Semantic feature analysis targeting verbs in a quadrilingual speaker with aphasia

Background: Semantic feature analysis (SFA) is a treatment approach aimed at enhancing lexical retrieval by improving access to the semantic network in speakers with aphasia. Although there are promising results on trained items, previous studies exploring the impact of SFA on verb production in monolingual speakers have shown mixed results for generalisation to untrained items and discourse. There are few published studies investigating SFA and action naming in multilingual speakers.

Aims: The study explores the impact of SFA on trained and untrained verbs, semantics and syntax, and narrative production in the trained and untrained languages of a multilingual speaker (Japanese–English–German–Norwegian) with moderate non-fluent aphasia. Treatment was conducted in a late-acquired language (Norwegian).

Methods & Procedures: SFA was provided during an intensive schedule of about 22 hr of therapy, with approximately 10 hr per week over two and a half weeks. The treatment focused on the production of verbs in sentence contexts.

Outcomes & Results: Outcome measures include the Bilingual Aphasia Test, an action-naming test, and production of semi-spontaneous narratives.

Outcomes in the treated language: Overall, the participant responded positively to the SFA treatment. The trained verbs improved significantly, but no transfer was observed to untrained verbs. There were no changes in the formal testing of semantics or syntax, but improvements were noted in narrative production.

Cross-linguistic outcomes: Transfer to verbs in untreated German was evident. There were significant increases in the semantics and syntax in both English and German. The participant showed an improvement in discourse in English and German, although not in Japanese.

Conclusions: SFA treatment in a late-acquired language can lead to gains in the treated language and transfer to both stronger and weaker languages, with different patterns for the various languages. This indicates that SFA may be a promising method for treating multilingual speakers with aphasia. The authors further advocate the use of narratives as an assessment tool. In addition to enhancing the ecological validity of the findings, the narratives provided information not obtainable from the other assessment tools for within- and cross-linguistic therapy gains for the participant.     

Pulmonary accumulation of drugs in vitamin a deficiency

The effect of vitamin A deficiency on the uptake of several drug substrates in rat lung slices was determined. Vitamin A deficiency resulted in significant increases in the pulmonary accumulation of imipramine, chlorpromazine, 5-hydroxytryptamine and norepinephrine. The enhanced uptake of 5-hydroxytryptamine by deficient slices was probably due to a decrease in pulmonary monoamine oxidase (MAO) activity, since accumulation of this amine was similar in control and deficient slices that had been preincubated in pargyline, an inhibitor of MAO. In contrast, pulmonary uptake of methadone and paraquat was not affected in vitamin A deficiency. These results suggest that the enhanced susceptibility of the respiratory tract of vitamin A deficient animals to toxic chemicals may be due in part to an increase in the accumulation of the chemicals by the lung.     

Induction and possible role of fibrinolysis in diabetes mellitus.

This article reviews the evidence supporting a relationship between an enhanced tissue injury, increased fibrin formation, defective fibrinolysis, and the evolution of the complications of late diabetic disease. Particular attention is drawn to the role of a defective endothelial cell mediated fibrinolysis with respect to increased fibrin formation and a delayed tissue repair in diabetic patients. Reviewed are studies that indicate that it is possible in patients with diabetes by means of sulfonylurea compounds to increase endothelial cell-produced t-PA without affecting PAI-1. It is advocated that potent compounds should be searched for, with the capability to modify the hemostatic process of the diabetic endothelial cell in order to express more fibrinolytic activity independent of the patient's metabolic state in an attempt to delay the complications of late diabetes.     

Bone geometry, density, and microarchitecture in the distal radius and tibia in adults with osteogenesis imperfecta type I assessed by high-resolution pQCT

Osteogenesis imperfecta (OI) is a hereditary disorder characterized by decreased biosynthesis or impaired morphology of type I collagen that leads to decreased bone mass and increased bone fragility. We hypothesized that patients with OI have altered bone microstructure and bone geometry. In this cross‐sectional study we compared patients with type I OI to age‐ and gender‐matched healthy controls. A total of 39 (13 men and 26 women) patients with OI, aged 53 (range, 21–77) years, and 39 controls, aged 53 (range, 21–77) years, were included in the study. Twenty‐seven of the patients had been treated with bisphosphonates. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) at the distal radius and distal tibia and dual‐energy X‐ray absorptiometry of total hip, femoral neck, trochanteric region, and the lumbar spine (L1–L4) were performed. The patients were shorter than the controls (159 ± 10 cm versus 170 ± 9 cm, p < 0.001), but had similar body weight. In OI, areal bone mineral density (aBMD) was 8% lower at the hip (p < 0.05) and 13% lower at the spine (p < 0.001) compared with controls. The trabecular volumetric bone mineral density (vBMD) was 28% lower in radius (p < 0.001) and 38% lower in tibia (p < 0.001) in OI compared with controls. At radius, total bone area was 5% lower in OI than in controls (p < 0.05). In the tibia, cortical bone area was 18% lower in OI (p < 0.001). In both radius and tibia the number of trabeculae was lower in patients compared to the controls (35% and 38%, respectively, p < 0.001 at both sites). Furthermore, trabecular spacing was 55% higher in OI in both tibia and radius (p < 0.001 at both sites) when compared with controls. We conclude that patients with type I OI have lower aBMD, vBMD, bone area, and trabecular number when compared with healthy age‐ and gender‐matched controls. © 2012 American Society for Bone and Mineral Research.     

Pharmacokinetics of Cefuroxime in Porcine Cortical and Cancellous Bone Determined by Microdialysis

Traditionally, the pharmacokinetics of antimicrobials in bone have been investigated using bone biopsy specimens, but this approach suffers from considerable methodological limitations. Consequently, new methods are needed. The objectives of this study were to assess the feasibility of microdialysis (MD) for measuring cefuroxime in bone and to obtain pharmacokinetic profiles for the same drug in porcine cortical and cancellous bone. The measurements were conducted in bone wax sealed and unsealed drill holes in cortical bone and in drill holes in cancellous bone and in subcutaneous tissue. As a reference, the free and total plasma concentrations were also measured. The animals received a bolus of 1,500 mg cefuroxime over 30 min. No significant differences were found between the key pharmacokinetic parameters for sealed and unsealed drill holes in cortical bone. The mean ± standard error of the mean area under the concentration-time curve (AUC) values from 0 to 5 h were 6,013 ± 1,339, 3,222 ± 1086, 2,232 ± 635, and 952 ± 290 min · μg/ml for free plasma, subcutaneous tissue, cancellous bone, and cortical bone, respectively (P < 0.01, analysis of variance). The AUC for cortical bone was also significantly different from that for cancellous bone (P = 0.04). This heterogeneous tissue distribution was also reflected in other key pharmacokinetic parameters. This study validates MD as a suitable method for measuring cefuroxime in bone. Cefuroxime penetration was impaired for all tissues, and bone may not be considered one distinct compartment.     

Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes,risk factors and genotypes

Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0–17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31–10.20) at 12 months from diagnosis. Patients aged ≥10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P<0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10^-6), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients <10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.