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Biomedical subjects

Claire M Lathers

Publications and source records attributed to Claire M Lathers.

10 recordsLinked to original sources
PubMed2006

Stress and sudden death.

Cardiac patients, psychiatric patients, and certain ethnic groups experiencing acute stressful circumstances are at risk for unexpected sudden death. Although stress is associated with changes in autonomic neural function, its role as a potential risk factor for sudden unexpected death in epilepsy (SUDEP) is not known. The association of epilepsy with cardiac abnormalities, such as neurogenic arrhythmias and microscopic perivascular and interstitial fibrosis, and with depression and anxiety indicates that emotional stress should be evaluated as a potential risk factor for SUDEP. The impact of adverse emotional states on the autonomic control of cardiac rhythm is a known important factor leading to cardiac dysrhythmias in humans and other species. The interaction between emotional factors and the arrythmogenic potential of epileptiform discharges and the possibility of benefit from stress management intervention need to be investigated.

Arrhythmias, Cardiac↗
PubMed2003

Clinical pharmacology of topiramate versus lamotrigine versus phenobarbital: comparison of efficacy and side effects using odds ratios.

Clinical pharmacologists, neurologists, internists, and all health care givers must consider the efficacy, safety, and side effect profile of a given antiepileptic drug (AED) when determining which drug is best for a given patient. The first purpose of this paper is to address whether the "new" AEDs have advantages over the "old" drugs. The second purpose is to teach those interested in clinical pharmacology about the use of Web-based information access to answer a neurology/clinical pharmacology problem: to compare the efficacy and side effects of topiramate versus lamotrigine versus phenobarbital using odds ratios. Cost of all three AEDs was also compared. A number of new AEDs, including topiramate and lamotrigine, have been developed for chronic focal and secondarily generalized epileptic seizures. Efficacy of these drugs as anticonvulsants does not seem to be superior to that of traditional anticonvulsants such as phenobarbital. However, the advantage of the new drugs is a different spectrum of possible adverse events. Newer AEDs may or may not induce sedation and may minimize noncompliance by reducing side effects of lethargy and cognitive impairment. The difficulty in achieving therapeutic dosage because of side effects makes one consider whether these agents are "better" than the oldest and most side effect-prone AED, phenobarbital. The new AEDs have less frequent interactions, leading to improved tolerability with comedication. This exercise compares two "new" AEDs, topiramate and lamotrigine, with phenobarbital by evaluating efficacies and side effects using relative odds ratios, a method commonly used in drug development research. Development of new algorithms and/or new knowledge will bring beneficial tools to all clinical pharmacologists.

Anticonvulsants↗
PubMed2002

Web-based sharing of cutting-edge teaching strategies.

The need to implement improved teaching methods in clinical pharmacology is critically important for health care globally. This need is driven by the overwhelming amount of information currently available on appropriate drug usage, by a proliferation of new biotechnology-derived pharmacologic agents, and by an expanded prescribing authority that is being granted to health professionals who have not traditionally had this responsibility and training. This discussion emphasizes the points that (a) the technology is available to share the best teaching materials for clinical pharmacology over the Internet, (b) clinical pharmacology organizations are best positioned to facilitate this exchange of educational materials, and that (c) continued discourse about problem-based learning and other curricular approaches to teaching clinical pharmacology is essential. The currently available information on the Internet includes case studies, slide sharing for lectures, educational programs and educational software. Clinical pharmacology organizations are not only starting to organize this information, but also to review the content of these programs and continuously add new material. These organizations have also developed a powerful tool through their journals in which to present educational series on rational therapeutics and to discuss educational approaches to instruction. Teaching forums, such as those presented annually at the American College of Clinical Pharmacology Annual Meeting, are essential to encourage discussion about teaching clinical pharmacology in the broadest context of the therapeutics, the economics and the legal aspects of clinical drug use.

Internet↗
PubMed2002

Endocrine disruptors: a new scientific role for clinical pharmacologists? Impact on human health, wildlife, and the environment.

