Validation and clinical utility of the executive function performance test in persons with traumatic brain injury.

This study examined the relationships between the Executive Function Performance Test (EFPT), the NIH Toolbox Cognitive Function tests, and neuropsychological executive function measures in 182 persons with traumatic brain injury (TBI) and 46 controls to evaluate construct, discriminant, and predictive validity. Construct validity: There were moderate correlations between the EFPT and the NIH Toolbox Crystallized (r = -.479), Fluid Tests (r = -.420), and Total Composite Scores (r = -.496). Discriminant validity: Significant differences were found in the EFPT total and sequence scores across control, complicated mild/moderate, and severe TBI groups. We found differences in the organisation score between control and severe, and between mild and severe TBI groups. Both TBI groups had significantly lower scores in safety and judgement than controls. Compared to the controls, the severe TBI group demonstrated significantly lower performance on all instrumental activities of daily living (IADL) tasks. Compared to the mild TBI group, the controls performed better on the medication task, the severe TBI group performed worse in the cooking and telephone tasks. Predictive validity: The EFPT predicted the self-perception of independence measured by the TBI-QOL (beta = -0.49, p < .001) for the severe TBI group. Overall, these data support the validity of the EFPT for use in individuals with TBI.

Polymorphism of Fc receptor on murine B cells is Igh-linked.

Analysis of mouse IgG binding to Fc receptors on mouse B cells indicates that the IgG1, IgG2a, and IgGb subclasses bind to the same receptor. No differences in affinity were detected among subclass or between mouse strains. This same receptor bound rat IgG with an affinity that differed between mouse strains. This polymorphism in affinity for rat IgG maps to chromosome 12 distal to the Igh locus.

Validation of the NIH Toolbox in Individuals with Neurologic Disorders.

OBJECTIVE: Individuals with spinal cord injury (SCI), traumatic brain injury (TBI), and stroke experience a variety of neurologically related deficits across multiple domains of function. The NIH Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) examines motor, sensation, cognition, and emotional functioning. The purpose of this paper is to establish the validity of the NIHTB in individuals with neurologic conditions. METHODS: Community-dwelling individuals with SCI (n = 209), TBI (n = 184), or stroke (n = 211) completed the NIHTB. Relative risks for impaired performance were examined relative to a matched control groups. RESULTS: The largest group differences were observed on the Motor domain and for the Fluid Cognition measures. All groups were at increased risk for motor impairment relative to normative standards and matched controls. Fluid cognitive abilities varied across groups such that individuals with stroke and TBI performed more poorly than individuals with SCI; increased relative risks for impaired fluid cognition were seen for individuals in the stroke and TBI groups, but not for those in the SCI group. All three neurologic groups performed normally on most measures in the Sensation Battery, although TBI participants evidenced increased risk for impaired odor identification and the stroke group showed more vision difficulties. On the Emotion Battery, participants in all three groups showed comparably poor psychological well-being, social satisfaction, and self-efficacy, whereas the TBI group also evidenced slightly increased negative affect. CONCLUSIONS: Data provide support for the validity of the NIHTB in individuals with neurologic conditions.

Mobilization of peripheral-blood stem cells by concurrent administration of daniplestim and granulocyte colony-stimulating factor in patients with breast cancer or lymphoma.

PURPOSE: To evaluate the safety and hematopoietic activity of daniplestim administered concurrently with granulocyte colony-stimulating factor (G-CSF) for peripheral-blood stem-cell (PBSC) mobilization. PATIENTS AND METHODS: In the initial dose-escalation phase, 25 patients with adenocarcinoma of the breast (AB; 13 patients) or lymphoma (12 patients) were given daniplestim at doses ranging from 0.1 to 3.75 microgram/kg/d plus G-CSF 10 microgram/kg/d. In the randomized phase, 52 patients with AB (27 patients) or lymphoma (25 patients) were randomized within disease categories to the daniplestim dose chosen in the dose-escalation phase plus G-CSF 10 microgram/kg/d (D+G) or placebo plus G-CSF 10 microgram/kg/d (P+G) for up to 7 days. RESULTS: A daniplestim dose of 2. 5 microg/kg/d was chosen for further study because it was hematopoietically active and had an acceptable side-effect profile. In the randomized phase, in patients with AB, D+G was associated with a higher probability (P =.0696) of collecting >/= 2.5 x 10(6) CD34(+) cells/kg and significantly higher circulating CD34(+) cell counts (P =.0498) on days 6 through 9 after the initiation of dosing. The target level was more likely to be reached with additional leukaphereses in the patients given D+G. Patients given P+G did not benefit from additional leukaphereses beyond the first procedure. The type of mobilization did show a trend toward a shorter duration of neutropenia in the D+G group. The adverse events with D+G consisted largely of mild to moderate flu-like symptoms, including headache and fever, and occurred more frequently than with P+G. CONCLUSION: Daniplestim administered at 2.5 microgram/kg/d is tolerable and active when combined with G-CSF, and the combination may prove more effective than G-CSF alone in promoting the collection of adequate numbers of CD34(+) cells for PBSC infusion in patients with AB.

B-cell subsets: functional and structural characteristics.

