Asymptomatic, edematous upper lip in a 39-year-old woman. Cheilitis granulomatosa (CG).
Adult; Female; Humans; Lip Diseases/*diagnosis/pathology; Melkersson-Rosenthal Syndrome/*diagnosis/pathology
Cernik Christina; Kerns Mary Jo; Moad John C; Heffernan Michael
Archives of dermatology
2009
2009-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1001/archdermatol.2008.558-a" target="_blank" rel="noreferrer noopener">10.1001/archdermatol.2008.558-a</a>
Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression.
Butadienes/pharmacology; Carcinoma; Cell Line; Chenodeoxycholic Acid/*pharmacology; Cholesterol 7-alpha-Hydroxylase/*biosynthesis; Cytoplasmic and Nuclear/metabolism/physiology; DNA-Binding Proteins/metabolism; Fibroblast Growth Factor; Fibroblast Growth Factors/drug effects/*physiology; Gene Expression/drug effects; Hepatocellular/metabolism; Hepatocytes/metabolism; Humans; Isoxazoles/pharmacology; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Nitriles/pharmacology; Receptor; Receptors; Signal Transduction/drug effects; Transcription Factors/metabolism; Tumor; Type 4/antagonists & inhibitors
UNLABELLED: Mouse fibroblast growth factor 15 (FGF15) and human ortholog FGF19 have been identified as the bile acid-induced intestinal factors that mediate bile acid feedback inhibition of cholesterol 7alpha-hydroxylase gene (C YP7A1) transcription in mouse liver. The mechanism underlying FGF15/FGF19 inhibition of bile acid synthesis in hepatocytes remains unclear. Chenodeoxycholic acid (CDCA) and the farnesoid X receptor (FXR)-specific agonist GW4064 strongly induced FGF19 but inhibited CYP7A1 messenger RNA (mRNA) levels in primary human hepatocytes. FGF19 strongly and rapidly repressed CYP7A1 but not small heterodimer partner (SHP) mRNA levels. Kinase inhibition and phosphorylation assays revealed that the mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MAPK/Erk1/2) pathway played a major role in mediating FGF19 inhibition of CYP7A1. However, small interfering RNA (siRNA) knockdown of SHP did not affect FGF19 inhibition of CYP7A1. Interestingly, CDCA stimulated tyrosine phosphorylation of the FGF receptor 4 (FGFR4) in hepatocytes. FGF19 antibody and siRNA specific to FGFR4 abrogated GW4064 inhibition of CYP7A1. These results suggest that bile acid-activated FXR is able to induce FGF19 in hepatocytes to inhibit CYP7A1 by an autocrine/paracrine mechanism. CONCLUSION: The hepatic FGF19/FGFR4/Erk1/2 pathway may inhibit CYP7A1 independent of SHP. In addition to inducing FGF19 in the intestine, bile acids in hepatocytes may activate the liver FGF19/FGFR4 signaling pathway to inhibit bile acid synthesis and prevent accumulation of toxic bile acid in human livers.
Song Kwang-Hoon; Li Tiangang; Owsley Erika; Strom Stephen; Chiang John Y L
Hepatology (Baltimore, Md.)
2009
2009-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/hep.22627" target="_blank" rel="noreferrer noopener">10.1002/hep.22627</a>
A new perspective.
*Attitude of Health Personnel; *Hospitalists; *Internship and Residency; Anti-Bacterial Agents/therapeutic use; Antibiotics – Therapeutic Use; Attitude of Health Personnel; Emergency Service; Emergency Service – Administration; Hospital/*organization & administration; Hospitalists; Humans; Internship and Residency; Pneumonia – Diagnosis; Pneumonia – Drug Therapy; Pneumonia/diagnosis/*drug therapy
Duggal Abhijit
Journal of hospital medicine
2009
2009-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jhm.528" target="_blank" rel="noreferrer noopener">10.1002/jhm.528</a>
Gender differences in the association between antidepressant use and restless legs syndrome.
