Drug Associations (drug + association)

Distribution by Scientific Domains


Selected Abstracts


Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management

CLINICAL TRANSPLANTATION, Issue 2 2003
Richard Kowalski
Abstract:, Each year, 55 000 organ transplants are performed worldwide. Cumulatively, the number of living organ recipients is now estimated to be over 300 000. Most of these transplant recipients will remain on immunosuppressive drugs for the remainder of their lives to prevent rejection episodes. Controlled doses of these drugs are required to prevent over-medication, which may leave the patient susceptible to opportunistic infection and drug toxicity effects, or under-dosing, which may lead to shortened graft survival because of rejection episodes. This paper describes the result of a multicenter study conducted at the Universities of Pittsburgh, Alabama and Maryland to evaluate an in vitro assay (CylexTM Immune Cell Function Assay) for the measurement of global immune response in transplant patients receiving immunosuppressive therapy. The assay uses a whole blood sample to maintain the presence of the drug during incubation. Following overnight incubation of blood with phytohemagglutinin (PHA), CD4 cells are selected using paramagnetic particles coated with a monoclonal antibody to the CD4 epitope. The CD4-positive cells are targeted as major immunosuppressive drugs are designed to specifically inhibit T-cell activation which has been implicated in rejection. The data generated at these three sites were submitted in support of an Food and Drug Association (FDA) application for the use of this assay in the detection of cell-mediated immunity in an immunosuppressed population. The assay was cleared by the FDA on April 2, 2002. This cross-sectional study was designed to establish ranges for reactivity of this bioassay in the assessment of functional immunity for an individual solid organ recipient at any point in time. [source]


Childhood Epilepsy Due to Neurocysticercosis: A Comparative Study

EPILEPSIA, Issue 11 2001
Lisiane S. Ferreira
Summary: ,Purpose: To assess the clinical profile of pediatric patients with epilepsy and neurocysticercosis (NC), and compare them with a group of pediatric patients with benign partial epilepsy to determine clinical differences, response to treatment, and prognosis. Methods: We studied 28 patients (16 girls) with probable or definitive diagnosis of NC and epilepsy and 32 patients (16 girls) with partial benign epilepsy (BE). All patients had normal neurologic examination. We compared NC and BE patients looking for differences in demographics (age at first seizure, gender, family history); clinical presentation (type, frequency, duration, and total number of seizures, duration of epilepsy, status epilepticus, cluster, and postictal deficit); treatment [duration, number of antiepileptic drugs (AEDs), maximal dose, drug association, number of seizure-free patients, time to obtain control and recurrence after medication discontinuation]; complementary examinations (the first and the last EEG). Results: The mean follow-up was 5.4 years for the 28 NC patients and 4.6 years for the 32 BE patients (p = 0.98). We did not find statistical differences between NC and BE in gender, family history, types of seizures, frequency and length of seizures, previous status epilepticus, seizure clustering, and presence of postictal deficits. However, we found that NC compared with BE patients had significant longer AED treatment, more seizures after AED introduction, tried more AEDs and at maximal dose, and in 20%, required polytherapy. The recurrence rate in NC was 54.4% and this was not significantly associated with number of lesions and disease activity seen on CT scans or the presence of EEG abnormalities. Conclusions: NC presents with a mild form of epilepsy in terms of seizure severity; however, it is more challenging in regard to drug management and has a less favorable long-term prognosis in terms of seizure remission. The number of lesions or disease activity seen on computed tomography (CT) as well as EEG abnormalities have no prognostic value in childhood epilepsy due to NC. [source]


Context-dependent behavioural and neuronal sensitization in striatum to MDMA (ecstasy) administration in rats

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2006
Kevin T. Ball
Abstract To investigate the neuronal mechanisms underlying the behavioural alterations that accompany repeated exposure to MDMA (ecstasy), we recorded the activity of >,200 striatal units in response to multiple, intermittent, locomotor-activating doses (5.0 mg/kg) of MDMA. Rats were treated with once-daily injections of either saline or MDMA for 5 days when housed in their home cage, followed by a challenge injection 3,5 days later when housed in a recording chamber. Because contextual drug associations might be particularly important to the expression of behavioural sensitization to chronic MDMA, a separate group of rats received repeated injections of MDMA alternately in the recording chamber or home cage, according to the above timeline. A sensitized locomotor response was observed only in rats that had previously experienced MDMA in the context of the recording chamber, and only on the challenge day. These sensitized animals also showed a decreased basal firing rate in neurons that were subsequently excited by MDMA when compared with the same category of neurons earlier in the treatment regimen. This resulted in a greater percentage increase from the baseline firing rate on the challenge day compared with the first and fifth days of treatment, even though this trend was not evident with an analysis of absolute firing rate. These results strongly support a role for context in the expression of MDMA-induced locomotor sensitization, and implicate striatal involvement in the neurobehavioural changes associated with the repeated use of MDMA. [source]


Practical pharmacovigilance analysis strategies

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2003
A. Lawrence Gould
Abstract Purpose To compare two recently proposed Bayesian methods for quantitative pharmacovigilance with respect to assumptions and results, and to describe some practical strategies for their use. Methods The two methods were expressed in common terms to simplify identifying similarities and differences, some extensions to both methods were provided, and the empirical Bayes method was applied to accumulated experience on a new antihypertensive drug to elucidate the pattern of adverse-event reporting. Both methods use the logarithm of the proportional risk ratio as the basic metric for association. Results The two methods provide similar numerical results for frequently reported events, but not necessarily when few events are reported. Using a lower 5% quantile of the posterior distribution gives some assurance that potential signals are unlikely to be noise. The calculations indicated that most potential adverse event,drug associations that were well-recognized after 6 years of use could be identified within the first year, that most of the associations identified in the first year persisted over time. Other insights into the pattern of event reporting were also noted. Conclusion Both methods can provide useful early signals of potential drug,event associations that subsequently can be the focus of detailed evaluation by skilled clinicians and epidemiologists. Copyright © 2002 John Wiley & Sons, Ltd. [source]