Antiplatelet effects of a 600 mg loading dose of clopidogrel are not attenuated in patients receiving atorvastatin or simvastatin for at least 4 weeks prior to coronary artery stenting.

AIMS: To test prospectively whether the antiplatelet effect of a 600 mg loading dose of clopidogrel is attenuated in patients receiving atorvastatin and simvastatin for at least 4 weeks prior to coronary artery stenting. METHODS AND RESULTS: Blood samples were obtained at least 2 h after receiving 100 mg aspirin and 600 mg clopidogrel and prior to coronary stenting from 90 patients without statin therapy and 90 patients with statin (atorvastatin and simvastatin) therapy for at least 4 weeks. Maximal and residual platelet aggregation was evaluated with optical aggregometry in response to ADP (5 and 20 micromol/l). Surface expression of IIb/IIIa (CD61) and P-selectin (CD62) was assessed with whole blood flow-cytometry at baseline and following stimulation (5 and 20 micromol/l ADP). Inhibition of ADP-induced platelet aggregation was not impaired in the presence of concomitant statin therapy. Moreover, patients with and without statin therapy did not differ in respect to all flow-cytometric parameters obtained. CONCLUSION: The antiplatelet effect of a high, 600 mg loading dose of clopidogrel is not diminished in patients receiving atorvastatin and simvastatin for at least 4 weeks prior to coronary stenting.     

Time course of 23Na signal intensity after myocardial infarction in humans.

Experimental studies demonstrated persistently increased 23Na content in nonviable myocardium post-myocardial infarction (MI). We hypothesized that nonviable myocardium in humans would show elevated 23Na content at all stages of infarct development, and therefore could be imaged with 23Na MRI. Ten patients were examined on days 4, 14, and 90 after infarction, and five of these patients participated in a 12-month follow-up. Double angulated short-axis cardiac 23Na images were obtained with the use of a 23Na surface coil and an ECG-triggered, 3D gradient-echo sequence. 1H T2-weighted imaging (N = 9) was performed on days 4, 14, and 90. Wall motion was assessed by cine MRI, and the infarct size was determined by late enhancement on day 90. The 23Na signal intensity (SI) of infarcted myocardium was expressed as the percentage increase over 23Na SI of noninfarcted myocardium. All of the patients showed an area of elevated SI on 23Na and 1H T2-weighted images that correlated with wall motion abnormalities and late enhancement. 23Na SI was highest on day 4. It then decreased until day 90, but remained elevated (39% +/- 18%, 31% +/- 17%, 28% +/- 13% on days 4, 14, and 90, respectively, P = 0.001). No further decrease was found 1 year after infarction (25% +/- 7%, P = 0.89 vs. day 90). 1H T2-weighted SI decreased between days 4 and 14, but on day 90 only six of nine patients had a residual elevated SI. Thus, 23Na SI is elevated in nonviable infarction at all time points following MI, and 23Na MRI may become a suitable technique for imaging nonviable myocardium in humans.     

Amyloid-β peptides in plasma and cognitive decline after 1 year follow-up in Alzheimer's disease patients

Plasma levels of amyloid-β (Aβ) peptides are potential biomarkers of early cognitive impairment and of Alzheimer's disease (AD) risk. However, the association of Aβ peptides with the rate of cognitive decline in AD patients is still unclear. In the present study we demonstrate that Aβ???? plasma levels show a significant correlation with the rate of cognitive decline and are significantly increased in AD patients with fast cognitive decline (decrease of Mini-Mental Status Examination (MMSE) score ≥ 5/year; n = 12) compared to AD patients with slow cognitive decline (decrease of MMSE score ≤ 4/year; n = 28), independent of baseline MMSE scores, age and cholinesterase inhibitor intake, but dependent on history of myocardial infarction and history of stroke in a multivariate analysis. These results suggest that Aβ???? plasma levels are associated with the rate of cognitive decline in AD patients and may be influenced by atherosclerotic vasculopathies such as stroke and myocardial infarction.     

Multiparametric MRI of the prostate with three functional techniques in patients with PSA elevation before initial TRUS-guided biopsy

Objective:

Multiparametric MRI (mp-MRI) of the prostate is increasingly being used for local staging and detection of recurrence of prostate cancer (PCA). In patients with elevated prostate-specific antigen (PSA), mp-MRI could provide information on the position of the cancer, allowing adjustments to be made to the needle depth and direction before repeat transrectal ultrasound (TRUS)-guided biopsy to ensure accurate sampling of lesions. The purpose of the prospective study was to evaluate mp-MRI of the prostate in patients with PSA elevation before initial TRUS-guided biopsy.

Methods:

mp-MRI was performed in 94 patients using a 1.5-T scanner (MAGNETOM Aera^®; Siemens Healthcare, Erlangen, Germany) and 16-channel phased-array body coil (Siemens Healthcare). T₂ weighted images (T2WI), diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) MRI and MR spectroscopy were obtained. TRUS-guided random biopsies and additional targeted biopsies of suspicious MRI areas were performed.

Results:

Additional targeted biopsies were obtained in 17 of 43 (40%) patients with PCA. 11 of 17 targeted biopsies contained PCA. 5 of 11 PCAs were diagnosed only by additional targeted biopsies. Sensitivity of mp-MRI in patients was 97.7% and specificity was 11.8%. mp-MRI was false negative in one patient. Sensitivity of mp-MRI in 207 lesions was 80.9% and specificity was 44.7%. In a logistic regression model, the apparent diffusion coefficient value was the only significant parameter to differentiate malignant and benign lesions.

Conclusion:

mp-MRI should be performed in patients with PSA elevation before initial TRUS-guided biopsy to allow additional targeted biopsies from suspicious areas of MRI. We recommend mp-MRI with T2WI, DWI, DCE MRI and MR spectroscopy. DWI as the most reliable technique should be used in every mp-MRI.

Advances in knowledge:

DWI is the most reliable technique in mp-MRI of the prostate.     

Novel desmoplakin mutation: juvenile biventricular cardiomyopathy with left ventricular non-compaction and acantholytic palmoplantar keratoderma

Two sons of a consanguineous marriage developed biventricular cardiomyopathy. One boy died of severe heart failure at the age of 6 years, the other was transplanted because of severe heart failure at the age of 10 years. In addition, focal palmoplantar keratoderma and woolly hair were apparent in both boys. As similar phenotypes have been described in Naxos disease and Carvajal syndrome, respectively, the genes for plakoglobin (JUP) and desmoplakin (DSP) were screened for mutations using direct genomic sequencing. A novel homozygous 2 bp deletion was identified in an alternatively spliced region of DSP. The deletion 5208_5209delAG led to a frameshift downstream of amino acid 1,736 with a premature truncation of the predominant cardiac isoform DSP-1. This novel homozygous truncating mutation in the isoform-1 specific region of the DSP C-terminus caused Carvajal syndrome comprising severe early-onset heart failure with features of non-compaction cardiomyopathy, woolly hair and an acantholytic form of palmoplantar keratoderma in our patient. Congenital hair abnormality and manifestation of the cutaneous phenotype in toddler age can help to identify children at risk for cardiac death.