Early Mortality After Radical Radiotherapy for Non-small-cell Lung Cancer: Comparison of PET-staged and Conventionally Staged Cohorts Treated at a Large Tertiary Referral Center

International Journal of Radiation Oncology, Biology, Physics. Feb, 2002  |  Pubmed ID: 11872280

At our center, approximately 30% of radical radiotherapy (RRT) candidates become ineligible for RRT for non-small-cell lung cancer (NSCLC) after positron emission tomography (PET). We hypothesized that early cancer death rates would be lower in patients receiving RRT after PET staging compared with conventionally staged patients.

Mutational and Functional Analysis of a Segment of the Sigma Family Bacteriophage T4 Late Promoter Recognition Protein Gp55

The Journal of Biological Chemistry. Feb, 2003  |  Pubmed ID: 12496274

Bacteriophage T4 late promoters, which consist of a simple 8-base pair TATA box, are recognized by the gene 55 protein (gp55), a small, highly diverged member of the sigma family proteins that replaces sigma(70) during the final phase of the T4 multiplication cycle. A 16-amino acid segment of gp55 that is proposed to be homologous to the sigma(70) region 2.2 has been subjected to alanine scanning and other mutagenesis. The corresponding proteins have been examined in vitro for binding to Escherichia coli RNA polymerase core enzyme and for the ability to generate accurately initiating basal as well as sliding clamp-activated T4 late transcription. Mutations in the amino acid 68-83 segment of gp55 generate a wide range of effects on these functions. The changes are interpreted in terms of the multiple steps of involvement of gp55, like other sigma proteins, in transcription. Effects of mutations on RNA polymerase core binding are consistent with the previously proposed homology of amino acids 68-82 of gp55 with sigma(70) region 2.2 and the recently determined structures of the Thermus thermophilus and Thermus aquaticus sigma(70)-RNA polymerase holoenzymes.

Selective Reovirus Killing of Bladder Cancer in a Co-culture Spheroid Model

Virus Research. May, 2003  |  Pubmed ID: 12727337

Up to 50% of the transitional cell carcinomas (TCC) express an activated EGF pathway involving MAP/MEK and RAF kinase thus providing a novel means to selectively eliminate transformed cells expressing such proteins. This EGF pathway expression phenotype was also confirmed in our MGH-U3 and room temperature-112 human TCC cell lines, which makes them a suitable model target for the reovirus oncolysis. We report here on an in vitro assay of co-culture spheroids using either human or rat TCC cells with their corresponding fibroblasts to examine the potential of viral selective lysis for TCC. Reovirus, a respiratory enteric orphan virus, which mammals are exposed to early in life, was used in this study. Selective killing of transformed versus normal cells was assayed by time-lapse photography, vital dye staining, immunohistochemistry, and MTT assay. In this in vitro bladder cancer model, reovirus selectively destroyed the transformed cells by lysis or induction of apoptosis. Based on these findings we have initiated an in vivo pre-clinical study on intravesical administration of reovirus in an animal model to further explore the effect of reovirus-mediated oncolysis of TCC.

Using Swaystar to Measure Sway Amplitude in an Office Setting

The Journal of Otolaryngology. Feb, 2004  |  Pubmed ID: 15291271

The study was conducted to determine if Swaystar (University Hospital, Basel), a device that measures trunk sway, could be used in the office to detect abnormalities in patients who had vestibular abnormalities.

A Randomised Phase III Study of Palliative Radiation with Concomitant Carboplatin for Brain Metastases from Non-small Cell Carcinoma of the Lung

Lung Cancer (Amsterdam, Netherlands). Oct, 2004  |  Pubmed ID: 15364138

To determine if the addition of carboplatin chemotherapy to whole brain irradiation improves response and survival in patients with brain metastases from non-small cell lung cancer (NSCLC).