It is important for the clinical pharmacologist to understand the potential human health implications of exposure to environmental chemicals that may act as hormonally active agents. It is necessary to have an understanding of how pharmaceutical and personal care products and other chemicals affect the ecosystem of planet Earth and to understand how they may negatively contribute to human disease. Clinical pharmacologists must understand the various definitions of endocrine disruptors and be able to "decipher" these terms for their patients. Understanding the need for the EPA endocrine disruptor screening program and possessing knowledge of the screening assays used to assess endocrine activity potential are two essential components relevant to the topic of endocrine disruptors. Clinical pharmacologists have an opportunity to play an important role in resolving the question of what role endocrine disruptors play in initiating human disease since some scientists argue that the present evidence is not compelling. Clinical pharmacologists can also play an important role in the evaluation of the risk assessment and use of risk management and risk communication tools required to address public health concerns related to actions of endocrine disruptors. It is important that clinical pharmacologists work with veterinary clinical pharmacologists, toxicologists, industrial chemists, regulators, the scientific community, the general public, and environmental groups to understand the impact of endocrine disruptors on human health, wildlife, and the environment with an ultimate goal to minimize and/or alleviate the unwanted, detrimental effects of the endocrine disruptors.

Animals↗
PubMed2002

Clinical pharmacology: drugs as a benefit and/or risk in sudden unexpected death in epilepsy?

Death may be the consequence of natural or unnatural causes, such as accidents, homicide, and suicide, which have no relationship to the disease of epilepsy. Direct causes of death include status epilepticus, and indirect causes may be head trauma or drowning subsequent to a seizure. When death occurs suddenly and without explanation, the term sudden unexpected unexplained death is used. Unexplained is a term that clinicians and research scientists are working to clarify. Numerous preclinical animal studies have been conducted as models for sudden death and have led to clinical studies in persons with epilepsy. These studies show that sympathetic nerve stimulation, ouabain, or coronary occlusion increased temporal dispersion of recovery of ventricular excitability and led to an underlying electrical instability that predisposed the ventricularmyocardium to arrhythmia. Cardiac arrhythmias in an animal model for ouabain-induced toxicity were associated with neural autonomic dysfunction. Neural discharges were characterized by increases, decreases, or no change in the discharge of postganglionic cardiac sympathetic nerves monitored simultaneously, predisposing to cardiac arrhythmia. Stimulation of the sympathetic ventrolateral cardiac nerve produced a shift in the origin of the pacemaker and tachyarrhythmias because the nerve is not uniformly distributed to the various regions of the heart but is localized to the atrioventricular junctional and ventricular regions. Such nonuniform distribution of sympathetic nerves would also contribute to initiation of arrhythmia as a nonuniform neural discharge occurred. Studies examining the physiology and pharmacology of this finding in multiple animal models found that subconvulsant, interictal discharge was associated with autonomic cardiac neural non-uniform discharge and cardiac arrhythmias. As a result of further investigations, Lathers and Schraeder edited a book in 1990 that summarized the clinical problem of sudden unexpected death and epilepsy (SUDEP). The contributors concluded that there was a paucity of clinical data addressing the mechanism of death. Regulatory response resulting from the consequent increased awareness of SUDEP occurred in 1993, when the FDA focused attention of practitioners and pharmaceutical manufacturers on the question of whether use of anticonvulsant drugs contributes to or prevents sudden unexpected death in epileptic persons. The FDA-convened panel of scientists considered the prevalence of sudden unexpected death in patients involved in studies associated with developing new anticonvulsant drugs and reviewed data on the risk of sudden unexpected death in patients taking lamotrigine. The risk of SUDEP was no different from thatfound in the young epilepsy population in general. Estimated SUDEP rates in patients receiving the new anticonvulsant drugs lamotrigine, gabapentin, topiramate, tigabine, and zonisamide were found to be similar to those in patients receiving standard anticonvulsant drugs, suggesting that SUDEP rates reflect population rates and not a specific drug effect. The FDA required warning labels on the risk of SUDEP in association with the use of each of the above-mentioned drugs. Another effect of bringing SUDEP to the attention of epilepsy researchers has been the expansion of basic science and the development of epidemiological and clinical studies directed at this phenomenon. Results from some of these studies are discussed in this article.

