Acknowledgement to Referees 2003

Surgical and Radiologic Anatomy -     

Reproducibility and validity of the stair-climb test for fire fighters

Purpose  

A new job-specific test for fire fighters, the stair-climb test (FFstair-climb) was evaluated for reproducibility and validity for use in future workers’ health surveillance.     

Pharmacokinetic characterization in xenografted mice of a series of first-generation mimics for HLA-DR antibody, Lym-1, as carrier molecules to image and treat lymphoma.

Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab. METHODS: A lysine-polyethylene glycol (PEG) backbone was used to synthetically link 2 of the following ligands: deoxycholate, 5-leuenkephalin, triiodothyronine, thyronine, dabsyl-L-valine, and N-benzoyl-L-arginyl-4-amino-benzoic acid to generate a series of 13 bidentate SHALs with a biotin or 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) chelate attached to the linker. These SHALs have been assessed for their selectivity in binding to HLA-DR10-expressing cells and for their pharmacokinetics and tissue biodistribution in mice. Biotinylated versions of these SHALs discriminated cell lines positive for HLA-DR10 expression with near-nanomolar affinity. The DOTA versions of 4 SHALs were labeled with (111)In for pharmacokinetic studies in mice with HLA-DR10-expressing malignant Raji xenografts. RESULTS: The bidentate, biotinylated, and DOTA-SHALs were synthesized in high-purity, multimilligram amounts. Mean radiochemical and product yields and purities were 90%, 75%, and 90% at mean specific activities of 3.9 MBq/microg (105 microCi/microg) for the (111)In-labeled SHALs. As expected, rapid blood clearance and tumor targeting were observed. The pharmacokinetics of the SHALs was influenced by the component ligands. Biliary clearance, kidney localization, and serum receptor binding contributed to less favorable tumor targeting. CONCLUSION: A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting.     

Assessing Illness Representations of Chronic Illness: Explorations of Their Disease-Specific Nature

Elaborating on the five-dimensional structure of illness representation, as described in the self-regulation model of Leventhal (1980), the present study is aimed at identifying the relevance of this generic structure for two chronic illnesses: chronic fatigue syndrome (CFS) and Addison's disease (AD). Factor analyses showed the importance of the five dimensions identity, time-line, control/cure, cause, and consequences to differ according to the type of disease. That is, the items representing the five dimensions merged together for CFS patients and AD patients in a different manner and thereby produced different factor solutions for the two patient groups. In CFS patients, a four-factor solution was identified with manageability, seriousness, personal responsibility, and external cause as the factors. In AD patients a four-factor solution was also identified but with seriousness, cause, chronicity, and controllability as the factors. The value of these findings for our understanding of the disease-specific nature of illness representation is discussed.     

Mood state and cerebral metabolism in persons with age-associated memory impairment

People undergoing medical procedures sometimes experience feelings that may influence the results. In this study, we explore the relationship between changes in mood state self-ratings and cerebral glucose metabolism during positron emission tomography (PET) in persons with age-associated memory impairment (mean age 59.4±9.8 years). Brain regions of interest involved in both mood and memory were examined. Mood ratings of increased boredom correlated significantly with mesial temporal and parietal asymmetry and decreased parietal metabolism. Mood ratings of increased fatigue correlated with basal ganglia asymmetry and the right basal ganglia and left mesial temporal metabolism. These findings suggest that subjective mood state changes during PET may influence metabolism in brain regions implicated in emotion and memory function in people with age-related memory complaints.     

Chorea as a presenting feature of variant Creutzfeldt-Jakob disease.

We report on a patient with pathologically proven variant Creutzfeld-Jakob disease in whom chorea was a presenting feature of the disease, and was unaccompanied by the typical prodrome of psychiatric disturbance or sensory symptoms.