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Biomedical subjects

Steven C Schachter

Publications and source records attributed to Steven C Schachter.

At least 19 recordsLinked to original sources
PubMed2007

Currently available antiepileptic drugs.

Many new antiepileptic drugs (AEDs) have become available over the past 15 years. At the same time, the emphasis on treating patients with epilepsy has grown from stopping seizures to avoiding side effects and maximizing quality of life. This review summarizes currently available AEDs, and presents general treatment principles and guidelines for AED selection. Unfortunately, despite the increased treatment options of today, seizure freedom without side effects remains unattainable for too many patients with epilepsy. Consequently, there remains a significant need for further development of new therapies.

Anticonvulsants↗
PubMed2006

Effects of huperzine A on amyloid precursor protein processing and beta-amyloid generation in human embryonic kidney 293 APP Swedish mutant cells.

The amyloid precursor protein (APP) is cleaved enzymatically by nonamyloidogenic and amyloidogenic pathways. alpha-Secretase (alpha-secretase), cleaves APP within the beta-amyloid (Abeta) sequence, resulting in the release of a secreted fragment of APP (alphaAPPs) and precluding Abeta generation. In this study, we investigated the effects of an acetylcholinesterase inhibitor, huperzine A (Hup A), on APP processing and Abeta generation in human embryonic kidney 293 cells transfected with human APP bearing the Swedish mutation (HEK293 APPsw). Hup A dose dependently (0-10 microM) increased alphaAPPs release and membrane-coupled APP CTF-C83, suggesting increased APP metabolism toward the nonamyloidogenic alpha-secretase pathway. The metalloprotease inhibitor TAPI-2 inhibited the Hup A-induced increase in alphaAPPs release, further suggesting a modulatory effect of Hup A on alpha-secretase activity. The synthesis of full-length APP and cell viability were unchanged after Hup A incubation, whereas the level of Abeta(Total) was significantly decreased, suggesting an inhibitory effect of Hup A on Abeta production. Hup A-induced alphaAPPs release was significantly reduced by the protein kinase C (PKC) inhibitors GF109203X and Calphostin C. These data, together with the finding that the PKCalpha level was enhanced prior to the increase of alphaAPPs secretion, indicate that PKC may be involved in Hup A-induced alphaAPPs secretion by HEK293 APPsw cells. Our data suggest alternative pharmacological mechanisms of Hup A relevant to the treatment of Alzheimer's disease.

Alkaloids↗
PubMed2006

Therapeutic effects of vagus nerve stimulation in epilepsy and implications for sudden unexpected death in epilepsy.

Vagus nerve stimulation (VNS) is a non-pharmacological therapy approved by the FDA for treatment of patients with partial-onset epilepsy. The most frequently encountered adverse effects typically occur during stimulation, are usually mild to moderate in severity, and resolve with reduction in current intensity or spontaneously over time. There are no apparent effects of VNS on vagally mediated visceral function. Though the precise mechanism of action of VNS remains unknown, available evidence suggests that central autonomic nervous system pathways are involved, which have also been implicated in sudden unexpected death in epilepsy (SUDEP). Studies to date of VNS and SUDEP are limited and do not conclusively show an association between VNS and SUDEP rates independent of other epilepsy-specific variables.

Anticonvulsants↗
PubMed2006

Quality of life for patients with epilepsy is determined by more than seizure control: the role of psychosocial factors.

Antiepileptic drugs remain the cornerstone of epilepsy treatment for minimizing, if not eliminating, seizures. However, many factors other than the degree of seizure control influence the quality of life for patients with epilepsy. This review focuses on psychosocial factors that have been associated with quality of life in this population, especially mood disorders, stigma seizure worry, self-esteem and self-mastery. Irrespective of their level of seizure control from antiepileptic drugs, patients may also benefit from targeted psychosocial interventions that reduce the negative impact of these factors on their quality of life.