Animals↗
PubMed2002

Development of innovative teaching materials: clinical pharmacology problem-solving (CPPS) units: comparison with patient-oriented problem-solving units and problem-based learning--a 10-year review.

The First Teaching Clinic in Clinical Pharmacology, sponsored by the American College of Clinical Pharmacology in September 1992, was designed for the preparation and development of new clinical pharmacology problem-solving (CPPS) units. CPPS units are case histories that illustrate pertinent principles in clinical pharmacology. Each unit consists of the following sections: introduction, learning objectives, pretest, four clinical pharmacology scenarios, posttest, answers to pre- and posttest questions, and selected references. The clinical pharmacology content of the CPPS units place greater emphasis on clinical information, drug selection, and risk/benefit analyses, and thus they complement the basic pharmacology presented in the patient-oriented problem-solving (POPS) units. In general, the CPPS units are intended for use by students more advanced in clinical pharmacology than first- and second-year medical students. The CPPS unit "Clinical Pharmacology of Antiepileptic Drug Use: Clinical Pearls about the Perils of Patty" was developed for use by third- and fourth-year medical students doing rotations in neurology or clinical pharmacology; advanced pharmacy students; residents in neurology, pediatrics, internal medicine, and family practice; fellows in clinical pharmacology, and those taking the board examination in clinical pharmacology. The CPPS unit titled "Geriatric Clinical Psychopharmacology" was written for third- and fourth-year medical students; residents in psychiatry, family practice, and internal medicine;fellows in clinical pharmacology; and those studying for boards in clinical pharmacology. The CPPS unit "Anisocoria and Glaucoma" was written for more advanced students of clinical pharmacology. The CPPS unit titled "Antiepileptic Drugs" was intended for second-year medical students. The second teaching clinic was held in November 1993 and focused on the development and editing of the CPPS units and their evaluations by faculty and students from academic centers. Evaluations by faculty and students have been overwhelmingly positive. Requests to use the CPPS units in various clinical pharmacology teaching programs were received from numerous schools within the United States and from abroad. The third teaching clinic in September 1995 included a follow-up focused on the uses of drug information databases in case problem exercises. These examples are presented to demonstrate the variety of educational activities the American College of Clinical Pharmacology is sponsoring to fulfill its strategic initiative dedicated to offer innovative teaching programs and to develop new teaching materials in clinical pharmacology. Collectively, all of the teaching clinics, symposia, and workshop efforts, sponsored by the various academic professional societies alone or together over the past decade, are necessary if new and innovative teaching materials in the field of basic science and in the fields of pharmacology and clinical pharmacology are to be continuously developed to keep pace with the new, rapidly changing developments in medicine to provide the best treatment for patients in the 21st century.

Anisocoria↗
PubMed2002

Educational issues in clinical pharmacology: who are our audiences and what are their specialized needs? One specialized need: "understanding the role of veterinary medicine in public health".

When considering educational issues and the need to update the curriculum for clinical pharmacologists for the new millennium, a number of questions must be raised. Who are our audiences? What are the specialized needs? This educational article identifies the audience, which includes those with diverse degrees such as MDs, PhDs, PharmDs, RNs, DVMs, and other non-MD prescribers working in academia, industry, clinical research organizations, and government in multifaceted disciplines requiring a knowledge base of physiology, pharmacology, biochemistry, anatomy, microbiology, pathology, medicine, and the drug development process of preclinical and clinical studies complete with protocols, pharmacokinetics, and statistics. One specialized current educational issue for clinical pharmacologists to understand is the impact of animal therapeutic and subtherapeutic use of antimicrobials on antibiotic use in human medicine.

Animal Diseases↗
PubMed2002

Risk assessment in regulatory policy making for human and veterinary public health.

