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.     

A comparison of energy expenditure during rowing and cycling ergometry

Metabolic and cardiorespiratory responses of healthy adults were compared at similar incremental power outputs during a variable-resistance rowing exercise and a fixed-resistance cycle ergometer exercise. Repeated measurements of power (watts), VEBTPS, VO2 STPD, and HR were obtained on 60 men and 47 women ranging in age from 20 to 74 yr. Average maximal power output for the men was significantly higher (P less than 0.05) for cycling than rowing: 207 +/- 5.2 W vs 195 +/- 58 W (mean +/- SE). A similar difference was also observed for women favoring cycling: 135 +/- 4.1 W vs 126 +/- 4.9 W (mean +/- SE). VEBTPS, VO2 STPD, and HR were significantly higher at all power increments during the rowing graded exercise test (RGXT) when compared with the same exercise intensity during the cycle graded exercise test (CGXT). Consistent linearity was found between VEBTPS and VO2 STPD and between HR and VO2 STPD for both exercises. The linear relationship between VEBTPS and VO2 STPD for men during RGXT was r = 0.976, P less than 0.001, slope = 44.6 +/- 1.03, and for women during RGXT it was r = 0.990, P less than 0.001, slope = 19.6 +/- 0.36. The relationship between HR and VO2 STPD for men during rowing was r = 0.989, P less than 0.001, slope = 29.1 +/- 0.76, and for women during rowing it was r = 0.971, P less than 0.001, slope = 35.7 +/- 0.89. The linear relationship between VEBTPS and VO2 STPD for men during CGXT was r = 0.991, P less than 0.001, slope = 31.1 +/- 0.98, and for women it was r = 0.959, P less than 0.991, slope = 29.6 +/- 0.87. The relationship between HR and VO2 STPD for men during CGXT was r = 0.997, P less than 0.001, slope = 28.1 +/- 0.83, and for women it was r = 0.990, R less than 0.001, slope = 35.9 +/- 0.96. Results indicated that energy costs for rowing ergometry was significantly higher than cycle ergometry at all comparative power outputs including maximum levels. It was concluded that rowing ergometry could be an effective alternative activity for physical fitness and exercise rehabilitation programs.     

Cognitive profiles and the spectrum of clinical manifestations in heterozygous fra (X) females

We investigated the possibility that fra(X) heterozygotes had a distinct or specific set of mental deficits ("cognitive profile") which would allow for accurate diagnosis. Wechsler Intelligence Scale for Children-Revised (WISC-R) subtest scores obtained on 8 fra(X) school age girls were compared with similar scores obtained on 8 "learning-disabled" non fra(X) girls matched on the basis of Full Scale IQ (FSIQ). The Block Design subtest score was significantly lower in fra(X) girls. In a larger sample of 22 fra(X) females, a characteristic combination of low Arithmetic, Digit Span, and Block Design subtest scores was observed. The mean discrepancy between these 3 subtest scores from the total Verbal or Performance subtest means was significant for the fra(X) group but not for a comparison group of 20 learning-disabled females. Verbal IQ (VIQ) and Performance IQ (PIQ) discrepancy was not significant in fra(X) females. Percent fra(X) positive cells was negatively correlated with VIQ and FSIQ but not with PIQ.     

An analysis of autism in fifty males with the fragile X syndrome

Fifty males with the fragile X [fra(X)] syndrome, which we consider synonymous with the Martin-Bell syndrome, were identified by a chromosome analysis of patients with developmental delays or mental retardation and family studies of known fra(X) pedigrees. These males were evaluated for autism using three criteria: 1) the DSM III diagnostic criteria for Infantile Autism; 2) the Autism Behavior Checklist (ABC); and 3) the Diagnostic Checklist for Behavior Disturbed Children, Form E2. Sixteen percent of patients fulfilled all of the DSM III criteria for Infantile Autism and an additional 30% fulfilled criteria for Infantile Autism Residual State. Thirty-one percent of patients had autism using the ABC checklist but none of the patients fit the classical Kanner syndrome as described by the E2 questionnaire. Some autistic traits were seen in almost all of the 50 fra(X) patients, including eye avoidance in 90%, handflapping, handbiting or handstereotypies in 88%, and language delays with language peculiarities, usually echolalic speech, in 96%. A pervasive lack of responsiveness was seen in 18% at their present age and in 44% in earlier childhood only. Autistic symptoms are common in the fra(X) syndrome. Therefore, any patient with developmental delays and autism or autistic manifestations should have a chromosomal analysis, including fra(X) examination.     

