Axial myopathy due to primary amyloidosis

A 74-year-old man presented with progressive weakness involving only his back muscles. Serum protein electrophoresis revealed the presence of a monoclonal gammopathy. Muscle biopsy of affected muscles demonstrated amyloid light chain deposition surrounding individual muscle fibers as well as in the walls of blood vessels in association with vasculitis. Selective involvement of axial muscles in isolated amyloid myopathy has not been previously described. We report the occurrence of axial myopathy with associated vasculitis as a presenting feature of primary (AL) amyloidosis. Amyloidosis should be considered in the differential diagnosis of focal myopathies, since the condition may be responsive to chemotherapy.     

A novel multidomain computerized cognitive assessment for attention-deficit hyperactivity disorder: evidence for widespread and circumscribed cognitive deficits

Multidomain assessment may enhance the diagnosis of cognitive impairment in children with attention-deficit hyperactivity disorder (ADHD). A set of novel Web-enabled computerized tests has recently been shown to be valid for identifying mild cognitive impairment and characterizing the cognitive profile associated with various disorders. It was anticipated that these tests would be well suited for use in children with ADHD. The authors tested this idea in a pilot study of 15 children (12 males, 3 females; mean age, 11 years 10 months; range, 9-15 years) with ADHD and 15 age-, education-, and gender-matched controls. The profile of cognitive impairment in ADHD children off methylphenidate across 6 cognitive domains (memory, executive function, visual-spatial skills, verbal function, attention, and motor skills) was described relative to controls. The effect of treatment with methylphenidate was examined by comparing the ADHD children on methylphenidate and on placebo (administered in a double-blind randomized fashion) relative to controls and by comparing the ADHD children on methylphenidate relative to placebo. Significant impairment in ADHD was evident in memory, visual-spatial, verbal, and attention domains, and near-significant impairment was observed in executive function and motor skills. On methylphenidate but not placebo, performance was comparable to controls in immediate verbal memory, psychomotor accuracy, visual-spatial, verbal rhyming, and overall battery performance. Significant improvement with administration of methylphenidate relative to placebo was evident for psychomotor accuracy, verbal rhyming, and overall battery performance. Hence, on the limited basis of this pilot study, the set of computerized tests studied appears to be useful for measuring cognitive function in ADHD; however, additional studies are needed to confirm this.     

Neurological manifestations of folate transport defect: case report and review of the literature

Folate is essential for normal brain development. This report describes a 15-month-old boy who presented with generalized and focal seizures and a decline in mental status. Laboratory tests revealed low folate levels in blood (1.13 nmol/L) and cerebrospinal fluid, accompanied by pancytopenia. Bone marrow aspiration confirmed the presence of megaloblastic anemia. Treatment with high-dose intravenous folinic acid led to normalization of cerebrospinal folate levels. These findings apparently indicate a defect in folic acid transport to the central nervous system. A clinical picture of developmental arrest, seizures, somnolence, and megaloblastic anemia should alert physicians to the possibility of folate deficiency.     

Validation of a swallowing disturbance questionnaire for detecting dysphagia in patients with Parkinson's disease.

Underreporting of swallowing disturbances by Parkinson's disease (PD) patients may lead to delay in diagnosis and treatment, alerting the physician to an existing dysphagia only after the first episode of aspiration pneumonia. We developed and validated a swallowing disturbance questionnaire (SDQ) for PD patients and compared its findings to an objective assessment. Fifty-seven PD patients (mean age 69 +/- 10 years) participated in this study. Each patient was queried about experiencing swallowing disturbances and asked to complete a self-reported 15-item "yes/no" questionnaire on swallowing disturbances (24 replied "no"). All study patients underwent a physical/clinical swallowing evaluation by a speech pathologist and an otolaryngologist. The 33 patients who complained of swallowing disturbances also underwent fiberoptic endoscopyic evaluation of swallowing (FEES). According to the ROC test, the "optimal" score (where the sensitivity and specificity curves cross) is 11 (sensitivity 80.5%, specificity 81.3%). Using the SDQ questionnaire substantially reduced Type I errors (specifically, an existing swallowing problem missed by the selected cutoff point). On the basis of the SDQ assessment alone, 12 of the 24 (50%) noncomplaining patients would have been referred to further evaluation that they otherwise would not have undergone. The SDQ emerged as a validated tool to detect early dysphagia in PD patients.     

Risk-taking behaviors among Israeli adolescents exposed to recurrent terrorism: provoking danger under continuous threat?

OBJECTIVE: This study aimed to assess 1) the relationship between risk-taking behaviors and exposure to terrorism, 2) the relationship between posttraumatic symptoms and risk-taking behaviors, and 3) gender differences in the type and frequency of risk-taking behaviors and their differential associations with posttraumatic symptoms. METHOD: The participants were 409 Israeli adolescents 15 to 18 years of age. Exposure to terrorism was assessed with a questionnaire developed specifically for the Israeli security situation. Posttraumatic symptoms were measured with the University of California at Los Angeles Reaction Index. Functional impairment was measured with the Diagnostic Interview Schedule for Children. Risk-taking behavior-and the adolescents' perceptions of such behavior-was assessed with a self-report questionnaire. RESULTS: Israeli adolescents exposed to continuous threats of terrorist attacks reported high levels of risk-taking behaviors. The severity of risk-taking was associated with greater terrorism exposure. Adolescents suffering from posttraumatic symptoms reported more risk-taking behaviors than nonsymptomatic adolescents. Although there was no gender difference in the degree of exposure to terrorism, boys reported taking more risks than girls. The association between posttraumatic symptoms and risk-taking behaviors was stronger in boys than girls. Functional impairment, gender, avoidance symptoms, level of exposure, and degree of fear predicted the severity of risk-taking behaviors. CONCLUSIONS: Clinicians and educators should be aware of the strong link between posttraumatic distress and risk-taking behaviors. Risk-taking behaviors may be a manifestation of functional impairment and posttraumatic distress, especially for boys exposed to terrorism.     

