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Biomedical subjects

Reynold Spector

Publications and source records attributed to Reynold Spector.

8 recordsLinked to original sources
PubMed2006

Micronutrient and urate transport in choroid plexus and kidney: implications for drug therapy.

With application of molecular biology techniques, there has been rapid progress in understanding how many drugs and micronutrients (e.g., vitamins) are transferred across the choroid plexus (CP), the main transport locus of the blood-cerebrospinal fluid (CSF) barrier, and the renal tubular epithelial cells. In many cases, these molecules are transported by separate, specific carriers or receptors on the apical and/or basal side of the CP or renal epithelial cells. This commentary focuses on four micronutrient transport systems in CP (ascorbic acid, folate, inositol, and riboflavin), all of which have been recently cloned, expressed and for which knockout mice models were developed and transporter localization studies performed. Also reviewed is the recently cloned uric acid transport system in human kidney in which there exists a human "knockout" model. The implications of these transport systems for drug therapy of central nervous system and renal disorders are discussed, especially with regard to methods to circumvent the blood-brain and blood-CSF barriers to deliver drugs to the brain.

Animals↗
PubMed2006

Pharmacology and statistics: recommendations to strengthen a productive partnership.

Critical to the discovery, development and rational use of drugs and vaccines are the foundational principles and proper application of statistics. However, in too many cases, there has been misuse of statistics and/or overemphasis on statistical significance (p < 0.05), as though this criterion possessed truth-guaranteeing properties. To clarify confusion about the proper use of statistics in pharmacology, we summarize briefly the foundational principles of probability; the role of statistics in assessment of causality; the three basic uses of statistical methods, especially those employed in hypothesis testing; and current statistical issues in pharmacological research. We then review and provide examples of the meaning of statistical significance, the consequences of lack of randomization in epidemiology/observation studies, the criteria for measurement instrument validation, the problems with subgroup analyses, the need for multiple comparison statistical methods, and how to handle dropouts and missing data. Finally, based on sound experimental and statistical principles, we make a series of recommendations to both experimentalists and journal editors to improve published pharmacological experiments. These include widespread use of blinding and randomization and/or random selection of subjects in both basic and clinical pharmacology, mandatory use of rigorous evidentiary criteria in epidemiology/observation studies claiming causal associations, proper interpretation of statistical versus clinical/pharmacological significance, appropriate interpretation of meta-analyses, meaningful validation of methods, and a more rational statistical approach to subgroup analyses and genetic association studies.

Bias↗
PubMed2006

The heart of drug discovery and development: rational target selection.

Critical to the discovery and development of drugs and vaccines is the rational selection of biochemical, immunologic or molecular targets. To understand the rationale for target selection, we review strengths and weaknesses of the four main approaches: whole animal disease models; molecular targeting; epidemiology/observation studies, and genomics. After classifying diseases into those with a relatively stable pathophysiology (e.g., hypertension and gout) versus those with an unstable pathophysiology (e.g., AIDS and influenza) to aid in understanding target selection, we provide examples of successful and unsuccessful selection of drug and vaccine targets, focusing on the molecular and epidemiological/observational approaches. We discuss the reasons that molecular targeting has led to successful control of many diseases, whereas the epidemiological/observational approach has had a checkered history. We also assess the potential power of the genomic approach, specifically the curative versus controlling/preventive strategies. With combined genetic and molecular approaches and judicious use of whole animal models and properly performed epidemiology/observation studies to select the appropriate targets, the future for controlling, preventing and even curing many diseases is very bright indeed.

Animals↗
PubMed2006

The power of pharmacological sciences: the example of proton pump inhibitors.

Critics have questioned the foundational principles of pharmacological sciences and modern drug therapy; they also claim that drug therapy is often too expensive or of uncertain value. Contemporaneously, alternative medicine has bloomed. Yet the US government began to pay for drug therapy under Medicare in 2006, an explicit recognition of the value of modern drug therapy. To clarify this confusion, we review the philosophical and scientific foundations of pharmacology, drug discovery and development, the attendant strategies and successful results. We also review and answer the major attacks on the philosophical and scientific foundations of modern pharmacology and drug therapy. Finally, we define the characteristics of an ideal drug. As an example of the principles and strategies of modern pharmacological sciences and their successful application, we focus on the discovery and development of proton pump inhibitors (PPIs) of stomach acid production. This class of drugs approaches the ideal and exemplifies successful application of modern pharmacological principles to drug discovery and development. Moreover, the use of PPIs as a pharmacological tool allowed the resolution of important scientific questions, e.g., the role of stomach acid in peptic diseases of the stomach, duodenum and esophagus.

Drug Costs↗
PubMed2002

Progress in the search for ideal drugs.

The search for ideal drugs to improve patient care requires applications of modern scientific methods to both discovery and development. Using these modern methods, the pharmaceutical industry with strong academic and government collaboration has introduced in the last 25 years many new drugs that approach the ideal. After reviewing Björnsson's classification of drug action and the notion of contributory causality, this commentary defines an ideal drug from the perspectives of pharmacodynamics, pharmacokinetics, and therapeutics. Examples of new drugs for hypertension, heart disease, stroke, osteoporosis, asthma, ulcer, and migraine headaches are described. Finally, the profound implications of progress in developing ideal drugs not only for the patient but also for the academic, educational, and regulatory establishments are briefly reviewed.

Drug Industry↗
PubMed2002

A rational approach to the selection of useful drugs for clinical practice.

Confusion exists concerning optimal selection of drugs for clinical practice. Many reasons contribute to this confusion which derives from various sources including industry, the FDA and often less than ideal education of physicians in clinical pharmacology during medical school and thereafter. This presentation does not focus on allocating blame for the current unsatisfactory situation, but rather offers a solution to improve drug therapy. Our educational solution consists of a paradigm for rational drug therapy, specifically a checklist of eight criteria for physicians to review before prescribing drugs. Such a review would facilitate better estimation by physicians of risk/benefit ratios involving new, often expensive and, in some cases, questionably effective and safe drugs.

Decision Making↗
PubMed2002

Which studies of therapy merit credence? Vitamin E and estrogen therapy as cautionary examples.

A vast and continuously growing amount of material on drugs exists in the literature to read and evaluate. Frequently, the papers and their recommendations are conflicting and contradictory. Readers are faced with the dilemma of deciding what to believe. The need for evidence-based medicine as a foundation for optimal clinical research and patient care requires application of the best scientific methods. Various methods are discussed. Generally, the most powerful method to test a clinical hypothesis is the randomized, controlled clinical trial. By contrast, epidemiology/observation studies have certain inherent weaknesses that can lead to erroneous conclusions. The examples of estrogen therapy in postmenopausal women and of vitamin E therapy to reduce cardiovascular risk are discussed extensively to provide historical perspective and to demonstrate erroneous conclusions reached using epidemiology/observation studies. The sociology of journal publication is briefly described, and an attempt is made to assess who benefits and who is harmed when leading medical journals publish erroneous results. Types of bias and confounding issues leading to errors are discussed, and the need is emphasized for publication of rigorous studies after careful evaluation by editors to avoid repetition of past mistakes and to ensure publication of correct medical information.

Aged↗