ABSTRACT
The accuracy of the diagnostic criteria for Friedreich's ataxia proposed by Harding and by the Quebec Cooperative Study on Friedreich's Ataxia was studied in 142 patients with progressive unremitting ataxia of autosomal recessive inheritance or sporadic occurrence. Eighty-eight patients received the molecular diagnosis of Friedreich's ataxia. Traditional diagnostic criteria are characterized by high specificity, but they yield a high number of false-negative diagnoses. We suggest three levels of diagnostic certainty: (1) possible Friedreich's ataxia, defined as sporadic or recessive progressive ataxia with (a) lower limb areflexia and dysarthria, Babinski sign, or electrocardiographic repolarization abnormalities, or (b) with lower limb retained reflexes and electrocardiographic repolarization abnormalities (95% sensitivity and 88% positive predictive value); (2) probable Friedreich's ataxia as defined by Harding's criteria (63% sensitivity and 96% positive predictive value) or by Quebec Cooperative Study on Friedreich's Ataxia criteria (63% sensitivity and 98% positive predictive value); (3) definite diagnosis, molecularly confirmed.
Subject(s)
Friedreich Ataxia/diagnosis , Friedreich Ataxia/genetics , Point Mutation , Adolescent , Adult , Age of Onset , Child , Child, Preschool , DNA Mutational Analysis/methods , Diagnosis, Differential , Female , Heterozygote , Homozygote , Humans , Male , Middle Aged , Predictive Value of Tests , Reference Standards , Sensitivity and Specificity , Trinucleotide Repeat ExpansionABSTRACT
OBJECTIVES: To investigate the effects of ischemic preconditioning in hearts from adult and both sedentary and trained senescent rats. BACKGROUND: Ischemic preconditioning does not prevent postischemic dysfunction in the aging heart, probably because of reduction of cardiac norepinephrine release. Exercise training can reverse the age-related decrease of norepinephrine production. METHODS: We investigated the effects on mechanical parameters of ischemic preconditioning against 20 min of global ischemia followed by 40 min of reperfusion in isolated perfused hearts from adult (six months) and sedentary or trained (six weeks of graduated swim training) senescent (24 months) rats. Norepinephrine release in coronary effluent was determined by high-performance liquid chromatography. RESULTS: Final recovery of percent-developed pressure was significantly improved after preconditioning in adult hearts (91.6+/-9.6%) versus unconditioned controls (54.2+/-5.1%, p<0.01). The effect of preconditioning on developed pressure recovery was absent in sedentary but present in trained senescent hearts (39.6+/-4.1% vs. 64.3+/-7.1%, p<0.05). Norepinephrine release significantly increased after preconditioning in adult and in trained but not in sedentary senescent hearts. The depletion of myocardial norepinephrine stores by reserpine abolished preconditioning effects in adult and trained senescent hearts. CONCLUSIONS: In adult and trained but not in sedentary senescent hearts, preconditioning reduces postischemic dysfunction and is associated with an increase in norepinephrine release. Preconditioning was blocked by reserpine in both adult and trained senescent hearts. Thus, exercise training may restore preconditioning in the senescent heart through an increase of norepinephrine release.