*Sex Characteristics; 80 and over; 80 and Over; Adult; Aged; Antidepressive Agents – Adverse Effects; Antidepressive Agents – Classification; Antidepressive Agents/*adverse effects/classification; Female; Human; Humans; Male; Middle Age; Middle Aged; Observation; Observational Methods; Primary Health Care – Statistics and Numerical Data; Primary Health Care/statistics & numerical data; Regression; Regression Analysis; Reproduction; Restless Legs – Chemically Induced; Restless Legs Syndrome/*chemically induced; Risk Factors; Veterans; Young Adult
Contradictory results have been reported for the association between antidepressant use and Restless Legs Syndrome (RLS). Our aim was to clarify the relationship and examine possible gender differences. We interviewed 1,693 veterans receiving primary care from the Cleveland VA Medical Center and obtained prescription drug information from their medical records. Overall, use of an antidepressant was associated with RLS for men (RR = 1.77, CI = 1.26, 2.48) but not for women (RR = 0.79, CI = 0.43, 1.47). Analyses of individual antidepressants revealed an association between RLS and fluoxetine for women (RR = 2.47, CI = 1.33, 4.56), and associations between RLS and citalopram, (RR = 2.09, CI = 1.20, 3.64), paroxetine (RR = 1.97, CI = 1.02, 3.79), and amitriptyline (RR = 2.40, CI = 1.45, 4.00) for men. We conclude that RLS may be associated with antidepressant use, but the association varies by gender and type of antidepressant. Antidepressant use is more strongly associated with RLS in men than in women.
Baughman Kristin R; Bourguet Claire C; Ober Scott K
Movement disorders : official journal of the Movement Disorder Society
2009
2009-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/mds.22517" target="_blank" rel="noreferrer noopener">10.1002/mds.22517</a>
A unique case of ovarian psammocarcinoma with mediastinal, pulmonary, subcutaneous, and omental metastases.
Cystadenocarcinoma; Female; Humans; Lung Neoplasms/*secondary; Lung/pathology; Mediastinal Neoplasms/*secondary; Mediastinum/pathology; Middle Aged; Ovarian Neoplasms/*pathology; Pelvis/pathology; Peritoneal Neoplasms/*secondary; Serous/*secondary; Soft Tissue Neoplasms/*secondary; Subcutaneous Fat/pathology
Psammocarcinoma is a rare form of serous ovarian and peritoneal carcinoma, characterized by abundant psammoma bodies, invasiveness, and low-grade cytological features. Many of the cases which have been reported had extraovarian spread and peritoneal seeding at the time of presentation. We present a case of
Chase Daniel M; Sparks Dorothy A; Gener Melissa; Smith James
Archives of gynecology and obstetrics
2009
2009-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00404-008-0883-1" target="_blank" rel="noreferrer noopener">10.1007/s00404-008-0883-1</a>
HSV-2 ICP34.5 protein modulates herpes simplex virus glycoprotein processing.
*Protein Processing; Animals; Cercopithecus aethiops; Cloning; Gene Expression; Herpesvirus 1; Herpesvirus 2; Human/*genetics; Molecular; Post-Translational; Vero Cells; Viral Envelope Proteins/*metabolism; Viral Proteins/genetics/*metabolism
The ICP34.5 gene from HSV-2 strain 333 was cloned and, when expressed in Vero cells, enhanced the efficiency and extent of glycoprotein processing of glycoprotein C (gC1), a representative viral glycoprotein, during infection with
Chatterjee Somik; Wang Jason W; Cismowski Mary J; Bower John R; Rosenthal Kenneth Steven
Archives of virology
2009
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00705-009-0341-9" target="_blank" rel="noreferrer noopener">10.1007/s00705-009-0341-9</a>
Terpenoids and breast cancer chemoprevention.
