Care Management to Promote Treatment Adherence in Patients with Cognitive Impairment and Vascular Risk Factors: A Demonstration Project.

Dementia prevention is highly important. Improved control of vascular risk factors has the potential to decrease dementia risk, but may be difficult. Therefore, we developed and piloted a care management protocol for Veterans at risk for dementia. We enrolled 32 Veterans with diabetes and hypertension, at least one of which was poorly controlled, and cognitive impairment. Participants were randomly assigned to a 6-month care management intervention or to usual care. At enrollment, 6-months and 12-months, we assessed cognitive performance, mood, and diabetes and hypertension control. At follow-up, diastolic blood pressure was lower in intervention participants at 6 months (p=.041) and 12 months (p=.022); hemoglobin A1c, global mental status and mood did not differ between groups. Recall of a distractor list (p=.006) and logical memory long-delay recall (p=.036) were better at 6 months in the intervention group (p=.006). Care management may contribute to improved control of dementia risk factors.

The ontogeny of the chin: an analysis of allometric and biomechanical scaling.

The presence of a prominent chin in modern humans has been viewed by some researchers as an architectural adaptation to buttress the anterior corpus from bending stresses during mastication. In contrast, ontogenetic studies of mandibular symphyseal form suggest that a prominent chin results from the complex spatial interaction between the symphysis and surrounding soft tissue and skeletal anatomy during development. While variation in chin prominence is clearly influenced by differential growth and spatial constraints, it is unclear to what degree these developmental dynamics influence the mechanical properties of the symphysis. That is, do ontogenetic changes in symphyseal shape result in increased symphyseal bending resistance? We examined ontogenetic changes in the mechanical properties and shape of the symphysis using subjects from a longitudinal cephalometric growth study with ages ranging from 3 to 20+ years. We first examined whether ontogenetic changes in symphyseal shape were correlated with symphyseal vertical bending and wishboning resistance using multivariate regression. Secondly, we examined ontogenetic scaling of bending resistance relative to bending moment arm lengths. An ontogenetic increase in chin prominence was associated with decreased vertical bending resistance, while wishboning resistance was uncorrelated with ontogenetic development of the chin. Relative to bending moment arm lengths, vertical bending resistance scaled with significant negative allometry whereas wishboning resistance scaled isometrically. These results suggest a complex interaction between symphyseal ontogeny and bending resistance, and indicate that ontogenetic increases in chin projection do not provide greater bending resistance to the mandibular symphysis.

External beam radiation therapy (EBRT) for patients with malignant pheochromocytoma and non-head and -neck paraganglioma: combination with 131I-MIBG.

In patients with malignant pheochromocytoma and paraganglioma, 131I-MIBG radiotherapy can achieve an objective response rate of 30-50% with the dose limiting toxicity being hematologic. Patients with disseminated disease, who also have a few index bulky or symptomatic lesions, may benefit from the addition of targeted external beam radiotherapy alone or in combination with systemic 131I-MIBG. The records of patients with malignant paraganglioma who were treated with external beam radiotherapy at the University of Pennsylvania from February 1973 to February 2011 were reviewed in an institutional review board approved retrospective study. Of the 17 patients with tumors in the thorax, abdomen, or pelvis, 76% had local control or clinically significant symptomatic relief for at least 1 year or until death. As expected, the predominant toxicity was due to irradiation of tumor-adjacent normal tissues without clinically significant hematologic toxicity. Due to widespread systemic metastases with areas of bulky, symptomatic tumor, 5 of the 17 patients were treated with sequential 131I-MIBG (2 mCi/kg per treatment) and external beam radiotherapy to 9 sites. In these patients, all areas that were irradiated with external beam radiotherapy showed durable objective response despite all patients eventually experiencing out-of-field systemic progression requiring other treatment. Four of these patients remain alive with excellent performance status 16, 18, 23, and 24 months after external beam radiotherapy. External beam radiotherapy can be highly effective in local management of malignant paraganglioma and can be used in conjunction with 131I-MIBG due to nonoverlapping toxicities with excellent control of locally bulky tumors.

Beta-synuclein gene alterations in dementia with Lewy bodies.

OBJECTIVE: To determine whether mutations in the genes for alpha-synuclein or beta-synuclein are responsible for dementia with Lewy bodies (DLB), a disorder closely related to Parkinson disease (PD). METHODS: The authors ascertained 33 sporadic cases of DLB and 10 kindreds segregating DLB. DNA samples from the 43 index cases were screened for alterations in the genes for alpha-synuclein and beta-synuclein, as alpha-synuclein alterations cause PD and beta-synuclein may modulate alpha-synuclein aggregation and neurotoxicity. RESULTS: Two amino acid alterations were identified in unrelated DLB index cases: a valine to methionine substitution at codon 70 (V70M) and a proline to histidine substitution at codon 123 (P123H), both in the beta-synuclein gene. These amino acid substitutions occur at conserved residues in highly conserved regions of the beta-synuclein protein. Screening of at least 660 chromosomes from control subjects matched to the patients' population groups failed to identify another V70M or P123H allele. Cosegregation analysis of an extended pedigree segregating the P123H beta-synuclein alteration suggested that it is a dominant trait with reduced penetrance or a risk factor polymorphism. Histopathology and immunohistochemistry analysis of index case brain sections revealed widespread Lewy body pathology and alpha-synuclein aggregation without evidence of beta-synuclein aggregation. CONCLUSION: Mutations in the beta-synuclein gene may predispose to DLB.