术中大剂量放疗治疗局部复发头颈癌

该文旨在介绍Beth Israel医疗中心采用大剂量术中放疗(HDR-IORT)治疗复发头颈癌的经验。对2001-2010年间头颈癌局部复发接受大剂量HDR-IORT的患者进行回顾分析。结果,76例患者的87个部位在肿瘤切除后接受了治疗。术后2年控制率为62%。平均总生存期为19个月,其中42%的患     

Membrane fluidity changes accompanying phagocytosis in normal and in chronic granulomatous disease polymorphonuclear leukocytes

We have studied membrane fluidity changes in polymorphonuclear leukocytes (PMN) during phagocytosis. Membrane fluidity was assessed by electron spin resonance (ESR) using a nitroxide-substituted stearic acid analog (5DS) as a spin probe. PMN from normal subjects and from 3 CGD patients (2 males, 1 female) were incubated in Kreb's Ringers phosphate with or without opsonized zymosan. ESR spectra were obtained and the order parameter (S), which is inversely related to membrane fluidity, was calculated. Without zymosan addition, S for normal (0.638) and for CGD (0.635) were not significantly different (p less than 0.35). The S values indicate that under resting conditions the molecular environment of the CGD membrane is similar to that of normal PMN membranes. However, with addition of opsonized zymosan, the normal, but not the CGD, PMN showed a significant increase (CGD, S = 0.638; normal, S = 0.647; p less than 0.001). This change in S for the normals is consistent with a more restricted movement of 5DS. Treatment of normal PMN with a mixture of scavengers specific for H2O2 (catalase, 1600 U/ml), O2-.(superoxide dismutase, 100 micrograms/ml), and for HO., (sodium benzoate, 1mM) during zymosan stimulation gave S values similar to those of resting cells. Catalase alone also lowered S value, suggesting that H2O2 was instrumental in causing the initial S value increase. This idea was supported by studies in which CGD cells were incubated with zymosan in the presence of glucose oxidase, an enzyme that catalyzes glucose oxidation resulting in the direct reduction of molecular oxygen to H2O2. Our results indicate that reduced O2 by- products, particularly H2O2, can cause altered biophysical properties of PMN membrane during phagocytosis.     

Surface antigens on malignant Sezary and T-CLL cells correspond to those of mature T cells

Tumor cells from eight adult patients with T-cell chronic malignancies were investigated with a series of monoclonal antibodies recognizing T- cell differentiation antigens. This series allowed definition of discrete subpopulations of mature T cells with functional specialization. All six patients with Sezary syndrome and one patient with T-chronic lymphocytic leukemia had cells with the same phenotype as normal helper/inducer T cells, whereas the other patient with T- chronic lymphocytic leukemia had cell with the same phenotype as normal cytotoxic/suppressor T cells. Some clinical manifestations observed in these patients may reflect retention of functional activities by their malignant cells.     

Neuropsychological dysfunction among affected heterozygous fragile X females.

Fragile X (or Martin-Bell) syndrome is an X-linked disorder that often produces mental retardation in males, but usually affects heterozygous females to a lesser degree. Here we report the results of a brief neuropsychological examination of 20 heterozygous fra(x) girls and women and two control groups of 20 individuals each. One control group was composed of fra(x)-negative mothers (obligate carriers) and sisters of male probands with fra(x) syndrome, whereas the other was composed of 14 head-injured and six learning disabled women and girls. In addition to general intellectual impairment, several specific cognitive deficits were consistently found in individuals with the Martin-Bell syndrome, suggesting focal neuropsychological dysfunction. Significant differences were noted between fra(x) individuals and controls on most cognitive and neuropsychological measures studied. Over one-third of the fra(x) individuals demonstrated neuropsychological symptoms characteristic of the full developmental Gerstmann syndrome, whereas another third had three or four of the five signs of possible parietal lobe dysfunction. In our sample, there was an association between improved performance and increasing age. Differences among heterozygous individuals in number of focal symptoms may reflect some variability in the penetrance of the fra(x) gene, as well as in the functional organization of the brain.