Animals; Anticarcinogenic Agents/therapeutic use; Breast Neoplasms/*prevention & control; Chemoprevention; Female; Humans; Terpenes/*therapeutic use
Cancer chemoprevention is defined as the use of natural or synthetic agents that reverse, suppress or arrest carcinogenic and/or malignant phenotype progression towards invasive cancer. Phytochemicals obtained from vegetables, fruits, spices, herbs and medicinal plants, such as terpenoids, carotenoids, flavanoids, phenolic compounds, and other groups of compounds have shown promise in suppressing experimental carcinogenesis in various organs. Recent studies have indicated that mechanisms underlying chemopreventive action may include combinations of anti-oxidant, anti-inflammatory, immune-enhancing, and anti-hormone effects. Further, modification of drug-metabolizing enzymes, and influences on cell cycling and differentiation, induction of apoptosis, and suppression of proliferation and angiogenesis that play a role in the initiation and secondary modification of neoplastic development, have also been under investigation as possible mechanisms. This review will highlight the biological effects of terpenoids as chemopreventive agents on breast epithelial carcinogenesis, and the utility of intermediate biomarkers as indicators of premalignancy. Selected breast chemoprevention trials are discussed with a focus on strategies for trial design, and clinical outcomes. Future directions in the field of chemoprevention are proposed based on recently acquired mechanistic insights into breast carcinogenesis.
Rabi Thangaiyan; Bishayee Anupam
Breast cancer research and treatment
2009
2009-05
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<a href="http://doi.org/10.1007/s10549-008-0118-y" target="_blank" rel="noreferrer noopener">10.1007/s10549-008-0118-y</a>
The medical humanities: toward a renewed praxis.
*Curriculum; *Education; CURRICULUM planning; ESSAYS; Health Care Surveys; HUMANITIES education; Humanities/*education; Humans; Medical; MEDICAL education; United States; UNITED States
In this essay, I explore medical humanities practice in the United States with descriptions offered by fifteen faculty members who participated in an electronic survey. The questions posed focused on the desirability of a core humanities curriculum in medical education; on the knowledge, skills, and values that are found in such a curriculum; and on who should teach medical humanities and make curriculum decisions regarding content and placement. I conclude with a call for a renewed interdisciplinarity in the medical humanities and a move away from the territorial aspects of disciplinary knowledge and methods sometimes found in medical humanities practice.
Wear Delese
The Journal of medical humanities
2009
2009-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s10912-009-9091-7" target="_blank" rel="noreferrer noopener">10.1007/s10912-009-9091-7</a>
Effects of bariatric surgery on inflammatory, functional and structural markers of coronary atherosclerosis.
*Gastric Bypass; Adult; Biological Markers – Blood; Biomarkers/blood; Blood Flow Velocity – Physiology; Blood Flow Velocity/physiology; Blood Vessels – Pathology; Body Mass Index; Brachial Artery – Ultrasonography; Brachial Artery/diagnostic imaging; C-Reactive Protein – Analysis; C-Reactive Protein/analysis; Carotid Arteries – Pathology; Carotid Arteries/pathology; Cholesterol – Blood; Cholesterol/blood; Coronary Arteriosclerosis – Blood; Coronary Arteriosclerosis – Pathology; Coronary Arteriosclerosis – Physiopathology; Coronary Artery Disease/*blood/pathology/*physiopathology; Female; Follow-Up Studies; Gastric Bypass; Human; Humans; Male; Muscle; Prospective Studies; Smooth – Pathology; Triglycerides – Blood; Triglycerides/blood; Tunica Intima/pathology; Tunica Media/pathology; Ultrasonography; Vasodilation – Physiology; Vasodilation/physiology
This study was designed to assess the effects of bariatric weight loss surgery on structural, functional, and inflammatory markers of coronary atherosclerosis. Obesity is a worldwide epidemic and an independent risk factor for coronary atherosclerosis. It remains unclear whether surgically induced weight loss reduces cardiovascular risk. This prospective study enrolled 50 consecutive subjects with morbid obesity who underwent Roux-en-Y gastric bypass surgery (GBS) after failed attempts at medical weight loss. Subjects were recruited through a comprehensive weight loss center affiliated with an academic tertiary care hospital. All subjects had body mass indexes \textgreater or =40 kg/m(2) or body mass indexes of 35 to 40 kg/m(2) with \textgreater or =2 co-morbid obesity-related conditions. Markers of coronary atherosclerosis, including brachial artery flow-mediated dilation, carotid intima-media thickness, and high-sensitivity C-reactive protein, were measured before GBS and 6, 12, and 24 months after GBS. There were statistically significant improvements in all measured markers of coronary atherosclerosis after GBS. The mean body mass index decreased from 47 to 29.5 kg/m(2) at 24 months (p \textless0.001), the mean carotid intima-media thickness regressed from 0.84 to 0.50 mm at 24 months (p \textless0.001), mean flow-mediated dilation improved from 6.0% to 14.9% at 24 months (p \textless0.05), and mean high-sensitivity C-reactive protein decreased from 1.23 to 0.65 mg/dl at 6 months (p \textless0.001) and to 0.35 mg/dl at 24 months (p \textless0.001). In conclusion, GBS results in significant improvements in inflammatory, structural, and functional markers of coronary atherosclerosis.
