P/Q and N-type Voltage-gated Calcium Channel Binding Antibodies Associated with Paraneoplastic Chorea and Mixed Invasive Ductal and Lobular Carcinoma of the Breasts in an Elderly Patient.

Paraneoplastic neurologic syndromes are a group of immune-mediated, cancer-associated disorders affecting the nervous system. While these syndromes are not understood fully, they are reportedly caused by an immune response against common antigens expressed by the cancer and nervous system. We describe the course of a patient who suffered paraneoplastic chorea before being diagnosed with breast cancer.

Blood glucose and stroke.

Current recommendations for the treatment of abnormal blood glucose levels for stroke rely on evidence-based guidelines. Ongoing advances in neuroimaging, tissue studies, animal studies, and case series and reports present findings that expose additional variables to be considered in the causal analysis of the role of diabetes and glucose control for stroke occurrence and outcome. The physician when treating the individual patient must fold this information into that provided by large clinical trials.

Principled versus statistical thinking in diagnosis and treatment of stroke.

Medical science is now synonymous with probability-based statistics. Statistics deals with a group; it does not need probability theory. Probability theory is consistent with the worldview that the universe is infinite, bounded, random, and governed by chance.

Artificial adaptive systems and fuzzy measures for translation of clinical trial results to the bedside.

Medical science relies uniquely on statistical evidence from large clinical trials or laboratory experiments to deal with uncertainties regarding clinical decisions. The statistical evidence is stated in probabilities. Probability theory is based on the logical rules set forth by Aristotle: the law of noncontradiction, excluded middle, and identity.

Influence of cyclooxygenase-1 genotype on ex vivo aspirin response in patients at risk for stroke.

Background: We sought to determine whether cyclooxygenase-1 (PTGS1) genotype is associated with the ability of aspirin to inhibit platelet aggregation in patients at risk for stroke.

Methods: Blood and urine samples were collected from 60 subjects, including 28 African Americans, who were taking aspirin for primary or secondary stroke prevention. Samples were analyzed for the PTGS1 A-707G, PTGS1 P17L, and glycoprotein IIIa (ITGB3)P1(A1/A2) genotypes, ex-vivo platelet aggregation, serum cholesterol, plasma salicylate levels, and urinary 11-dehydrothromboxane B(2) (11-dhTxB(2)) concentrations.

Measurable prediction for the single patient and the results of large double blind controlled randomized trials.

Background: It has been shown that the clinical state of one patient can be represented by known measured variables of interest, each of which then form the element of a fuzzy set as point in the unit hypercube. We hypothesized that precise comparison of a single patient with the average patient of a large double blind controlled randomized study is possible using fuzzy theory.

Methods/principle Findings: The sets as points unit hypercube geometry allows fuzzy subsethood to define in measures of fuzzy cardinality different conditions, similarity and comparison between fuzzy sets.

Platelet aggregation and recruitment with aspirin-clopidogrel therapy.

Background: Aspirin-clopidogrel combination therapy inhibits platelet aggregation. The effect on platelet recruitment is unknown.

Methods: Thirty chronic ischemic stroke patients taking aspirin alone followed by aspirin-clopidogrel combined therapy had platelet reactivity tests performed over 3 months: ex vivo platelet aggregation, platelet recruitment and urinary 11-dehydro-thromboxane B(2) (11-dhTxB(2))excretion.

Factors influencing warfarin dose requirements in African-Americans.

Introduction: African-Americans are under-represented in studies assessing contributors to warfarin response. Our primary objective was to determine whether the genes for cytochrome P450 (CYP) 2C9, nicotinamide adenine dinucleotide phosphate, reduced, quinone oxidoreductase (NQO1) and vitamin K epoxide reductase complex subunit 1 (VKORC1) are associated with warfarin dose requirements in African-Americans.

Patients And Methods: The following factors were assessed: demographics; clinical data; the CYP2C9 Arg144Cys (*2), Ile358Leu (*3) and Asp360Glu (*5); NQO1 Pro187Ser (*1/*2); and VKORC1 G6853C genotypes were analyzed in 115 African-Americans on stable warfarin doses.

Warfarin in patients with stroke and reasons for discontinuation.

Background: Reasons for warfarin prescription in patients who have had ischemic stroke, and its discontinuation, are complex and unique for each individual patient.

Objective: We sought to discover the reasons for discontinuation of warfarin therapy in patients followed up in a medical center antithrombosis clinic after stroke occurrence.

Materials: In all, 229 patients on warfarin therapy with history of stroke were followed up in our antithrombosis clinic between January 1997 and March 2003.

The difference between a dynamic and mechanical approach to stroke treatment.

The current classification of stroke is based on causation, also called pathogenesis, and relies on binary logic faithful to the Aristotelian tradition. Accordingly, a pathology is or is not the cause of the stroke, is considered independent of others, and is the target for treatment. It is the subject for large double-blind randomized clinical therapeutic trials.

Carotid endarterectomy for asymptomatic plaque.

Statistical correlations are linear noninteractive relationships, but the dynamics of causation are nonlinear and involve complex interactions where variables change through their effect on one another and interact with the context of the patient over time. The discovery and interpretation of plaque vulnerable features in the individual patient are not determined for the asymptomatic patient being considered for carotid endarterectomy. New technologies for identification of plaque chemical and morphologic composition are on the horizon and may be applicable to certain patients but change in their usefulness as the plaque and patient change over time.

Thrombophilia in ischemic stroke subtypes: implications for treatment.

The current understanding of thrombogenesis is modeled on Virchow's triad: stasis, hypercoagulability, and vessel wall injury. There is a dynamic (always changing) nonlinear interaction between the vascular wall, blood components, and flow, which at times defined "pathologic" leads to thrombosis or hemorrhage, at other times called "healthy" to normal hemostasis. The triad named after Virchow was not designated as such in Virchow's work.

