Derivation of Power M-Mode Transcranial Doppler Criteria for Angiographic Proven MCA Occlusion

BACKGROUND: Stringent transcranial Doppler (TCD) criteria for diagnosing occlusion are needed for more reliable TCD performance at bedside in the acute stroke setting. SUBJECTS AND METHODS: At three academic stroke centers, we performed TCD examination for patients with symptoms of cerebral ischemia who underwent digital subtraction angiography (DSA). We used a standard insonation protocol with power M-mode Doppler (PMD) TCD (TCD 100 M, Spencer Technologies Inc., Seattle, WA). We collected mean flow velocity (MFV), pulsatility indices (PI), and power M-mode resistance signature (absent, high, or low) in symptomatic middle (MCA), anterior (ACA), posterior (PCA), and in affected (a), ipsilateral (i), and contralateral (c-lat) cerebral arteries. Ratios of aMCA/c-lat MCA, aMCA/iACA, and aMCA/iPCA MFV were subsequently calculated. PMD-TCD flow findings were evaluated with a receiver-operating characteristic (ROC) analysis for angiographically proven MCA occlusion. RESULTS: We studied 120 patients with acute cerebral ischemia with PMD-TCD examinations prior to or immediately after DSA. Lower aMCA velocities pointed to higher probability of occlusion (P= .055). The aMCA/iPCA MFV ratio was superior to the aMCA/iACA ratio and strongly predictive of occlusion at a threshold ratio of 0.5 (RR 2.31 CI(95) 2.13-2.51). High resistance or absent M-mode flow signatures in the proximal MCA were present in 87% of M1 and M2 MCA occlusions (probability 87%). In the presence of a low-resistance PMD signature, obtaining the aMCA/iPCA MFV ratio <0.5 increases probability of occlusion to 87%. Normal MFV ratios and low-resistance M-mode signatures are highly predictive of a negative angiogram for MCA occlusion. CONCLUSION: In acute cerebral ischemia, reliable criteria for proximal MCA occlusion have been developed based on combination of MFV ratios and M-mode flow resistance signatures. Validation of these criteria will require multicenter studies.     

Determinants of left ventricular systolic function recovery after an acute coronary syndrome.

INTRODUCTION: Ischemic heart disease is a major cause of heart failure in western societies. However, the factors that may influence left ventricular function (LVF) recovery after an acute coronary syndrome (ACS) are still unclear. OBJECTIVE: To identify variables that may influence LVF evolution one year after ACS. METHODS: 104 patients hospitalized with ACS between 7/1/2001 and 12/31/2002 and with systolic dysfunction--defined as an echocardiographic ejection fraction (EF) < or = 45%--were randomly allocated to a planned coronary follow-up program (FUP) or a general cardiology clinic (GC); patients from both groups were also randomly referred to a structured cardiac rehabilitation program (CRP). EF was re-assessed at one year. We compared differences between patients who recovered left ventricular function (EF > 45%; group 1) and those who did not (group 2). RESULTS: One year after discharge, 44.2% of the patients had recovered function. There were no significant differences between the groups in gender (77.7 vs. 76.5% male), age (56 vs. 59 years), hypertension, diabetes, dyslipidemia, smoking habits or family history. A previous history of cardiovascular events was more frequent in group 2 (11.1% vs. 35.3%, p = 0.03). Cardiac catheterization was performed before discharge in 88.8% and 88.2% in groups 1 and 2 respectively (p = NS); no differences were found in coronary anatomy between the two groups. Angioplasty was performed in 54.2% in group 1 and 50% in group 2 (p = NS). There were no differences in the use of angiotensin-converting enzyme inhibitors (83.3% vs. 87.5%), beta-blockers (87.5% vs. 87.5%), nitrates (37.5% vs. 33.3%), aspirin (95.8% vs. 95.8%), statins (79.1% vs. 75%) or diuretics (20.8% vs. 45.8%). There was no significant difference in LVF recovery between patients randomized to FUP or GC (38.5% vs. 54.5%). 87.5% of patients who completed the CRP had normal EF at one year compared to 32.7% of patients not referred to the program (p = 0.009). Although EF improved in both groups, this improvement was greater in patients who completed a CRP (EF 8% vs. 5%, p = 0.003). CONCLUSION: A previous cardiovascular event and completion of a CRP were the only variables that influenced LVF recovery. Thus, enrollment in a CRP, in addition to standard therapy, could be an important therapeutic measure in patients with systolic dysfunction after ACS; our data suggest that these programs should be more widely used.     