Clinical evaluation (Phase I) of a human monoclonal antibody against hepatitis C virus: safety and antiviral activity

BACKGROUND/AIMS: HCV-AB68, a human monoclonal antibody against the envelope protein of hepatitis C virus (HCV), neutralizes HCV in cell-culture and in the HCV-Trimera mouse model. A Phase 1 clinical trial was designed to test safety, tolerability, and antiviral activity of HCV-AB68 in patients with chronic HCV-infection. METHODS/RESULTS: Single doses of HCV-AB68, 0.25-40 mg, administered to 15 patients were well tolerated with no moderate or serious adverse events (SAEs) reported. In six patients, HCV-RNA levels transiently decreased by 2- to 100-fold immediately following infusion and rebound to baseline in 24-48 h. Multiple doses of HCV-AB68, 10-120 mg, were administered to 25 patients. Doses were given weekly for 3 weeks, then 3x a week during the fourth week, after which patients were followed for 3 months. No drug-related SAEs were reported and no specific pattern of adverse events was evident. Eight out of 25 patients had at least a 1-log reduction and 17 had at least a 0.75-log reduction in HCV-RNA levels from baseline at one or more time points following HCV-AB68 infusion. CONCLUSIONS: These data support the investigation of HCV-AB68 in the prevention of recurrent HCV-infection in patients who had received hepatic allografts for end-stage liver disease.     

ADHD and dysgraphia: underlying mechanisms

Multiple complaints in the domain of writing are common among children with Attention Deficit Hyperactivity Disorder (ADHD). In this work we sought to characterize the writing disorder by studying dysgraphia in twenty 6th grade boys with ADHD and normal reading skills matched to 20 healthy boys who served as a comparison group. Dysgraphia, defined as deficits in spelling and handwriting, was assessed according to neuropsychological explanatory processes within 3 primary domains: linguistic processing, motor programming and motor kinematics. Children with ADHD made significantly more spelling errors, but showed a unique pattern introducing letter insertions, substitutions, transpositions and omissions. This error type, also known as graphemic buffer errors, can be explained by impaired attention aspects needed for motor planning. Kinematic manifestations of writing deficits were fast, inaccurate and an inefficient written product accompanied by higher levels of axial pen pressure. These results suggest that the spelling errors and writing deficits seen in children with ADHD and normal reading skills stem primarily from non-linguistic deficits, while linguistic factors play a secondary role. Recommendations for remediation include educational interventions, use of word processing and judicious use of psychostimulants.     

Erythropoietin delays disease onset in an amyotrophic lateral sclerosis model

Erythropoietin (Epo) has been shown in the recent years to have neuroprotective activity in a variety of settings. In this study, we investigated its impact on the progression of paralysis in a mouse model simulating the human disorder amyotrophic lateral sclerosis (ALS). We found that Epo can delay the onset of motor deterioration in transgenic SOD G93A mice without prolonging their survival. Notably this effect was selective for the females only. These initial findings encourage further investigation of this biological avenue in the search for improved remedies for this fatal disease.     

Ultra-small-sample molecular structure detection using microslot waveguide nuclear spin resonance

We here report on the design of a planar microslot waveguide NMR probe with an induction element that can be fabricated at scales from centimeters to nanometers to allow analysis of biomolecules at nano- or picomole quantities, reducing the required amount of materials by several orders of magnitude. This device demonstrates the highest signal-to-noise ratio for a planar detector to date, measured by using the anomeric proton signal from a 15.6-nmol sample of sucrose. This probe had a linewidth of 1.1 Hz for pure water without susceptibility matching. Analysis of 1.57 nmol of ribonuclease-A shows high sensitivity in one- and two-dimensional NMR spectra. Along with reducing required sample volumes, this integrated geometry can be packed in parallel arrays and combined with microfluidic systems. Further development of this device may have broad implications not only for advancing our understanding of many intractable protein structures and their folding, molecular interactions, and dynamic behaviors, but also for high-sensitivity diagnosis of a number of protein conformational diseases.     

CD74 induces TAp63 expression leading to B-cell survival

Most mature follicular B cells circulate within the periphery in a quiescent state, without actively contributing to an acute immune response. Lasting B-cell persistence in the periphery is dependent on survival signals that are transduced by cell surface receptors. We recently demonstrated that cell surface CD74 controls mature B-cell survival. Stimulation of cell surface CD74 leads to NF-kappaB activation, which enables entry of the stimulated B cells into the S phase, induction of DNA synthesis, and cell division, and augments the expression of survival genes. In the present study, we investigated CD74 target genes to determine the identities of the molecules whose expression is modulated by CD74, thereby regulating B-cell survival. We report that CD74 activates the p65 member of the NF-kappaB family, which in turn up-regulates the expression of p53-related TAp63 proteins. TAp63 then binds and transactivates the Bcl-2gene and induces the production of Bcl-2 protein, thereby providing the cells with increased survival capacity. Thus, the CD74/NF-kappaB/TAp63 axis defines a novel antiapoptotic pathway in mature B cells, resulting in the shaping of both the B-cell repertoire and the immune response.