Habib Phillip; Scrocco John David; Terek Megan; Vanek Vincent; Mikolich J Ronald
The American journal of cardiology
2009
2009-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.amjcard.2009.06.042" target="_blank" rel="noreferrer noopener">10.1016/j.amjcard.2009.06.042</a>
Forkhead box transcription factor O1 inhibits cholesterol 7alpha-hydroxylase in human hepatocytes and in high fat diet-fed mice.
Adenoviridae/genetics; Animals; Bile Acids and Salts/biosynthesis; Cell Line; Cell Nucleus/drug effects/metabolism; Cholesterol 7-alpha-Hydroxylase/*antagonists & inhibitors/genetics/metabolism; Dietary Fats/*administration & dosage/*pharmacology; Down-Regulation/drug effects; Enzymologic/drug effects; Feeding Behavior/*drug effects; Forkhead Box Protein O1; Forkhead Transcription Factors/genetics/*metabolism; Gene Expression Regulation; Gene Knockdown Techniques; Gene Transfer Techniques; Hepatocytes/drug effects/*enzymology; Humans; Inbred C57BL; Insulin Resistance; Insulin/metabolism; Male; Messenger/genetics/metabolism; Mice; RNA; RNA Interference/drug effects; Tumor
The conversion of cholesterol to bile acids is the major pathway for cholesterol catabolism. Bile acids are metabolic regulators of triglycerides and glucose metabolism in the liver. This study investigated the roles of FoxO1 in the regulation of cholesterol 7alpha-hydroxylase (CYP7A1) gene expression in primary human hepatocytes. Adenovirus-mediated expression of a phosphorylation defective and constitutively active form of FoxO1 (FoxO1-ADA) inhibited CYP7A1 mRNA expression and bile acid synthesis, while siRNA knockdown of FoxO1 resulted in a approximately 6-fold induction of CYP7A1 mRNA in human hepatocytes. Insulin caused rapid exclusion of FoxO1 from the nucleus and resulted in the induction of CYP7A1 mRNA expression, which was blocked by FoxO1-ADA. In high fat diet-fed mice, CYP7A1 mRNA expression was repressed and inversely correlated to increase hepatic FoxO1 mRNA expression and FoxO1 nuclear retention. In conclusion, our current study provides direct evidence that FoxO1 is a strong repressor of CYP7A1 gene expression and bile acid synthesis. Impaired regulation of FoxO1 may cause down-regulation of CYP7A1 gene expression and contribute to dyslipidemia in insulin resistance.
Li Tiangang; Ma Huiyan; Park Young Joo; Lee Yoon-Kwang; Strom Stephen; Moore David D; Chiang John Y L
Biochimica et biophysica acta
2009
2009-10
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<a href="http://doi.org/10.1016/j.bbalip.2009.05.004" target="_blank" rel="noreferrer noopener">10.1016/j.bbalip.2009.05.004</a>
Genetic alteration in the dopamine transporter differentially affects male and female nigrostriatal transporter systems.
