A new transthyretin variant (Glu61Gly) associated with cardiomyopathy.

We report the identification of a new transthyretin (TTR) gene mutation and variant protein, Glu61Gly, in a 55-year-old man with progressive cardiomyopathy, mild peripheral neuropathy and bilateral carpal tunnel syndrome. A diagnosis of TTR-associated familial amyloidosis (ATTR) was considered after an endomyocardial biopsy revealed amyloid deposits in the heart of a patient who had no family history of amyloidosis and no evidence of a plasma cell dyscrasia. Serum screening for a TTR variant by isoelectric focusing (IEF) was positive and prompted further studies to identify the genetic abnormality and to characterize the amyloidogenic protein. Direct DNA sequence analysis of all four coding regions in the TTR gene demonstrated heterozygosity in exon 3. Near equal amounts of guanine (G) and adenine (A) were observed at the second base position of codon 61. The wild-type (GAG) and mutated (GGG) sequences found in codon 61 correspond to glutamic acid (Glu) and glycine (Gly) residues, amino acids which differ in mass by -72 Da. Mass spectrometric analyses of TTR immunoprecipitated from serum showed the presence of both wild-type and variant proteins. The observed mass results for the wild-type and variant proteins were consistent with the predicted values calculated from the genetic analysis data.     

A simple and inexpensive particle agglutination test to distinguish recent from established HIV-1 infection.

OBJECTIVES: We sought to modify the Serodia HIV-1/HIV-2 particle agglutination assay (PA), a simple and cost-effective HIV assay that is used globally for the detection of HIV antibodies, as a sensitive/less sensitive test (S/LS) to identify recently infected individuals and to estimate HIV incidence. METHODS: The Serodia PA test was modified as an S/LS test (PA-LS) by using HIV antigen-coated gelatin particles at a dilution of 1:68 and a specific diluent, and calibrated using 37 HIV clade B seroconversion panels (309 samples) from Trinidad and from a commercial source that were tested at dilution intervals from 1:10 to 1:80,000. The greatest sensitivity for correctly classifying samples from recent and established infections was determined by receiver operator curve (ROC) analysis. RESULTS: At a 1:40,000 sample dilution and a days post-seroconversion cutoff of 190 days, the PA-LS test yielded a 97% sensitivity for classifying recent and established infection samples. Furthermore, at a 1:20,000 dilution, the positive predictive value for correctly identifying recently infected individuals was 99%. The PA-LS test offers a 30-44-fold cost saving over currently available S/LS tests. CONCLUSION: A modified, low cost and simple-to-perform PA test is appropriate for use in resource-limited countries, and has exhibited excellence in distinguishing recent from established HIV infection.     

Regulation of muscarinic receptors by intrahippocampal injections of gallamine.

Multiple intrahippocampal injections of gallamine impair performance of a representational memory task in rats. The binding of [3H]-(-)-quinuclidinyl benzilate (QNB) to rat brain sections was measured to determine if changes in receptor binding were associated with the deleterious effects of gallamine. [3H]-(-)-QNB binding to sections taken from gallamine-injected animals was compared with binding in saline-injected control animals. Autoradiographic analyses indicated an increase in [3H]-(-)-QNB binding sites within all layers of the cerebral cortex and in the superior colliculus in gallamine-treated animals as compared to saline-injected controls. Significant increases were noted in cortical layers IV and V (P less than 0.025) in gallamine-treated animals. No significant changes (P greater than 0.05) in the number of binding sites were observed in the hippocampus, neostriatum or various thalamic nuclei. The ability of unlabeled pirenzepine, gallamine and carbamylcholine to inhibit 0.2 nM [3H]-(-)-QNB binding also was measured to determine changes in the distribution of receptor subtypes. No significant changes were observed in any brain region for the binding of the selective antagonists pirenzepine and gallamine or the agonist carbamyl-choline. Although other possibilities are considered, the data suggest that an increase in the number of muscarinic receptors may contribute to the observed behavioral deficits associated with long-term gallamine treatment.     

Occupational therapy workforce needs: a model for demand-based studies.

PURPOSE: To provide a model for assessing occupational therapy workforce needs by using a demand-based approach to determine current workforce status in the Northwest region. Regional information may have implications for addressing national occupational therapy service needs. METHOD: A questionnaire was sent to a proportional random sample of 234 facilities that hire occupational therapy practitioners. Data were collected in July-August 2003 using structured mailing and follow-up procedures. RESULTS: Response rate was 79%. Twenty-four percent reported occupational therapy vacancies and 11% occupational therapy assistant vacancies; 48% predicted an increase in occupational therapy positions in the next 2 years and 41% an increase in occupational therapy assistant positions. Sixty-three percent of respondents reported difficulty in hiring. DISCUSSION: This study identifies an occupational therapy workforce shortage in the Northwest. Management of a shortage is critical, for even short-term adjustments could lead to permanent changes in service provision. This study demonstrates the importance of current information on the status of the national workforce and serves as a model for future studies.