The internal validity of aphasiological single-subject studies

Abstract

Several years ago I encountered a severely aphasic patient who happened to be the Cribbage champion of the hospital in which I was an intern (his competition being nonaphasic patients from the Medical and Orthopaedic Wards). Cribbage is a card game with a set ofcomplex rules that places a premium on arithmetic ability, strategy and memory. He was capabIe oflittle speech output, showed at least moderate deficits in auditory comprehension and suffered from a dense right hemiparesis that made it nearly impossible for him to hold the playing cards himself. In spite ofthese problems he was able to consistently out-play patients with simiIar educational backgrounds who had no difficulty speaking or understanding speech.     

Selective impairment of frontal-executive cognitive function in african americans with cardiovascular risk factors

OBJECTIVES: To determine whether a summary cardiovascular risk score is associated with an increased risk of frontal-executive cognitive impairment. DESIGN: Cross-sectional study. SETTING: Subjects were recruited from senior centers, senior housing complexes, and communities in the Boston metropolitan area. PARTICIPANTS: Forty-three predominantly female elderly African Americans. MEASUREMENTS: Cardiovascular risk factors were assessed during an interview and clinical examination. For each subject, the total number of cardiovascular (CV) risk factors was summed to compute a CV risk score. A battery of neuropsychological tests was administered that examined memory, visuospatial abilities, and frontal-executive functions. Cognitive test scores were transformed into domain-specific (memory, visuospatial, frontal-executive) composite z scores. Cognitive impairment for each composite z score was defined as performance less than the median for the study group. Multivariate logistic regression was used to examine the relationship between the CV risk score and the risk for cognitive impairment in the three cognitive domains of interest. RESULTS: After controlling for age and education, the CV risk score was associated only with frontal-executive cognitive impairment (odds ratio (OR)=2.44, 95% confidence interval (CI)=1.06-5.65). The CV risk score was not associated with the risk of memory (OR=1.30, 95% CI=0.64-2.67) or visuospatial impairment (OR=1.49, 95% CI=0.66-3.36). Greater CV risk scores were associated with an increased likelihood of having frontal-executive cognitive impairment. CONCLUSION: CV risk factors may exert a specific deleterious effect on frontal-executive cognitive abilities as opposed to memory or visuospatial functions. Associated executive dysfunction may compromise the ability of patients with CV risk factors to comply with recommendations for risk reduction.     

Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice

PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent increase in megakaryocytes and platelets. At the same time that platelet numbers are increased, the mean platelet volume (MPV) and platelet distribution width (PDW) can be either decreased, normal, or increased depending on the dose and time after administration. Thus, PEG-rHuMGDF at a low dose causes decreases in MPV and PDW, MGDF at an intermediate dose causes an initial increase followed by a decrease in MPV and PDW, and PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a gradual normalization of these platelet indices. In addition to the expected thrombocytosis after 7 to 10 days of daily injection of high doses of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers and hemoglobin is noted accompanied in the bone marrow by megakaryocytic hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and deposition of a fine network of reticulin fibers. Splenomegaly, an increase in splenic megakaryocytes, and extramedullary hematopoiesis accompany the hematologic changes in the peripheral blood and marrow to complete a spectrum of pathologic features similar to those reported in patients with myelofibrosis and megakaryocyte hyperplasia. However, all the PEG-rHuMGDF-initiated hematopathology including the increase in marrow reticulin is completely and rapidly reversible upon the cessation of administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation of megakaryocytes does not cause irreversible tissue injury. Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.     

Effect of blood pressure on cognitive functions in elderly persons

BACKGROUND: Little is known about what specific cognitive functions are affected by elevated blood pressure (BP) and how orthostatic BP change is related to cognitive impairment. The aim of this study was to determine the effect of BP and its postural change on cognitive functions in otherwise healthy elders. METHODS: In 70 healthy persons (mean age, 72 +/- 4 years), supine systolic BP (SBP) was assessed 3 times using a sphygmomanometer, and the average values were obtained for the analysis. After 1, 3, and 5 minutes of standing, 3 BP measurements were obtained and the orthostatic SBP changes were determined by subtracting these values from the supine average. Neuropsychological tests were administered to assess short-term and long-term verbal and visual memory, visuospatial skills, and frontal-executive functions. Participants were considered impaired in the specific cognitive performance if their scores fell below the 25th percentile of the study population. Multiple logistic regression models were used to evaluate the relation of SBP and the magnitude of orthostatic SBP decline to risk for impairment in each of the cognitive tests. RESULTS: Controlling for potential confounders, each 10 mmHg increase in supine SBP was associated with a 2.31-fold increase (95% confidence interval, 1.14 to 4.66) in risk for impairment in psychomotor speed and set shifting as measured using the Trailmaking Part-B test. There was no significant association between cognitive functions and orthostatic SBP decline at 1, 3, and 5 minutes of standing. CONCLUSION: Elevation of BP is associated with a selective impairment in executive function in otherwise healthy community-dwelling elders.     

New Insights into the Beneficial Electrophysiologic Profile of Ranolazine in Heart Failure: Prevention of Ventricular Fibrillation With Increased Postrepolarization Refractoriness and Without Drug-Induced Proarrhythmia

BackgroundRanolazine inhibits late Na⁺ and K⁺ currents. Earlier studies have reported an antiarrhythmic effect. The aim of the present study was to understand whether ranolazine could still preserve its antiarrhythmic properties in the settings of chronic heart failure (CHF).Methods and ResultsIn 12 female rabbits, CHF was induced by 4 weeks of rapid ventricular pacing leading to a decrease in ejection fraction. Twelve rabbits underwent sham operation. Isolated hearts were Langendorff perfused and demonstrated a significant QT prolongation after induction of heart failure. Ranolazine caused a concentration-dependent (10 and 30 μmol/L) increase of action potential duration (APD₉₀) in sham-operated and failing hearts. Eight endo- and epicardial monophasic action potentials revealed a nonsignificant increase in spatial and temporal dispersion of repolarization. The increase in APD₉₀ was accompanied by a greater increase in refractory period, resulting in a significant increase in postrepolarization refractoriness in sham-operated (+29 ms and +55 ms; P < .01) and failing (+22 ms and +30 ms; P < .05) hearts. In control conditions, programmed ventricular stimulation and a burst pacing protocol led to ventricular fibrillation (VF) in 5 of the 12 sham-operated (6 episodes) and in 7 of the 12 failing (18 episodes) hearts. In the presence of ranolazine, VF was inducible in only 2 of 12 failing hearts (5 episodes). In the presence of low [K⁺], only 1 ranolazine-treated sham-operated heart developed early afterdepolarizations and ventricular tachyarrhythmias despite significant QT prolongation.ConclusionsRanolazine decreases inducibility of VF in the presence of a significant increase in postrepolarization refractoriness. This antiarrhythmic effect in the intact heart is preserved in CHF and is not associated with drug-induced proarrhythmia.