Spontaneous regression of an idiopathic arteriovenous fistula of the right vertebral artery.

A previously healthy 53-year-old male presented with a 2-month history of pulsatile tinnitus, worsening headaches, and neck pain. Given the clinical symptoms, a workup was initiated to assess for a vascular etiology such as a dural arteriovenous fistula.

TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis.

Quiescent phases of inflammatory bowel disease (IBD) are often accompanied by chronic abdominal pain. Although the transient receptor potential vanilloid 1 (TRPV1) ion channel has been postulated as an important mediator of visceral hypersensitivity, its functional role in postinflammatory pain remains elusive. This study aimed at establishing the role of TRPV1 in the peripheral sensitization underlying chronic visceral pain in the context of colitis. Wild-type and TRPV1-deficient mice were separated into three groups (control, acute colitis, and recovery), and experimental colitis was induced by oral administration of dextran sulfate sodium (DSS). Recovery mice showed increased chemically and mechanically evoked visceral hypersensitivity 5 wk post-DSS discontinuation, at which point inflammation had completely resolved. Significant changes in nonevoked pain-related behaviors could also be observed in these animals, indicative of persistent discomfort. These behavioral changes correlated with elevated colonic levels of substance P (SP) and TRPV1 in recovery mice, thus leading to the hypothesis that SP could sensitize TRPV1 function. In vitro experiments revealed that prolonged exposure to SP could indeed sensitize capsaicin-evoked currents in both cultured neurons and TRPV1-transfected human embryonic kidney (HEK) cells, a mechanism that involved TRPV1 ubiquitination and subsequent accumulation at the plasma membrane. Importantly, although TRPV1-deficient animals experienced similar disease severity and pain as wild-type mice in the acute phase of colitis, TRPV1 deletion prevented the development of postinflammatory visceral hypersensitivity and pain-associated behaviors. Collectively, our results suggest that chronic exposure of colon-innervating primary afferents to SP could sensitize TRPV1 and thus participate in the establishment of persistent abdominal pain following acute inflammation.

Antimicrobial Properties of Bacterial Cellulose Films Enriched with Bioactive Herbal Extracts Obtained by Microwave-Assisted Extraction.

The use of bacterial cellulose (BC) as scaffold for active biofilms is one of the most interesting applications, especially for the biomedical and food industries. However, there are currently few studies evaluating the potential of incorporating herbal extracts into various biomaterials, including BC. Thus, the aim of this study is to report a screening of the total phenolic content and antioxidant and antimicrobial activity of ethanolic extracts of oregano, rosemary, parsley, and lovage. At the same time, the bioactive potential of BC enriched with the four ethanolic extracts is described. Microwave-assisted extraction was used to extract bioactive compounds from the four selected herbs. The physical, mechanical, structural, and chemical properties of BC were also assessed. Next, BC was enriched with the extracts, and their effect against Escherichia coli, Staphylococcus aureus, and Candida albicans was evaluated. The results showed that the bioactivity of the herbs varied significantly, with rosemary extract being the most bioactive. The BC films possessed good mechanical properties, and a three-dimensional network fibrillar structure appropriate for ethanolic-extract incorporation. The BC samples enriched with rosemary extracts had the highest antibacterial activity against S. aureus, while E. coli. and C. albicans seemed to be resistant to all extracts, regardless of herbs.

The neuronal tyrosine kinase receptor ligand ALKAL2 mediates persistent pain.

The anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase known for its oncogenic potential that is involved in the development of the peripheral and central nervous system. ALK receptor ligands ALKAL1 and ALKAL2 were recently found to promote neuronal differentiation and survival. Here, we show that inflammation or injury enhanced ALKAL2 expression in a subset of TRPV1+ sensory neurons. Notably, ALKAL2 was particularly enriched in both mouse and human peptidergic nociceptors, yet weakly expressed in nonpeptidergic, large-diameter myelinated neurons or in the brain. Using a coculture expression system, we found that nociceptors exposed to ALKAL2 exhibited heightened excitability and neurite outgrowth. Intraplantar CFA or intrathecal infusion of recombinant ALKAL2 led to ALK phosphorylation in the lumbar dorsal horn of the spinal cord. Finally, depletion of ALKAL2 in dorsal root ganglia or blocking ALK with clinically available compounds crizotinib or lorlatinib reversed thermal hyperalgesia and mechanical allodynia induced by inflammation or nerve injury, respectively. Overall, our work uncovers the ALKAL2/ALK signaling axis as a central regulator of nociceptor-induced sensitization. We propose that clinically approved ALK inhibitors used for non-small cell lung cancer and neuroblastomas could be repurposed to treat persistent pain conditions.

