Reduction in oral corticosteroid use with mometasone furoate dry powder inhaler improves health-related quality of life in patients with severe persistent asthma.

Severe persistent asthma can have a substantial impact on a patient's health-related quality of life (HRQL), both as a result of symptoms and from side effects of treatment. The HRQL impact of two doses (400 and 800 microg twice daily) of mometasone furoate dry powder inhaler (MF DPI) was compared with placebo in patients with severe persistent asthma previously maintained on oral steroids as a component of a previously published randomized, 12-week, double-blind, placebo-controlled, multicenter trial. A 9-month open-label extension (OLE), with all patients treated with MF DPI, followed. Patients 12 years of age or older completed a generic HRQL measure, the Medical Outcomes Trust Short Form-36 (SF-36), and an asthma-specific measure, the Marks Asthma Quality of Life Questionnaire (AQLQ-M), at baseline, at endpoint (last evaluable visit) of the double-blind phase (EODBP), and after the first 3 months of the OLE. Of 132 patients enrolled in the study, 128 provided HRQL data at baseline and at EODBP. Mean SF-36 scores at baseline showed significant HRQL impairment compared with U.S. general population norms. With treatment, the reduction in oral corticosteroid (OCS) requirements of the MF-DPI-treated groups was accompanied by significant (p < 0.05) improvement over placebo in the physical domain of HRQL (SF-36 physical component summary score and the physical function subscale) at EODBP. MF-DPI-treated patients also showed significant improvements at EODBP in each of the four subscales of the AQLQ-M (p<0.05). From EODBP to the OLE 3-month endpoint, patients treated with MF DPI twice daily maintained, or improved, SF-36 scores in most domains. Symptomatic improvement and reduction in OCS use with MF DPI were accompanied by significant improvement in HRQL in patients with severe persistent asthma. These improvements were maintained during the 3-month period of the OLE in which HRQL was evaluated.     

Cerebral autoregulation is preserved in multiple system atrophy: A transcranial Doppler study.

Patients with multiple system atrophy (MSA) present large changes in blood pressure (BP) due to autonomic disturbances. We analyzed how this change may influence dynamic cerebral autoregulation (DCA). Simultaneous recordings of arterial BP (Finapres) and middle cerebral artery (MCA) blood flow velocity (BFV) (transcranial Doppler) were performed in 10 patients with MSA (61 +/- 12 yr of age) and 12 healthy volunteers (61 +/- 11 yr of age): cerebral BFV response to oscillations in mean BP was studied in the supine position by cross-spectral analysis of mean BP and mean MCA BFV. The DCA was also studied during the decrease in BP the first seconds when standing up from a sitting position by the assessment of the cerebrovascular resistance index (CR; mean BP/mean MCA BFV ratio). The MCA BFV/BP cross-spectral analysis showed a phase for the mid-frequency band (0.07-0.2 Hz) significantly larger in MSA, suggesting more active autoregulation in response to larger changes in BP. Changes in CR reflecting the rate of autoregulation, when standing did not differ between the two groups. These data suggest that dynamic cerebral autoregulation is preserved in MSA.     

A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

Academic Degrees and Clinical Practice Characteristics: The University of Washington Physician Assistant Program: 1969-2000

CONTEXT: The physician assistant profession has been moving toward requiring master's degrees for new practitioners, but some argue this could change the face of the discipline. PURPOSE: To see if there is an association between physician assistants' academic degrees and practice in primary care, in rural areas, and with the medically underserved. METHODS: Surveys were sent to 880 graduates of the first 32 University of Washington physician assistant classes through 2000. Respondents noted their academic degree at program entry and the highest degree attained at any time up to the time of survey. Relationships between practice characteristics and academic degree levels were tested by unadjusted odds ratios and logistic regression after controlling for year of graduation and sex. RESULTS: Of the 478 respondents, 54% worked in primary care, about 30% practiced in nonmetropolitan communities, and 42% reported providing care for the medically underserved. Respondents with no degree (33% of total at entry, 24% at survey) were significantly more likely than degree holders to work in primary care and nonmetropolitan areas. Respondents with no degree at program entry were significantly more likely, and those with no degree at the time of the survey were marginally more likely, to self-report work with the medically underserved. CONCLUSION: Respondents with no academic degree are significantly more likely to demonstrate a commitment to primary, rural, and underserved health care. These findings may inform the national debate about the impact of required advanced degrees on the practice patterns of nonphysician providers.