Central nervous system dysfunction in a mouse model of FA2H deficiency

Fatty acid 2-hydroxylase (FA2H) is responsible for the synthesis of myelin galactolipids containing hydroxy fatty acid (hFA) as the N-acyl chain. Mutations in the FA2H gene cause leukodystrophy, spastic paraplegia, and neurodegeneration with brain iron accumulation. Using the Cre-lox system, we developed two types of mouse mutants, Fa2h(-/-) mice (Fa2h deleted in all cells by germline deletion) and Fa2h(flox/flox) Cnp1-Cre mice (Fa2h deleted only in oligodendrocytes and Schwann cells). We found significant demyelination, profound axonal loss, and abnormally enlarged axons in the CNS of Fa2h(-/-) mice at 12 months of age, while structure and function of peripheral nerves were largely unaffected. Fa2h(-/-) mice also exhibited histological and functional disruption in the cerebellum at 12 months of age. In a time course study, significant deterioration of cerebellar function was first detected at 7 months of age. Further behavioral assessments in water T-maze and Morris water maze tasks revealed significant deficits in spatial learning and memory at 4 months of age. These data suggest that various regions of the CNS are functionally compromised in young adult Fa2h(-/-) mice. The cerebellar deficits in 12-month-old Fa2h(flox/flox) Cnp1-Cre mice were indistinguishable from Fa2h(-/-) mice, indicating that these phenotypes likely stem from the lack of myelin hFA-galactolipids. In contrast, Fa2h(flox/flox) Cnp1-Cre mice did not show reduced performance in water maze tasks, indicating that oligodendrocytes are not involved in the learning and memory deficits found in Fa2h(-/-) mice. These findings provide the first evidence that FA2H has an important function outside of oligodendrocytes in the CNS.     

Outcome measures in neurological physical therapy practice: part II. A patient-centered process

Physical therapists working in neurological practice must make choices about which standardized outcome measures are most appropriate for each patient. Significant time constraints in the clinic limit the number of measures that one can reasonably administer. Therapists must choose measures that will provide results that guide the selection of appropriate interventions and are likely to show clinically meaningful change. Therefore, therapists must be able to compare the merits of available measures to identify those that are most relevant for each patient and setting. This article describes a process for selecting outcome measures and illustrates the use of that process with a patient who has had a stroke. The link between selecting objective outcome measures and tracking patient progress is emphasized. Comparisons are made between 2 motor function measures (the Fugl-Meyer Assessment [FMA] of Physical Performance vs the Stroke Rehabilitation Assessment of Movement), and 2 balance measures (Berg Balance Scale vs the Activities-specific Balance Confidence Scale). The use of objective outcome measures allows therapists to quantify information that previously had been described in subjective terms. This allows the tracking of progress, and the comparison of effectiveness and costs across interventions, settings, providers, and patient characteristics.     

Traumatic and trauma-related amputations: part I: general principles and lower-extremity amputations

Deliberate attention to the management of soft tissue is imperative when performing an amputation. Identification and proper management of the nerves accompanied by the performance of a stable myodesis and ensuring robust soft-tissue coverage are measures that will improve patient outcomes. Limb length should be preserved when practicable; however, length preservation at the expense of creating a nonhealing or painful residual limb with poor soft-tissue coverage is contraindicated. While a large proportion of individuals with a trauma-related amputation remain severely disabled, a chronically painful residual limb is not inevitable and late revision amputations to improve soft-tissue coverage, stabilize the soft tissues (revision myodesis), or remove symptomatic neuromas can dramatically improve patient outcomes. Psychosocial issues may dramatically affect the outcomes after trauma-related amputations. A multidisciplinary team should be consulted or created to address the multiple complex physical, mental, and psychosocial issues facing patients with a recent amputation.     

Radiological pitfalls with laryngopharyngeal injectables

The aim of this report was to describe the computed tomography features of injected carboxymethylcellulose and how it can be mistaken for tumor recurrence. Carboxymethylcellulose is a low-density injectable indicated for short-term vocal fold augmentation. When used in patients with head and neck cancer, differentiating this agent from a neoplastic recurrence can be difficult on imaging. The imaging findings of five patients who received carboxymethylcellulose augmentation are presented to illustrate a potential pitfall of image interpretation. When injectable carboxymethylcellulose is used in cancer patients, knowledge of the injection sites, material used, and procedural history can avoid misinterpretation of monitory imaging.     

Non-steroidal anti-inflammatory drugs and small cell lung cancer risk in the VITAL study

Few studies have examined the association between non-steroidal anti-inflammatory drug (NSAID) use and risk of small cell lung cancer (SCLC); among them, findings are mixed. Recently, we found that use of NSAIDs was differentially associated with lung cancer risk by histology. Here, we examine, more comprehensively, the association between individual NSAIDs and SCLC risk. 75,546 residents of western Washington State, ages 50-76, completed a baseline questionnaire in 2000-2002 and reported on their use of individual NSAIDs over the past 10 years. NSAID use was categorized as non-users, low (<4 days/week or <4 years), and high (≥4 days/week and ≥4 years). 111 SCLC were identified through linkage to a population-based cancer registry. Multivariable-adjusted Cox proportional hazards models including strong adjustment for smoking were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Compared to non-use, high use of regular-strength aspirin was associated with an elevated risk of SCLC (HR 1.78, 95% CI: 1.05-3.02; P-trend=0.03). Findings for low-dose aspirin were elevated but did not reach statistical significance. Use of non-aspirin NSAIDs was not associated with SCLC risk. Our findings provide further indication of heterogeneity in the association between aspirin and lung cancer morphologies. Large, prospective studies with comprehensive assessments of NSAID use and smoking history and data on both men and women, are needed in order to better understand the association between use of aspirin and SCLC.     

Retinoblastoma and deletion of the long arm of chromosome 13: An underestimated diagnosis?

We report an infant with normal neurological development and phenotype who developed bilateral retinoblastoma (RB). This patient, despite lack of dysmorphic features, demonstrated constitutional abnormality of the long arm of chromosome 13 on standard karyotype. We recommend systematic cytogenetic examinations complemented by fluorescent in situ hybridization as second-line screening in all patients suspected for hereditary RB despite negative RB1 molecular screening and normal phenotype.     

Developing a Quality Screening Colonoscopy Referral System in Primary Care Practice: A Report from the National Colorectal Cancer Roundtable

The use of colonoscopy in colorectal cancer (CRC) screening has increased substantially in recent years. Media messages and changes in insurance reimbursement, as well as new screening guidelines from the American Cancer Society and the US Preventive Services Task Force, have contributed to this increase. Primary care providers (PCPs) are frequently responsible for making the recommendation and referral for screening. The process of successfully referring a patient for screening colonoscopy can be cumbersome and requires a coordinated effort between the PCP and the endoscopist. In recognition of the potential complexity of this process, the National Colorectal Cancer Roundtable has issued a report to describe the components of a quality screening colonoscopy referral system in primary care practice. The elements of a quality program include an optimal scheduling and referral system, the appropriate patient preparation information, consistent reporting and follow–up systems, and a detailed approach to dealing with special situations. CA Cancer J Clin 2010. © 2009 American Cancer Society, Inc.