Previous statin use is not associated with an increased prevalence or degree of gradient-echo lesions in patients with acute ischemic stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Microhemorrhages on gradient-echo T2*-weighted MRI sequences are often found in patients with cerebrovascular disease and are related to intracerebral hemorrhage. Because statin therapy is associated with increased risk of intracerebral hemorrhage, we investigated whether statin use was also associated with microhemorrhages in patients with acute ischemic stroke or transient ischemic attack. METHODS: We performed a retrospective analysis on prospectively collected data from a stroke registry containing patients with acute ischemic stroke or transient ischemic attack. The primary and secondary outcome variables were the prevalence and degree of microhemorrhages as detected on gradient-echo MRI sequences and categorized as mild (1-2), moderate (3-10), or severe (>10). The location of the microhemorrhages was noted and rated by 2 neuroradiologists. Previous use of statins and other covariates were assessed as potential predictors. RESULTS: Three hundred forty-nine patients were admitted from June 2008 to July 2009, and 300 of which were analyzed. Microhemorrhages were detected in 70 subjects (23%); 35 had only lobar lesions, 16 had only deep lesions, and 19 had both lobar and deep lesions. On univariate and multivariate analysis, statin therapy was not associated with the prevalence (OR, 0.73; 95% CI, 0.36-1.51; P=0.40) or degree of microhemorrhages modeled for lesser severity (OR, 2.31; 95% CI, 0.61-8.75; P=0.22). CONCLUSIONS: Previous statin therapy was not associated with the prevalence or degree of microhemorrhages in patients with acute ischemic stroke or transient ischemic attack. The association between statins and intracerebral hemorrhage does not appear to be mediated through microhemorrhages.

Modeling temperature- and Cav3 subtype-dependent alterations in T-type calcium channel mediated burst firing.

T-type calcium channels are important regulators of neuronal excitability. The mammalian brain expresses three T-type channel isoforms (Cav3.1, Cav3.2 and Cav3.3) with distinct biophysical properties that are critically regulated by temperature. Here, we test the effects of how temperature affects spike output in a reduced firing neuron model expressing specific Cav3 channel isoforms. The modeling data revealed only a minimal effect on baseline spontaneous firing near rest, but a dramatic increase in rebound burst discharge frequency for Cav3.1 compared to Cav3.2 or Cav3.3 due to differences in window current or activation/recovery time constants. The reduced response by Cav3.2 could optimize its activity where it is expressed in peripheral tissues more subject to temperature variations than Cav3.1 or Cav3.3 channels expressed prominently in the brain. These tests thus reveal that aspects of neuronal firing behavior are critically dependent on both temperature and T-type calcium channel subtype.

Regulation of neuronal T-type calcium channels.

T-type calcium channels are critically important for regulating neuronal excitability, both in the central and peripheral nervous system, and are essential mediators of hormone secretion. Conversely, T-type channel hyperactivity has been linked to neurological disorders such as absence epilepsy and neuropathic pain. Hence, it is critical to understand the cellular mechanisms that control T-type channel activity, including means of altering expression patterns of the channels, activation of intracellular messenger cascades that directly affect channel activity, and the regulation of alternate splicing of T-type channel genes. Although there is substantial literature dealing with regulation of native T-type channels, the underlying molecular mechanism have only recently been addressed. Here, we highlight recent advances in our understanding of T-type channel regulation, and their implications for brain function.

On color texture normalization for active appearance models.

The extension of the standard grayscale active appearance model (AAM) techniques to color images is investigated. Prior work in this field has mainly focused on RGB color models which did not demonstrate noticeable benefits over grayscale models from the point of view of convergence accuracy. We improve on previous work by normalizing the color texture vector separately for intensity and chromaticity components. Where an appropriate color space is chosen, we demonstrate improvements in convergence accuracy as well as image synthesization quality for AAMs. Optimal results are achieved when a color space in which the image channels are strongly decorrelated is chosen. Our best results are achieved using the I1I2I3 color space, originally proposed by Ohta.

Determination of blood longitudinal relaxation time (T1) at high magnetic field strengths.

