Formal alkyne aza-prins cyclization: gold(I)-catalyzed cycloisomerization of mixed N,O-acetals generated from homopropargylic amines to highly substituted piperidines.

A new gold(I)-catalyzed cycloisomerization to access highly substituted piperidines has been developed. By combining a conceptually new way of generating iminium ions using cationic gold(I) complexes and an efficient cyclization reaction that can minimize a potentially competing aza-Cope rearrangement, the proposed reaction successfully circumvents a long-standing problem in the classical aza-Prins reaction. Synthetic utility of the catalytic reaction was demonstrated by a synthesis of optically active 2-alkyl-piperidin-4-one.

Organized Comprehensive Stroke Center is Associated with Reduced Mortality: Analysis of Consecutive Patients in a Single Hospital.

BACKGROUND AND PURPOSE: Organized inpatient stroke care is one of the most effective therapies for improving patient outcomes. Many stroke centers have been established to meet this need, however, there are limited data on the effectiveness of these organized comprehensive stroke center (CSC) in the real-world setting. Our aim is to determine whether inpatient care following the establishment of CSC lowers mortality of patients with acute ischemic stroke (AIS). METHODS: Based on a prospective stroke registry, we identified AIS patients hospitalized before and after the establishment of a CSC. We observed all-cause mortality within 30 days from time of admission. Logistic regression was used to determine whether the establishment of the CSC affects independently the 30-day all-cause mortality. RESULTS: A total of 3,117 consecutive patients with AIS were admitted within seven days after the onset of the symptoms. Unadjusted 30-day mortality was lower for patients admitted to our hospital after the establishment of the CSC than before (5.9% vs. 8.2%, P=0.012). Advanced age, female gender, previous coronary artery disease, non-smoking, stroke subtype, admission on a holiday, referral from other hospitals, high NIHSS on admission, and admission before the establishment of CSC were associated with increased 30-day stroke case fatality. After adjustment for these factors, stroke inpatient care subsequent to the establishment of the CSC was independently associated with lower 30-day mortality (OR, 0.57; 95% CI, 0.412-0.795). CONCLUSIONS: Patients treated after the establishment of a CSC had lower 30-mortality rates than ever before, even adjusting for the differences in the baseline characteristics. The present study reveals that organized stroke care in a CSC might improve the outcome after AIS.

Orthostatic hypotension in drug-naïve patients with Parkinson's disease.

BACKGROUND AND PURPOSE: Orthostatic hypotension (OH) is known to be present even in patients with early Parkinson's disease (PD). To affirm the presence of OH and find correlation between OH and other dysautonomic symptoms in PD, this study has done in newly-diagnosed PD patients. METHODS: Forty-five non-demented patients with no prior history of treatment for PD were recruited (17 men, 63.8 ± 10.1 years of age). All the patients were evaluated for OH before starting medications. Autonomic symptoms were evaluated with structured questionnaires. Clinical characteristics of PD were evaluated (median Hoehn and Yahr stage 2.0 (1-3), 1.3 ± 1.1 years of disease duration), and comorbid medical conditions that could affect blood pressure were also recorded. RESULTS: OH was prevalent, and eighteen patients (40%) showed orthostatic hypotension, and twenty-seven (60%) did not (normotensive group). There was no significant difference in demographic and clinical characteristics between groups. The presence or severity of symptoms of autonomic dysfunction in the OH group also not differed from those of the normotensive group. CONCLUSIONS: OH was prevalent even in the early stage of PD, and was not related to presence or severity of any other symptoms of autonomic dysfunction. Our findings suggest that clinicians should pay attention to OH from the early stage of disease.

Leukoaraiosis on magnetic resonance imaging is related to long-term poor functional outcome after thrombolysis in acute ischemic stroke.

OBJECTIVE: Leukoaraiosis (LA) has been suggested to be related to the poor outcome or the occurrence of symptomatic intracerebral hemorrhage (sICH) after acute ischemic stroke. We retrospectively investigated the influences of LA on long-term outcome and the occurrence of sICH after thrombolysis in acute ischemic stroke (AIS). METHODS: In this study, we recruited 164 patients with AIS and magnetic resonance image (MRI)-detected thrombolysis. The presence and extent of LA were assessed using the Fazekas grading system. The National Institutes of Health Stroke Scale score was used to assess the baseline measure of neurologic severity, and the modified Rankin Scale score assessment was used up to 1 year after thrombolysis. RESULTS: Of 164 subjects, 56 (34.2%) showed LA on MRI. Compared to the 108 patients without LA, the patients with LA were of much older age (p<0.01), had a higher prevalence of hypertension (p<0.01), and had a much poorer outcome at 90 days (p=0.05) and 1 yr (p=0.01) after thrombolysis. There were no significant differences in sICH between patients with and without LA on MRI. In univariate analysis for the occurrence of poor outcome at 90 days after thrombolysis, the size of ischemic lesion on diffusion weighted images (DWI), [odds ratio (OR), 1.03; 95% confidence interval (95% CI), 1.01-1.04; p<0.01], recanalization (OR, 0.03; 95% CI, 0.01-0.10; p<0.01), sICH (OR, 12.2; 95% CI, 1.54-95.8), neurologic severity (OR, 1.17; 95% CI, 1.09-1.25; p<0.01), blood glucose level (OR, 1.01; 95% CI, 1.00-1.02; p=0.03), and the presence of LA on MRI (OR, 2.01; 95% CI, 1.04-3.01; p=0.04) were statistically significant. In multivariate analysis, neurologic severity (OR, 1.14; 95% CI, 1.04-1.24; p<0.01), recanalization (OR, 0.03; 95% CI, 0.01-0.11; p<0.01), lesion size on DWI (OR, 1.02; 95% CI, 1.01-1.03; p=0.02), serum glucose level (OR, 1.01; 95% CI; 1.01-1.02; p=0.03), and the presence of LA on MRI (OR, 3.2; 95% CI, 1.22-8.48; p<0.01) showed statistically significant differences. These trends persisted up to 1 yr after thrombolysis. CONCLUSION: In this study, we demonstrated that the presence of LA on MRI might be related to poor outcome after use of intravenous tissue plasminogen activator in AIS.

