White matter tract signatures of the progressive aphasias

The primary progressive aphasias (PPA) are a heterogeneous group of language-led neurodegenerative diseases resulting from large-scale brain network degeneration. White matter (WM) pathways bind networks together, and might therefore hold information about PPA pathogenesis. Here we used diffusion tensor imaging and tract-based spatial statistics to compare WM tract changes between PPA syndromes and with respect to Alzheimer's disease and healthy controls in 33 patients with PPA (13 nonfluent/agrammatic PPA); 10 logopenic variant PPA; and 10 semantic variant PPA. Nonfluent/agrammatic PPA was associated with predominantly left-sided and anterior tract alterations including uncinate fasciculus (UF) and subcortical projections; semantic variant PPA with bilateral alterations in inferior longitudinal fasciculus and UF; and logopenic variant PPA with bilateral but predominantly left-sided alterations in inferior longitudinal fasciculus, UF, superior longitudinal fasciculus, and subcortical projections. Tract alterations were more extensive than gray matter alterations, and the extent of alteration across tracts and PPA syndromes varied between diffusivity metrics. These WM signatures of PPA syndromes illustrate the selective vulnerability of brain language networks in these diseases and might have some pathologic specificity.     

Neoadjuvant docetaxel and capecitabine and the use of thymidine phosphorylase as a predictive biomarker in breast cancer.

PURPOSE: Thymidine phosphorylase (TP) induction by docetaxel is a proposed mechanism for the observed preclinical synergy of docetaxel and capecitabine (DC). We evaluated whether TP protein expression is increased by docetaxel and correlates with pathologic complete response (pCR) in breast cancer patients. EXPERIMENTAL DESIGN: Women with stage II to III breast cancer were given four cycles of neoadjuvant docetaxel 36 mg/m(2) i.v. over 30 min on days 1, 8, and 15 and capecitabine 2,000 mg/d, in two divided doses, on days 5 to 21 of a 28-day cycle. Radiology-directed biopsies of the breast tumors were done at baseline and 5 days after the first dose of docetaxel to evaluate TP expression. Following DC therapy, patients had core breast biopsies, and if residual disease was present, received four cycles of standard dose-dense doxorubin and cyclophosphamide (AC). RESULTS: The pCR rate was 26.9% (95% confidence interval, 11.6-47.8). Up-regulation of TP expression was not observed by either quantitative immunofluorescence (QIF) or immunohistochemistry. Radiology-directed core biopsy after neoadjuvant chemotherapy accurately predicted pathologic response in 88% (95% confidence interval, 69.8-97.6) of the cases. Neither level of TP expression nor TP up-regulation correlated with pCR. Significant toxicity resulted in therapy discontinuation in 3 of 26 patients. CONCLUSIONS: DC chemotherapy exhibited a similar pCR rate compared with standard taxane regimens, with increased toxicity. TP expression was not up-regulated after docetaxel and did not correlate with therapeutic response. Core breast biopsy after neoadjuvant chemotherapy accurately predicted pathologic response.     

Role of the nose in inspiration in mouth breathing: quantitative determination by analysis of expiratory gases

It is widely accepted that increased nasal resistance plays a major role in habitual mouth breathing. We investigated oronasal air flow distribution during voluntary mouth breathing in subjects without nasal obstruction. To determine whether nasal air flow contributes to total inspiratory flow, we administered 100% O2 by a nasal mask while the lips were kept apart by a mouth piece. Expired O2 concentrations measured at the mouth were a sensitive indicator of nasal admixture during inspiration. Theoretical considerations predict that mixed expired pO2 from two consecutive steady state periods should allow calculation of nasal admixture. Measurements made on 22 healthy volunteers revealed a very variable degree of nasal contribution to inspiratory air flow (mean +/- SD, 25 +/- 15%, range 3-70%). There was no correlation between this proportion and anthropometric data, smoking habits, nasal resistance, or presence of rhinitis. We suggest that changes in the position of the soft palate, tongue, and/or pharyngeal wall associated with respiration are mainly responsible for the within and between subject variation observed in this study. This explanation is consistent with recent experimental findings on the pharyngeal dilating muscles.     

Genetics and cardiac arrhythmias

The identification of the first gene locus of hereditary arrhythmias was made over 10 years ago. In the last few years, considerable progress has been made and the number of culprit genes for cardiac arrhythmias has rapidly increased. This has been the fruit of close collaboration between clinicians, geneticists and physiologists. This work has demonstrated the heterogenous nature of genetics of diseases. It has led to a better understanding of underlying physiopathological mechanisms by the study of the relationship between gene and clinical abnormalities. In addition, analysis of phenotypes and genotypes has improved our knowledge of the clinical presentation of diseases and opened up new therapeutic approaches. These new diagnostic methods have enabled preventive measures to be taken to avoid potentially serious arrhythmias. The genetics of cardiac arrhythmias is still in its infancy: many culprit genes remain undetected and their identification should led to considerable progress in the understanding of the physiopathology of arrhythmias and their treatment.     

MR-guided biopsy of musculoskeletal lesions in a low-field system

Thirty magnetic resonance (MR)-guided biopsies were obtained from 20 skeletal and 10 soft-tissue lesions in 31 patients using an open 0.2 T MR system equipped with interventional accessories. The results from aspiration (N = 3), core biopsy (N = 15), and transcortical trephine biopsy (N = 12) were evaluated for accuracy and clinical efficacy. Specimens were successfully obtained from 29 patients. Results were clinically effective in 23 patients, rated definitive in 16, nonconclusive in 9, and unspecific in 2 patients. A false diagnosis due to sampling error occurred in 2 patients, and biopsy sampling was impossible in one case. The best diagnostic yield was achieved from nontranscortical biopsies of osteolytic or soft-tissue masses. Results from transcortical biopsies were less specific due to the predominance of benign lesions. MR fluoroscopy for needle guidance was applied in 13 patients. Complete needle placement inside the magnet could be performed in 16 patients. MR-guided biopsy using an open low-field MR imager is feasible and clinically effective and will become a valuable tool in the management of musculoskeletal lesions. J. Magn. Reson. Imaging 2001;13:761-768.