Epilepsy↗
PubMed2005

Emerging credentialing practices, malpractice liability policies, and guidelines governing complementary and alternative medical practices and dietary supplement recommendations: a descriptive study of 19 integrative health care centers in the United States.

BACKGROUND: Little is known about policies governing the integration of complementary and alternative medical (CAM) therapies and providers. METHODS: To document emerging approaches in 19 US hospitals regarding credentialing, malpractice liability, and pharmacy policies governing integration of CAM therapies and providers into conventional medical settings, we surveyed 21 academic medical centers and 13 non-academically affiliated hospitals that are nationally visible and are integrating CAM therapies into conventional medical settings. Of the 19 respondents, 11 were tertiary care hospitals, 6 were community hospitals, 1 was a freestanding center associated with a community-based hospital, and 1 was a university-based rehabilitation hospital. RESULTS: Institutions had no consistent approach to provider mix and authority within the integrative care team, and minimum requirements for professional liability insurance, informed consent disclosure, and hiring status. Less than a third had a formal (stated) policy concerning dietary supplements; those selling supplements in their pharmacy lacked consistent, evidence-based rationales regarding which products and brands to include or exclude. Although many hospitals confiscated patient supplements on admission, institutions had inconsistent criteria regarding allowance of home supply. CONCLUSIONS: Hospitals are using heterogeneous approaches to address licensure, credentialing, scope of practice, malpractice liability, and dietary supplement use in developing models of integrative care. The environment creates significant impediments to the delivery of consistent clinical care and multisite evaluations of the safety, efficacy, and cost-effectiveness (or lack thereof) of CAM therapies (or integrative models) as applied to management of common medical conditions. Consensus policies need to be developed.

Complementary Therapies↗
PubMed2005

Lack of herbal supplement characterization in published randomized controlled trials.

PURPOSE: Herbal supplements in the United States and abroad have poor quality control and high content variability. We assessed the extent to which recently published randomized controlled trials of herbal supplements characterized and verified the content of the supplement under study. METHODS: We identified all MEDLINE-indexed English language randomized controlled trials evaluating single-herb preparations of echinacea, garlic, ginkgo, saw palmetto, or St. John's wort that were published between January 1, 2000, and February 9, 2004. From each article we extracted information characterizing the herbal supplement studied. RESULTS: Of 81 randomized controlled trials meeting inclusion criteria, 12 (15%) reported performing tests to quantify actual contents, and 3 (4%) provided adequate data to compare actual with expected content values of at least one chemical constituent. In those 3 studies, actual content varied between 80% and 113% of expected values. Studies of higher overall quality (Jadad score > or =3) performed testing somewhat less frequently (5/54; 9%) than those with lower Jadad scores (7/27; 26%) (P = .09). CONCLUSION: Documented characterization of herbal supplements in published randomized controlled trials is inadequate. Investigators may be unaware of the extent to which herbal quality-control issues may detract from the value of otherwise well-designed clinical trials. The scientific and clinical utility of future herbal randomized controlled trials would be enhanced if authors provided evidence that the herbal products studied were of high quality.

Drug Contamination↗
PubMed2005

Transcranial magnetic stimulation treatment for epilepsy: can it also improve depression and vice versa?

Comorbidity with depression is an important determinant of the quality of life for patients with epilepsy. Antidepressant medications can effectively treat depression in epileptic patients, but drug-drug interactions and epileptogenic effects of these drugs pose therapeutic challenges. The mood-stabilizing effects of antiepileptic medications may not be sufficient to treat depression. Therefore, treatments that alleviate the burden of depression without increasing seizure risk or, better yet, with the possibility of improving seizure control are worth exploring. Neuroimaging techniques, such as functional magnetic resonance imaging, are providing novel insights into the pathophysiology of depression in epilepsy. For example, there appears to be prominent brain prefrontal hypoactivity, which may be sustained by the hyperactivity of the seizure focus. If so, neuromodulatory approaches that suppress epileptic focus hyperactivity and concurrently enhance prefrontal activity may be ideally suited. Indeed, vagus nerve stimulation has been shown to yield simultaneous antiseizure and mood effects. Another neuromodulatory technique, transcranial magnetic stimulation (TMS), can also modulate brain activity, but in a noninvasive, painless, and focal manner. Depending on the stimulation parameters, it is possible to enhance or reduce activity in the targeted brain region. Furthermore, TMS has been shown to be effective in treating depression, and preliminary data suggest that this treatment may also be effective for epilepsy treatment. This article reviews these data and explores further the question of whether depression and epilepsy can be simultaneously treated with TMS for optimal therapeutic impact.