Inhibitory effect of phospholipase A2 isolated from Crotalus durissus terrificus venom on macrophage function

Recent work demonstrated that crotoxin, the main toxin of Crotalus durissus terrificus venom, inhibits macrophage spreading and phagocytic activities. The crotoxin molecule is composed of two subunits, an acidic non-toxic and non-enzymatic polypeptide named crotapotin and a weakly toxic basic phospholipase A₂ (PLA₂). In the present work, the active subunit responsible for the inhibitory effect of crotoxin on macrophage function was investigated. Peritoneal macrophages harvested from naive rats were used. Crotapotin (2.12, 3.75, or 8.37 nM/ml), added for 2 h to the medium of peritoneal cell incubation, did not modify the spreading and phagocytic activities of these cells. On the other hand, the PLA₂ (1.43, 2.86, or 6.43 nM/ml) subunit caused a significant reduction (30, 33, and 35%, respectively) of the spreading activity. The PLA₂ also inhibited the phagocytosis of opsonised zymosan, opsonised sheep erythrocytes, and Candida albicans, indicating that this inhibitory effect is not dependent on the type of receptor involved in the phagocytosis process. The inhibitory effect of PLA₂ was not due to loss of cell membrane integrity, since macrophage viability was higher than 95%. These findings indicate that the inhibitory effect of crotoxin on macrophage spreading and phagocytic activities is caused by the phospholipase A₂ subunit.     

Local excision for ypT2 rectal cancer--much ado about something.

BACKGROUND: The role of local excision for pT2 distal rectal cancer has been challenged because of the observation of high rates of lymph node metastases and local failure. However, neoadjuvant chemoradiation therapy (CRT) has led to increased local disease control and significant tumor downstaging, possibly decreasing rates of lymph node metastases. In this setting, a possible role for local excision of ypT2 has been suggested. METHODS: A total of 401 patients with distal rectal cancer underwent neoadjuvant CRT. Tumor response assessment was performed after at least 8 weeks from CRT completion. One hundred and twelve patients with complete clinical response were not immediately operated on and were excluded from the study, and 289 patients with incomplete clinical response were managed by radical surgery. Patients with final pathological stage ypT2 were analyzed to determine the risk of unfavorable pathological features that could represent unacceptable risk for local failure after local excision. RESULTS: Eighty-eight (30%) patients had ypT2 rectal cancer. Final ypT status was not associated with pretreatment radiological staging (p = 0.62). ypT status was significantly associated with the risk of lymph node metastases, risk of perineural and vascular invasion, and recurrence (p = 0.001). Lymph node metastases were present in 19% of patients with ypT2 rectal cancer. The risk of lymph node metastases in ypT2 was associated with the presence of perineural invasion (47% vs 4%; p = <0.001), vascular invasion (59% vs 6%; p < 0.001), and decreased mean interval CRT surgery (12 vs 18 weeks; p < 0.001), but not with mean tumor size (3.2 vs 3.1 cm; p = 0.8). Disease-free and overall survival rates were significantly better for patients with ypT2N0 (p = 0.02 and 0.006, respectively). Fifty-five (63%) patients with ypT2 had at least one unfavorable pathological feature for local excision (lymph node metastases, vascular or perineural invasion, mucinous type or tumor size >3 cm). CONCLUSION: Lymph node metastases were present in 19% of patients with ypT2 and were significantly associated with poor overall and disease-free survival rates. The risk of lymph node metastases could not be predicted by radiological staging or tumor size. Radical surgery should be considered the standard treatment option for ypT2 rectal cancer after CRT.