Plasma Cytokine Analysis in Patients with Advanced Extremity Melanoma Undergoing Isolated Limb Infusion

Background

Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity melanoma.

Methods

Multiplex immunobead assay technology (Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel, Millipore Corp., Billerica, MA; and Magpix analytical test instrument, Luminex Corp., Austin, TX) was performed on pre-ILI plasma to determine concentrations of selected cytokines (MIP-1α, IL-1Rα, IP-10, IL-1β, IL-1α, MCP-1, IL-6, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β) on a subset of patients (n = 180) who experienced CR (n = 23) or PD (n = 24) after ILI. Plasma from normal donors (n = 12) was also evaluated.

Results

Of 180 ILIs performed, 28 % (95 % confidence interval 22–35, n = 50) experienced a CR, 14 % (n = 25) experienced a partial response, 11 % (n = 21) had stable disease, 34 % (n = 61) had PD, and 13 % (n = 23) were not evaluable for response. Tumor characteristics and pharmacokinetics appeared similar between CR (n = 23) and PD (n = 24) patients who underwent cytokine analysis. Although there were no differences in cytokine levels between CR and PD patients, there were differences between the melanoma patients and controls. MIP-1α, IL-1Rα, IL-1β, IL-1α, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β were significantly higher in normal controls compared to melanoma patients, while IP-10 was lower (p < 0.001) in controls compared to melanoma patients.

Conclusions

Patients with unresectable in-transit melanoma appear to have markedly decreased levels of immune activating cytokines compared to normal healthy controls. This further supports a potential role for immune-targeted therapies and immune monitoring in patients with regionally advanced melanoma.     

Identification and Treatment of TBI and Co-occurring Psychiatric Symptoms Among OEF/OIF/OND Veterans Seeking Mental Health Services Within the State of Colorado: Establishing Consensus for Best Practices

This paper highlights the results of a consensus meeting regarding best practices for the assessment and treatment of co-occurring traumatic brain injury (TBI) and mental health (MH) problems among Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Veterans seeking care in non-Veterans Affairs Colorado community MH settings. Twenty individuals with expertise in TBI screening, assessment, and intervention, as well as the state MH system, convened to establish and review questions and assumptions regarding care for this Veteran population. Unanimous consensus regarding best practices was achieved. Recommendations for improving care for Veterans seeking care in community MH settings are provided.     

Effects of neurological damage on production of formulaic language

Early studies reported preserved formulaic language in left hemisphere damaged subjects and reduced incidence of formulaic expressions in the conversational speech of stroke patients with right hemispheric damage. Clinical observations suggest a possible role also of subcortical nuclei. This study examined formulaic language in the spontaneous speech of stroke patients with left, right, or subcortical damage. Four subjects were interviewed and their speech samples compared to normal speakers. Raters classified formulaic expressions as speech formulae, fillers, sentence stems, and proper nouns. Results demonstrated that brain damage affected novel and formulaic language competence differently, with a significantly smaller proportion of formulaic expressions in subjects with right or subcortical damage compared to left hemisphere damaged or healthy speakers. These findings converge with previous studies that support the proposal of a right hemisphere/subcortical circuit in the management of formulaic expressions, based on a dual‐process model of language incorporating novel and formulaic language use.     

Adenosine A2A receptor contributes to ischemic brain damage in newborn piglet

Pharmacologic inactivation or genetic deletion of adenosine A_2A receptors protects ischemic neurons in adult animals, but studies in neonatal hypoxia-ischemia (H-I) are inconclusive. The present study in neonatal piglets examined the hypothesis that A_2A receptor signaling after reoxygenation from global H-I contributes to injury in highly vulnerable striatal neurons where A_2A receptors are enriched. A_2A receptor immunoreactivity was detected in striatopallidal neurons. In nonischemic piglets, direct infusion of the selective A_2A receptor agonist CGS 21680 through microdialysis probes into putamen increased phosphorylation of N-methyl-D-aspartic acid (NMDA) receptor NR1 subunit and Na⁺,K⁺-ATPase selectively at protein kinase A (PKA)-sensitive sites. In ischemic piglets, posttreatment with SCH 58261, a selective A_2A receptor antagonist, improved early neurologic recovery and preferentially protected striatopallidal neurons. SCH 58261 selectively inhibited the ischemia-induced phosphorylation of NR1, Na⁺,K⁺-ATPase, and cAMP-regulated phosphoprotein 32 KDa (DARPP32) at PKA-sensitive sites at 3 hours of recovery and improved Na⁺,K⁺-ATPase activity. SCH 58261 also suppressed ischemia-induced protein nitration and oxidation. Thus, A_2A receptor activation during reoxygenation contributes to the loss of a subpopulation of neonatal putamen neurons after H-I. Its toxic signaling may be related to DARPP32-dependent phosphorylation of PKA-sensitive sites on NR1 and Na⁺,K⁺-ATPase, thereby augmenting excitotoxicity-induced oxidative stress after reoxygenation.     

