecutive days. Local tolerance was evaluated clinically, by Maddox score, and ultrasonically before the infusion and on days 1, 4 and 8 after the infusion. RESULTS: In the study, 56 out of 60 (93%) planned infusions were administered and 157 out of 168 (93%) clinical evaluations were successfully performed. The ultrasonic evaluation revealed that the utilized veins had a diameter of 2.15+/-0.8 mm (range, 1.0--4.4 mm). There were no signs of thrombophlebitis in any single vein. CONCLUSION: Administration of a glutamine-containing dipeptide concentrate (20%) by peripheral veins is safe in terms of local tolerance, if a strict protocol is adapted for this purpose is used.

Adult↗
PubMed2002

Pharmacokinetic behaviour of antithrombin III following intravenous infusion in healthy volunteers.

Antithrombin III (CAS 52014-67-2) is produced from plasma of healthy donors and is purified from any detectable agent of transmissible infection. This drug is used in therapy by i.v. route to manage acute thrombotic episodes and to treat patients suffering from its deficiency. The present trial was conducted with the aim to evaluate the pharmacokinetics and the safety of a new preparation of antithrombin III, which in the purification procedure has included a nanofiltration step to increase the safety against the transmission of any agent of infection. The trial was conducted in twelve healthy volunteers of either sex. All the ethics procedures were fully respected, namely the approval from Ethics Committee, the notification to the central regulatory authority, the approval of consent form in writing. Volunteers were hospitalized about 36 h before drug treatment. The baseline situation was investigated throughout the day before the treatment (day-1). On day 1, the drug was infused i.v. for 20 min. Twenty blood samples were drawn from each volunteer, in baseline situation, during and after the infusion. Functional antithrombin III, antithrombin III antigen, prothrombin time, partial thromboplastin time were evaluated in all plasma samples. Both functional antithrombin III and antithrombin III antigen produced well defined plasma concentration-time profiles after the infusion, which allowed net values of these two analytes to be obtained subtracting baseline from post-infusion concentrations. Net pharmacokinetic parameters of functional antithrombin III and antithrombin III antigen proved to be almost superimposable. A comparison of data obtained in this trial on healthy volunteers with those previously obtained by other authors on target population demonstrates similar and fully comparable results. The authors conclude that the nanofiltration step neither affects at all the pharmacokinetics/pharmacodynamics nor the safety of the formulation investigated.

Adult↗
PubMed1991

Fibrinolytic therapy of deep vein thrombosis with continuous intravenous infusion of a recombinant tissue plasminogen activator.

Recombinant human rt-PA was administered to 22 patients with deep vein thrombosis at a dosage of 30 to 120 mg/day (0.5 to 1.76 mg/kg body weight/24 hr) over 2 to 10 days. rt-PA induced phlebographically documented substantial recanalization in 18 of 21 patients. The lowest dose of 0.5 mg/kg/24 hr tested here was thrombolytically effective, whereas a dose of 0.95 mg/kg/24 hours and more led to hemorrhagic complications and premature discontinuation of therapy in four of six patients. Blood clotting analysis did not reveal any substantial decrease in fibrinogen concentrations, whereas the euglobulin clot lysis time and thromboelastography demonstrated a systemic fibrinolytic effect. Therapy with rt-PA can thus be considered as an alternative and effective method of therapy in treatment of deep vein thrombosis. The results of this study show that even a dosage of lower than 0.5 mg/kg/24 hr might prove to be effective. Further studies would be required to show whether the fibrin specificity of rt-PA leads to a superiority of this fibrinolytic substance over the conventional thrombolytic agents, streptokinase and urokinase.

Blood Coagulation Tests↗
PubMed1990

Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease.