Endoscopic Resection of Isolated Inverted Papilloma of the Sphenoid Sinus

The Journal of Otolaryngology. Apr, 2004  |  Pubmed ID: 15518104

A Novel Intravesical Therapy for Superficial Bladder Cancer in an Orthotopic Model: Oncolytic Reovirus Therapy

The Journal of Urology. Nov, 2004  |  Pubmed ID: 15540781

To our knowledge this is the first report of intravesical oncolytic reovirus for therapy of superficial bladder cancer in an orthotopic bladder tumor model. Superficial bladder carcinomas are often multifocal and have high recurrences after surgical resection. In 20% of cases intravesical immunotherapy fails to prevent recurrence and complications from bacillus Calmette-Guerin (BCG) are common. Human reovirus is an oncolytic virus that selectively destroys cancer cells with an activated Ras pathway. We examined the ability of this virus to kill bladder cancer cells in vitro and inhibit tumor growth in vivo.

Giant Cell Tumour of the Larynx: Case Report and Review of the Literature

The Journal of Otolaryngology. Jun, 2004  |  Pubmed ID: 15842001

Reovirus Salvage of Squamous Cell Cancer-contaminated Wounds

The Journal of Otolaryngology. Feb, 2005  |  Pubmed ID: 15966474

To assess the susceptibility of human squamous cell carcinoma to reovirus infection in vitro and in vivo using a murine model of cancer-contaminated wounds.

Parathyroid Adenoma Presenting As Paraneoplastic Syndrome Secondary to Renal Cell Carcinoma

The Journal of Otolaryngology. Aug, 2005  |  Pubmed ID: 16048706

Plasma Membrane Requirements for 1alpha,25(OH)2D3 Dependent PKC Signaling in Chondrocytes and Osteoblasts

Steroids. Apr, 2006  |  Pubmed ID: 16325216

1,25-Dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] acts on chondrocytes and osteoblasts through traditional nuclear Vitamin D receptor (VDR) mechanisms as well as through rapid actions on plasma membranes that initiate intracellular signaling pathways. We have investigated the mechanisms involved in activation of protein kinase C (PKC) and downstream biological responses that depend on the latter pathway. These studies show that PKC activation depends on presence of a membrane receptor ERp60 and rapid increases in phospholipase A(2) (PLA(2)) activity. Cells that are responsive to 1alpha,25(OH)(2)D(3) express PLA(2) activating protein (PLAA), suggesting a link between ERp60 and PLA(2). Increased PLA(2) results in increased arachidonic acid release and formation of lysophospholipid, which then activates phospholipase C beta (PLCbeta), leading to rapid formation of inositol-trisphosphate (IP3) and diacylglycerol (DAG). PLA(2), PLC, and DAG are all associated with lipid rafts including caveolae in many cells, suggesting that the caveolar environment may be an important mediator of PKC activation by 1alpha,25(OH)(2)D(3). Here, we use the VDR(-/-) mouse costochondral cartilage growth plate to examine the expression of ERp60 and PLAA in vivo in 1alpha,25(OH)(2)D(3)-responsive hypertrophic chondrocytes (growth zone cells) and in resting zone cells that do not respond to this Vitamin D metabolite in vitro. In addition, we determined if intact lipid rafts are required for the response of rat costochondral cartilage growth zone cells to 1alpha,25(OH)(2)D(3). The results show that ERp60 and PLAA are localized to 1alpha,25(OH)(2)D(3)-responsive growth zone cells and metaphyseal osteoblasts, even in VDR(-/-) mice. Disruption of lipid rafts using beta-cyclodextrin blocks the activation of PKC by 1alpha,25(OH)(2)D(3) and reduces the ability of 1alpha,25(OH)(2)D(3) to regulate [(35)S]-sulfate incorporation.

Reovirus Salvage of Positive Resection Margin: A Novel Treatment Adjunct

The Journal of Otolaryngology. Apr, 2006  |  Pubmed ID: 16527027

We hypothesized that the use of reovirus as an intraoperative adjunct would improve local control of positive margins in a human squamous cell carcinoma nude mouse model.