Depressive Disorder↗
PubMed2005

Improving quality of life beyond seizure control.

More than 50 years ago, Lennox and Markham urged physicians who treated patients with epilepsy to "match modern drug and surgical therapy with practical sociopsychological therapy" and to be "concerned not only with turbulent brain waves but with disturbed emotions". Indeed, while seizure frequency and severity correlate with quality of life and psychosocial outcomes for patients with drug-resistant epilepsy, numerous other epilepsy-related factors may also be significant determinants. These factors include medical and psychiatric co-morbidities, side effects of therapy, stigma, parental anxiety, employment status, seizure worry, self-esteem and self-mastery. Importantly, these epilepsy-related factors may be amenable to educational or therapeutic interventions, which if successful may benefit patients even without a concomitant reduction in seizure frequency or severity. Therefore, while further research is needed, physicians and other health care providers should comprehensively attend to these factors and refer patients with treatment-resistant seizures, when appropriate, for further evaluation and treatment to improve their quality of life beyond seizure control.

Anxiety↗
PubMed2004

Vagus nerve stimulation: mood and cognitive effects.

Many antiepileptic medications modulate affective and cognitive functions. In keeping with these observations, a growing body of literature suggests that vagus nerve stimulation (VNS) may have similar effects. This review evaluates the published evidence for VNS-associated changes in mood and cognition in patients with neuropsychiatric disorders.

Adult↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs, I: Treatment of new-onset epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003. RESULTS: Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Acetates↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs, II: Treatment of refractory epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) [gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS)] in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 to March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. GBP can be effective for the treatment of mixed seizure disorders, and GBP, LTG, OXC, and TPM for the treatment of refractory partial seizures in children. Limited evidence suggests that LTG and TPM also are effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox-Gastaut syndrome. CONCLUSIONS: The choice of AED depends on seizure and/or syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Acetates↗
PubMed2002

Drug-mediated antiepileptogenesis in humans.

The goal of pharmacologic therapy for patients with epilepsy is to suppress seizures without side effects. There is growing interest in developing antiepileptogenic drugs capable of preventing the onset of seizures in patients at high risk and inducing a permanent remission of seizures in patients with epilepsy, i.e., a cure. Whether any anticonvulsant drugs in current use have antiepileptogenic properties is the subject of this overview.

Anticonvulsants↗
PubMed2002

The evolving place of vagus nerve stimulation therapy.

Approximately 40% of patients with epilepsy have seizures that do not adequately respond to medical therapy. Vagus nerve stimulation (VNS) therapy, approved 5 years ago by the Food and Drug Administration, offers a therapeutic option for patients with pharmacoresistant seizures. This supplement updates developments with VNS therapy since its approval and suggests future directions for this still-evolving treatment.

Electric Stimulation Therapy↗
PubMed2002

Vagus nerve stimulation therapy summary: five years after FDA approval.

With more than 16,000 patients implanted with the vagus nerve stimulation (VNS) therapy system (Cyberonics, Inc., Houston, Texas), VNS therapy has assumed an increasingly important role in the treatment of medically refractory seizures since its approval 5 years ago by the United States FDA. This review discusses the clinical trials that provided evidence for the approval, long-term efficacy, efficacy in special populations and co-morbid conditions, and safety and tolerability. Additional studies are suggested to further explore the capabilities of VNS therapy.

Device Approval↗