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1.
ABSTRACTObjective: Hydroxychloroquine (HCQ) has been used for a long time worldwide as a therapy for rheumatoid arthritis (RA). This trial was designed to determine whether HCQ was efficacious and safe in Indian patients with RA. Research design and methods: The trial was a multicentre, placebo controlled, randomized and double-blind study. One hundred and twenty-two patients with RA were enrolled in 3 different centres for the trial (26 males and 96 females in the age group of 18–60 years). Patients were randomized to receive either hydroxychloroquine tablets ( n = 61) two tablets of 200?mg daily or placebo ( n = 61) two tablets daily. After 8 weeks all patients received one tablet of hydroxychloroquine 200?mg daily for 4 weeks. Every patient also received one tablet of Nimesulide 100?mg twice daily. Main outcome measures: Assessment of response at 12 weeks using modified ACR 20 (American College of Rheumatology 20) criteria where Health Assessment Questionnaire (HAQ) was replaced by ARA (American Rheumatology Association) functional class. Results: 40.4% of patients on hydroxychloroquine showed improvement by modified ACR response criteria whereas only 20.7% (? p = 0.02) showed improvement in the placebo group. No significant side effects were observed in any of the patients. There were no ocular toxicities. Conclusions: Hydroxychloroquine was found to be an effective and well-tolerated drug in rheumatoid arthritis in Indian patients. 相似文献
2.
ABSTRACTObjective: Many osteoporosis patients have low 25-hydroxyvitamin D (25OHD) and do not take recommended vitamin D amounts. A single tablet containing both cholecalciferol (vitamin D 3) and alendronate would improve vitamin D status concurrently, with a drug shown to reduce fracture risk. This study assessed the efficacy, safety, and tolerability of a once-weekly tablet containing alendronate 70?mg and cholecalciferol 70 μg (2800 IU) (ALN + D) versus alendronate 70?mg alone (ALN). Methods: This 15‐week, randomized, double-blind, multi-center, active-controlled study was conducted during a season when 25OHD levels are declining, and patients were required to avoid sunlight and vitamin D supplements for the duration of the study. Men (? n = 35) and postmenopausal women ( n = 682) with osteoporosis and 25OHD ≥ 9?ng/mL were randomized to ALN + D (? n = 360) or ALN ( n = 357). Main outcome measures: Serum 25OHD, parathyroid hormone, bone-specific alkaline phosphatase (BSAP), and urinary N‐telopeptide collagen cross-links (NTX). Results: Serum 25OHD declined from 22.2 to 18.6?ng/mL with ALN (adjusted mean change = –3.4;95% confidence interval [CI]: –4.0 to –2.8), and increased from 22.1 to 23.1?ng/mL with ALN + D (adjusted mean change = 1.2; 95% CI: 0.6 to 1.8). At 15 weeks, adjusted mean 25OHD was 26% higher (? p < 0.001, ALN + D versus ALN), the adjusted relative risk (RR) of 25OHD < 15?ng/mL (primary endpoint) was reduced by 64% (incidence 11% vs. 32%; RR = 0.36; 95% CI: 0.27 to 0.48 [? p < 0.001]), and the RR of 25OHD < 9?ng/mL (a secondary endpoint) was reduced by 91% (1% vs. 13%; RR = 0.09; 95% CI: 0.03 to 0.23 [? p < 0.001]). Antiresorptive efficacy was unaltered, as measured by reduction in bone turnover (BSAP and NTX). Conclusion: In osteoporosis patients who avoided sunlight and vitamin D supplements, this once-weekly tablet containing alendronate and cholecalciferol provided equivalent antiresorptive efficacy, reduced the risk of low serum 25OHD, improved vitamin D status over 15 weeks, and was not associated with hypercalcemia, hypercalciuria or other adverse findings, versus alendronate alone. Trial registration: ClinicalTrials.gov identifier: NCT00092066. 相似文献
4.