Regulation of Growth Plate Chondrocytes by 1,25-dihydroxyvitamin D3 Requires Caveolae and Caveolin-1

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. Oct, 2006  |  Pubmed ID: 16995819

We examined the role of caveolae and caveolin-1 in the mechanism of 1alpha,25(OH)(2)D(3) action in growth plate chondrocytes. We found that caveolae are required for rapid 1alpha,25(OH)(2)D(3)-dependent PKC signaling, and caveolin-1 must be present based on studies using chondrocytes from Cav-1(-/-) mice.

1alpha,25(OH)2D3 is an Autocrine Regulator of Extracellular Matrix Turnover and Growth Factor Release Via ERp60 Activated Matrix Vesicle Metalloproteinases

The Journal of Steroid Biochemistry and Molecular Biology. Mar, 2007  |  Pubmed ID: 17224270

Growth plate chondrocytes produce proteoglycan-rich type II collagen extracellular matrix (ECM). During cell maturation and hypertrophy, ECM is reorganized via a process regulated by 1alpha,25(OH)(2)D(3) and involving matrix metalloproteinases (MMPs), including MMP-3 and MMP-2. 1alpha,25(OH)(2)D(3) regulates MMP incorporation into matrix vesicles (MVs), where they are stored until released. Like plasma membranes (PM), MVs contain the 1alpha,25(OH)(2)D(3)-binding protein ERp60, phospholipase A(2) (PLA(2)), and caveolin-1, but appear to lack nuclear Vitamin D receptors (VDRs). Chondrocytes produce 1alpha,25(OH)(2)D(3) (10(-8)M), which binds ERp60, activating PLA(2), and resulting lysophospholipids lead to MV membrane disorganization, releasing active MMPs. MV MMP-3 activates TGF-beta1 stored in the ECM as large latent TGF-beta1 complexes, consisting of latent TGF-beta1 binding protein, latency associated peptide, and latent TGF-beta1. Others have shown that MMP-2 specifically activates TGF-beta2. TGF-beta1 regulates 1alpha,25(OH)(2)D(3)-production, providing a mechanism for local control of growth factor activation. 1alpha,25(OH)(2)D(3) activates PKCalpha in the PM via ERp60-signaling through PLA(2), lysophospholipid production, and PLCbeta. It also regulates distribution of phospholipids and PKC isoforms between MVs and PMs, enriching the MVs in PKCzeta. Direct activation of MMP-3 in MVs requires ERp60. However, when MVs are treated with 1alpha,25(OH)(2)D(3), PKCzeta activity is decreased and PKCalpha is unaffected, suggesting a more complex feedback mechanism, potentially involving MV lipid signaling.

Lenalidomide and CC-4047 Inhibit the Proliferation of Malignant B Cells While Expanding Normal CD34+ Progenitor Cells

Cancer Research. Jan, 2007  |  Pubmed ID: 17234786

Clinical studies involving patients with myelodysplastic syndromes or multiple myeloma have shown the efficacy of lenalidomide by reducing and often eliminating malignant cells while restoring the bone marrow function. To better understand these clinical observations, we investigated and compared the effects of lenalidomide and a structurally related analogue, CC-4047, on the proliferation of two different human hematopoietic cell models: the Namalwa cancer cell line and normal CD34+ progenitor cells. Both compounds had antiproliferative effects on Namalwa cells and pro-proliferative effects on CD34+ cells, whereas p21WAF-1 expression was up-regulated in both cell types. In Namalwa cells, the up-regulation of p21WAF-1 correlated well with the inhibition of cyclin-dependent kinase (CDK) 2, CDK4, and CDK6 activity leading to pRb hypophosphorylation and cell cycle arrest, whereas in CD34+ progenitor cells the increase of p21WAF-1 did not inhibit proliferation. Similarly, antiproliferation results were observed in two B lymphoma cell lines (LP-1 and U266) but interestingly not in normal B cells where a protection of apoptosis was found. Finally, CC-4047 and lenalidomide had synergistic effects with valproic acid [a histone deacetylase (HDAC) inhibitor] by increasing the apoptosis of Namalwa cells and enhancing CD34+ cell expansion. Our results indicate that lenalidomide and CC-4047 have opposite effects in tumor cells versus normal cells and could explain, at least in part, the reduction of malignant cells and the restoration of bone marrow observed in patients undergoing lenalidomide treatment. Moreover, this study provides new insights on the cellular pathways affected by lenalidomide and CC-4047, proposes new potential clinical uses, such as bone marrow regeneration, and suggests that the combination of lenalidomide or CC-4047 with certain HDAC inhibitors may elevate the therapeutic index in the treatment of hematologic malignancies.

