Cognitive rehabilitation in the elderly: overview and future directions.

This study provides an overview of the papers emanating from the experimental trial that evaluated a new cognitive rehabilitation program in older adults who were experiencing normal cognitive decline. The main features of the design are summarized, along with evidence that the training produced long-lasting improvement in memory performance, goal management, and psychosocial status. The benefits were attributed to several factors, including the program's emphasis on techniques that promoted efficient strategic processing. Limitations of the program and directions for future research are discussed.     

TNF alpha and Fas mediate tissue damage and functional outcome after traumatic brain injury in mice.

Tumor necrosis factor-alpha (TNFalpha) and Fas are induced after traumatic brain injury (TBI); however, their functional roles are incompletely understood. Using controlled cortical impact (CCI) and mice deficient in TNFalpha, Fas, or both (TNFalpha/Fas-/-), we hypothesized that TNFalpha and Fas receptor mediate secondary TBI in a redundant manner. Compared with wild type (WT), TNFalpha/Fas-/- mice had improved motor performance from 1 to 4 days (P<0.05), improved spatial memory acquisition at 8 to 14 days (P<0.05), and decreased brain lesion size at 2 and 6 weeks after CCI (P<0.05). Protection in TNFalpha/Fas-/- mice from histopathological and motor deficits was reversed by reconstitution with recombinant TNFalpha before CCI, and TNFalpha-/- mice administered anti-Fas ligand antibodies had improved spatial memory acquisition versus similarly treated WT mice (P<0.05). Tumor necrosis factor-alpha/Fas-/- mice had decreased the numbers of cortical cells with plasmalemma damage at 6 h (P<0.05 versus WT), and reduced matrix metalloproteinase-9 activity in injured brain at 48 and 72 h after CCI. In immature mice subjected to CCI, genetic inhibition of TNFalpha and Fas conferred beneficial effects on histopathology and spatial memory acquisition in adulthood (both P<0.05 versus WT), suggesting that the beneficial effects of TNFalpha/Fas inhibition may be permanent. The data suggest that redundant signaling pathways initiated by TNFalpha and Fas play pivotal roles in the pathogenesis of TBI, and that biochemical mechanisms downstream of TNFalpha/Fas may be novel therapeutic targets to limit neurological sequelae in children and adults with severe TBI.     

Loss of cables, a novel gene on chromosome 18q, in ovarian cancer.

Cables, a cyclin-dependent kinase (cdk) interacting protein, has recently been identified and mapped to human chromosome 18q11. Cables appears to be primarily involved in cell cycle regulation and cell proliferation. Overexpression of Cables in Hela and other cell lines inhibits cell proliferation and tumor formation. We hypothesize that loss of Cables expression is associated with ovarian cancer. To test our hypothesis, we examined Cables expression in the four most common subtypes of ovarian carcinomas: serous, endometrioid, mucinous, and clear cell. In addition, mucinous and serous borderline tumors were also included. Loss of Cables expression was observed at high frequency in ovarian serous (11 of 14 cases, 79%) and endometrioid (5 of 10 cases, 50%) carcinomas. In contrast, strong Cables staining was detected in all clear cell carcinomas (10 cases) and mucinous tumors (5 carcinomas and 5 borderline tumors). The majority of serous borderline tumors (11 of 14 cases, 79%) showed positive Cables staining, with the rest showing focal loss of Cables expression. Furthermore, RT-PCR revealed the lack of Cables mRNA in a human ovarian cancer xenograft. No correlation was noted between loss of Cables and histologic grade, tumor stage, and survival. In conclusion, our results indicate that loss of Cables is common in ovarian serous and endometrioid carcinomas and imply that Cables may be involved in the pathogenesis of these two types of ovarian carcinomas.     

Inhibition of in Vitro Generation of Cytotoxicity Against Tumor Cells by Monoclonal Antibody to Thy-1

The Thy-1 molecule on murine T lymphocytes has been suggested to play a role in cellular activation events leading to a variety of immunologic functions. We present evidence that this molecule may be involved in signals leading to the in vitro generation of cytotoxic T cells against several tumor cell lines used as stimulators in mixed tumor-lymphocyte culture. The presence of monoclonal antibody against a polymorphic determinant on the Thy-1 molecule markedly reduced the generation of cytotoxicity after three days of culture of murine splenocytes with stimulator tumor cells bearing low levels of Ia antigen. In contrast, no effect was seen when the stimulators were either allogeneic splenocytes, or a tumor cell line expressing large amounts of Ia. These results suggest that the Thy-1 molecule is critically involved in events leading to the generation of cytotoxic effectors under some, but not all conditions.     