ObjectiveEnhanced reactivity to substance related cues is a central characteristic of addiction and has been associated with increased activity in motivation, attention, and memory related brain circuits and with a higher probability of relapse. Modafinil was promising in the first clinical trials in cocaine dependence, and was able to reduce craving in addictive disorders. However, its mechanism of action remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study therefore, cue reactivity in cocaine dependent patients was compared to cue reactivity in healthy controls (HCs) under modafinil and placebo conditions. MethodsAn fMRI cue reactivity study, with a double-blind, placebo-controlled cross-over challenge with a single dose of modafinil (200 mg) was employed in 13 treatment seeking cocaine dependent patients and 16 HCs. ResultsIn the placebo condition, watching cocaine-related pictures (versus neutral pictures) resulted in higher brain activation in the medial frontal cortex, anterior cingulate cortex, angular gyrus, left orbitofrontal cortex, and ventral tegmental area (VTA) in the cocaine dependent group compared to HCs. However, in the modafinil condition, no differences in brain activation patterns were found between cocaine dependent patients and HCs. Group interactions revealed decreased activity in the VTA and increased activity in the right ACC and putamen in the modafinil condition relative to the placebo condition in cocaine dependent patients, whereas such changes were not present in healthy controls. Decreases in self-reported craving when watching cocaine-related cues after modafinil administration compared to the placebo condition were associated with modafinil‐induced increases in ACC and putamen activation. ConclusionsEnhanced cue reactivity in the cocaine dependent group compared to healthy controls was found in brain circuitries related to reward, motivation, and autobiographical memory processes. In cocaine dependent patients, these enhanced brain responses were attenuated by modafinil, mainly due to decreases in cue‐ reactivity in reward‐related brain areas (VTA) and increases in cue reactivity in cognitive control areas (ACC). These modafinil‐induced changes in brain activation in response to cocaine-related visual stimuli were associated with diminished self-reported craving. These findings imply that in cocaine dependent patients, modafinil, although mainly known as a cognitive enhancer, acts on both the motivational and the cognitive brain circuitry. 相似文献
6.
BackgroundHerbal combination of Itrifal Saghir (triphala) has been widely used in traditional medicine. And brings health benefits such as antioxidant effect and scavenger of hydroxyl radicals and nitric oxide radicals activity and substantiated in traditional medicine a anti-obesity. Material and methodIn this study we aimed to assess the efficacy of this herbal medicinal on reduction of weight and body mass index (BMI) of simple obese subjects in comparison with placebo. Obese subjects aged between 16 and 60 years were selected for 12-week, double-blind, randomized, placebo-controlled trial using a parallel design. Subjects were randomly assigned to take 5 grams of either the Itrifal Saghir ( n = 31) or placebo ( n = 31), 2 times daily for 12 weeks. Measures of body weight, BMI, waist circumference (WC), hip circumference (HC), were assessed at baseline and once every four weeks during the 12 week treatment period. The safety was evaluated by means of measuring the liver and kidney function. Homeostasis model of insulin resistance (HOMA-IR) was calculated as [fasting insulin (μU/mL) × fasting glucose (mmol/L)/22.5]. ResultsCompared to placebo group, in treatment group the mean difference of effective weight loss was 4.82Kg (CI95% 3.52 - 6.11, ρ < 0.001), the mean of decrease in waist circumference was 4.01 cm (CI 95% 2.13 - 5.90, ρ < 0.001), and the mean decrease in hip circumference was 3. 21 cm (CI 95% 1.96 - 4.45, ρ < 0.001) in treated subjects. No adverse effects or significant changes in liver and kidney function tests were observed in both placebo and treated groups. ConclusionsItrifal Saghir appears to produce a positive effect on weight loss in obese subjects. 相似文献
7.
Background: This comparison of PRAsugrel and clopidogrel in Japanese patients with ischemic STROke (PRASTRO)-I trial investigates the noninferiority of prasugrel to clopidogrel sulfate in the prevention of recurrence of primary events (ischemic stroke, myocardial infarction, and death from other vascular causes), and the long-term safety of prasugrel in Japanese patients with non-cardioembolic stroke. Research design and methods: This was an active-controlled, randomized, double-blind, double-dummy, parallel-group study conducted between July 2011 and March 2016 at multiple centers around Japan. Patients had to meet eligibility criteria before receiving 3.75 mg prasugrel or 75 mg clopidogrel orally once daily for a period of 96–104 weeks. Results: A total of 3747 patients were included in this trial; 1598 in the 3.75 mg prasugrel group and 1551 in the 75 mg clopidogrel group completed the study. During the study period, 287 (15.2%) patients in the prasugrel group and 311 (16.7%) in the clopidogrel group discontinued treatment. Baseline characteristics, safety, and efficacy results are forthcoming and will be published separately. Conclusions: This article presents the study design and rationale for a trial investigating the noninferiority of prasugrel to clopidogrel sulfate with regards to the inhibitory effect on primary events in patients with non-cardioembolic stroke. 相似文献
8.