In this study, a circulation system was used to measure T(1) values of bovine blood under physiological conditions at field strengths of 4.7, 7 and 9.4 T. Results show that T(1) increases linearly with magnetic field B(0) and can be described with the equation T(1)=129 ms/T B(0)+1167 ms for magnetic field strengths between 1.5 and 9.4 T.

Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen.

PURPOSE: The idiotype (Id) of the immunoglobulin on a given B-cell malignancy is a clonal marker that can serve as a tumor-specific antigen. We developed a novel vaccine formulation by incorporating Id protein with liposomal lymphokine that was more potent than a prototype, carrier-conjugated Id protein vaccine in preclinical studies. In the present study, we evaluated the safety and immunogenicity of this vaccine in follicular lymphoma patients. EXPERIMENTAL DESIGN: Ten patients with advanced-stage follicular lymphoma were treated with five doses of this second generation vaccine after chemotherapy-induced clinical remission. All patients were evaluated for cellular and humoral immune responses. RESULTS: Autologous tumor and Id-specific type I cytokine responses were induced by vaccination in 10 and 9 patients, respectively. Antitumor immune responses were mediated by both CD4+ and CD8+ T cells, were human lymphocyte antigen class I and II associated, and persisted 18 months beyond the completion of vaccination. Specific anti-Id antibody responses were detected in four patients. After a median follow-up of 50 months, 6 of the 10 patients remain in continuous first complete remission. CONCLUSIONS: This first clinical report of a liposomal cancer vaccine demonstrates that liposomal delivery is safe, induces sustained tumor-specific CD4+ and CD8+ T-cell responses in lymphoma patients, and may serve as a model for vaccine development against other human cancers and infectious pathogens.

Robust and Accurate Shape Model Matching Using Random Forest Regression-Voting.

A widely used approach for locating points on deformable objects in images is to generate feature response images for each point, and then to fit a shape model to these response images. We demonstrate that Random Forest regression-voting can be used to generate high quality response images quickly. Rather than using a generative or a discriminative model to evaluate each pixel, a regressor is used to cast votes for the optimal position of each point. We show that this leads to fast and accurate shape model matching when applied in the Constrained Local Model framework. We evaluate the technique in detail, and compare it with a range of commonly used alternatives across application areas: the annotation of the joints of the hands in radiographs and the detection of feature points in facial images. We show that our approach outperforms alternative techniques, achieving what we believe to be the most accurate results yet published for hand joint annotation and state-of-the-art performance for facial feature point detection.

'Do not touch' lesions of the skull base.

Imaging of the skull base presents many challenges due to its anatomical complexity, numerous normal variants and lack of familiarity to many radiologists. As the skull base is a region which is not amenable to physical examination and as lesions of the skull base are generally difficult to biopsy and even more difficult to operate on, the radiologist plays a major role in directing patient management via accurate image interpretation. Knowledge of the skull base should not be limited to neuroradiologists and head and neck radiologists, however, as the central skull base is routinely included in the field of view when imaging the brain, cervical spine, or head and neck with computed tomography or magnetic resonance imaging, and hence, its nuances should be familiar to general radiologists as well. We herein review the imaging findings of a subcategory of lesions of the central skull base, the 'do not touch' lesions.

Medical student radiology externs: increasing exposure to radiology, improving education, and influencing career choices.

PURPOSE: The radiology externship program at the authors' institution introduces medical students to radiology using a hands-on approach and is tailored to interested third-year medical students. There are currently limited data available on whether the program increases exposure to radiology in a positive fashion and how it influences medical students' education and career choices. METHODS: In September 2010, current and former externs between 2007 and 2010 were surveyed using an anonymous, Web-based survey. RESULTS: The response rates were 100% (11 of 11) for current externs and 52% (15 of 29) for former externs, for an overall response rate of 65% (26 of 40). The respondents included 20 men and 5 women. The average age of respondents was 27.3 ± 2.5 years. Forty-six percent of former externs (6 of 13) had matched to radiology residencies, whereas the remainder had matched to various surgical and nonsurgical subspecialties. Eighty-four percent (21 of 25) had overall positive ratings of the program. Ninety-two percent (23 of 25) felt they had a better understanding of which test was most appropriate to order for common indications, and 88% (22 of 25) felt that they had a better understanding of imaging contraindications. Sixty-eight percent (17 of 25) felt that they had a better understanding of risk-benefit analysis involving imaging using ionizing radiation, and 56% (14 of 25) felt more confident in discussing these matters with their patients. CONCLUSIONS: This radiology externship program increases exposure to radiology in a positive fashion, increases understanding of the appropriate use of imaging modalities and their associated clinical benefits and risks, and influences medical students' career choices. These results add to the evidence that this type of program is mutually beneficial to medical students, residents, and clinical colleagues and suggest that more medical schools and radiology departments should evaluate the feasibility of starting radiology externship programs.