Animals; Corpus Striatum/*metabolism; Dopamine Plasma Membrane Transport Proteins/*genetics; Female; Male; Messenger/biosynthesis; Mice; Mutant Strains; Protein Binding; Reserpine/pharmacology; RNA; Sex Characteristics; Substantia Nigra/*metabolism; Vesicular Monoamine Transport Proteins/antagonists & inhibitors/biosynthesis/*physiology
Female mice with a heterozygous mutation of their dopamine transporter (+/- DAT) showed relatively robust reductions in striatal DAT specific binding (38-50%), while +/- DAT males showed modest reductions (24-32%). Significant decreases in substantia nigra DAT specific binding (42%) and mRNA (24%) were obtained in +/- DAT females, but not +/- DAT males (19% and 5%, respectively). The effects of this DAT perturbation upon vesicular monoamine transporter-2 (VMAT-2) function revealed significantly greater reserpine-evoked DA output from +/+ and +/- DAT female as compared to male mice and the DA output profile differed markedly between +/+ and +/- DAT females, but not males. No changes in VMAT-2 protein or mRNA levels were present among these conditions. On the basis of these data, we propose: (1) a genetic mutation of the DAT does not exert equivalent effects upon the DAT in female and male mice, with females being more affected; (2) an alteration in the DAT may also affect VMAT-2 function; (3) this interaction between DAT and VMAT-2 function is more prevalent in female mice; and (4) the +/- DAT mutation affects VMAT-2 function through an indirect mechanism, that does not involve an alteration in VMAT-2 protein or mRNA. Such DAT/VMAT-2 interactions can be of significance to the gender differences observed in drug addiction and Parkinson's disease.
Ji Jing; Bourque Melanie; Di Paolo Therese; Dluzen Dean E
Biochemical pharmacology
2009
2009-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bcp.2009.07.004" target="_blank" rel="noreferrer noopener">10.1016/j.bcp.2009.07.004</a>
Projections from auditory cortex to cholinergic cells in the midbrain tegmentum of guinea pigs.
Animals; Auditory Cortex/*metabolism; Auditory Pathways/metabolism; Axonal Transport; Axons/metabolism; Choline O-Acetyltransferase/*metabolism; Efferent Pathways/metabolism; Female; Fluorescent Antibody Technique; Guinea Pigs; Immunohistochemistry; Male; Neurons/*metabolism; Tegmentum Mesencephali/*metabolism
Anterograde and retrograde tracing techniques were used to characterize projections from the auditory cortex to the pedunculopontine and laterodorsal tegmental nuclei (PPT and LDT, respectively) in the midbrain tegmentum in guinea pigs. For anterograde tracing, tetramethylrhodamine dextran (FluoroRuby) was injected at several sites within auditory cortex. After sufficient time for transport, the brain was processed for immunohistochemistry with anti-choline acetyltransferase to reveal presumptive cholinergic cells. Anterogradely labeled axons were observed ipsilaterally and, in smaller numbers, contralaterally, in both the pedunculopontine and laterodorsal tegmental nuclei. In all four nuclei, tracer-labeled boutons appeared to contact immunolabeled (i.e., cholinergic) cells. The contacts occurred on cell bodies and dendrites. The results were similar following injections that spread across multiple auditory cortical areas or injections that were within primary auditory cortex. In order to confirm the anterograde results, in a second series of experiments, retrograde tracers were deposited in the pedunculopontine tegmental nucleus. These injections labeled layer V pyramidal cells in the auditory cortex. The results suggest an excitatory projection from primary auditory cortex bilaterally to cholinergic cells in the midbrain tegmentum. Such a pathway could allow auditory cortex to activate brainstem cholinergic circuits, possibly including the cholinergic pathways associated with arousal and gating of acoustic stimuli.
Schofield Brett R; Motts Susan D
Brain research bulletin
2009
2009-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.brainresbull.2009.06.015" target="_blank" rel="noreferrer noopener">10.1016/j.brainresbull.2009.06.015</a>
Resveratrol-mediated chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis: inhibition of cell proliferation and induction of apoptosis.