Purpose: A threeway crossover study with seven healthy male volunteers was conducted to determine the relative bioavailability of phenobarbital after single dose administration of 100 mg of phenobarbital as oral solution in Myvacet 908, and as a suspension, compared with a 100 mg phenobarbital tablet. Materials and methods: At 4week intervals each subject received the solution in Myvacet 908, the suspension and the tablet in randomized order. Blood samples were collected for 48 h after each dose for analysis of phenobarbital. From the individual serum concentrationversustime curves C
maxand T
max were determined and AUC 048 was calculated. Results: All three oral dosage forms of phenobarbital are bioequivalent. No significant diffences in T
maxwere observed. Conclusion: The oral solution in Myvacet 908, and the suspension of phenobarbital proved to be bioequivalent to a tablet. 相似文献
9.
ABSTRACTObjective: This trial evaluated the efficacy and safety of pregabalin dosed twice daily (BID) for relief of neuro-pathic pain associated with postherpetic neuralgia (PHN). Research design and methods: The 13‐week, double-blind, placebo-controlled study randomized 370 patients with PHN to pregabalin (150, 300, or 600?mg/day BID) or placebo. Main outcome measures: Primary efficacy measure was endpoint mean pain score from daily pain diaries. Secondary efficacy measures included endpoint mean sleep-interference score from daily sleep diaries and Patient Global Impression of Change (PGIC). Safety evaluations included adverse events (AEs), physical and neurologic examinations, 12-lead ECG, vital signs, and laboratory testing. Results: Pregabalin provided significant, dose-proportional pain relief at endpoint: difference from placebo in mean pain score, 150?mg/day, –0.88, p = 0.0077; 300?mg/day, –1.07, p = 0.0016; 600?mg/day, –1.79, p = 0.0003. Weekly mean pain scores significantly improved as early as week 1. Sleep interference in all pregabalin groups was also significantly improved at endpoint, compared with placebo (? p < 0.001), beginning at week 1 (? p < 0.01). At study termination, patients in the 150 ( p = 0.02) and 600?mg/day ( p = 0.003) groups were more likely to report global improvement than were those in the placebo group.Most AEs were mild or moderate. Among pregabalin-treated patients, 13.5% withdrew due to AEs, most commonly for dizziness (16 patients, 5.8%), somnolence (8, 2.9%), or ataxia (7, 2.5%). Conclusions: Pregabalin, dosed BID, reduced neuropathic pain associated with PHN and was well tolerated. It also reduced the extent to which pain interfered with sleep. Pregabalin's effects were seen as early as week 1 and were sustained throughout the 13‐week study. 相似文献
10.
