The present state of aspirin and clopidogrel resistance.

Antiplatelet therapy has demonstrated significant clinical benefit in the treatment of acute coronary syndrome. However, as with any treatment strategy it has been unable to prevent all cardiovascular events. This is far from surprising when considering the complexity of arterial thrombosis and more specifically platelet physiology. This lack of treatment success has provoked the introduction of various diagnostic tests and testing platforms with the intent of guiding and optimizing clinical treatment. Such tests have resulted in the generation of clinical data that suggest suboptimal response to antiplatelet agents such as aspirin and clopidogrel. In the case of both aspirin and clopidogrel, this suboptimal response has been termed resistance. Drug resistance would imply a lack of pharmacological response that has not been specifically investigated in many of the clinical studies performed to date. Rather, the term resistance has been used to describe various facets of platelet activation and aggregation relative to the testing method. Many of these measured parameters are not addressed in the therapeutic intent of the antiplatelet drug in question.

Whole blood platelet function assay on the ICHOR point-of-care hematology analyzer.

The role of platelets as the initial defense against insult to the vasculature is well established. Moreover, platelets are now recognized as having a critical role in the acute care settings of cardiopulmonary bypass (CPB) procedures and cardiac catheterization. In the environment of CPB, both platelet count and function have been demonstrated as being markedly compromised during and following the procedure. Unfortunately, current assays that are used to evaluate the parameters of platelet count and function are limited in regard to their utility in a near patient format. Here, we describe a practical, rapid, and user-friendly whole blood platelet function assay that has been developed for the ICHOR point-of-care hematology analyzer. This analyzer is capable of performing an eight parameter blood profile including platelet count. In comparable studies, platelet aggregation in whole blood demonstrated good correlation (for ADP the values were n = 14, r2 = 0.81, p = 0.0001; for collagen, n = 10, r2 = 0.93, p = 0.0001; for ristocetin, n = 10, r2 = 0.89, p = 0.0001; and for epinephrine, n = 10, r2 = 0.81, p = 0.0003) with traditional platelet-rich aggregometry, which uses increased light transmission as an indication of platelet aggregation. Furthermore, early feasibility studies in CPB patients demonstrated both decreased platelet count and a marked reduction in platelet function peri-procedurally. This new assay of platelet function is extremely suitable for the clinical environment with rapid turnaround time and provides a full hematology profile to enhance transfusion decisions.

A study of medical students and physicians referred for learning disabilities.

This study presents descriptive data on 86 medical students and physicians, referred for testing to determine the presence and type of learning problems. The major results indicate that most subjects had either a learning disability or attention deficit hyperactivity disorder (ADHD). Twenty-one subjects had a reading learning disability (LD); 21 subjects had a potential visual/spatial learning problem; 10 subjects had ADHD; 15 subjects had both a reading disability and ADHD; and 19 subjects had no detectable problem. Subtest analysis or WAIS-R scores indicated that sequential information processing may be the major difficulty for this sample.

Spelling improvement for college students who are dyslexic.

Academic problems of the dyslexic child often persist in adult life. Such problems as spelling can interfere with the performance of such adult learners in college. Federal legislation requires reasonable accommodation for these students. At some colleges, this consists of allowing use of tape recorders in lectures and sometimes allowing extra time on examinations. Remediation of reading, writing, and spelling among dyslexic college students is often not addressed. This study reports the use of a modified Orton-Gillingham approach in comparison with a nonphonetic approach and with a group receiving no remediation. The results indicate a significant increase in spelling performance for the group receiving the modified Orton-Gillingham remediation. This contrasts with no significant change in the group receiving nonphonetic remediation and in the control group (no remediation), and indicates that adulthood is not too late for appropriate intervention for the dyslexic student. Colleges offering such intervention and the students receiving it will benefit from improved performance.

Clinical effects of fenfluramine on children with autism: a review of the research.

A review of research studies published to date on the effects of fenfluramine on children with autism is presented. The current status of the fenfluramine research on children with autism is assessed. The review analyzed the methodological aspects of the research, the toxicity of fenfluramine, and the relationship between fenfluramine, neurotransmitter activity, cognitive ability, and subsequent behavioral change. The review of published data indicated that fenfluramine had positive effects on the reduction of hyperactivity and stereotypic behaviors in 33% of the subjects. The best responders were children with the highest baseline IQs. The conclusions address the need for appropriate subgrouping of autistic syndromes, which may lead to identification of responders to pharmacological treatments. The need for further study of the possible long-term adverse side effects of flenfluramine is noted. Further experimental research on the effects of fenfluramine on children with autism is endorsed.

Serum vitamin A in premature and term neonates.

