Response to chemoradiatiotherapy in squamous cell carcinoma of the esophagus: evaluation of some prognostic factors

Dag Stockeld1, Ursula Falkmer2, Sture Falkmer3, Lars Backman1, Lars Granström1, Jan Fagerberg41Department of Surgery, Danderyd Hospital, Stockholm, Sweden; 2Department of Oncology; 3Department of Pathology, University Hospital, Trondheim, Norway; 4Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, SwedenObjective: To evaluate the predictive values of the expression of factor VIII, CD-34, p53, bcl-2, and DNA ploidy regarding the response to chemoradiation of squamous cell carcinoma of the esophagus.Design: Retrospective analysis of pretreatment biopsies with immunohistochemistry and flow cytometry. The results were correlated to tumor response (complete vs. noncomplete) following chemoradiation with three cycles of 5-FU and cisplatin combined with 40–64 Gy of radiation.Subjects: 44 consecutive patients with squamous cell carcinoma of the esophagus treated with chemoradiation with a curative intent from 1992–2000.Main outcome measures: Treatment response.Results: No correlations were found between the expressions of p53, bcl-2, or DNA ploidy and tumor response to chemoradiation. A positive correlation was found between factor VIII expression and a complete tumor response (p = 0.0357). However the other marker for angiogenesis, CD-34, showed a negative correlation (p = 0.0493). Both markers indicate blood vessel density meaning that, in this study, many vessels indicated a favorable response if measured with factor VIII, but a poor response if measured with CD-34. Conclusion: It is not possible to predict tumor response to our chemoradiation protocol through the analysis of pretreatment expression of p53, bcl-2 or DNA ploidy in biopsy specimens. In spite of significant correlations between complete tumor responses and the expressions of the markers for angiogenesis this significance may be questionable since one of the two markers, factor VIII had a positive and the other, CD-34, a negative correlation to tumor response.Keywords: chemoradiation, response, prognostic factor, apoptosis, p-53, angiogenesis, DNA ploid

Effects of Adult Age and Level of Skill on the Ability to Cope With High-Stress Conditions in a Precision Sport

Younger and older highly skilled and moderately skilled miniature golf players were studied in training and competition. All of the players showed an increase of heart rate and rated anxiety from training to competition. A performance decline in competition was observed for both older players and less accomplished players. Results from a cognitive task (incidental recall of shots) suggest that older players are less proficient in coping with the high-stress conditions in competition, due to an age-related decline in task-relevant cognitive abilities. In a recent field study, Backman and Molander (1986) examined highly skilled miniature golf players varying in age in training, minor competitions (MCs), and large competitions (LCs). Results showed that older adult players deteriorated markedly in LCs, whereas youth players, junior players, and younger adult players performed equally well in all three activities. In addition, all groups showed a similar increase of arousal from training and MCs to LCs, as indicated by measures of heart rate and ratings of anxiety. In agreement with Broadbent's (1971) theory of arousal and performance, it was suggested that younger players may compensate for the nonoptimal levels of arousal during LCs through self-initiated efforts such as concentration and narrowing of attention. Older players, on the other hand, may have a deficit in this compensatory mechanism, due to an age-related decline in task-relevant cognitive abilities. There are several cognitive abilities that are critical to successful miniature golf performance: (a) memory of which shots were good and which shots were bad in previous rounds, in order to maintain the shot if it was good (or to adjust it if it was a miss) on a later round; (b) decisions about the swing and estimation of angles; (c) encoding and interpretation of the visual feedback from a miss, so that motor behavior could be changed for the next shot; and (d) focusing of attention on the game, while closing out distracting information. It is well-known that the aging process is associated with deficits in many of these task-relevant abilities: attention, memThis research was supported by grants from the Swedish Council for Research in the Humanities and the Social Sciences, and the Swedish Sports Research Council. We are indebted to David Chalom for his assistance in collecting data. Correspondence concerning this article should be addressed to Lars Backman, who is now at the Department of Psychology, University of Umea, Radhusesplanaden 2, S-902 47 Umea, Sweden. ory, and decision making Method Subjects The subjects were 12 younger adults and 12 older adults, all of them community residents in Umea, Sweden, with comparable socioeconomic background. Each age group comprised six highly skilled players and six moderately skilled players. In the highly skilled group the mean age of the younger subjects (4 men and 2 women) was 25.5 years (SD = 4.72), and the mean age of the older subjects (3 men and 3 women) was 50.7 years (SD = 4.18). In the moderately skilled group the mean age of the younger subjects (all men) was 27.7 years (SD = 4.55), and the mean age of the older subjects (5 men and 1 woman) was 51.5 years (SD = 3.51). Participation in the experiment was voluntary, and none of the subjects was on medication. 33

