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Test Dose (test + dose)
Selected AbstractsStability of Alemtuzumab for Low-Dose Induction and Test DosesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009L. C. Vermeulen No abstract is available for this article. [source] Growth and nutrient uptake of tea under different aluminium concentrationsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 9 2008Ka Fai Fung Abstract BACKGROUND: The uptake of essential nutrients such as P, Fe, K, Ca and Mg is depressed by Al in most plants. This study aimed to investigate the concentrations at which Al could be toxic to C. sinensis. The suppression of nutrient uptake was investigated by comparing growth and nutrient uptake at different Al doses. The quantification of Al in apoplasm, symplasm and cell wall of C. sinensis was also studied. RESULTS: In the absence of Al, the growth of C. sinensis was retarded. Test doses over 1 mM Al were toxic to C. sinensis. At concentrations of 0.25 or 0.5 mM, distinct rhizostimulation was noted, and within a short period (2 weeks), the biomass of these seedlings increased by 44 and 35%, respectively, compared to 0 and 14% in control and 1 mM Al, respectively. In general, at beneficial doses (0.25, 0.5), Al stimulated the uptake of Ca, Mg, K and Mn, whereas the uptake of Fe, Cu and Zn was retarded. Fine roots of the seedlings had the highest levels of Al, compared to leaves, branches and main roots. In the root tips, most of the Al was present in the soluble fractions of the apoplasm and symplasm, and very low levels of Al was bound to the cell walls, which was in good agreement with the observed mobility of Al in C. sinensis. CONCLUSION: The results of the present study support the view that Al plays a nutritive role for C. sinensis. The rhizostimulatory effects of Al on C. sinensis have been explained as a consequence of enhanced nutrient uptake. Copyright © 2008 Society of Chemical Industry [source] Assessment of balsam of Peru patch testsCONTACT DERMATITIS, Issue 6 2000Bolli Bjarnason To find an ideal test technique for as low a dose of balsam of Peru (Myroxylon Pereirae) as possible, subjects testing positive to balsam of Peru are re-tested with a 25% concentration of balsam of Peru in petrolatum. Applications are with Finn Chambers® for 6 different application times, and directly by foils for 96 h (4 days (D)). The goals are to confirm which subjects are positive and which are not, and, using that information, to see if it is possible to distinguish between these 2 groups, tested concomitantly at much lower serial dose levels, in terms of perfusion or by visual assessments. 5 different serial doses are applied with strips for 3,96 h (4D) and with foils for 96 h (4D). The Finn Chamber® tests allow a distinction between visually positive and negative subjects supported by perfusion assessments. With the foils, a 24× lower serial dose level than with the 25% test substance is sufficient to distinguish between positive and negative subjects in terms of perfusion values. This approach requires readings up to 9 days. With this test, the visual approach yields only 3 of 10 positive subjects. This study demonstrates that a lower test dose is possible with perfusion assessments compared to visual ones. [source] Sensitivity to sulphonylureas in patients with hepatocyte nuclear factor-1, gene mutations: evidence for pharmacogenetics in diabetesDIABETIC MEDICINE, Issue 7 2000E. R. Pearson SUMMARY Introduction Maturity-onset diabetes of the young (MODY) is characterized by autosomal dominantly inherited, early-onset, non-insulin-dependent diabetes. Mutations in the hepatocyte nuclear factor (HNF)-1, gene are the commonest cause of MODY. Individual patients with HNF-1, mutations have been reported as being unusually sensitive to the hypoglycaemic effects of sulphonylurea therapy. We report three patients, attending a single clinic, with HNF-1, mutations that show marked hypersensitivity to sulphonylureas. Case reports In cases 1 and 2 there were marked changes in HbA1c on cessation (4.4% and 5.8%, respectively) and reintroduction (5.0% and 2.6%) of sulphonylureas. Case 3 had severe hypoglycaemic symptoms on the introduction of sulphonylureas despite poor glycaemic control and was shown with a test dose of 2.5 mg glibenclamide to have symptomatic hypoglycaemia (blood glucose 2 mmol/l) after 4 h despite eating. Conclusions HNF-1, MODY diabetic subjects are more sensitive to sulphonylureas than Type 2 diabetic subjects and this is seen in different families, with different mutations and may continue up to 13 years from diagnosis. This is an example of pharmacogenetics, with the underlying aetiological genetic defect altering the pharmacological response to treatment. The present cases suggest that in HNF-1, MODY patients: (i) sulphonylureas