Spontaneously ruptured intraspinal epidermoid cyst causing chemical meningitis.

We report a 53-year-old woman with a rare ruptured lumbar intraspinal epidermoid cyst causing chemical meningitis evaluated with MRI (including diffusion-weighted imaging), with histopathologic correlation.

D1 receptors physically interact with N-type calcium channels to regulate channel distribution and dendritic calcium entry.

Dopamine signaling through D1 receptors in the prefrontal cortex (PFC) plays a critical role in the maintenance of higher cognitive functions, such as working memory. At the cellular level, these functions are predicated to involve alterations in neuronal calcium levels. The dendrites of PFC neurons express D1 receptors and N-type calcium channels, yet little information exists regarding their coupling. Here, we show that D1 receptors potently inhibit N-type channels in dendrites of rat PFC neurons. Using coimmunoprecipitation, we demonstrate the existence of a D1 receptor-N-type channel signaling complex in this region, and we provide evidence for a direct receptor-channel interaction. Finally, we demonstrate the importance of this complex to receptor-channel colocalization in heterologous systems and in PFC neurons. Our data indicate that the N-type calcium channel is an important physiological target of D1 receptors and reveal a mechanism for D1 receptor-mediated regulation of cognitive function in the PFC.

A novel proteoliposomal vaccine elicits potent antitumor immunity in mice.

Therapeutic vaccination against idiotype is a promising strategy for immunotherapy of B-cell malignancies. Its feasibility, however, is limited by the requirement for a patient-specific product. Here we describe a novel vaccine formulation prepared by simply extracting cell-membrane proteins from lymphoma cells and incorporating them together with IL-2 into proteoliposomes. The vaccine was produced in 24 hours, compared with more labor-intensive and time-consuming hybridoma or recombinant DNA methods. The vaccine elicited T-cell immunity in vivo, as demonstrated by secretion of type 1 cytokines. It protected against tumor challenge at doses of tumor antigen 50 to 100 times lower than that previously observed using either liposomes formulated with IL-2 and secreted lymphoma immunoglobulin or a prototype vaccine consisting of lymphoma immunoglobulin conjugated to keyhole limpet hemocyanin. The increased potency justifies testing similar patient-specific human vaccines prepared using extracts from primary tumor samples.

A novel proteoliposomal vaccine induces antitumor immunity against follicular lymphoma.

Clinical studies suggest that treatment with vaccines comprised of idiotype protein may be associated with improved clinical outcome in follicular lymphoma patients. The time-consuming process required to generate patient-specific vaccines is a major limitation, however. Here we report results of a pilot clinical trial with a novel autologous, tumor-derived proteoliposome vaccine formulation that could be rapidly produced within a single day. Vaccination was safe, induced autologous tumor-specific type 1 cytokine responses in 5 out of 10 follicular lymphoma patients, and was associated with induction of a sustained complete response in one patient. Other patients had large tumor burdens and progressed after a median duration of 8 months. These results suggest that further testing of this vaccine formulation, particularly in the setting of minimal disease, is warranted. Furthermore, the proteoliposome formulation may provide a model for vaccine development for other human cancers, for which tumor-associated antigens need not be defined.

[The effect of chemical noxae on the health status of a group of workers in the chemical industry of Savinesti]. / Influenta unor noxe chimice asupra starii de sanatate, la un grup de muncitori din industria chimica, Savinesti.

The paper presents the study on the effect of the industrial xenobiotics against some biochemical indicators, in view to detect, precociously, the probable significant changes. There are presented the medium, minimum, maximum and median value for the following parameters: total proteins, haemoglobin and glucose for 112 workers exposed or not exposed to specific noxae--benzen, phenol, cyclohexanone. The analysis of the results shows decreased values for some workers, even at the inferior limit, in rapport with the normal values, for the parameters studied. These persons have been directed for complex investigations, in view to determine the causes and to establish the adequate treatment.