Training-Induced Changes in Subsequent-Memory Effects: No Major Differences Among Children, Younger Adults, and Older Adults

The neural correlates of encoding mode, or the state of forming new memory episodes, have been found to change with age and mnemonic training. However, it is unclear whether neural correlates of encoding success, termed subsequent memory (SM) effects, also differ by age and mnemonic skill. In a multi-session training study, we investigated whether SM effects are altered by instruction and training in a mnemonic skill, and whether such alterations differ among children, younger adults, and older adults. Before and after strategy training, fMRI data were collected while participants were memorizing word pairs. In all age groups, participants receiving training showed greater performance gains than control group participants. Analysis of task-relevant regions showed training-induced reductions in SM effects in left frontal regions. Reductions in SM effects largely generalized across age, and primarily reflected greater training-induced activation increases for omissions than for remembered items, indicating that training resulted in more consistent use of the mnemonic strategy. The present results reveal no major age differences in SM effects in children, younger adults, and older adults

Neural Activation Patterns of Successful Episodic Encoding: Reorganization During Childhood, Maintenance in Old Age

The two-component framework of episodic memory (EM) development posits that the contributions of medial temporal lobe (MTL) and prefrontal cortex (PFC) to successful encoding differ across the lifespan. To test the framework’s hypotheses, we compared subsequent memory effects (SME) of 10-12 year-old children, younger adults, and older adults using functional magnetic resonance imaging (fMRI). Memory was probed by cued recall, and SME were defined as regional activation differences during encoding between subsequently correctly recalled versus omitted items. In MTL areas, children’s SME did not differ in magnitude from those of younger and older adults. In contrast, children’s SME in PFC were weaker than the corresponding SME in younger and older adults, in line with the hypothesis that PFC contributes less to successful encoding in childhood. Differences in SME between younger and older adults were negligible. The present results suggest that, among individuals with high memory functioning, the neural circuitry contributing to successful episodic encoding is reorganized from middle childhood to adulthood. Successful episodic encoding in later adulthood, however, is characterized by the ability to maintain the activation patterns that emerged in young adulthood

Age-differential relationships among dopamine D1 binding potential, fusiform BOLD signal, and face-recognition performance

Facial recognition ability declines in adult aging, but the neural basis for this decline remains unknown. Cortical areas involved in face recognition exhibit lower dopamine (DA) receptor availability and lower blood-oxygen-level-dependent (BOLD) signal during task performance with advancing adult age. We hypothesized that changes in the relationship between these two neural systems are related to age differences in face-recognition ability. To test this hypothesis, we leveraged positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to measure D1 receptor binding potential (BPND) and BOLD signal during facerecognition performance. Twenty younger and 20 older participants performed a face-recognition task during fMRI scanning. Face recognition accuracy was lower in older than in younger adults, as were D1 BPND and BOLD signal across the brain. Using linear regression, significant relationships between DA and BOLD were found in both age-groups in face-processing regions. Interestingly, although the relationship was positive in younger adults, it was negative in older adults (i.e., as D1 BPND decreased, BOLD signal increased). Ratios of BOLD:D1 BPND were calculated and relationships to face-recognition performance were tested. Multiple linear regression revealed a significant Group BOLD:D1 BPND Ratio interaction. These results suggest that, in the healthy system, synchrony between neurotransmitter (DA) and hemodynamic (BOLD) systems optimizes the level of BOLD activation evoked for a given DA input (i.e., the gain parameter of the DA input-neural activation function), facilitating task performance. In the aged system, however, desynchronization between these brain systems would reduce the gain parameter of this function, adversely impacting task performance and contributing to reduced face recognition in older adults