Background and PurposeA major obstacle to islet cell transplantation is the early loss of transplanted islets resulting from the instant blood‐mediated inflammation reaction (IBMIR). The activation of complement pathways plays a central role in IBMIR. The aim of this study was to test the inhibitory effect of “painting” human islets with APT070, a membrane‐localizing C3 convertase inhibitor, on inflammation evoked by exposure to human serum in vitro and by transplantation in vivo in a humanized diabetic mouse model. Experimental Approach
In vitro, human islets pre‐incubated with APT070 were exposed to allogeneic whole blood. In vivo, similarly treated islets were transplanted underneath the kidney capsule of streptozotocin‐induced diabetic NOD‐SCID IL2rγ −/− mice that had been reconstituted with human CD34 + stem cells. Complement activation and islet hormone content were assayed using enzyme‐linked immunosorbent assays. Supernatants and sera were assayed for cytokines using cytometric beads array. Morphology of the islets incubated with human serum in vitro and in graft‐bearing kidney were evaluated using immunofluorescence staining. Key ResultsPre‐incubation with APT070 decreased C‐peptide release and iC3b production i n vitro, with diminished deposition of C4d and C5b‐9 in islets embedded in blood clots. In vivo, the APT070‐treated islets maintained intact structure and showed less infiltration of inflammatory cells than untreated islets. The pretreatments also significantly reduced pro‐inflammatory cytokines in supernatants and sera. Conclusions and ImplicationsPre‐treatment of islets with APT070 could reduce intra‐islet inflammation with accompanying preservation of insulin secretion by beta cells. APT070 could be as a potential therapeutic tool in islet transplantation. Abbreviations- CR1
- complement receptor 1
- hu‐NSG
- humanized NSG
- IBMIR
- instant blood‐mediated inflammation reaction
- iC3b
- inactivated C3b
- IEQs
- islet equivalents
- LDH
- lactate dehydrogenase
- NSG
- non‐obese diabetic/severe combined immunodeficiency/interleukin‐2 receptor γ‐chain knockout
- sCR1
- soluble complement receptor 1 (sCR1)
- UCB
- umbilical cord blood
相似文献
11.
ABSTRACTBackground and methods: The efficacy and safety of etoricoxib 60?mg/day in patients with established chronic low back pain (CLBP) were compared with those of diclofenac 150?mg/day in a 4‐week, multicentre, randomized, double-blind, parallel-group trial. Four hundred and forty-six adult patients with CLBP (Quebec Task Force on Spinal Disorders Class 1 or 2) and with worsening pain upon discontinuation of pre-study analgesic medication were enrolled in the study.The study primary efficacy endpoint was change from baseline in Low Back Pain Intensity Scale (LBP‐IS) score over the 4‐week treatment period. Secondary and other efficacy endpoints included: changes in Roland and Morris Disability Questionnaire (RMDQ), Patient Global Assessment of Response to Therapy (PGART) and Low Back Pain Bothersomeness Scale (LBP-BS) scores. Early efficacy was assessed using PGART and LBP‐IS scores 4?h after the first dose on the mornings of Days 1, 2 and 3. The overall safety and tolerability of etoricoxib 60?mg/day during 4 weeks of treatment were also assessed. Results: The least-squares mean time-weighted change from baseline LBP‐IS score over 4 weeks was –32.94?mm (95% CI –36.25, –29.63) for etoricoxib, indicating substantial efficacy in relief of pain. The treatment difference for the primary outcome was 2.51?mm (95% CI –1.50, 6.51), fulfilling the prespecified equivalence criterion of 95% confidence interval wholly within ± 10?mm. Etoricoxib improved all secondary and other efficacy outcomes.There were no statistically significant between-group differences in the proportion of patients with one or more clinical adverse events (AEs) (etoricoxib 35%, diclofenac 39%), or the proportion of patients who discontinued due to AEs (etoricoxib 7%, diclofenac 5%). Conclusions: The results of this study confirm that, for adult patients with CLBP, etoricoxib 60?mg once daily over 4 weeks is effective for relief of pain and improvement of physical function and comparable to high-dose diclofenac 150?mg daily. 相似文献
12.
ABSTRACTObjective: To compare the efficacy and safety of low-dose chlorthalidone + atenolol combination with atenolol and atenolol + amlodipine combination in stage I hypertensive patients uncontrolled on active run-in monotherapy. Methods: Newly diagnosed stage I hypertensive patients were randomized to active run-in monotherapy either with atenolol 25?mg (98/300) or chlorthalidone 6.25?mg (100/300) or amlodipine 2.5?mg (102/300). A total of 282/300 patients (atenolol 92, chlorthalidone 91, amlodipine 99) completed the active run-in phase successfully. Patients uncontrolled on active run-in monotherapy (atenolol 33, chlorthalidone 45, amlodipine 47) received the study treatment, namely atenolol 50?mg alone, chlorthalidone 6.25?mg + atenolol 25?mg and atenolol 25?mg + amlodipine 2.5?mg, respectively. Efficacy of the therapy was evaluated by BP measurement at weeks 12 and 20 post-therapy. Results: Post-active run-in monotherapies, the study treatment groups showed a significant fall in mean SBP and DBP from baseline ( p?<?0.05). The mean fall in SBP and DBP was comparable for study treatments (atenolol 50?mg, atenolol 25?mg + chlorthalidone 6.25?mg and atenolol 25?mg + amlodipine 2.5?mg) ( p = 0.337 for SBP and p = 0.054 for DBP) at week 12 and ( p = 0.744 for SBP and p = 0.855 for DBP) at week 20; also, the percentage of responders was comparable for the three study treatment groups ( p = 0.799) indicating that the low-dose chlorthalidone + atenolol combination is non-inferior to the high-dose atenolol alone and atenolol + amlodipine combination. No serious laboratory/clinical adverse events were reported in this study. Conclusion: Chlorthalidone 6.25?mg in combination with atenolol 25?mg is effective and safe in stage I (JNC 7) essential hypertensive patients. This low dose of chlorthalidone could reduce dose-related concerns over metabolic adverse effects and may lead to wider usage of this proven antihypertensive agent in combination therapy. 相似文献
13.