can dramatically improve glycaemic control and should be considered as initial treatment for patients with poor glycaemic control on an appropriate diet; (ii) hypoglycaemia may complicate the introduction of sulphonylureas and therefore very low doses of short acting sulphonylureas should be used initially; and (iii) cessation of sulphonylureas should be undertaken cautiously as there may be marked deterioration in glycaemic control. Keywords, genetics, HNF-1,, MODY, pharmacogenetics, sulphonylurea sensitivity [source] Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusersADDICTION, Issue 4 2010Sandra D. Comer ABSTRACT Background Sublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, cross-over study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs). Methods Intravenous heroin users (n = 12) lived in the hospital for 8,9 weeks and were maintained on each of three different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the three buprenorphine maintenance dose conditions. Results Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of ,drug liking' and ,desire to take the drug again' were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient. Conclusions These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, that potential is lower than it is for buprenorphine alone, particularly when participants received higher maintenance doses and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment. [source] MEGX disposition in critically-ill trauma patients: subsequent assessments during the first week following traumaFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2002Federico Pea ABSTRACT The objective of this study was to evaluate MEGX disposition as a surrogate marker in assessing the influence that injury may exert on liver function during the first week after the traumatic event in young vs. elderly patients. The MEGX exposure over time was assessed at 0.25, 0.5, 1, 2, 4 and 6 h after the intravenous administration of a 1 mg/kg lidocaine test dose in 12 young and 7 elderly trauma patients on days1, 4 and 7 after a severe injury (Apache II score > 10). MEGX plasma concentration,time profiles were consistently different on day 1 in the elderly vs. young, consistent with a statistically significant lower rate of both lidocaine clearance and MEGX formation, and with a considerably longer MEGX elimination in the elderly than in the young. This suggests an impairment of liver blood flow as a result of splanchnic vasoconstriction occurring mainly in elderly trauma patients. A significant improvement in MEGX disposition occurred on days 4 and 7 vs. the day of trauma in most elderly, whereas minor changes were observed in the young. Multiple factors may account for these major changes in the elderly: the more severe status, the major sensitivity to the pathophysiologic changes induced by trauma, and also at least partially the ageing processes. Although referring to a limited number of observations, our findings on MEGX disposition suggest that liver function may be affected by the severity of injury, even if the influence of age should not be underestimated in these patients. [source] Testing whether the epidural works: too time consuming?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2010J. LARSSON Background: When using epidural anaesthesia (EDA) for pain relief after major surgery, a failure rate of 10% is common. A crucial step in improving the care of patients with EDA is to define the position of the epidural catheter. The aim of this study was to investigate how much time it takes to determine whether the block is sufficient by assessing the extent of loss of cold sensation before induction of anaesthesia. Methods: One hundred patients listed for abdominal surgery were included in the study. After an epidural catheter had been inserted and an intrathecal or an intravenous position had been made unlikely by the use of a test dose, the patient was given a bolus dose of local anaesthetic plus an opioid in the epidural catheter. The epidural block was tested every 2 min, starting at 5 min and ending at 15 min. When at least four segments were blocked bilaterally, the testing was stopped, the time was noted and the patient was anaesthetised. Results: An epidural block was demonstrated after 5,6 min in 37 patients, after 7,8 min in 43 additional patients and after 9,10 min in 15 patients. In one patient, it took 12 min and in three patients, it took 15 min. In two patients, no epidural block could be demonstrated. Conclusion: Testing an epidural anaesthetic before the induction of anaesthesia takes only 5,10 extra minutes. Knowing whether the catheter is correctly placed means better quality of care, giving the anaesthetist better prerequisites for taking care of the patient post-operatively. [source] Synergistic effects of nicotine