The review will examine B-cell differentiation with an emphasis on B-cell subpopulations. We will begin with an analysis of current evidence concerning B-cell ontogeny. The development of the B-cell repertoire will be traced from stem cell to effector cells. The CBA/N mouse, which expresses an X-linked immunodeficiency, will serve as a basis for discussing the delineation of B cells into subpopulations. The CBA/N mouse provides evidence for distinct populations of B cells which can be differentiated by cell surface antigens as well as function. We intend to focus on the functional diversity of B-cell subpopulations and how they develop. The CBA/N mouse is not the only evidence for distinct B cell subpopulations and we will attempt to organize these data into a coherent story of B-cell subsets.

Effective ex vivo generation of granulopoietic postprogenitor cells from mobilized peripheral blood CD34(+) cells.

OBJECTIVE: Neutropenia following high-dose chemotherapy and peripheral blood progenitor cell (PBPC) transplantation might be abrogated by an additional transplantation of ex vivo generated granulopoietic postprogenitor cells (GPPC). Therefore, the ex vivo expansion of CD34(+) PBPC was systematically studied aiming for optimum GPPC production. MATERIALS AND METHODS: CD34(+) PBPC were cultured in serum-free medium comparing different (n = 32) combinations of stem cell factor (S), interleukin 1 (1), interleukin 3 (IL-3) (3), interleukin-6 (6), erythropoietin (E), granulocyte colony-stimulating factor (G), granulate-macrophage colony-stimulating factor (GM), daniplestim (D, a novel IL-3 receptor agonist), and Flt3 ligand (FL) under various culture conditions. Ex vivo generated cells were assessed by flow cytometry, morphology, and progenitor cell assays. RESULTS: Addition of G +/- GM but not GM alone to cultures stimulated with S163E effectively induced the generation of GPPC. GPPC production was maximum after 12 to 14 days. Best expansion rates were observed when cells were cultured at 1.5x10(4)/mL in 21% O(2). Modifications of culture conditions were either less or equally effective (i.e., modification of starting cell concentrations, low oxygen, addition of serum albumin or autologous plasma, repetitive feeding). Comparison of different cytokine combinations revealed that the optimum GPPC expansion cocktail consisted of S6GD+FL (day 12: 130-fold cellular expansion, 32% myeloblasts/promyelocytes, 49.4% myelocytes/metamyelocytes, 12.4% bands/segmented), which furthermore expanded CD34(+) cells (3.4-fold) and clonogenic progenitors (13.4-fold). CONCLUSION: Using the S6DG+FL expansion cocktail, GPPC could be effectively produced ex vivo starting from positively selected CD34 PBPC, possibly enabling amelioration or even abrogation of posttransplant neutropenia.

Effective ex vivo generation of megakaryocytic cells from mobilized peripheral blood CD34(+) cells with stem cell factor and promegapoietin.

OBJECTIVE: The additional transplantation of ex vivo-generated megakaryocytic cells might enable the clinician to ameliorate or abrogate high-dose chemotherapy-induced thrombocytopenia. Therefore, the ex vivo expansion of CD34(+) PBPC was systematically studied aiming for an optimum production of megakaryocytic cells. MATERIALS AND METHODS: CD34(+) PBPC were cultured in serum-free medium comparing different (n = 23) combinations of stem cell factor (SCF) (S), IL-1beta (1), IL-3 (3), IL-6 (6), erythropoietin (EPO) (E), thrombopoietin (TPO) (T) and promegapoietin (PMP, a novel chimeric IL-3/TPO receptor agonist). Ex vivo-generated cells were assessed by flow cytometry, morphology, and progenitor cell assays. RESULTS: Addition of TPO to cultures stimulated with S163E, a potent progenitor cell expansion cocktail previously described by our group, effectively induced the generation of CD61(+) cells (day 12: 31.4 +/- 7.9%). The addition of PMP tended to be more effective than TPO +/- IL-3. Whereas EPO was not required to maximize TPO- or PMP-induced megakaryocytic cell production, the use of IL-6 and IL-1beta augmented cellular expansion as well as CD61(+) cell production rates in the majority of cytokine combinations studied. Thus, the most effective CD61(+) cell expansion cocktail consisted of S163 + PMP which resulted in 65.9 +/- 3.0% CD61(+) at day 12 and an overall production of 40.7 +/- 4.5 CD61(+) cells per seeded CD34(+) PBPC. However, the basic 2-factor combination S + PMP also allowed for an effective CD61(+) cell production (day 12 CD61(+) cell production: 15.1 +/- 1.6). Moreover, maximum amplification of CFU-Meg was observed after 7 days using this two-factor cocktail (12.9 +/- 2.6-fold). The majority of CD61(+) cells generated in TPO- or PMP-based medium were low-ploidy 4N and 8N cells, and ex vivo-generated CD61(+), CD41(+), and CD42b(+) cells were mainly double positive for FACS-measured intracellular von Willebrand Factor (vWF) (76.7 +/- 3.3%, 58.8 +/- 4.4%, and 82.7 +/- 2.5%, respectively). CONCLUSIONS: Taken together, this study demonstrates that megakaryocytic cells can be effectively produced ex vivo with as little as two-factors (SCF + PMP), an approach that might be favorably employed in a clinical expansion trial aiming to ameliorate high-dose chemotherapy-induced thrombocytopenia.