Using primary care-based mental health registers to reduce social exclusion in patients with severe mental illness.

Reducing social exclusion and improving mental health are key themes within the government's modernization programme. Despite this, little is known about the social exclusion experienced by people with severe and enduring mental illness living in specific communities, apart from their over-representation amongst various socially excluded groups. This paper describes a 3-year research study that focused on the impact of introducing mental health registers into general practices in an English health district. The registers were expected to facilitate improvements in linking patients with appropriate services and so improve the healthcare they received. The overall result should have been reductions in the levels of social exclusion experienced by these patients; however, findings revealed a lack of change in unmet needs and quality of life, even amongst those in contact with a community mental health nurse.

Development of gaze aversion as disengagement from visual information.

Older children, but not younger children, were found to look away more from the face of an interlocutor when answering difficult as opposed to easy questions. Similar results were found in earlier work with adults, who often avert their gaze during cognitively difficult tasks (A. M. Glenberg, J. L. Schroeder, & D. A. Robertson, 1998). Twenty-five 8-year-olds and 26 5-year-olds answered verbal reasoning and arithmetic questions of varying difficulty. The older children increased gaze aversion from the face of the adult questioner in response to both difficult verbal reasoning questions and difficult arithmetic questions. In contrast, younger children (5-year-olds) responded less consistently to cognitive difficulty. It is concluded that adultlike patterns of gaze aversion in response to cognitive difficulty are certainly acquired by 8 years of age. The implications of appropriate gaze aversion for children's management of cognitive processing resources are considered.

Cognitive demands of face monitoring: evidence for visuospatial overload.

Young children perform difficult communication tasks better face to face than when they cannot see one another (e.g., Doherty-Sneddon & Kent, 1996). However, in recent studies, it was found that children aged 6 and 10 years, describing abstract shapes, showed evidence of face-to-face interference rather than facilitation. For some communication tasks, access to visual signals (such as facial expression and eye gaze) may hinder rather than help children's communication. In new research we have pursued this interference effect. Five studies are described with adults and 10- and 6-year-old participants. It was found that looking at a face interfered with children's abilities to listen to descriptions of abstract shapes. Children also performed visuospatial memory tasks worse when they looked at someone's face prior to responding than when they looked at a visuospatial pattern or at the floor. It was concluded that performance on certain tasks was hindered by monitoring another person's face. It is suggested that processing of visual communication signals shares certain processing resources with the processing of other visuospatial information.

Isolation of cDNA clones encoding eight different human G protein gamma subunits, including three novel forms designated the gamma 4, gamma 10, and gamma 11 subunits.

With the growing awareness that the G protein beta and gamma subunits directly regulate the activities of various enzymes and ion channels, the importance of identifying and characterizing these subunits is underscored. In this paper, we report the isolation of cDNA clones encoding eight different human gamma subunits, including three novel forms designated gamma 4, gamma 10, and gamma 11. The predicted protein sequence of gamma 4 shares the most identity (60-77%) with gamma 2, gamma 3, and gamma 7 and the least identity (38%) with gamma 1. The gamma 4 is modified by a geranylgeranyl group and is capable of interacting with both beta 1 and beta 2 but not with beta 3. The predicted protein sequence of gamma 10 shows only modest to low identity (35-53%) with the other known gamma subunits, with most of the differences concentrated in the N-terminal region, suggesting gamma 10 may interact with a unique subclass of alpha. The gamma 10 is modified by a geranylgeranyl group and is capable of interacting with beta 1 and beta 2 but not with beta 3. Finally, the predicted protein sequence of gamma 11 shows the most identity to gamma 1 (76% identity) and the least identity to the other known gamma (33-44%). Unlike most of the other known gamma subunits, gamma 11 is modified by a farnesyl group and is not capable of interacting with beta 2. The close resemblance of gamma 11 to gamma 1 raises intriguing questions regarding its function since the mRNA for gamma 11 is abundantly expressed in all tissues tested except for brain, whereas the mRNA for gamma 1 is expressed only in the retina where the protein functions in phototransduction.

Comparison of three anaesthetic scavenging devices using cuffed and noncuffed nasal endotracheal tubes during dental anaesthesia.

During maxillofacial and oral surgery the effect of three anaesthetic scavenging devices used with cuffed and non-cuffed endotracheal tubes was investigated. All the devices produced reductions in nitrous oxide concentrations in the breathing zone and peripheral air, ranging from 36% to 76%. Of the three devices evaluated, the Stellenbosch valve produced the greatest reduction in pollution compared with the control.

Early and late scavenging of anaesthetic gases.

The effectiveness of two waste gas scavenger devices, the Carstens box and the Ventex apparatus, with regard to nitrous oxide pollution was studied under comparable conditions in an operating theatre. The scavengers were brought into use in the early and late stages of induction of anesthesia, and nitrous oxide concentrations in the breathing zone and theatre peripheral air were measured. Both scavengers reduced nitrous oxide pollution at the sampling points. Similar reductions in nitrous oxide pollution in the breathing zone were obtained with both scavengers, but the Carstens box was more effective in reducing nitrous oxide pollution in the peripheral air.