Caveolin-1 Knockout Mice Have Increased Bone Size and Stiffness

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. Sep, 2007  |  Pubmed ID: 17550335

The skeletal phenotype of the cav-1(-/-) mouse, which lacks caveolae, was examined. muCT and histology showed increased trabecular and cortical bone caused by the gene deletion. Structural changes were accompanied by increased mechanical properties. Cell studies showed that cav-1 deficiency leads to increased osteoblast differentiation. These results suggest that cav-1 helps to maintain osteoblast progenitors in a less differentiated state.

Creating the "double Curved" Suctions for Sinus Endoscopy and Surgery

The Laryngoscope. Aug, 2007  |  Pubmed ID: 17572639

Recombinant Prostate-specific Antigen Proaerolysin Shows Selective Protease Sensitivity and Cell Cytotoxicity

Anti-cancer Drugs. Aug, 2007  |  Pubmed ID: 17581303

Native proaerolysin is a channel-forming bacterial protoxin that binds to cell-surface receptors and then is activated by furin or furin-like proteases. We genetically engineered proaerolysin by replacing the furin-cleavage sequence with a prostate-specific antigen-selective sequence. The recombinant modified proaerolysin was expressed and purified from Aeromonas salmonicida in good yields and purity. Recombinant modified proaerolysin had no furin sensitivity and markedly increased prostate-specific antigen sensitivity relative to wild-type proaerolysin. Human prostate cancer cells were significantly more sensitive to recombinant modified proaerolysin in the presence of active prostate-specific antigen when compared with the absence of prostate-specific antigen or the presence of potent prostate-specific antigen inhibitors. Most normal human cells with the exception of prostate and renal epithelial cells showed very low sensitivity to recombinant modified proaerolysin. Our results suggest that recombinant modified proaerolysin is a potent prostate-specific antigen-sensitive protoxin that deserves further development for regional therapy of benign and malignant prostate growths.

Return to Home, School, and Sports After Electrosurgical Adenoidectomy: when is It Safe?

The Journal of Otolaryngology. Jun, 2007  |  Pubmed ID: 17711769

To determine when it is safe for healthy children to return to home, school, and sports after uncomplicated electrosurgical adenoidectomy (EA).

A Chimera of Interleukin 2 and a Binding Variant of Aerolysin is Selectively Toxic to Cells Displaying the Interleukin 2 Receptor

The Journal of Biological Chemistry. Jan, 2008  |  Pubmed ID: 17981806

Aerolysin is a bacterial toxin that binds to glycosylphosphatidylinositol-anchored proteins (GPI-AP) on mammalian cells and oligomerizes, inserting into the target membranes and forming channels that cause cell death. We have made a variant of aerolysin, R336A, that has greatly reduced the ability to bind to GPI-AP, and as a result it is only very weakly active. Fusion of interleukin 2 (IL2) to the N terminus of R336A-aerolysin results in a hybrid that has little or no activity against cells that do not have an IL2 receptor because it cannot bind to the GPI-AP on the cells. Strikingly, the presence of the IL2 moiety allows this hybrid to bind to cells displaying high affinity IL2 receptors. Once bound, the hybrid molecules form insertion-competent oligomers. Cell death occurs at picomolar concentrations of the hybrid, whereas the same cells are insensitive to much higher concentrations of R336A-aerolysin lacking the IL2 domain. The targeted channel-forming hybrid protein may have important advantages as a therapeutic agent.