Risk assessment is the method of systematically identifying and assessing factors that influence the probability and consequences of a negative event occurring. One responsibility of veterinary medicine is to protect animal and human health. Food animal production uses antibiotics to enhance production. Regulators evaluate new production technology to ensure animal safety and safe, edible products and to make public policy decisions by assessing risks/benefits. The U.S. Food and Drug Administration, Center for Veterinary Medicine's (CVM's) first risk assessment addressed the potential human health impact of campylobacter effects associated with the use of fluoroquinolines in food-producing animals. CVM used the Monte Carlo method to estimate risk byprobability distributions that reflect the uncertainty and variability in the data used for the assessment. Enterococci faecium is a species more likely to be resistant to antibiotics of last resort. Effective control of multidrug-resistant enterococci will requirea better understanding of the transfer of E. faeciumfrom animals to humans and the interaction between E. faecium, the hospital environment, and humans; prudent antibiotic use; better contact isolation in hospitals; and better surveillance. CVM will model these factors in a second, more complex risk assessment designed to examine the indirect transfer of resistance from animals to humans. Use of risk assessments allows researchers, the industry, regulatory authorities, and educators to make better policy decisions regarding antimicrobial use in food animals and humans and the development of resistance. Today the question of whether the use of antimicrobials for growth enhancement infood animals should or should not be terminated for the benefit of human health remains unresolved.

Animals↗
PubMed2002

Clinical pharmacology of antimicrobial use in humans and animals.

Veterinary public health is a frontier in the fight against human disease, charged to control and eradicate zoonotic diseases that are naturally transmitted between vertebrate animals and man. Currently there is a need for clinical pharmacologists and all health care givers to limit the development of bacterial resistance in humans to contain the increased health care expenditures related to morbidity and mortality associated with the use of antimicrobials. The development of resistance predates the use of antibiotics and will always be a problem to the successful treatment of patients. Ongoing discussion debates the extent to which antibiotic use in animals contributes to the development of antibiotic resistance in humans. The veterinary use ofantibiotics as antimicrobial growth promoters is thought to influence the prevalence of resistance in animal bacteria and to be a risk factor for the emergence of antibiotic resistance in human pathogens. Transfer of antibiotic resistant bacteria from animals to humans may occur via contact, including occupational exposure and via the food chain. Resistance genes may transferfrom bacteria of animals to human pathogens in the intestinal flora of humans. Prevention of the development of resistance in humans necessitates good animal husbandry and hygienic measures to prevent cross contamination and a decrease in the use of antibiotics. Appropriate use of antibiotics for food animals will preserve the long-term efficacy of existing antibiotics, support animal health and welfare, and limit the risk of transfer of antibiotic resistance to humans. Investigators must also develop new antimicrobial agents. Poole (J Pharmacy Pharmacol 2001;53:283) recommends targeting the three predominate mechanisms of development of resistance by antimicrobials (i.e., antibiotic inactivation, target site modification, and altered uptake via restricted entry and/or enhanced efflux) to specifically complement the development of novel agents with novel bacterial targets. Bacterial resistance and its selection may be evaluated by comparing the relationship to antibiotic pharmacokinetic (PK) values obtained from serum concentrations and organism MICs (minimum inhibitory concentrations; concentration-dependent killing) to reveal culture and sensitivity tests in patients. Pharmacodynamic (PD) models may be developed to identify factors associated with the probability that bacterial resistance will develop. Thomas et al (Antimicrobial Agents Chemotherapy 1998;42:521) used this combined approach of PK/PD and MICs to examine data retrospectively. The role of clinical pharmacology is to work with PK/PD models such as these to determine the best use of antibiotics in humans to minimize the development of resistance. The role of any regulatory body responsible for the protection of the public health and food safety for consumers is to assess risk and to then communicate and manage the risk. Scientific uncertainty must be interpreted to propose sound policy options. The conversion of sound science into an appropriate regulatory policy to protect the public health is most important.

Animals↗