Coagulation activation and ultrasound characteristics in patients with carotid artery disease

Introduction

Elevated levels of markers for thrombin activation are associated with plaque echogenicity and degree of stenosis in patients with carotid artery stenosis. The Activated Protein C-Protein C Inhibitor (APC-PCI) complex reflects activation of the Protein C system and is a measure of thrombin generation. The aim of the present study was to examine APC-PCI complex in patients undergoing thrombendartherectomy for carotid artery stenosis, and to relate the findings to clinical characteristics and plaque morphology as determined by ultrasound.

Materials and Methods

Blood was obtained from 125 patients (39 female, median age 71 years) with carotid artery stenosis admitted from September 2005 to May 2007. The APC-PCI complex was measured using a sandwich immunofluorometric method and compared to an age- and sex-matched healthy control-group. Clinical and demographic characteristics, routine laboratory markers and ultrasound characteristics were analysed using univariate and multivariate analysis.

Results

APC-PCI complex concentration was significantly increased in patients with carotid artery stenosis (median 0.21 µg/L; 10th to 90th percentile 0.15-0.36) compared to a healthy control-group (0.19 µg/L; 0.11-0.31; P = .009). There was no significant difference in APC-PCI-values between asymptomatic (n = 48) and symptomatic (n = 77) patients with carotid artery stenosis (0.22 vs. 0.20 µg/L; p = 0.626). Patients with minor stroke (n = 31) had a higher median APC-PCI-concentration (0.27 µg/L; 0.15-0.63) than patients with amaurosis fugax (0.19 µg/L; 0.15-0.36) or transient ischemic attack (0.21 µg/L; 0.12-0.36) (p = 0.016). No association was found between APC-PCI-values and the degrees of carotid artery stenosis or the time from the latest neurological symptoms to blood sampling. Patients with echolucent plaques had significantly lower APC-PCI concentrations (0.20 µg/L; 0.14-0.35 vs. 0.24 µg/L; 0.15-0.60; p = 0.043), according to the Gray-Weale classification.

Conclusions

Patients with carotid artery disease exhibit increased concentrations of APC-PCI compared to a healthy control-group, particularly those patients with echogenic plaques, who have significantly higher APC-PCI levels than patients with echolucent plaques.     

Hippocampal dysfunction during free word association in male patients with schizophrenia

In schizophrenia, speech production deficits in patients with positive formal thought disorder (FTD e.g. loosening of associations and derailment) have been attributed to impairments in the semantic network. The brain area implicated in the retrieval of associated (i.e. relational) concepts is the hippocampus, a key region in the psychopathology of schizophrenia. However, its role in schizophrenic speech production and FTD in particular is yet little understood.

To investigate the neural correlates of associative verbal retrieval, twelve patients with schizophrenia with varying degrees of FTD and twelve matched healthy control subjects underwent a free verbal association (FVA), a semantic (SVF) and a phonological verbal fluency (PVF) task while brain activity was measured with fMRI. The tasks varied in the relational binding operations needed for linking the stimulus to the respective response.

Compared to control subjects, patients revealed attenuated left hippocampal activity during both semantic word generation tasks (FVA, SVF). Contrasting verbal fluency with FVA, a failure in recruiting the anterior cingulate gyrus emerged in the patient group. A negative correlation was found between right middle temporal activity and the severity of FTD during FVA.

The hippocampus seems to play a major role in word generation. In schizophrenia, attenuated hippocampal activity during semantic tasks strengthens the hypothesis of impaired relational memory processes, affecting thought and language.     

Ophthalmic Rosacea: Case Report in a Child and Treatment Recommendations

We report a rare case of rosacea with ocular involvement in a child that remitted with prolonged anti‐inflammatory oral tetracycline therapy and provide general expert recommendations. A 14‐year‐old girl presented with discrete papules and pustules on both cheeks with blepharitis and conjunctivitis. Ophthalmologic examination confirmed bilateral severe blepharitis, as well as a corneal infiltrate in the right eye with additional neovascularization. The diagnosis of rosacea with ocular involvement was made. In addition to the existing antibiotic and anti‐inflammatory topical eye therapy, systemic treatment with minocycline 50 mg twice a day was started. After marked improvement, the dose was reduced to 50 mg once a day. After further amelioration, treatment was switched to maintenance therapy with 40 mg of prolonged‐release doxycycline. Three years after a 12‐month course of anti‐inflammatory therapy, the patient remained recurrence free.     

Refining HPV 16 L1 purification from E. coli: Reducing endotoxin contaminations and their impact on immunogenicity

HPV 16 L1 capsomeres purified from Escherichia coli represent a promising and potentially cost-effective alternative to the recently licensed VLP-based vaccines for the prevention of cervical cancer. However, recombinant protein preparations from bacteria always bear the risk of contaminating endotoxins which are highly toxic in humans and therefore have to be eliminated from vaccine preparations. In this study, we measured the LPS concentration at various stages of the purification of HPV 16 L1 from E. coli and determined that it enhances the immunogenicity of HPV 16 VLPs and capsomeres. We confirmed the immunogenicity of the L1 capsomeres in TLR4^−/− mice without the enhancing effect of the LPS and then elaborated a suitable protocol using Triton X-114 phase separation for the removal of LPS without any significant protein loss or influence on the structural integrity of the particles. The LPS-free capsomeres purified from E. coli induced neutralizing L1-specific antibodies. Our results demonstrate the excellent potential of capsomeres as an economically interesting alternative vaccine to prevent cervical cancer that could be made available in developing countries.     

Are PARKIN patients ideal candidates for dopaminergic cell replacement therapies?

Parkinson's is a heterogeneous, complex condition. Stratification of Parkinson's subtypes will be essential to identify those that will benefit most from a cell replacement therapy. Foetal mesencephalic grafts can alleviate motor symptoms in some Parkinson's patients. However, on‐going synucleinopathy results in the grafts eventually developing Lewy bodies, and they begin to fail. We propose that Parkinson's patients with PARKIN mutations may benefit most from a cell replacement therapy because (a) they often lack synucleinopathy, and (b) their neurodegeneration is often confined to the nigrostriatal pathway. While patients with PARKIN mutations exhibit clinical signs of Parkinson's, post‐mortem studies to date indicate the majority lack Lewy bodies suggesting the nigral dopaminergic neurons are lost in a cell autonomous manner independent of α‐synuclein mechanisms. Furthermore, these patients are usually younger, slow progressing and typically do not suffer from complex non‐nigral symptoms that are unlikely to be ameliorated by a cell replacement therapy. Transplantation of dopaminergic cells into the putamen of these patients will provide neurons with wild‐type PARKIN expression to re‐innervate the striatum. The focal nature of PARKIN‐mediated neurodegeneration and lack of active synucleinopathy in most young‐onset cases makes these patients ideal candidates for a dopaminergic cell replacement therapy. Strategies to improve the outcome of cell replacement therapies for sporadic Parkinson's include the use of adjunct therapeutics that target α‐synuclein spreading and the use of genetically engineered grafts that are resistant to synucleinopathy.