Role of Tonsillectomy in PFAPA Syndrome

Archives of Otolaryngology--head & Neck Surgery. Jan, 2008  |  Pubmed ID: 18209129

To examine the efficacy of tonsillectomy in ameliorating symptoms and preventing recurrence of episodes in children with PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, and adenitis).

An Ecological Acoustic Recorder (EAR) for Long-term Monitoring of Biological and Anthropogenic Sounds on Coral Reefs and Other Marine Habitats

The Journal of the Acoustical Society of America. Mar, 2008  |  Pubmed ID: 18345859

Keeping track of long-term biological trends in many marine habitats is a challenging task that is exacerbated when the habitats in question are in remote locations. Monitoring the ambient sound field may be a useful way of assessing biological activity because many behavioral processes are accompanied by sound production. This article reports the preliminary results of an effort to develop and use an Ecological Acoustic Recorder (EAR) to monitor biological activity on coral reefs and in surrounding waters for periods of 1 year or longer. The EAR is a microprocessor-based autonomous recorder that periodically samples the ambient sound field and also automatically detects sounds that meet specific criteria. The system was used to record the sound field of coral reefs and other marine habitats on Oahu, HI. Snapping shrimp produced the dominant acoustic energy on the reefs examined and exhibited clear diel acoustic trends. Other biological sounds recorded included those produced by fish and cetaceans, which also exhibited distinct temporal variability. Motor vessel activity could also be monitored effectively with the EAR. The results indicate that acoustic monitoring may be an effective means of tracking biological and anthropogenic activity at locations where continuous monitoring by traditional survey methods is impractical.

Patients' Perceptions and Experiences of Family Medicine Residents in the Office

Canadian Family Physician Médecin De Famille Canadien. Apr, 2008  |  Pubmed ID: 18411387

To examine patients' perceptions and experiences of having family medicine residents in the office.

Finite-element Model of Interaction Between Fungal Polysaccharide and Monoclonal Antibody in the Capsule of Cryptococcus Neoformans

The Journal of Physical Chemistry. B. Jul, 2008  |  Pubmed ID: 18588334

Many microorganisms such as bacteria and fungi possess so-called capsules made of polysaccharides which protect these microorganisms from environmental insults and host immune defenses. The polysaccharide capsule of Cryptococcus neoformans, a human pathogenic yeast, is capable of self-assembly, composed mostly of glucuronoxylomannan (GXM), a polysaccharide with a molecular weight of approximately 2,000,000, and has several layers with different densities. The objective of this study was to model pore-hindered diffusion and binding of the GXM-specific antibody within the C. neoformans capsule. Using the finite-element method (FEM), we created a model which represents the in vivo binding of a GXM-specific antibody to a C. neoformans cell taking into account the intravenous infusion time of antibody, antibody diffusion through capsular pores, and Michaelis-Menten kinetics of antibody binding to capsular GXM. The model predicted rapid diffusion of antibody to all regions of the capsule where the pore size was greater than the Stokes diameter of the antibody. Binding occurred primarily at intermediate regions of the capsule. The GXM concentration in each capsular region was the principal determinant of the steady-state antibody-GXM complex concentration, while the forward binding rate constant influenced the rate of complex formation in each region. The concentration profiles predicted by the model closely matched experimental immunofluorescence data. Inclusion of different antibody isotypes (IgG, IgA, and IgM) into the modeling algorithm resulted in similar complex formation in the outer capsular regions, but different depths of binding at the inner regions. These results have implications for the development of new antibody-based therapies.

A Systematic Review of Medication Safety and Clinical Outcomes Related to Drug Interaction Software

AMIA ... Annual Symposium Proceedings / AMIA Symposium. AMIA Symposium. 2008  |  Pubmed ID: 18999164

We conducted a systematic search of MEDLINE, EMBASE, IPA, HealthStar and CINAHL, for English language, post-1990, prospective studies examining electronic drug interaction checking (eDIC) on the outcome of adverse drug interactions (ADI). Excluded studies were not prospective or measured non-patient specific outcomes. Four of 5848 studies were included. Bayesian pooled meta-analysis showed no difference in ADIs (relative risk is 0.66, 95% CI 0.33 to 1.18.). Not only is there a lack of rigorous evaluations of eDIC, the evidence available does not suggest benefit even for the surrogate outcome of adverse drug interactions.

