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Biomedical subjects

C M Helgason

Publications and source records attributed to C M Helgason.

At least 19 recordsLinked to original sources
PubMed2001

Statistical versus fuzzy measures of variable interaction in patients with stroke.

UNLABELLED: Evidence-based medicine, founded in probability-based statistics, applies what is the case for the collective to the individual patient. An intuitive approach, however, would define structure in the (physiologic) system of interest, the human being, directly relevant to other systems (patients) composed of similar variables. A difference in measure of variable interaction in the patient from that in the collective would show how extrapolation of information from the latter to the single patient is counterintuitive. METHODS: We compare statistical to 'fuzzy' measures of variable interaction. Three diagnostic variables are considered in 30 stroke patients who underwent the same diagnostic tests. 'Fit' (fuzzy information) values [0, 1] for degree of variable severity were expertly assigned by 2 blinded raters for real and fabricated patients. Fabricated patients were composed of real-patient 'fit' values after shuffling. Real and fabricated patients were each numerically represented as a set. Three groups of fabricated patients and the real patient group were studied. Statistical [Pearson's product-moment (regression analysis) and Spearman's rank correlation] and three different fuzzy measures of variable interaction were applied to patient data. RESULTS: Interaction for blood-vessel measured strong in real patients, and weak after one shuffle, using all fuzzy measures. By comparison, the same interaction was found in real patients by only 1 rater (Rater 2) using 1 statistical technique (Spearman's rank correlation) which, as did Pearson product-moment correlation, found a 'significant' interaction between blood-heart in fabricated patients. CONCLUSION: Our study suggests that the measure of variable interaction in nature - as combined in the individual (real) patient - is captured robustly by fuzzy measures and not so by standard statistical measures.

Evidence-Based Medicine↗
PubMed2001

Novel approach for the determination of the redox status of homocysteine and other aminothiols in plasma from healthy subjects and patients with ischemic stroke.

BACKGROUND: Plasma "redox" status can be assessed by measurements of reduced (r)-, free (f)-, oxidized (ox)-, and protein-bound (b)-homocysteine (Hcy) plus the related aminothiols cysteine, cysteinylglycine (CysGly), and glutathione (GSH), but sample collection has been complex. The redox status has not been determined in ischemic stroke patients and may provide increased understanding of its role in pathogenesis. We wished to examine the feasibility of this measurement in samples collected in readily available acidic sodium citrate. METHODS: We measured aminothiols and their stability in stabilized protein-free filtrate using acidic sodium citrate (BioPool Stabilyte, pH 4.3) vs EDTA whole blood. Before analysis, plasma samples were also ultrafiltered to obtain a protein-free filtrate. The concentrations of total Hcy (tHcy), fHcy, and rHcy and their related aminothiols, cysteine, cysteinylglycine, and glutathione were simultaneously determined on acidic sodium-citrated blood using reversed-phase HPLC with fluorescence detection. Bound and oxidized aminothiols were calculated by difference using the concentrations of the total, free, and reduced fractions. Using this approach, we compared the redox status in newly diagnosed ischemic stroke patients (n = 20) and healthy age- and sex-matched subjects (n = 20). RESULTS: tHcy, tCys, tCysGly, and tGSH concentrations in whole blood with Stabilyte were stable for 8 h; the reduced fraction of each aminothiol was stable for 4 h. Recovery in the protein-free filtrate was 90-100% for all reduced thiols in acidified sodium-citrated blood. Patients with ischemic stroke had higher plasma tHcy, fHcy, bHcy, rHcy, and oxHcy (P <0.0005) and higher plasma t-, f-, r-, and oxCys (P <0.05). t-, b-, and rCysGly concentrations were lower in the stroke patients (P <0.05), as were t-, b-, and oxGSH (P <0.005). CONCLUSIONS: Collection of blood in acidic sodium citrate (BioPool Stabilyte) permits the determination of the redox status of Hcy and its related aminothiols, which may add to the understanding of their relationship to the etiology of cerebrovascular disease.

Adult↗
PubMed2000

The effects of St. John's Wort (Hypericum perforatum) on NK cell activity in vitro.