Prehospital notification from the emergency medical service reduces the transfer and intra-hospital processing times for acute stroke patients.

BACKGROUND AND PURPOSE: There is little information available about the effects of Emergency Medical Service (EMS) hospital notification on transfer and intrahospital processing times in cases of acute ischemic stroke. METHODS: This study retrospectively investigated the real transfer and imaging processing times for cases of suspected acute stroke (AS) with EMS notification of a requirement for intravenous (IV) tissue-type plasminogen activator (t-PA) and for cases without notification. Also we compared the intra-hospital processing times for receiving t-PA between patients with and without EMS prehospital notification. RESULTS: Between December 2008 and August 2009, the EMS transported 102 patients with suspected AS to our stroke center. During the same period, 33 patients received IV t-PA without prehospital notification from the EMS. The mean real transfer time after the EMS call was 56.0±32.0 min. Patients with a transfer distance of more than 40 km could not be transported to our center within 60 min. Among the 102 patients, 55 were transferred via the EMS to our emergency room for IV t-PA. The positive predictive value for stroke (90.9% vs. 68.1%, p=0.005) was much higher and the real transfer time was much faster in patients with an EMS t-PA call (47.7±23.1 min, p=0.004) than in those without one (56.3±32.4 min). The door-to-imaging time (17.8±11.0 min vs. 26.9±11.5 min, p=0.01) and door-to-needle time (29.7±9.6 min vs. 42.1±18.1 min, p=0.01) were significantly shorter in the 18 patients for whom there was prehospital notification and who ultimately received t-PA than in those for whom there was no prehospital notification. CONCLUSIONS: Our results indicate that prehospital notification could enable the rapid dispatch of AS patients needing IV t-PA to a stroke centre. In addition, it could reduce intrahospital delays, particularly, imaging processing times.

Autonomic dysfunctions in parkinsonian disorders.

BACKGROUND AND PURPOSE: Symptoms of autonomic dysfunctions are common in the patients with parkinsonian disorders. Because clinical features of autonomic dysfunctions are diverse, the comprehensive evaluation is essential for the appropriate management. For the appreciation of autonomic dysfunctions and the identification of differences, patients with degenerative parkinsonisms are evaluated using structured questionnaire for autonomic dysfunction (ADQ). METHODS: Total 259 patients, including 192 patients with [idiopathic Parkinson's disease (IPD, age 64.6 ± 9.6 years)], 37 with [multiple system atrophy (MSA, 62.8 ± 9.1)], 9 with [dementia with Lewy body (DLB, 73.9 ± 4.3)], and 21 with [progressive supranuclear palsy (PSP, 69.4 ± 9.6)]. The ADQ was structured for evaluation of the presence of symptoms and its severity due to autonomic dysfunction, covering gastrointestinal, urinary, sexual, cardiovascular and thermoregulatory domains. Patients were also evaluated for the orthostatic hypotension. RESULTS: Although dementia with Lewy body (DLB) patients were oldest and duration of disease was longest in IPD, total ADQ scores of MSA and PSP (23.9 ± 12.6 and 21.1 ± 7.8) were significantly increased than that of IPD (15.1 ± 10.6). Urinary and cardiovascular symptom scores of MSA and gastrointestinal symptom score of PSP were significantly worse than those of IPD. The ratio of patient with orthostatic hypotension in IPD was 31.2% and not differed between groups (35.1% in MSA, 33.3% in DLB and 33.3% in PSP). But the systolic blood pressure dropped drastically after standing in patients with MSA and DLB than in patients with IPD and PSP. CONCLUSIONS: Patients with degenerative parkinsonism showed widespread symptoms of autonomic dysfunctions. The severity of those symptoms in patients with PSP were comparing to that of MSA patients and worse than that of IPD.