Memory systems involved in professional skills: A case of dense amnesia due to herpes simplex viral encephalitis

JL, a 25-year-old physiotherapist, became densely amnesic following herpes simplex viral encephalitis (HSVE), causing bilateral damage to medial and ventral areas of her frontal and temporal lobes and their associated circuitry. Three years post-onset, her WAIS-R full scale IQ (Verbal 74, Performance 102) showed an estimated loss of ± 50 points. She displayed severe global amnesia and markedly impaired social cognition. However, her immediate memory, perceptual priming, and cognitive problem-solving abilities were relatively spared. Her retention of professional skills was assessed using simulated physiotherapy scenarios. JL was able to demonstrate some procedural skills spontaneously, but was unable to apply them precisely and flexibly to individual patient needs. She showed no memory of theoretical or propositional physiotherapy knowledge, and could neither plan treatment nor reason clinically. Her performance was well below that of four other physiotherapists who had also not practised for 4 years. Thus, despite the relative sparing of her implicit memory, JL's performance lacked the co-ordinated operation of declarative and implicit long-term memory and the links to working memory that are necessary for the flexible performance of complex professional procedures.     

Assessing awareness in early-stage Alzheimer's disease: Development and piloting of the Memory Awareness Rating Scale

There are indications that awareness may have an important impact on functioning and response to rehabilitative interventions in early-stage Alzheimer's disease (AD), yet studies have so far produced few clear findings, and a comprehensive explanatory model is needed together with a reliable assessment method. A theory-driven approach to assessing awareness in early-stage Alzheimer's disease was used to develop the Memory Awareness Rating Scale (MARS), a measure that addresses key methodological limitations of the assessment methods adopted in existing studies. The MARS was piloted with 12 couples where one partner had a diagnosis of AD. This demonstrated that the MARS has satisfactory psychometric properties, and suggested some refinements to the scale that may improve its usefulness. Results obtained with the MARS allow further consideration of theoretical and methodological issues that arise in attempting to understand and assess awareness. The development of this rigorous method of assessing awareness of memory difficulties in early-stage AD provides a basis for further investigation of the relationship between awareness of memory difficulties and outcome of neuropsychological rehabilitation in early-stage AD.     

Lacosamide-Induced Valproic Acid Toxicity

Valproic acid is commonly used in the treatment of both focal and generalized epilepsies and is often well tolerated. There are many reported cases of hyperammonemic encephalopathy and other well-known side effects reported during use of valproic acid either alone or in combination with other antiepileptics. This case report demonstrates valproic acid toxicity in the presence of lacosamide, which has not previously been reported. Full recovery occurred after withdrawal of both valproic acid and lacosamide.     

Aesthetic Amenities and Safety Hazards Associated with Walking and Bicycling for Transportation in New York City

Background

One strategy to address health problems related to insufficient physical activity is to examine modifiable neighborhood characteristics associated with active transportation.

Purpose

The aim of this study is to evaluate whether neighborhoods with more aesthetic amenities (sidewalk cafés, street trees, and clean sidewalks) and fewer safety hazards (pedestrian-auto fatalities and homicides) are associated with active transportation.

Methods

The 2003 Community Health Survey in New York City, which asked about active transportation (walking or bicycling >10 blocks) in the past 30 days, was linked to ZIP-code population census and built environment characteristics. Adjusted associations were estimated for dichotomous (any active transportation versus none) and continuous (trip frequency) active transportation outcomes.

Results

Among 8,034 adults, those living near sidewalk cafés were 10 % more likely to report active transportation (p?=?0.01). Homicide rate was associated with less frequent active transportation among those reporting any active transportation (p?=?0.002).

Conclusions

Investments in aesthetic amenities or homicide prevention may help to promote active transportation.

     

Perceptions of Neighborhood Park Quality: Associations with Physical Activity and Body Mass Index

Background

Parks are important resources for physical activity (PA), yet few studies have examined how perceptions of park characteristics relate to PA and health.

Purpose

This study investigated associations between perceptions of neighborhood park quality and overall moderate-to-vigorous PA (MVPA), park-based PA, and body mass index (BMI).

Methods

Data were collected via questionnaire from 893 households in Kansas City, Missouri.

Results

The newly developed neighborhood park quality scale demonstrated good test–retest and internal reliability. Residents’ perceptions of neighborhood park quality were related to PA and health outcomes. Perceiving parks as a benefit was positively related to overall MVPA and park-based PA and negatively related to BMI. Perceptions of well-used parks were positively related to BMI, while perceived cleanliness was negatively related to park-based PA.

Conclusions

Better measuring and understanding how perceptions of local parks are associated with PA and health can improve appreciation of how parks facilitate active living.