Serum vitamin A was determined in premature and term neonates by a specific spectrofluorometric method. Premature neonates (N = 42; gestational age = 32 +/- 0.4 weeks) had a serum vitamin A level (14.9 +/- 0.98 microgram/dl) significantly lower (P less than 0.001) than that of term neonates (N = 51; 22.4 +/- 0.99 microgram/dl). The vitamin A mean serum values of infants of 36 weeks' gestational age were not statistically different from those of the term neonates. Linear regression analysis for serum vitamin A values vs gestational age showed no significant correlation. A linear correlation (P less than 0.05), however, was found between serum vitamin A and serum protein protein concentrations, perhaps indicative of a lower concentration of retinol-binding protein. Since vitamin A is involved in the promotion of mucous-secreting cells, the premature neonate may be at greater risk than the term infant for diseases involving the mucosal epithelium, including necrotizing enterocolitis.

Urinary glucose and vitamin C.

The recent popularization of self-prescribed large doses of vitamin C has increased the possibility for erroneous conclusions to be drawn from standard clinical methods used in urinary glucose monitoring, due to interference with these methods by the greatly elevated excretion of vitamin C. The coupled-enzyme-chromogen strip tests showed erroneously negative glucose levels in urines of both a diabetic individual and a subject with a genetic low renal threshold for glucose when they were supplementing their normal diets with 1-2 g vitamin C per day. With this regimen, their urinary vitamin C levels reached 200 mg/dl (11.4 mmol/l). For normal urine with vitamin C added, false-positive tests for glucose were found using Benedict's reagent when vitamin C was present at 250 mg/dl (14.3 mmol/l) or higher concentrations. In diabetic individuals consuming large quantities of vitamin C, this interference with standard coupled-enzyme-chromogen strip tests or Benedict's test could present a significant problem in diagnosis and clinical management of the disease. A simple anion exchange method of treating the urine was used to correct the false results.

Hypocholesterolemic agents V: Inhibition of beta-hydroxy-beta-methylglutaryl coenzyme A reductase by substituted 4-biphenylylalkyl carboxylic acids and methyl esters.

Eleven substituted 4-biphenylylalkyl carboxylic acids and three methyl esters were synthesized and assayed for inhibition of rat liver beta-hydroxy-beta-methylglutaryl coenzyme A reductase. Five of the acids were analogs, resulting from various isosteric replacements of the carbonyl and ether oxygens of the previously described reversible inhibitor 1-(4-biphenylyl)pentyl hydrogen succinate. No significant change in activity was noted, except upon introduction of an amide linkage where a decrease in inhibition was found. Six carboxylic acids and three methyl esters, all containing the 4-biphenylyl radical but lacking the n-butyl side chain found in 1-(4-biphenylyl)pentyl hydrogen succinate, also were inhibitors of the reductase.

Hypocholesterolemic agents IV: inhibition of beta-hydroxy-beta-methyglutaryl coenzyme A reductase by arylalkenyl and arylepoxy hydrogen succinates and glutarates.

Two series of half acid esters of succinic and glutaric acids were synthesized and assayed for inhibition of rat liver beta-hydroxy-beta-methylglutaryl coenzyme A reductase. Irreversible inhibition was studied by incorporation of a potential alkylating group (the epoxide function) into the side chain of the alcohol portion of the half acid esters. Incorporation of a terminal olefin function into the side chain of the alcohol portion of the half acid esters provided a group that could form a charge-transfer complex. Neither irreversible inhibition nor formation of a charge-transfer complex was indicated from these studies; however, the two series of half acid esters exhibited reversible inhibition.

Hypocholesterolemic agents III: inhibition of beta-hydroxy-beta-methylglutaryl coenzyme A reductase by half acid esters of 1-(4-biphenylyl)pentanol.

A series of half acid esters of 1-(4-biphenylyl)pentanol was synthesized and assayed for inhibition of rat liver beta-hydroxy-beta-methylglutaryl coenzyme A reductase. The number of methylenes separating the carboxyl and ester groups was varied from zero to six. A minimum of one methylene was required for reasonable activity. Further separation of the carboxyl and ester groups produced small changes in activity. Investigation of several isomeric (cis and trans) half acid esters indicated that activity was independent of configuration. Modification of the acid portion of the glutarate analog by incorporating a 3-hydroxyl group increased activity sixfold.

Anatomy, biochemistry, and physiology laboratory programs in the education of physicians.

The amount of laboratory time devoted to anatomy, biochemistry, and physiology has decreased substantially while lecture time has remained essentially unchanged. Most laboratories consist of student conduction of assigned exercises with a sprinkling of demonstrations, conferences, and seminars. Various objectives for laboratory programs are discussed. A great percentage of the student's final anatomy grade (approximately 40%) still depends on his laboratory performance, while in biochemistry and physiology, lab work contributes only 12% and 10%, respectively, toward his final grade. There is great reluctance to abandon the laboratory program, however, because of the significant role it is thought to play in medical education.