Recent developments in anxiety disorders

Anxiety disorders are common and debilitating mental illnesses. Current pharmacological treatments are beset by problems of poor efficacy and side effect profiles. Increasing understanding of novel neurotransmitter systems and the interplay between these systems is broadening the scope of anxiolytic drug treatment. This article aims to describe the areas of current interest and possible future development of anxiolytic drugs by outlining recent patents in this field. A patent database was searched for 17 neurotransmitters and their synonyms as well as 23 compounds of recent known interest from May 2003 to May 2005. The internet resources Pubmed and Google Scholar were searched for peer reviewed literature using the same search parameters. Results were grouped into neurotransmitter systems to present an overview of recent developments in the neuropharmacology of anxiety disorders.     

Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution

An endogenous molecular--cellular network for both normal and abnormal functions is assumed to exist. This endogenous network forms a nonlinear stochastic dynamical system, with many stable attractors in its functional landscape. Normal or abnormal robust states can be decided by this network in a manner similar to the neural network. In this context cancer is hypothesized as one of its robust intrinsic states. This hypothesis implies that a nonlinear stochastic mathematical cancer model is constructible based on available experimental data and its quantitative prediction is directly testable. Within such model the genesis and progression of cancer may be viewed as stochastic transitions between different attractors. Thus it further suggests that progressions are not arbitrary. Other important issues on cancer, such as genetic vs epigenetics, double-edge effect, dormancy, are discussed in the light of present hypothesis. A different set of strategies for cancer prevention, cure, and care, is therefore suggested.     

Developing an 'interactive' booklet on respiratory tract infections in children for use in primary care consultations

Objective

To construct a systematic process for developing an ‘interactive’ booklet for use in primary care consultations and to use this process to develop a booklet on respiratory tract infections in children.

Methods

Booklet development occurred through a number of stages, which included: expert group brainstorming and literature review, professional graphic design, readability assessment, and consultation with users. Consultation was achieved through the use of focus groups and interviews with parents, focus groups and independent booklet review by general practitioners, and booklet review and feedback by paediatricians.

Results

All development stages led to meaningful enhancements to the booklet. Consultation with parents demonstrated a desire for more information than anticipated, with a particular emphasis on the interpretation of signs and symptoms, and the recognition of serious illness. General practitioners contributed to the design and clarity of the booklet and helped to ensure that it would be acceptable for use within consultations.

Conclusion

Written material needs to be developed in a systematic way and include consultation with the intended users. Focus groups are a valuable tool for consulting with consumers and practitioners in this regard.

Practice implications

The process described can be used as a guide for those wishing to develop similar written materials.     

Identification and characterization of novel SNPs in CHEK2 in Ashkenazi Jewish men with prostate cancer

Checkpoint kinase 2 (CHEK2) is a protein involved in arresting cell cycle in response to DNA damage. To investigate whether it plays an important role in the development of prostate cancer (PRCA) in the Ashkenazi Jewish (AJ) population, we sequenced CHEK2 in 75 AJ individuals with prostate, breast, or no cancer (n=25 each). We identified seven coding SNPs (five are novel) that changed the amino-acid sequence, resulting in R3W, E394F, Y424H, S428F, D438Y, P509S, and P509L. We determined the frequency of each variant in 76 AJ families collected by members of the International Consortium for Prostate Cancer Genetics (ICPCG) where >or=2 men were affected by PRCA. Only one variant, Y424H in exon 11, was identified in more than two families. Exon 11 was then screened in nine additional AJ ICPCG families (a total of 85 families). The Y424H variant occurred in nine affected cases from four different families; however, it did not completely segregate with the disease. We performed bioinformatics analysis, which showed that Y424H is a non-conservative missense substitution that falls at a position that is invariant in vertebrate CHEK2 orthologs. Both SIFT and Align-GVGD predict that Y424H is a loss of function mutation. However, the frequency of Y424H was not significantly different between unselected AJ cases from Montreal/Memorial Sloan Kettering Cancer Centre (MSKCC) and AJ controls from Israel/MSKCC (OR 1.18, 95%CI: 0.34-4.61, p=.99). Moreover, functional assays using Saccharomyces cerevisiae revealed that the Y424H substitution did not alter function of CHEK2 protein. Although we cannot rule out a subtle influence of the CHEK2 variants on PRCA risk, these results suggest that germline CHEK2 mutations have a minor role in, if any, PRCA susceptibility in AJ men.     

Amino-Acid Sequence of the Variable Region of the Heavy (Alpha) Chain of a Mouse Myeloma Protein with Anti-Hapten Activity

Cyanogen bromide cleavage of the heavy (alpha) chain of protein 315 (an immunoglobulin A mouse myeloma protein with anti-dinitrophenyl activity) yielded five fragments of which one (CN2), with 156 residues, contained the chain's entire variable region. Determination of the amino-acid sequence of CN2 showed that: (1) the variable region has appreciable homology (about 33% identities) with the variable region of the light chain from the same molecule; and (2) the constant-region sequence immediately following the probable transition from variable to constant domains is the same in the protein-315 alpha as in human gamma1 and mu chains (-Val-Ser-Ser-). The sequence of the cyanogen bromide octapeptide (CN5) from the carboxy terminus of the protein-315 heavy chain closely resembles the corresponding segments of human alpha and mu chains.     

A community-based psychogeriatric service

The elderly are most susceptible to mental illness, and they receive inadequate mental health services. The authors developed a community-based program to meet the needs of the psychiatrically impaired elderly by providing a multiplicity of indirect services to community caregivers. A psychiatrist and two clinical specialists in psychiatric nursing provide consultation, education, collaboration, and coordination to individuals and agencies dealing directly with elderly clients in the community. Evaluation of data show a high degree of consultee satisfaction, few recommendations for institutional care, satisfactory client outcomes, and a significant impact achieved by a formal educational program for community practitioners.