on arecoline-induced cytotoxicity in human buccal mucosal fibroblastsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2001Yu-Chao Chang Abstract: Areca quid chewing has been linked to oral submucous fibrosis and oral cancer. Arecoline, a major areca nut alkaloid, is considered to be the most important etiologic factor in the areca nut. In order to elucidate the pathobiological effects of arecoline, cytotoxicity assays, cellular glutathione S-transferase (GST) activity and lipid peroxidation assay were employed to investigate cultured human buccal mucosal fibroblasts. To date, there is a large proportion of areca quid chewers who are also smokers. Furthermore, nicotine, the major product of cigarette smoking, was added to test how it modulated the cytotoxicity of arecoline. At a concentration higher than 50 ,g/ml, arecoline was shown to be cytotoxic to human buccal fibroblasts in a dose-dependent manner by the alamar blue dye colorimetric assay (P<0.05). In addition, arecoline significantly decreased GST activity in a dose-dependent manner (P<0.05). At concentrations of 100 ,g/ml and 400 ,g/ml, arecoline reduced GST activity about 21% and 46%, respectively, during a 24 h incubation period. However, arecoline at any test dose did not increase lipid peroxidation in the present human buccal fibroblast test system. The addition of extracellular nicotine acted synergistically on the arecoline-induced cytotoxicity. Arecoline at a concentration of 50 ,g/ml caused about 30% of cell death over the 24 h incubation period. However, 2.5 mM nicotine enhanced the cytotoxic response and caused about 50% of cell death on 50 ,g/ml arecoline-induced cytotoxicity. Taken together, arecoline may render human buccal mucosal fibroblasts more vulnerable to other reactive agents in cigarettes via GST reduction. The compounds of tobacco products may act synergistically in the pathogenesis of oral mucosal lesions in areca quid chewers. The data presented here may partly explain why patients who combined the habits of areca quid chewing and cigarette smoking are at greater risk of contracting oral cancer. [source] Cervical epidural analgesia via a thoracic approach using nerve-stimulation guidance in adult patients undergoing total shoulder replacement surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2007B. C. H. Tsui Background:, Continuous cervical epidural anesthesia can provide excellent peri- and post-operative analgesia, although several factors prevent its widespread use. Advancing catheters from thoracic levels to the cervical region may circumvent these barriers, provided they are accurately positioned. We hypothesize that guiding catheters from thoracic to cervical regions using low-current epidural stimulation will have a high success rate and enable excellent analgesia in adults undergoing total shoulder arthroplasty. Methods:, After Institutional Review Board approval, adult patients were studied consecutively. A 17-G Tuohy needle was inserted into the thoracic epidural space using a right paramedian approach with loss of resistance. A 20-G styletted epidural catheter, with an attached nerve stimulator, was primed with saline and a 1,10 mA current was applied as it advanced in a cephalad direction towards the cervical spine. Muscle twitch responses were observed and post-operative X-ray confirmed final placement. After a test dose, an infusion (2,8 ml/h) of ropivacaine 2 mg/ml and morphine 0.05 mg/ml (or equivalent) was initiated. Verbal analog pain scale scores were collected over 72 h. Results:, Cervical epidural anesthesia was performed on 10 patients. Average current required to elicit a motor response was 4.8 ± 2.0mA. Post-operative X-ray of catheter positions confirmed all catheter tips reached the desired region (C4,7). The technical success rate for catheter placement was 100% and excellent pain control was achieved. Catheters were positioned two to the left, four to the right and four to the midline. Conclusion:, This epidural technique provided highly effective post-operative analgesia in a patient group that traditionally experiences severe post-operative pain and can benefit from early mobilization. [source] Genetic polymorphism of catechol- O -methyltransferase and levodopa pharmacokinetic,pharmacodynamic pattern in patients with Parkinson's disease,MOVEMENT DISORDERS, Issue 6 2005Manuela Contin PharmD Abstract We explored the potential effect of catechol- O -methyltransferase (COMT) genetic polymorphism on the pharmacokinetics and pharmacodynamics of a standard oral dose of levodopa in patients with Parkinson's disease (PD). We prospectively collected blood samples for COMT genotyping from a population of 104 PD patients. Each patient was examined by a standard oral levodopa/benserazide test, based on simultaneous serial measurements of plasma levodopa