AimThe hypothesis that postoperative pain would be reduced by using 1 μg/kg/min of ketamine, both intra- and post-operatively, for lumbar microdiscectomy surgery was assessed by measuring morphine consumption. Patient side effects were reported. MethodsForty-five patients undergoing microdiscectomy surgery were randomized under double-blind conditions into three groups: Group1 (G1) received normal saline, Group 2 (G2) ketamine (1 μg/kg/min) intra-operatively and Group 3 (G3) ketamine (1 μg/kg/min) both intra- and post-operatively. Morphine consumption, pain scores, nausea and vomiting, CNS disorders were recorded for 24 h post surgery. This study was conducted by applying the concept of a clinical pharmacist intervention. ResultsThe time for the first analgesia demand dose was significantly shorter ( P < 0.05) in G117 ± 1.7 min than for G2 and G3. In G3 morphine consumption 6, 12, and 24 h after surgery was 3 ± 2.26, 9.2 ± 2.11 and 26.9 ± 2.71 mg. Total morphine consumption was significantly lower for G3 than for G1 or G2 ( P < 0.05). The visual analog scale score (VAS) values were significantly lower in G3 ( P < 0.05) than for the other groups during the first 24 h. The rate of nausea and vomiting was significantly higher in G1 vs G3 ( P < 0.05). No difference in drug induced CNS disturbances was observed among the groups. ConclusionsUsing 1 μg/kg/min of ketamine hydrochloride intra- and post-operatively for microdiscectomy surgery could be an adjunct therapy to reduce postoperative morphine consumption minimizing its side effects.Collaborative clinical pharmacy practice on the basis of pharmacology had an effective role in improving the general outcome of microdiscectomy surgery. 相似文献
14.
Background: Smoking rates among people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS; PLWHA) are at least twice as high as rates in the general population. Consistent with the reciprocal model of pain and smoking, PLWHA with pain who smoke may use smoking as a means of coping with pain, thus presenting a potential barrier to quitting. The aim of this study is to better understand how pain relates to smoking cessation among 474 HIV-positive adults enrolled in a cell phone–delivered smoking cessation trial. Methods: Participants were randomly assigned to usual care (cessation advice and self-help materials) or 11 sessions of cell phone–delivered smoking cessation treatment. Pain, as assessed by the Medical Outcomes Study-HIV Health Survey (MOS-HIV), and point prevalence abstinence were collected at the 3-month treatment end and at 6- and 12-month follow-ups. Self-reported abstinence was biochemically verified by expired carbon monoxide (CO) level of <7 ppm. Results: Using multilevel modeling for binary outcome data, the authors examined the relationship between pain and abstinence, from treatment end through the 12-month follow-up. Consistent with the authors' hypothesis, less pain was associated with greater likelihood of 24-hour (β = .01, t(651) = 2.53, P = .01) and 7-day (β = .01, t(651) = 2.35, P = .02) point prevalence abstinence, controlling for age, gender, baseline pain, nicotine dependence, and treatment group. No pain × treatment group interaction was observed. Conclusions: These results can help us to better identify PLWHA at greater risk for relapse in smoking cessation treatment. Future research may examine the effectiveness of more comprehensive smoking cessation treatment that incorporates aspects of pain management for PLWHA who smoke and have high pain and symptom burden. 相似文献
15.