Sex difference in the antiplatelet effect of aspirin in patients with stroke.

Background: There is substantial interpatient variability in response to aspirin after an ischemic stroke or transient ischemic attack (TIA), as assessed by ex vivo effects of aspirin on platelet aggregation. The factors contributing to this variability are not well defined.

Objective: To determine whether demographic, social, or clinical characteristics are associated with ex vivo response to aspirin in patients with a history of stroke or TIA.

From fuzzy logic toward plurimonism: the science of active and empathic observation.

Plurimonism is a new philosophy and method of science. It holds that the revolution in computer science and artificial intelligence has reached the point that all the sciences in general can now account for the complex relations of an irreducible plurality of unique observers engaged in describing the same event. Plurimonism seeks to describe the conscious and unconscious relations of the scientific observer during the act of observation of a given event while preserving the historical uniqueness and indivisible identity of each such observer.

A fuzzy theory of cortical computation: neuropoietic engrams, fuzzy hypercubes, and the nature of consciousness.

We apply fuzzy logic to a theory of memory representation and computation in the human cerebral cortex. The theory termed neuropoiesis is based on the hypothetical transfer of mRNA polyribosomes from the post-synaptic dendritic spine of cortical pyramidal neurons to the presynaptic boutons of connecting axons through a hypothetical process termed retroduction. The net effect of this process is a vast increase in predicted memory storage.

Concomitant drug, dietary, and lifestyle issues in patients with atrial fibrillation receiving anticoagulation therapy for stroke prophylaxis.

Atrial fibrillation is a common cardiac arrhythmia and the leading risk factor for stroke. In those at moderate to high risk of stroke, oral anticoagulation therapy with warfarin (a vitamin K antagonist) significantly reduces not only the frequency of such events but also their severity and the associated risk of death. However, achieving optimal anticoagulation with this agent is clinically challenging in view of its complex pharmacokinetic and pharmacodynamic profile.

Fuzzy logic and continuous cellular automata in warfarin dosing of stroke patients.

"Evidence-based" recommendations for warfarin prescription in patients with history of ischemic stroke limit its use to prevention of stroke due to atrial fibrillation. Warfarin is also prescribed by the authors to prevent thrombosis in stroke patients with thrombophilia and potential cardiac or arterial source for thromboembolism. These potential conditions, in the face of thrombophilia, include, but may not be limited to, dilated cardiomyopathy, decreased left ventricular function, atrial septal aneurysm with or without patent foramen ovale (PFO), PFO with evidence of pelvic or lower extremity deep venous thrombosis or with clear thrombophilia, spontaneous echocardiographic contrast, intracardiac or intra-arterial thrombus, intra-aortic arch thrombus, high degree of stenosis of large- and medium-sized cerebrovascular arteries, and arterial dissection.

Fuzzy logic and causal reasoning with an 'n' of 1 for diagnosis and treatment of the stroke patient.

The current scientific model for clinical decision-making is founded on binary or Aristotelian logic, classical set theory and probability-based statistics. Evidence-based medicine has been established as the basis for clinical recommendations. There is a problem with this scientific model when the physician must diagnose and treat the individual patient.

New blood thinner offers first potential alternative in 50 years: ximelagatran.

Traditional anticoagulants employed in the treatment of thrombosis include the injectable heparins and oral warfarin. Though effective, these traditional agents are fraught with limitations in their ease of use in the clinical setting. Warfarin, for example, has many pharmacokinetic properties and food-and-drug interactions that result in unpredictable patient response and the need for expensive and time-consuming monitoring of coagulation status.

The application of fuzzy logic to the prescription of antithrombotic agents in the elderly.

The prescription of antithrombotic agents in the elderly depends, to certain degree, on the identity of the unique individual elderly patient. This dependence cannot be captured by viewing the patient as belonging to a group, but rather by viewing age in the context of unique individual biology. This context is historical, physiological, psychological, and time- and location-dependent.

Evolving concepts in the treatment of venous thromboembolism: the role of factor Xa inhibitors.

Anticoagulation is an essential component of the care of patients with venous thromboembolism (VTE). Traditional anticoagulants for the treatment of VTE include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and the oral vitamin K antagonist, warfarin. A variety of anticoagulant agents with improved pharmacologic and clinical profiles are emerging and offer benefits over the traditional therapies.

The fuzzy cube and causal efficacy: representation of concomitant mechanisms in stroke.

Twentieth century medical science has embraced nineteenth century Boolean probability theory based upon two-valued Aristotelian logic. With the later addition of bit-based, von Neumann structured computational architectures, an epistemology based on randomness has led to a bivalent epidemiological methodology that dominates medical decision making. In contrast, fuzzy logic, based on twentieth century multi-valued logic, and computational structures that are content addressed and adaptively modified, has advanced a new scientific paradigm for the twenty-first century.

The selection of antithrombotic agents in the prevention of recurrent ischemic stroke.

The scientific selection of antithrombotic therapy has been dominated by group-based interpretation of data in the form of probability-based statistics in evidence-based medicine. Because the data in large randomized trials are grouped and averaged, the relationship to initial conditions of the patient is lost. There is a pathologic model and basis by which antithrombotic agents may be chosen for prevention of recurrent thrombus and thromboembolism in patients with stroke.

Measurable differences between sequential and parallel diagnostic decision processes for determining stroke subtype: a representation of interacting pathologies.

Stroke diagnosis depends on causal subtype. The accepted classification procedure is a succession of diagnostic tests administered in an order based on prior reported frequencies of the subtypes. The first positive test result completely determines diagnosis.