When the right to be counted doesn’t count: The politics and challenges of researching the health of asylum seekers

A fundamental prerequisite of population health research is the ability to establish an accurate denominator. This in turn requires that every individual in the study population is counted. However, this seemingly simple principle has become a point of conflict between researchers whose aim is to produce evidence of disparities in population health outcomes and governments whose policies promote (intentionally or not) inequalities that are the underlying causes of health disparities. Research into the health of asylum seekers is a case in point. There is a growing body of evidence documenting the adverse affects of recent changes in asylum-seeking legislation, including mandatory detention. However, much of this evidence has been dismissed by some governments as being unsound, biased and unscientific because, it is argued, evidence is derived from small samples or from case studies. Yet, it is the policies of governments that are the key barrier to the conduct of rigorous population health research on asylum seekers. In this paper, the authors discuss the challenges of counting asylum seekers and the limitations of data reported in some industrialized countries. They argue that the lack of accurate statistical data on asylum seekers has been an effective neo-conservative strategy for erasing the health inequalities in this vulnerable population, indeed a strategy that renders invisible this population. They describe some alternative strategies that may be used by researchers to obtain denominator data on hard-to-reach populations such as asylum seekers.     

Changes in cognitive and Language functioning of Preschool children with autism

Preschool children with autism and their normally developing peers were compared on the Stanford-Binet IV and Preschool Language Scale before and after 1 school year. Both measures showed that although the children with autism functioned at a lower level than their normally developing peers, the children with autism had narrowed this gap after treatment, making a nearly 19-point increase in IQ and an 8-point gain in language quotient. The IQ measure remained stable for the normally developing peers while their language showed a 7.73-point increase. The data support the notion that young children with autism can make very significant developmental gains.Special thanks to the parents and the children who participated in this study. Thanks also to Michael Alessandri, Jean Burton, David Celiberti, Nancy Gera-Moglia, Anne Nathan, and Lisa Kamean who assisted in the data collection process. We appreciate the cooperation of Alicia MacWright and Leisa Tomchek who taught two of the classes from which participants were drawn.     

Treatment of experimental osteomyelitis by surgical debridement and the implantation of bioerodable,polyanhydride-gentamicin beads

Osteomyelitis was induced in the radius in 77 rabbits and confirmed by histological examination and culture. At 4 weeks, the wounds were debrided and the animals were treated with (a) fatty acid dimersebacic acid beads (a bioerodable composite) impregnated with 20% or (b) 10% gentamicin sulfate, (c) placebo beads and intramuscular gentamicin sulfate. (d) placebo beads alone, or (e) debridement only. After 4 weeks, eradication of infection was determined by histological examination and culture. Osteomyelitis was eradicated in 93% of the animals treated with the beads and 20% gentamicin, in 67% of those treated with the beads arid 10% gentamicin, in 25% of those treated with placebo beads and intramuscular gentamicin, in 7% of those treated with placebo beads alone, and in 12.5% of those treated with debridement only (p values from <0.001 to 0.02). Fatty acid dimer-sehacie acid beads with gentamicin were then implanted in noninfected rabbits, and gentamicin sulfate concentrations in bone, serum, urine, and wound exudate were measured. Gentamicin sulfate was detectable in bone for as long as 8 weeks after implantation. Levels as high as 4,746 g/ml were present in the wound exudate for the first 7 days. Levels in the serum peaked at 1.03 μg/ml. Urine levels peaked at 135 μg/ml.     

Cognitive impairment after unilateral hemispheric injury of congenital or adult origin.

OBJECTIVE: The purpose of this study was to assess and compare cognitive functioning in adults with unilateral hemispheric injury due to either congenital damage or an ischemic event in young adulthood. METHOD: Adults with cerebral palsy resulting from left hemispheric brain damage were compared with adults who had a unilateral stroke in either the left or the right hemisphere. Our primary interest was to determine the impact on hemispheric dominance as revealed by dichotic listening, a task that assesses the bias for preferential listening and processing of sounds. Performance also was determined on a language-related task (word finding) and a spatial task (dot localization). RESULTS: Scores on the Quick Neurological Screening Test indicated that all participants demonstrated significant neuromotor deficits, whereas scores on the Barthel Index indicated that the participants were functional in basic activities of daily living. On cognitive assessments, healthy control participants demonstrated a pronounced left-hemisphere dominance and right-ear advantage; participants with injury to the left hemisphere showed a strong shift toward a right-hemisphere and left-ear dominance. In particular, injury of congenital origin appeared to foster this neural reorganization and localization of language-related functions into the healthy hemisphere. This shift was associated with a deterioration of performance on both the language and the spatial tasks. CONCLUSION: The importance of appreciating subtle deficits after unilateral injury is important in therapy. The dichotic listening test may provide a simple and useful means for evaluating persistent unilateral brain dysfunction in the clinical setting.     

An Improved Method of Removing Polyurethane Foam-Covered Gel Prostheses

One of the advantages of polyurethane foam-covered prostheses has been that in the first 5 to 10 years after their use, the amount of capsular contraction was found much less than when similar ``slick' prostheses were used. Another advance was their fixation to the surrounding tissue thus giving a more natural appearance and movement with the muscles when the arms were moved in any direction. The formation of a thick capsule also acted as a protection against gel granuloma due to rupture of the prosthesis and has been thought to be a factor in the lower capsule contraction rate. The greatest disadvantage has been that its removal was extremely difficult and this has continued up until the technique described in this paper has been introduced.