Consideration of connective tissue dysfunction in the fragile X syndrome

Eleven cytogenetically documented patients with the fragile X syndrome were evaluated for hyperextensibility of the finger joints and the presence of other manifestations of connective tissue dysfunction. All of the patients had hyperextensibility of several finger joints and many had features such as flat feet, highly arched palate and the ability to voluntarily dislocate finger joints. These traits, particularly hyperextensibility of the joints, are a useful aid in the clinical diagnosis of the fragile X syndrome.     

Exercise improves biomarkers of health and stress in animals fed ad libitum

Voluntary and forced exercise decrease morbidity and mortality in laboratory animals. Caloric restriction has similar effects on health and unique benefits on life span. Nonetheless, in most experiments, animals do not have access to physical activity and are fed ad libitum (AL). We hypothesized that with regular access to either unlimited running wheel exercise (EX) or limited physical activity (PA), key biomarkers of health would be enhanced enough to counter some consequences of a sedentary AL lifestyle. This 16-month study compared body weight, tumor number and size, tissue lesions, oxidative stress, and reactive stress in (1) sedentary animals with no access to physical activity (SED); (2) animals with access to hour-long, twice weekly activity in a large box (PA); and (3) animals with access every other day to a running wheel (EX). At the end of the study, EX body weight was 8-9% lower than PA and SED. In addition, EX had no kidney lesions versus 50% in PA and SED, and had smaller tumor size (10+/-2 vs. 14+/-4 and 30+/-4 mm). Exhaustive exercise lowered glutathione/oxidized glutathione ratio in EX and PA, but in SED, the ratio was depressed even in resting animals. In all treatments, prolactin (PRL) levels were lower in resting animals than in acutely exercised animals. In conclusion, EX had the most favorable health biomarkers while SED had the least. PA did not confer gross health benefits different than the SED group, but was biochemically more similar to EX animals.     

Social cognition skills among females with fragile X

Emotion perception and perspective-taking skills were examined among women with or without the fragile X gene. The performance of 56 control women was compared to the performance of 46 women who were carriers of the fragile X gene. Twenty-seven of the carrier women had 0–1% cytogenetic expression and did not appear affected by the gene, whereas the remaining 19 women had 2% cytogenetic expression and did appear affected by the gene. The emotion perception task employed was one for which deficits have been reported among individuals with autism. The results show that performance on this emotion-perception test and the perspective-taking measure was significantly related to full-scale IQ scores, but not to fragile X group status when effects of IQ were removed. Thus the results do not support the hypothesis that perspective-taking or emotion perception deficits are a component of the fragile X phenotype in females and represent an important differentiation between fragile X and autism.This research was supported by NIMH Grant MCJOOO252 U.S. Department of Health and Human Services, Bureau of Maternal and Child Health; and by grant MH45916 U.S. National Institutes of Health (NIMH). Randi J. Hagerman and Michele M. M. Mazzocco received additional support from a grant from Joslins Department Store, Denver, Colorado. Hagerman received support from grant RR-69 from the General Clinical Research Program, National Center for Research Resources, National Institutes of Health. Bruce F. Pennington was supported by an RSDA (MH0419) and MERIT award (MH38870) from NIMH, as well as by an NICHD Center Grant (HD27802). The authors thank all the women who participated in the study and Dennis Lucky and Barrett Jeffers from the Kempe Research Center at The Children's Hospital.     

Hemin enhances the in vitro growth of primitive erythroid progenitor cells

Since exogenous hemin has been shown to exert a variety of stimulatory effects on erythroid cells, including the augmentation of hemoglobin synthesis, we determined its effect on early stages of erythroid development by employing clonal cells assays. The addition of hemin at a concentration of 2 X 10(-4) M to cultures of normal murine marrow substantially increased the observed number of primitive BFU-E, which was in contrast to its lack of an effect on more mature erythroid colony-forming cells. This cell-specific enhancement of primitive BFU-E resulted in marrow frequencies equivalent to or exceeding those reported in the presence of "burst-promoting activity." In the presence of hemin, the number of BFU-E was also observed to be linearly related to the number of cells plated at very low plating densities, and the cell titration curve was observed to extrapolate to the origin. The evidence suggests that hemin may be a primary growth regulator of early developmental stages of erythroid progenitor cells.     

Fragile X‐associated tremor/ataxia syndrome (FXTAS) in grey zone carriers

The grey zone (GZ; 45–54 CGG repeats in the FMR1 gene) is considered a normal allele; however, several studies have found a high frequency of GZ in movement disordered populations. Here, we describe neurological features of fragile X‐associated tremor/ataxia syndrome (FXTAS) in two carriers of GZ alleles, although FXTAS has been defined as occurring only in premutation carriers (55–200 CGG repeats). Both patients had family members who had premutation and were diagnosed with FXTAS. The presence of relatively high GZ alleles with elevated fragile X mental retardation 1 mRNA (FMR1‐mRNA) combined with a family history of FXTAS that may represent a facilitating genetic background for FXTAS are the factors that led to the presence of FXTAS in these individuals with a GZ allele. Further research into clinical involvement of GZ alleles is recommended and the definition of FXTAS may require revision.     

Neurological disease caused by Oropouche virus in northern Brazil: should it be included in the scope of clinical neurological diseases?

Journal of NeuroVirology - We describe two neurological cases of Oropouche virus infection in northern Brazil, where the virus is endemic but neglected as a pathogen. This study reiterates the...     

Electrocardiogram signal variance analysis in the diagnosis of coronary artery disease—A comparison with exercise stress test in an angiographically documented high prevalence population

Variance electrocardiography (variance ECG) is a new resting procedure for detection of coronary artery disease (CAD). The method measures variability in the electrical expression of the depolarization phase induced by this disease. The time-domain analysis is performed on 220 cardiac cycles using high-fidelity ECG signals from 24 leads, and the phase-locked temporal electrical heterogeneity is expressed as a nondimensional CAD index (CAD-I) with the values of 0–150. This study compares the diagnostic efficiency of variance ECG and exercise stress test in a high prevalence population. A total of 199 symptomatic patients evaluated with coronary angiography was subjected to variance ECG and exercise test on a bicycle ergometer as a continuous ramp. The discriminant accuracy of the two methods was assessed employing the receiver operating characteristic curves constructed by successive consideration of several CAD-I cutpoint values and various threshold criteria based on ST-segment depression exclusively or in combination with exertional chest pain. Of these patients, 175 with CAD (≥ 50% luminal stenosis in 1 + major epicardial arteries) presented a mean CAD-I of 88 ± 22, compared with 70 ± 21 in 24 nonaffected patients (p < 0.01). Variance ECG provided a stochastically significant discrimination (p < 0.01) which was matched by exercise test only when chest pain variable was added to ST-segment depression as a discriminating criterion. Even then, the exercise test diagnosed single-vessel disease with a significantly lower sensitivity. At a cutpoint of CAD-I ≥ 70, compared with ST-segment depression ≥ 1 mm combined with exertional chest pain, the overall sensitivity of variance ECG was significantly higher (p < 0.01) than that of exercise test (79 vs. 48 %). When combined, the two methods identified 93% of coronary angiography positive cases. Variance ECG is an efficient diagnostic method which compares favorably with exercise test for detection of CAD in high prevalence population.