Investigational New Drugs - Background This was a phase I/IIa study to investigate the tolerability, efficacy and pharmacokinetics (PK)/ pharmacodynamics (PD) of CRLX301, CDP-based nanoparticle... 相似文献
16.
Rationale: (±) 3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is an amphetamine analog and drug of abuse. In animals, MDMA damages
brain serotonin (5-HT) neurons at doses that overlap with those used recreationally by some humans. To date, few functional
sequelae of MDMA-induced 5-HT damage have been identified. Objective: Since serotonin is thought to be involved in cognitive processes, and since previous studies have reported verbal and visual
memory deficits in MDMA users, the present study sought to determine whether other cognitive processes are influenced by previous
exposure to MDMA. Methods: Twenty-two MDMA users who had not used MDMA for at least 3 weeks and 23 control subjects were tested repeatedly with a computerized
cognitive performance assessment battery while participating in a 5-day controlled inpatient study. Cerebrospinal fluid (CSF)
measures of monoamine metabolites were also collected as an index of brain monoaminergic function. Results:MDMA users and controls were found to perform similarly on several cognitive tasks. However, MDMA subjects had significant
performance deficits on a sustained attention task requiring arithmetic calculations, a task requiring complex attention and
incidental learning, a task requiring short term memory and a task of semantic recognition and verbal reasoning. MDMA users
also had significant selective decreases in CSF 5-HIAA. Conclusions: The present CSF data provide further evidence that MDMA is neurotoxic to brain 5-HT neurons in humans, and the behavioral
data suggest that brain 5-HT injury is associated with subtle, but significant, cognitive deficits.
Received: 4 August 1998/Final version: 12 November 1998 相似文献
17.
BACKGROUND AND PURPOSESome large antagonist ligands (ARC239, chlorpromazine, prazosin, spiperone, spiroxatrine) bind to the human α 2A-adrenoceptor with 10- to 100-fold lower affinity than to the α 2B- and α 2C-adrenoceptor subtypes. Previous mutagenesis studies have not explained this subtype selectivity. EXPERIMENTAL APPROACHThe possible involvement of the extracellular amino terminus and transmembrane domain 1 (TM1) in subtype selectivity was elucidated with eight chimaeric receptors: six where TM1 and the N-terminus were exchanged between the α 2-adrenoceptor subtypes and two where only TM1 was exchanged. Receptors were expressed in CHO cells and tested for ligand binding with nine chemically diverse antagonist ligands. For purposes of interpretation, molecular models of the three human α 2-adrenoceptors were constructed based on the β 2-adrenoceptor crystal structure. KEY RESULTSThe affinities of three antagonists (spiperone, spiroxatrine and chlorpromazine) were significantly improved by TM1 substitutions of the α 2A-adrenoceptor, but reciprocal effects were not seen for chimaeric receptors based on α 2B- and α 2C-adrenoceptors. Molecular docking of these ligands suggested that binding occurs in the orthosteric ligand binding pocket. CONCLUSIONS AND IMPLICATIONSTM1 is involved in determining the low affinity of some antagonist ligands at the human α 2A-adrenoceptor. The exact mechanism is not known, but the position of TM1 at a large distance from the binding pocket indicates that TM1 does not participate in specific side-chain interactions with amino acids within the binding pocket of the receptor or with ligands bound therein. Instead, molecular models suggest that TM1 has indirect conformational effects related to the charge distribution or overall shape of the binding pocket. 相似文献
18.