concentrations, finger-tapping motor effects and dyskinesia ratings, up to 4 hours after dosing. The main levodopa pharmacokinetic outcome variables were time to peak and peak plasma concentration, plasma elimination half-life, and the area under the plasma concentration,time curve. The main outcome levodopa pharmacodynamic variables were latency, duration, and magnitude of the motor effect elicited by the levodopa test dose, the area under the tapping effect,time curve, and the presence of dyskinesias. Nineteen patients (18%) harbored the low-activity homozygous COMT genotype (A/A), 63 patients (61%) carried the intermediate-activity heterozygous COMT genotype (A/G) and 22 patients (21%) had the high-activity homozygous COMT genotype (G/G). The three groups were comparable for vital and clinical characteristics. No significant difference was found in levodopa main pharmacokinetic,pharmacodynamic variables and dyskinesia incidence among the three subgroups of patients. We failed to identify clinically relevant levodopa pharmacokinetic,pharmacodynamic response patterns associated with the COMT polymorphism in PD patients. © 2005 Movement Disorder Society [source] Do results from studies of a simulated epidural test dose improve our ability to detect unintentional epidural vascular puncture in children?PEDIATRIC ANESTHESIA, Issue 9 2005NAVIL F. SETHNA MBChB First page of article [source] Superior palatability of crushed lercanidipine compared with amlodipine among childrenBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2010Gregorio Milani WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Among children, medication palatability is crucial for adherence to therapeutic regimen. , Since there is a lack of appropriate formulations for children prescribed drugs originally designed for adults, parents crush available tablets and administer the medication mixed with solid food or a palatable drink. , Crushed amlodipine, a very popular calcium channel blocker, is bitter and unpalatable. WHAT THIS STUDY ADDS , From the perspective of the child with arterial hypertension, the taste of pulverized lercanidipine is superior to that of pulverized amlodipine. AIMS To compare the taste of equivalent doses of pulverized amlodipine and lercanidipine, two calcium channel blockers, among children with kidney disease. METHODS Each child received a test dose of 1 mg of amlodipine besylate and 2 mg of lercanidipine in a single-blinded fashion. Children indicated their preference by pointing to the appropriate face on a visual analogue scale (VAS) that depicts five degrees of pleasure. RESULTS The VAS palatability score assigned to lercanidipine was higher than that assigned to amlodipine both in nine children 4,7 years of age (P < 0.005) and in 10 children 8,11 years of age (P < 0.005). The preference for lercanidipine was statistically significant in both girls (P < 0.02) and boys (P < 0.001) and in both children initially presented amlodipine (P < 0.005) and children initially presented lercanidipine (P < 0.005). CONCLUSIONS There is a lack of appropriate formulations for children prescribed drugs originally designed for adults, such as calcium channel blockers. Parents therefore crush available tablets and administer the medication mixed with solid food or a palatable drink. From the perspective of the child, the taste of pulverized lercanidipine is superior to that of pulverized amlodipine. [source] The effects of ritonavir and lopinavir/ritonavir on the pharmacokinetics of a novel CCR5 antagonist, aplaviroc, in healthy subjectsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2006Kimberly K. Adkison Aims This study assessed the effects of the CYP3A inhibitors lopinavir/ritonavir (LPV/r) on the steady-state pharmacokinetics (PK) of aplaviroc (APL), a CYP3A4 substrate, in healthy subjects. Methods In Part 1, APL PK was determined in eight subjects who received a single oral 50-mg APL test dose with/without a single dose of 100 mg ritonavir (RTV). Part 2 was conducted as an open-label, single-sequence, three-period repeat dose study in a cohort of 24 subjects. Subjects received APL 400 mg every 12 h (b.i.d.) for 7 days (Period 1), LPV/r 400/100 mg b.i.d. for 14 days (Period 2) and APL 400 mg +,LPV/r 400/100 mg b.i.d. for 7 days (Period 3). All doses were administered with a moderate fat meal. PK sampling occurred on day 7 of Periods 1 and 3 and day 14 of Period 2. Results In Part 1, a single RTV dose increased the APL AUC0,, by 2.1-fold [90% confidence interval (CI) 1.9, 2.4]. Repeat dose coadministration of APL with LPV/r increased APL exposures to a greater extent with the geometric least squares mean ratios (90% CI) being 7.7 (6.4, 9.3), 6.2 (4.8, 8.1) and 7.1 (5.6, 9.0) for the APL AUC, Cmax, and Cmin, respectively. No change in LPV AUC or Cmax and a small increase in