Study of the DBA/2Ha immunodeficiency: X-chromosome mosaicism and in vivo immunoresponses.

DBA/2Ha mice have an X-chromosome-linked immunodeficiency and lack the receptor to a TRF (T cell replacing factor) on a subpopulation of B cells. Their immunodeficiency is considered to resemble that of CBA/N, another X-chromosome-linked immunodeficiency. To facilitate direct comparisons of the two immunodeficiencies and to study the in vivo manifestations of DBA/2Ha immunodeficiency, we measured phenotypes and functions of B cells of DBA/2Ha mice. We found that the expression of sIgM among B cells is normal in DBA/2Ha mice, heterozygous females equally express both affected and normal B cell subpopulations, and DBA/2Ha mice respond well to a TI-2 antigen (TNP-Ficoll) and a polyclonal activator (LPS). Unlike CBA/N, DBA/2Ha mice demonstrate very little in vivo immunodeficiencies.

Home-based multidisciplinary diagnosis and treatment of inner-city elders with dementia.

The Memory and Aging Project Satellite (MAPS) of the Washington University Alzheimer's Disease Research Center was developed to meet the medical, social, and housing needs of minority and medically underserved elders with cognitive impairments. MAPS is located in the offices of the St. Louis Area Agency on Aging (AAA). This program provides multidisciplinary outreach, as well as home-based diagnosis, treatment, and case management. It differs from most other satellite programs in that it seeks to provide service to individuals who do not voluntarily seek help for dementia. Cognitively impaired clients had numerous, unmanaged medical conditions and social problems. Few clients were adequately served by health and social service systems. Despite recent contact, only 10% of clients received a formal diagnosis of dementia from a physician. Treatment was hampered by the absence or limitations of caregivers. Despite the complexities of these cases, the MAPS staff have been generally successful in addressing client problems.

Growth, renewal, and challenge: an important era for occupational therapy.

Occupational therapy is facing some important decisions as it approaches a changing health care system. By understanding the prospective payment system it is possible to promote occupational therapy services to a changing marketplace while avoiding major problems. Specific opportunities and strategies are defined to promote occupational therapy to new markets.

Addressing the needs of the cognitively impaired elderly from a family policy perspective.

Management of the cognitively impaired elderly person in the community is presumed to be cost-efficient and the American way. Although this is what should be done, most would agree that paying for the services that make it possible to do so is not currently within the means of the median income of the family ($25,986) or of the female head of household ($15,350) in this country. This paper reviews the changes in the family, current family policies, and practices of our businesses and government and proposes the services that could be used to support both the impaired person and the family in the management of this evolving societal issue. Strategies for development of payment mechanisms for the proposed services are presented.

Certification: serving the public interest.

The certification program has undergone an exciting change. The AOTA leadership and AOTA members are to be applauded for making this important step. The AOTCB is still a fledgling organization; nonetheless, it has already made great strides in carrying out its mission. The AOTCB will continue to build on the very excellent foundation AOTA has laid for the certification program. The AOTCB welcomes questions, comments, and suggestions concerning the certification program. To contact AOTCB, write to AOTCB, 1383 Piccard Drive, Rockville, MD 20850-4375 or call (301) 948-9626.

Occupational therapy practice: focusing on occupational performance.

Changes in the health system require occupational therapy practitioners to focus their concerns on the long-term health needs of people and to help them develop healthy behaviors not only to improve their health, but also to minimize the health care costs associated with dysfunction. Occupational therapy practitioners must initiate efforts in the community to integrate a range of services that promote, protect, and improve the health of the public. This article shares the experiences of Canadian occupational therapy practitioners, who were challenged by their government nearly 15 years ago to establish a system that demonstrates effectiveness by improving the health of occupational therapy clients. By focusing on occupational performance, occupational therapy practitioners assist clients in becoming actively engaged in their life activities. This requires client-centered and family-centered practice and services that span from the agency or institution to the community. Occupational therapy practitioners must work collaboratively with persons in the client's environment (e.g., family members, teachers, independent living specialists, employers, neighbors, friends) to assist the client in obtaining skills and to make modifications to remove barriers that create a social disadvantage. A focus on occupational performance requires occupational therapy personnel to reframe how we think about occupational therapy to a sociomedical context and to take an active role in building healthy communities.

Initiating occupational therapy clinical research.

The purpose of research is to give us indications of what the effectiveness of particular treatments are on groups of people. The similarities between what we accept as a standard of education and practice and what we conceive to be research are striking. In both cases, these are disciplined methods of collecting and analyzing data, and acting upon the results of it. Those of us with clinical populations have unanswered questions and thus, good reasons for conducting research. The professional who wants answers must be willing to work for them knowing that the rewards and personal satisfaction will be great. Hopefully, the membership will recognize the importance of providing support to research and will be generous in their contribution to the American Occupational Therapy Foundation. The AOTF provides the necessary seed money to answer the questions that we are all facing.