Incidence of early posterior shoulder dislocation in brachial plexus birth palsy

<p>Abstract</p> <p>Background</p> <p>Posterior dislocation of the shoulder in brachial plexus birth palsy during the first year of life is rare but the incidence increases with age. The aim was to calculate the incidence of these lesions in children below one year of age.</p> <p>Methods</p> <p>The incidence of brachial plexus birth lesion and occurrence of posterior shoulder dislocation was calculated based on a prospective follow up of all brachial plexus patients at an age below one in Malmö municipality, Sweden, 2000–2005.</p> <p>Results</p> <p>The incidence of brachial plexus birth palsy was 3.8/1000 living infants and year with a corresponding incidence of posterior shoulder dislocation (history, clinical examination and x-ray) during the first year of 0.28/1000 living infants and year, i.e. 7.3% of all brachial plexus birth palsies.</p> <p>Conclusion</p> <p>All children with a brachial plexus birth lesion (incidence 3.8‰) should be screened, above the assessment of neurological recovery, during the first year of life for posterior dislocation of the shoulder (incidence 0.28‰) since such a condition may occur in 7% of children with a brachial plexus birth lesion.</p

Occupational complexity and cognition in the FINGER multidomain intervention trial

Introduction Lifetime exposure to occupational complexity is linked to late-life cognition, and may affect benefits of preventive interventions. Methods In the 2-year multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we investigated, through post hoc analyses (N = 1026), the association of occupational complexity with cognition. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. Results Higher levels of occupational complexity were associated with better baseline cognition. Measures of occupational complexity had no association with intervention effects on cognition, except for occupational complexity with data, which was associated with the degree of intervention-related gains for executive function. Discussion In older adults at increased risk for dementia, higher occupational complexity is associated with better cognition. The cognitive benefit of the FINGER intervention did not vary significantly among participants with different levels of occupational complexity. These exploratory findings require further testing in larger studies.Peer reviewe

Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment

BACKGROUND: Mild cognitive impairment (MCI) was recently described as a heterogeneous group with a variety of clinical outcomes and high risk to develop Alzheimer's disease (AD). Regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) was used to study the heterogeneity of MCI and to look for predictors of future development of AD. METHODS: rCBF was investigated in 54 MCI subjects using Tc-99m hexamethylpropyleneamine oxime (HMPAO). An automated analysis software (BRASS) was applied to analyze the relative blood flow (cerebellar ratios) of 24 cortical regions. After the baseline examination, the subjects were followed clinically for an average of two years. 17 subjects progressed to Alzheimer's disease (PMCI) and 37 subjects remained stable (SMCI). The baseline SPECT ratio values were compared between PMCI and SMCI. Receiver operating characteristic (ROC) analysis was applied for the discrimination of the two subgroups at baseline. RESULTS: The conversion rate of MCI to AD was 13.7% per year. PMCI had a significantly decreased rCBF in the left posterior cingulate cortex, as compared to SMCI. Left posterior cingulate rCBF ratios were entered into a logistic regression model for ROC curve calculation. The area under the ROC curve was 74%–76%, which indicates an acceptable discrimination between PMCI and SMCI at baseline. CONCLUSION: A reduced relative blood flow of the posterior cingulate gyrus could be found at least two years before the patients met the clinical diagnostic criteria of AD