RTV AUC and Cmax (28% and 32%) were observed. The combination of APL and LPV/r was well tolerated and adverse events were mild in severity with self-limiting gastrointestinal complaints most commonly reported. Conclusions Coadministration of APL and LPV/r was well tolerated and resulted in significantly increased APL plasma concentrations. [source] An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczemaBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2007S.C. Weatherhead Summary Background, Treatment options for moderate-to-severe atopic eczema are limited. Although methotrexate (MTX) is a widely used and effective treatment for psoriasis, there have been no previous prospective trials of its use in refractory atopic eczema, despite a few small, retrospective reports suggesting that it is a well-tolerated and effective treatment. Objectives, We have assessed the safety and efficacy of oral MTX in 12 adults with moderate-to-severe atopic eczema in an open-label, dose-ranging, prospective trial using objective outcome measures. Methods, All patients had previously received other second-line therapies and had disease only partially responsive to potent topical steroids and emollients. During the 24-week MTX treatment period, unrestricted use of standard topical therapy was permitted. We used an incremental MTX dose regime, starting at 10 mg per week (following a 5-mg test dose) and increasing by 2·5 mg weekly until response was achieved or treatment was limited by toxicity. Disease activity [six area six sign atopic dermatitis (SASSAD) score] was assessed every 4 weeks during treatment and 12 weeks after stopping MTX. The primary endpoint was 24-week change in disease activity. Results, On average, disease activity improved by 52% from baseline (95% confidence interval 45,60%). There were significant improvements in quality of life, body surface area affected and loss of sleep and itch scores. Global response was rated as ,marked improvement' in five of 12 and six of 12 patients, by investigators and patients, respectively. In all patients, the majority of improvement in disease activity was seen by week 12, and, interestingly, patients who had not responded well over this period despite reaching a dose of 15 mg weekly failed to improve with further dose escalation. Only one patient withdrew due to minor adverse effects. MTX was well tolerated by the remaining 11 patients, all of whom completed treatment, achieving a median dose of 15 mg weekly. Importantly, eight of nine patients had a persistent improvement 12 weeks after stopping MTX, with mean disease activity remaining 34% below baseline. Conclusions, We have shown that MTX is an effective, well-tolerated treatment for moderate-to-severe atopic eczema, and response appears to compare favourably with other second-line therapies. A randomized, controlled trial is now warranted. [source] Comparison of effects and plasma concentrations of opioids between elderly and middle-aged patients after cardiac surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2009A. PESONEN Background: In elderly patients, opioids may cause prominent postoperative sedation and respiratory depression. We evaluated the influence of age on the effects of opioids and plasma concentrations of fentanyl and oxycodone in cardiac surgery patients. Methods: Thirty (,75 years, gender M9/F21) and 20 (,60 years, gender M20/F0) patients scheduled to undergo cardiac surgery. A standard anesthesia with fentanyl as an opioid was used. Fentanyl plasma concentrations were measured at the end of surgery and 2 h later. After tracheal extubation, when the pain intensity was at least moderate, blood samples for fentanyl and oxycodone plasma concentration measurements were taken. Thereafter, oxycodone hydrochloride 0.05 mg/kg i.v. was administered. After 15 and 45 min, pain intensity, sedation and oxycodone plasma concentration were determined. This test protocol was repeated twice. Results: The elderly had a higher plasma concentration of fentanyl at the end of surgery than younger patients (5.7±2.2 vs. 3.8±1.2 ng/ml, P=0.001). The plasma concentrations of oxycodone were comparable between the groups. The interval between the second and the third oxycodone dose was longer in the elderly patients (P=0.036). Pain intensity on the verbal rating scale was lower at the 45-min assessment point after all three oxycodone test doses (P=0.008) and sedation scores were significantly higher after the third dose in the elderly patients (P=0.035). Conclusions: In elderly patients, the plasma concentration of fentanyl was higher but plasma levels of oxycodone were at a similar level compared with middle-aged patients. However, the elderly patients had less pain and were more sedated after doses of oxycodone. 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