Rationale An increase in the potency of the cannabis cigarettes has been observed over the past three decades. Objectives In this study, we aimed to establish the impact of Δ9-tetrahydrocannabinol (THC) on the rating of subjective effects (intensity and duration of the effects), up to 23 % THC potency (69 mg THC) among recreational users. Methods Recreational users ( N = 24) smoked cannabis cigarettes with four doses of THC (placebo 29, 49 and 69 mg of THC) on four separate test days in a randomized, double-blind, placebo-controlled, crossover study. The participants filled in three different questionnaires measuring subjective effects during the exposure up to 8 h post-smoking. The ‘high’ feeling, heart rate, blood pressure and THC serum concentrations were also regularly recorded during these 8 h. Results THC significantly increased the high feeling, dizziness, dry-mouthed feeling, palpitations, impaired memory and concentration, and ‘down’, ‘sedated’ and ‘anxious’ feelings. In addition, THC significantly decreased alertness, contentment and calmness. A cubic relationship was observed between ‘feeling the drug’ and ‘wanting more’. The THC-induced decrease in ‘feeling stimulated’ and increase in anxiety lasted up to 8 h post-smoking. Sedation at 8 h post-smoking was increased by a factor of 5.7 with the highest THC dose, compared to the placebo. Conclusions This study shows a strong effect of cannabis containing high percentages of THC on the rating of subjective effects. Regular users and forensic toxicologists should be aware that the THC-induced increase in ‘feeling sedated’ continues longer with a 69 mg THC dose than with a 29 mg THC dose. 相似文献
19.
BACKGROUND: Peginterferon alpha-2a and alpha-2b, the two commercially available pegylated interferons, have different pharmacokinetic properties that produce differing abilities to suppress replication of the hepatitis C virus. AIM: To compare the pharmacodynamics of peginterferon alpha-2a and peginterferon alpha-2b in interferon-naive patients with chronic hepatitis C. METHODS: Patients were randomized to receive peginterferon alpha-2a, 180 microg (n = 10) or peginterferon alpha-2b 1.0 microg/kg (n = 12) once weekly. The enzymatic activity of 2'5'-oligoadenylate synthetase and levels of neopterin and beta(2)-microglobulin were measured at baseline and at 24, 48, 120 and 168 h. RESULTS: Oligoadenylate synthetase activity and serum neopterin and beta(2)-microglobulin concentrations did not differ significantly between the two patient groups at any time point, nor was there a significant correlation between the serum area under the concentration-time curve of either peginterferon and the area under the concentration-time curve for 2',5'-oligoadenylate synthetase, neopterin and beta(2)-microglobulin. The area under the concentration-time curves calculated for these three markers did not correlate with body mass index stratified at <25 and >or=25 kg/m(2) for either peginterferon. CONCLUSIONS: Despite pharmacokinetic differences between peginterferon alpha-2a and peginterferon alpha-2b, the pharmacodynamic profiles of the two formulations appear to be comparable. 相似文献
20.
ABSTRACTObjective: Patients with growth hormone deficiency (GHD), both Japanese and Caucasian, have an abnormal body composition with pronounced abdominal obesity. This study aimed to evaluate changes in trunk fat with GH treatment. Design: Double-blind, placebo-controlled study. Patients and measurements: Sixty-one Japanese adult GH deficient patients (mean age 37 years) were randomised to either GH, titrated to 0.012?mg/kg/day, ( n = 30) or placebo ( n = 31) for 24 weeks. Body composition, by dual-energy X-ray absorptiometry (DXA), was evaluated at a central laboratory for trunk fat, total body fat and lean body mass. Serum lipid levels were also determined centrally. Results: At baseline, 26 (42.6%) patients had a body mass index (BMI) ≥ 25 kg/m 2, the threshold for obesity-related complications for Japanese subjects. Median trunk fat mass (FM) was ≥ 9.0 kg for each treatment and gender group, higher than the cut-off for increased age-adjusted risk for cardiovascular complications reported in the normal Japanese population. After 24 weeks of GH treatment, the change in percentage trunk FM was –3.4 ± 0.6%, versus 0.4 ± 0.6% with placebo (? p < 0.001). Change in total body FM was –2.8 ± 0.5% with GH and 0.0 ± 0.5% with placebo, indicating that the decrease in trunk fat was more pronounced than for total body fat. Total and low density lipoprotein (LDL)-cholesterol were both significantly (? p < 0.001) decreased compared with placebo. One patient discontinued due to a subdural haematoma and one had GH dose reduced due to hyperglycaemia. Conclusions: Japanese patients with GHD have abnormal central fat accumulation, which is reduced by GH treatment over 24 weeks. This may reduce cardiovascular risk but the GH dose should be individualised to maintain IGF-I in the normal range. 相似文献
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