St. John's Wort (Hypericum perforatum; H. perforatum) is a popular herbal supplement used to treat mild to moderate depression. H. perforatum possesses serotonergic properties such as inhibition of serotonin (5-hydroxytryptamine; 5-HT) reuptake. Serotonergic pharmacotherapy is associated with amelioration of depression as well as increases in natural killer (NK) cell activity (NKCA). Also, 5-HT and 5-HT analogs augment NKCA in vitro. Considering the serotonergic properties of H. perforatum, the effects of H. perforatum on NKCA were assessed in vitro. Mononuclear cells (MNCs) from normal donors were exposed in vitro to an extract of H. perforatum (LI160s) or established 5-HT stimulators of NKCA. After an overnight incubation, cells were washed and a standard 51Cr-release cytotoxicity assay performed to assess NKCA. LI160s at all concentrations failed to augment NKCA. However, in corroboration of previous studies, 5-HT, the selective serotonin reuptake inhibitors (SSRIs), paroxetine and norfluoxetine, and alpha-interferon augmented NKCA above control levels. Though an efficacious treatment for mild to moderate depression, H. perforatum differs from commonly prescribed serotonergic antidepressants insofar as H. perforatum fails to enhance NKCA in vitro. Therefore, the present results are consistent with pharmacologic studies indicating that H. perforatum possesses, at best, weak serotonergic activity.

Adult↗
PubMed1999

Causal interactions, fuzzy sets and cerebrovascular 'accident': the limits of evidence-based medicine and the advent of complexity-based medicine.

In evidence-based medicine, stroke subtype is diagnosed after a sequential search for etiology; the first positive test result of significant severity rounds off to one overwhelming cause. Degree of severity, interaction among variables, and concomitant variable conditions are not considered in defining the cause of stroke. Yet, thrombus formation, and possibly vascular rupture, is an interactive process involving the vascular wall, flow properties of the blood and blood constituents; this process occurs in homeostasis and pathology. Evidence-based medicine ignores this process and instead studies stroke using crisp 'all or none' classification where subtypes are distinct and interactively relate only to outcome. As a result, scientific inquiry is focused on prediction for the collective of patients. The statistical approach of evidence-based medicine is founded on probability theory, itself rooted in classical set theory where elementhood is all (1) or none (0), and opposites interact only to form the null set. Fuzzy set theory, where set membership is to degree [0, 1], encompasses classical set theory, allows for an interactive process between variables, and therefore becomes the measure of complexity. Fuzzy set theory can change the scientific method of evidence-based medicine.

Cerebrovascular Disorders↗
PubMed1994

Carotid stenosis in patients with atrial fibrillation. Prevalence, risk factors, and relationship to stroke in the Stroke Prevention in Atrial Fibrillation Study.

BACKGROUND: Several mechanisms contribute to the increased stroke rate of patients with atrial fibrillation (AF). We assessed the frequency of carotid artery stenosis in patients with AF and its relationship to stroke during aspirin or warfarin therapy. METHODS: Carotid ultrasonography was done in 676 patients with AF enrolled in the Stroke Prevention in Atrial Fibrillation Study to detect cervical carotid stenosis of 50% or more of the luminal diameter. The presence of carotid stenosis was correlated with patient features and subsequent stroke during a mean of 2.6 years of follow-up. RESULTS: In patients with AF who were older than 70 years, the frequency of carotid stenosis was 12% in men and 11% in women. Carotid stenosis was independently associated with systolic hypertension (relative risk, 2.4; P = .002), diabetes (relative risk, 1.8; P = .04), and tobacco use (relative risk, 1.8; P = .02). Carotid stenosis did not add significantly to prediction of stroke when analyzed with other clinical risk factors for stroke in patients with AF (relative risk, 1.3; 95% confidence interval, 0.5 to 3.6; P = .55). CONCLUSIONS: Carotid artery stenosis of 50% or more occurs in about 12% of elderly patients with AF, reflecting the substantial prevalence of hypertension and diabetes in these patients. Carotid stenosis was not usefully predictive of stroke in patients with AF who were given aspirin or warfarin. Routine ultrasonography to detect carotid stenosis does not appear warranted in patients with AF without previous symptoms of brain ischemia.

Aged↗
PubMed1994

Development of aspirin resistance in persons with previous ischemic stroke.