Systemic Absorption of Topical Gentamicin Sinus Irrigation

Journal of Otolaryngology - Head & Neck Surgery = Le Journal D'oto-rhino-laryngologie Et De Chirurgie Cervico-faciale. Jun, 2008  |  Pubmed ID: 19128645

Evidence surrounding systemic absorption of gentamicin during intraoperative irrigation of the paranasal sinuses is lacking. The objectives of this study were to determine (1) if topical gentamicin is absorbed from the paranasal sinuses, (2) if hearing loss occurs following topical administration of gentamicin, and (3) if gentamicin placed within the sinuses travels retrograde (against mucociliary clearance) up the auditory tube to the middle ear.

TaqMan-based, Real-time Quantitative Polymerase Chain Reaction Method for RNA Editing Analysis

Analytical Biochemistry. Jul, 2009  |  Pubmed ID: 19371717

Abnormal adenosine to inosine (A-to-I) messenger RNA (mRNA) editing has been linked to several disease states afflicting the central nervous system. Here we report an assay to determine RNA editing frequencies at specific sites that is based on quantitative polymerase chain reaction (qPCR) with TaqMan probes. The assay was tested by measuring the frequency of the A-to-I mRNA editing at the Q/R site of the human kainate receptor subunit GluR5 and was compared with two established methods of assessing RNA editing: sequencing of individual clones and restriction analysis. The qPCR assay displayed high sensitivity and reproducibility, demonstrated exceptional discrimination between edited and unedited transcript variants, and proved to have several advantages over the other editing methods. Due to the fact that TaqMan-based qPCR technology can be easily adapted to different editing targets, the increased capabilities afforded by this new technique should facilitate various RNA editing studies that aim to elucidate the role of this process in normal physiology and in disease.

Laryngeal Candidiasis in the Outpatient Setting

Journal of Otolaryngology - Head & Neck Surgery = Le Journal D'oto-rhino-laryngologie Et De Chirurgie Cervico-faciale. Dec, 2009  |  Pubmed ID: 19958724

We present the largest case series on laryngeal candidiasis and review the literature on the diagnosis and management of laryngeal candidiasis.

Transforming Growth Factor-beta1 Shows an Incremental Osteoinductive Dose-response Relationship

The Laryngoscope. Jan, 2009  |  Pubmed ID: 19117297

To determine if there is a dose-response curve for TGF-beta1 in a rabbit calvarial defect model.

Septoplasty Retards Midfacial Growth in a Rabbit Model

The Laryngoscope. Mar, 2010  |  Pubmed ID: 20058320

Septoplasty in the prepubertal age group is a controversial operation because of concerns regarding retardation of subsequent midfacial growth. This study uses a validated rabbit snout model to determine if septoplasty results in midfacial growth retardation, and if the retardation can be averted by replacing resected cartilage with a porous polyethylene implant.

Microvascular Reconstruction in the Vessel-depleted Neck

Current Opinion in Otolaryngology & Head and Neck Surgery. Aug, 2010  |  Pubmed ID: 20543700

Microvascular reconstruction for head and neck cancers has improved both cosmesis and functionality of patients undergoing treatment. Many patients have had prior surgery (neck dissection), radiation and/or chemotherapy as part of their management. When microvascular reconstruction is required after previous treatment, finding appropriate vessels for anastomosis can be difficult. In this paper we explore the options for microvascular reconstruction in the vessel-depleted neck.