Enzyme replacement has been under consideration as a therapeutic strategy for patients with Gaucher disease for more than two decades. Previous studies indicated that single injections of purified glucocerebrosidase reduced the amount of storage material in the liver. It was important to determine whether administration of exogenous enzyme on a regular basis would be of clinical benefit. We report here that weekly i.v. infusions of a macrophage-targeted preparation of human placental glucocerebrosidase in a child with type 1 Gaucher disease increased hemoglobin from 6.9 +/- 0.8 g/dl (+/- 1 SD) to 10.2 +/- 0.4 g/dl (+/- 1 SD) over a 20-week period. The platelet count also increased from a pretreatment value of 30,000 +/- 7000/mm3 (+/- 1 SD) to 54,000 +/- 11,000/mm3 (+/- 1 SD). Phagocytic activity in the spleen decreased during the period of enzyme administration, and there was radiographic evidence of skeletal improvement. These observations document objective clinical responses to enzyme supplementation in a patient with a sphingolipid storage disorder.

Bone and Bones↗
PubMed1997

Synthesis and intravenous infusion into the rat of glyceryl bisacetoacetate, 1-acetoacetamido-2, 3-propane diol, and partially reduced glucosyl pentaacetoacetate.

The efficacy of parenteral nutrition could be improved by finding a more effective energy source. Esters of short-chain fatty acids have exhibited some promise as alternatives to glucose. The present study reports on two new esters and one amide, each containing acetoacetate as the organic acid. The three compounds: glyceryl bisacetoacetate, N-2',3'-dihydroxypropyl-3-oxo-butanamide (1-acetoacetamido-2,3-propane diol), and partially reduced glucosyl pentaacetoacetate, were synthesized and then continuously infused into rats for 7 d. The infusion rate provided 50% of the rats' estimated metabolic energy requirements, and rats were fed with a reduced-energy oral diet that provided the remaining 50% of energy plus adequate protein. Rat groups for each compound were: (1) experimental-compound-infused and ad libitum-fed, (2) isoenergetic glucose-infused and pairfed, and (3) saline infused and pair-fed. Body-weight changes, N losses and N retention were measured daily. All rats died from partially reduced glucosyl pentaacetoacetate infusion at 100% and 50% of the intended rate. Rats infused with 1-acetoacetamido-2,3-propane diol failed to gain weight and to increase the plasma ketone-body concentration. Glyceryl bisacetoacetate produced hyperketonaemia, and weight gain and N variables that were similar to those for glucose-infused rats. It was concluded that only glyceryl bisacetoacetate would make a satisfactory parenteral nutrient.

Acetoacetates↗
PubMed1987

Plasma concentrations and toxicity of chloroquine after slow intravenous infusion in patients with falciparum malaria.

Five male patients with acute Plasmodium falciparum or Plasmodium vivax infections were infused with chloroquine diphosphate (15 mg kg-1) over four hours. Further does of chloroquine diphosphate (5 mg kg-1) were given at 12, 24, 36 and 60 hours. Plasma chloroquine concentrations were determined before and four hours after each dose and then daily until discharge. No serious cardiovascular toxicity was observed, and plasma chloroquine concentrations exceeding the putative minimum inhibitory concentration (MIC) of sensitive P. falciparum strains were reached within four hours of starting treatment. Further doses produced plasma concentrations which were sustained above the putative MIC, but showed no rapid increase into the range associated with toxicity.

Adolescent↗
PubMed2004

Therapeutic efficacy and safety of multiple intravenous infusions of infliximab in refractory ankylosing spondylitis patients with axial involvement.

OBJECTIVE: To evaluate the clinical response and safety profile of infliximab in refractory ankylosing spondylitis patients. METHODS: Patients with active ankylosing spondylitis, despite methotrexate therapy, were included in an open-label, single-centre study. Patients were given 3-5 mg/kg infliximab infusions at Weeks 0, 2, 6, and q8 etc up to Week 30, together with methotrexate at the dosage taken prior to study inclusion, and were followed-up for a 34-week period. RESULTS: Nine patients with mean age 43 years and mean disease duration 7 years, diagnosed with pure axial ankylosing spondylitis were included. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), duration of morning stiffness, physician's global assessment of disease activity (PhGADA), visual analogue scale (VAS) pain, enthesis index, occiput-to-wall test, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI) significantly improved by Week 6. No adverse events related with the drug were recorded during the 34-week follow-up period. CONCLUSION: Efficacy results are similar to those previously published. No adverse events were seen during therapy, and antinuclear antibody profiles were negative. The association of methotrexate with infliximab can improve the safety profile.

Adult↗