BACKGROUND AND PURPOSE: The ex vivo effect of aspirin (ASA) on platelet aggregation, the platelet component of thrombosis, was studied at repeated intervals in a cohort of patients taking aspirin for recurrent ischemic stroke prevention to define the maintenance of efficacy over time. METHODS: We administered increasing doses of aspirin (from 325 to 1300 mg/d) to patients with previous ischemic stroke and determined the extent of inhibition of platelet aggregation after 2 weeks and thereafter at approximately 6-month intervals. RESULTS: Over 33 months, 306 patients had platelet aggregation studies performed to define their initial response to ASA therapy. Of these, 228 had complete and 78 had partial inhibition of platelet aggregation at initial testing. To date, 119 of those who had complete inhibition and 52 who had partial inhibition have undergone repeat testing at least once. At repeat testing 39 of the 119 (32.7%) with complete inhibition at initial testing had lost part of the antiplatelet effect of ASA and converted from complete to partial inhibition without change in ASA dosage. Of the 52 with partial inhibition at initial testing, 35 achieved complete inhibition either by ASA dosage escalation (in 325 mg/d increments) or fluctuation of response at the same dosage, but 8 of those 35 (22.8%) had reverted to partial inhibition when tested again. Overall, 8.2% of patients ultimately exhibited ASA resistance to 1300 mg/d-8 of 52 (15.4%) with partial inhibition and 6 of 119 (5.0%) with complete inhibition at initial testing. CONCLUSIONS: The antiplatelet (and presumably the antithrombotic) effect of a fixed dose of ASA is not constant over time in all individuals. The mechanisms by which increased dosage requirement or ASA resistance develops and the clinical significance of this development are currently undefined.

Adenosine Diphosphate↗
PubMed1993

Platelet aggregation in patients with atrial fibrillation taking aspirin or warfarin.

BACKGROUND AND PURPOSE: Although warfarin and perhaps aspirin may be effective in preventing thromboembolism in patients with nonvalvular atrial fibrillation, some patients develop cerebral infarction despite these therapies. The purpose of this study was to determine inhibition of platelet aggregation in patients on aspirin and platelet reactivity in those on warfarin in the Stroke Prevention in Atrial Fibrillation study. METHODS: Twenty-four patients in the Stroke Prevention in Atrial Fibrillation study at the University of Illinois at Chicago, 17 on enteric-coated aspirin 325 mg/d and 7 on warfarin to produce an International Normalized Ratio of 2.0 to 4.5, had platelet aggregation studies performed during a 10-month period and interpreted by an investigator blinded to therapy. Epinephrine, adenosine diphosphate, collagen, and arachidonic acid were used as aggregating agents. Compliance was determined by pill count for those patients on aspirin. RESULTS: Seven patients taking aspirin had partial and 10 had complete inhibition of platelet aggregation. Three of seven patients on warfarin had hyperaggregable platelets. Compliance was 80% or greater for those patients taking aspirin. One patient on warfarin had partial inhibition of platelet aggregation. CONCLUSIONS: Some patients in the Stroke Prevention in Atrial Fibrillation trial on aspirin 325 mg/d did not achieve complete inhibition of platelet aggregation. Others had hyperaggregable platelets. These findings suggest platelet-dependent mechanisms for aspirin and warfarin failure to prevent stroke in these patients.

Adenosine Diphosphate↗
PubMed1993

Aspirin response and failure in cerebral infarction.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the biological effect of aspirin as measured by the inhibition of platelet aggregation in patients taking aspirin for stroke prevention and in patients with acute stroke. METHODS: We administered increasing doses of aspirin (325, 650, 975, and 1,300 mg daily) to 113 patients for stroke prevention and measured the inhibition of platelet aggregation in these patients and in 33 patients with acute stroke taking aspirin before stroke onset. RESULTS: Eighty-five patients on < or = 325 and six on > or = 650 mg aspirin had complete inhibition of platelet aggregation. Increase of the dose by 325 mg in nine of the 22 patients with partial inhibition of platelet aggregation produced complete inhibition in five patients at 650 mg and in one at 975 mg. At 1,300 mg, three patients still had only partial inhibition of platelet aggregation (aspirin resistance). Of the 33 inpatients with acute stroke, 24 had platelet aggregation studies done before further administration of aspirin. Of these, 19 had complete inhibition of platelet aggregation and three had partial inhibition, with production of complete inhibition of platelet aggregation at dose escalation; one patient was aspirin-resistant and the other noncompliant. CONCLUSIONS: How the inhibition of platelet aggregation relates to stroke prevention remains unclear. The ability of aspirin and the dose required to inhibit platelet aggregation may depend upon the individual.

Aged↗