A Systematic Review of Medication Safety Outcomes Related to Drug Interaction Software

Journal of Population Therapeutics and Clinical Pharmacology = Journal De La Thérapeutique Des Populations Et De La Pharamcologie Clinique. 2010  |  Pubmed ID: 20664117

Adverse drug events (ADEs) represent an important problem for hospital and primary care. Software that detects potential adverse drug interactions has been widely implemented in an effort to reduce the rate of ADEs. However, the impact of drug interaction detection software (DIS) on patient safety outcomes remains unknown.

Cost-effectiveness of Simultaneous Versus Sequential Surgery in Head and Neck Reconstruction

Journal of Otolaryngology - Head & Neck Surgery = Le Journal D'oto-rhino-laryngologie Et De Chirurgie Cervico-faciale. Feb, 2011  |  Pubmed ID: 21303601

To determine whether simultaneous (ablation and reconstruction overlaps by two teams) head and neck reconstruction is cost effective compared to sequentially (ablation followed by reconstruction) performed surgery.

Cartilage on the Floor: How Effective is Antibiotic Sterilization?

Journal of Otolaryngology - Head & Neck Surgery = Le Journal D'oto-rhino-laryngologie Et De Chirurgie Cervico-faciale. Jun, 2011  |  Pubmed ID: 21518644

To determine the incidence of positive cultures from contaminated nasal cartilage and to demonstrate the effectiveness of antibiotic irrigation as a means of sterilization.

Prevalence and Treatment Patterns of Lower Extremity Peripheral Arterial Disease Among Patients at Risk in Ambulatory Health Settings

The Canadian Journal of Cardiology. May-Jun, 2011  |  Pubmed ID: 21601776

Lower extremity peripheral arterial disease (PAD) is underdiagnosed and undertreated in Canada, although data are limited. We sought to measure PAD prevalence and treatment patterns in ambulatory settings.

Sequential Mechanisms Underlying Concentration Invariance in Biological Olfaction

Frontiers in Neuroengineering. Nov, 2011  |  Pubmed ID: 22287949

Concentration invariance-the capacity to recognize a given odorant (analyte) across a range of concentrations-is an unusually difficult problem in the olfactory modality. Nevertheless, humans and other animals are able to recognize known odors across substantial concentration ranges, and this concentration invariance is a highly desirable property for artificial systems as well. Several properties of olfactory systems have been proposed to contribute to concentration invariance, but none of these alone can plausibly achieve full concentration invariance. We here propose that the mammalian olfactory system uses at least six computational mechanisms in series to reduce the concentration-dependent variance in odor representations to a level at which different concentrations of odors evoke reasonably similar representations, while preserving variance arising from differences in odor quality. We suggest that the residual variance then is treated like any other source of stimulus variance, and categorized appropriately into "odors" via perceptual learning. We further show that naïve mice respond to different concentrations of an odorant just as if they were differences in quality, suggesting that, prior to odor categorization, the learning-independent compensatory mechanisms are limited in their capacity to achieve concentration invariance.

Cutaneous Myoepithelioma Arising Within Hidradenoma of the Scalp

Journal of Cutaneous Pathology. Feb, 2012  |  Pubmed ID: 22077442

A 62-year-old man presented with a 2-year history of a 2-cm cystic mass involving his occiput. There had been recent enlargement, and the clinical impression was that of a pilar cyst. Histopathological sections showed a partially dermal solid and cystic proliferation. The tumor contained areas of glandular differentiation with cuboidal to columnar cells lining luminal and cystic spaces. A concurrent spindle cell proliferation was seen interspersed between glands and also formed broad, cellular sheets of cells. The stroma was sclerotic and without chondroid or myxoid elements. Immunohistochemistry showed that the spindled cells expressed S100 protein, cytokeratin and smooth muscle myosin. The immunohistochemical profile and the relationship with ductal elements supported myoepithelial differentiation. The proliferation warranted the diagnosis of myoepithelioma arising from a hidradenoma, which to our knowledge has not been previously described. In addition to discussing this case, we provide a brief review of epithelial-myoepithelial neoplasms encountered in the skin. Jakate K, Wong K, Sirbovan J, Hanna W. Cutaneous myoepithelioma arising within hidradenoma of the scalp.