Stability of amitriptyline hydrochloride in a commercial aqueous solution

A commercial amitriptyline hydrochloride solution was stored at 80 degrees for up to 3 months. High-performance liquid chromatography showed no evidence of amitriptyline hydrochloride degradation. The method also indicated that two reported degradates, 3-(propa-1,3-dienyl)-1,2;4,5-dibenzocyclohepta-1,4-diene and dibenzosuberone, were present at levels less than 0.1% (the detection limit of the method) under the storage conditions. The stability of the commercial solutions is attributed to their relatively low ratio of headspace oxygen to amitriptyline hydrochloride.     

Neural progenitor cells from an adult patient with fragile X syndrome

Background  

Currently, there is no adequate animal model to study the detailed molecular biochemistry of fragile X syndrome, the leading heritable form of mental impairment. In this study, we sought to establish the use of immature neural cells derived from adult tissues as a novel model of fragile X syndrome that could be used to more fully understand the pathology of this neurogenetic disease.     

Low efficacy of the combination artesunate plus amodiaquine for uncomplicated falciparum malaria among children under 5 years in Kailahun, Sierra Leone

OBJECTIVE: In 2004, Sierra Leone adopted artesunate plus amodiaquine as first-line antimalarial treatment. We evaluated the efficacy of this combination in Kailahun, where a previous study had shown 70.2% efficacy of amodiaquine in monotherapy. METHODS: Method and outcome classification of the study complied with WHO guidelines. Children 6-59 months with uncomplicated malaria were followed-up for 28 days. PCR genotyping was used to distinguish recrudescence from reinfection. Reinfections were reclassified as cured. RESULTS: Of 172 children who were referred to the study clinic, 126 satisfied inclusion criteria and were enrolled. No early treatment failures were reported. The day 14, efficacy was 98.2% (95% CI: 93.8-99.8). Of 65 recurrent parasitaemias analysed by PCR, 17 were recrudescences. The PCR-adjusted day 28 efficacy was 84.5% (95% CI: 76.4-90.7). All true failures occurred in the last 8 days of follow-up. Of 110 children who completed the 28-day follow-up, 54 (49.1%) experienced a novel infection. CONCLUSION: The efficacy of this combination was disappointing. The high reinfection rate suggested little prophylactic effect. In Kailahun a more efficacious combination might be necessary in the future. The efficacy of AS + AQ needs to be monitored in Kailahun and in the other regions of Sierra Leone.     

Surface modification and initial adhesion events for intestinal epithelial cells

Rapid resealing of the mucosal epithelia is imperative following injuries to the small intestine because the mucosa is responsible for the adsorption of nutrients as well as providing a barrier to noxious agents present in the lumen. Tissue engineering may provide a possible solution for treating intestinal erosions, ulcerations, inflammatory bowel disease, and infection. Cell-biomaterial interaction is a critical component in tissue engineering that can determine the success of the tissue construct. Cell-biomaterial interactions can be enhanced by various types of surface modification, which promote integrin ligation leading to increased cell function. In order to relate the effect of surface adhesion molecules to signaling events and macroscopic cell response, an intestinal epithelial cell line, IEC-6, was plated on fibronectin (receptor-mediated) and poly-L-lysine (non-specific) surfaces. Focal adhesion kinase (FAK) phosphorylation, cell spreading, and cell adhesion strength were measured. Results showed increases in FAK phosphorylation generally corresponded to increases in cell spreading and adhesion strength for IEC-6 cells. Therefore, in a simplified system, initial adhesion and signaling mechanisms appeared to correspond to subsequent physical responses in IEC-6 cells relevant to tissue engineering applications.     

A girl with fragile X premutation from sperm donation

We present a girl with the fragile X premutation who obtained the premutation allele from donated sperm. Our patient has clinical characteristics of fragile X syndrome including emotional problems and neuropsychological difficulties presenting as learning disabilities. She is also at high risk for premature ovarian failure and low risk for the fragile X-associated tremor ataxia (FXTAS). We suggest fragile X DNA screening in gamete donor candidates to decrease the chance of fragile X involvement in their offspring.     

A quantitative assessment of tremor and ataxia in FMR1 premutation carriers using CATSYS

While an established protocol exists for diagnosing individuals with the fragile X-associated tremor/ataxia syndrome (FXTAS), a quantitative measure of tremor and ataxia is needed. Using the CATSYS system to quantify movement abnormalities, we were able to record tremor, postural sway, manual (hand and finger) coordination, and reaction time in males with the FMR1 premutation, both with and without FXTAS, and compare them to controls. We evaluated 16 males diagnosed with FXTAS, 16 males with the premutation without FXTAS (non-FXTAS), and 14 age-matched controls. The CATSYS system detected, in the dominant hand, a difference in intention tremor between the FXTAS group and controls (P = 0.0008). The 30-sec postural sway tasks revealed differences between the FXTAS group and controls, both with eyes open and closed (P = 0.0004 and P = 0.0031, respectively). There was also a difference between FXTAS and non-FXTAS 30-sec postural sway performances with eyes open (P = 0.0008). The 10-sec postural sway tasks (with eyes closed) served to confirm the differences between the FXTAS group and both the controls (P = 0.0017) and non-FXTAS premutation carriers (P = 0.0016). These results demonstrate that the quantitative measures of the CATSYS system can document significant differences in intention tremor and postural sway in patients with FXTAS compared to controls.     

Noise-induced tinnitus: a comparison between four clinical groups without apparent hearing loss

The number of people with normal hearing thresholds seeking medical help for tinnitus and other hearing problems is increasing. For diagnostic purposes, existence/nonexistence of lesions or combinations of lesions in the inner ear not reflected in the audiogram was evaluated with advanced hearing tests applied to tinnitus patients with certain backgrounds, including noise exposure. For forty-six patients with pronounced tinnitus, and other symptoms, tentative diagnoses were established, including judgments of the influence of four causative factors: (1) acoustic trauma, (2) music, (3) suspected hereditary, and (4) nonauditory, for example, stress or muscular tension. They were analyzed with a test battery sensitive to lesions involving the outer hair cells, damage from impulse noise, and dysfunction of the efferent system. There were significant differences in test results between groups with individuals with the same most likely causative factor. Most patients claiming acoustic trauma had a specific type of result, 'hyper-PMTF' (psychoacoustical modulation transfer function), and abnormal test results of the efferent system. Everyone in the hereditary group had dysfunction of the efferent system. All patients working with music, except one, had some abnormality, but without specific pattern. The nonauditory group mostly had normal test results. The investigation shows that it is possible to diagnose minor cochlear lesions as well as dysfunction of the efferent system, which might be causing the tinnitus. Those abnormalities could not be detected with routine audiological tests. Malfunctioning caused by impulse noise is an obvious example of this. These findings facilitate choice of treatment, rehabilitation programs, and medicolegal decisions.     

Fragile X syndrome and selective mutism

This is the first report that details an association between fragile X syndrome (FXS) and selective mutism (SM). This 12-year-old girl with heterozygous full mutation at FMR1 has a long history of social anxiety and shyness in addition to SM. Her sister also has the full mutation and a history of SM that resolved in adolescence. A beneficial response to fluoxetine and psychotherapy is described. The FMR1 mutation appears to be the first gene mutation associated with SM and further studies are recommended to assess what percentage of patients with SM have the FMR1 mutation.