Animal; Animals; Anticarcinogenic Agents/*antagonists & inhibitors/pharmacology; Antitumor; Apoptosis/*drug effects; Body Weight/drug effects; Cell Proliferation/drug effects; Diethylnitrosamine; Disease Models; Dose-Response Relationship; Drinking/drug effects; Drug; Drug Screening Assays; Eating/drug effects; Experimental/chemically induced/pathology/*prevention & control; Female; Immunohistochemistry; Liver Neoplasms; Organ Size/drug effects; Phenobarbital; Proto-Oncogene Proteins c-bcl-2/biosynthesis; Rats; Resveratrol; Sprague-Dawley; Stilbenes/*pharmacology
Hepatocellular carcinoma (HCC) is one of the most common cancers and lethal diseases. In view of the limited treatment and a grave prognosis of liver cancer, preventive control has been emphasized. Resveratrol, a polyphenol found in grape skins, peanuts, berries and red wine, has been shown to possess potent growth inhibitory effects against various human cancer cells. Although resveratrol has been found to exhibit chemopreventive actions in experimentally induced skin, breast, colon and esophagus rodent tumors, chemopreventive potential of this dietary constituent has not been explored well against experimental liver cancer. We evaluated the inhibitory effect of resveratrol using a two-stage model of rat hepatocarcinogenesis in Sprague-Dawley rats. Initiation was performed by a single intraperitoneal injection of diethylnitrosamine (DENA, 200 mg/kg), followed by promotion with phenobarbital (0.05%) in drinking water. The rats had free access to food supplemented with resveratrol equivalent to 50, 100 or 300 mg/kg body weight/day. Resveratrol treatment was started 4 weeks prior to the initiation and continued for 20 weeks. Resveratrol dose-dependently reduced the incidence, total number and multiplicity of visible hepatocyte nodules. Mean nodular volume and nodular volume as percentage of liver volume were also inhibited upon resveratrol treatment. Histopathological examination of liver tissue confirmed the protective effect of resveratrol. Immunohistochemical detection of cell proliferation and assay of apoptosis indicated a decrease in cell proliferation and increase of apoptotic cells in the livers of resveratrol-supplemented rats. Resveratrol also induced the expression of pro-apoptotic protein Bax, reduced anti-apoptotic Bcl-2 expression, with a concurrent increase in Bax/Bcl-2 ratio with respect to DENA control. The present study provides evidence, for the first time, that resveratrol exerts a significant chemopreventive effect on DENA-initiated hepatocarcinogenesis through inhibition of cell proliferation and induction of apoptosis. Resveratrol-induced apoptogenic signal during rat liver carcinogenesis may be mediated through the downregulation of Bcl-2 and upregulation of Bax expression. Due to a favorable toxicity profile, resveratrol can potentially be developed as a chemopreventive drug against human HCC.
Bishayee Anupam; Dhir Neetika
Chemico-biological interactions
2009
2009-05
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<a href="http://doi.org/10.1016/j.cbi.2008.11.015" target="_blank" rel="noreferrer noopener">10.1016/j.cbi.2008.11.015</a>
Effects of a novel dopamine uptake inhibitor upon extracellular dopamine from superfused murine striatal tissue.
Animals; Biological Transport/drug effects; Buffers; Calcium Channels/metabolism; Dopamine Plasma Membrane Transport Proteins/metabolism; Dopamine Uptake Inhibitors/*pharmacology; Dopamine/*metabolism; Extracellular Space/*drug effects/*metabolism; In Vitro Techniques; Male; Methamphetamine/pharmacology; Mice; Neostriatum/*cytology/drug effects; PC12 Cells; Perfusion; Potassium Channel Blockers/pharmacology; Potassium Channels; Potassium Chloride/pharmacology; Rats; Voltage-Gated/antagonists & inhibitors
The dopamine transporter (DAT) plays an important role in substance abuse, schizophrenia, and dopaminergic toxicity associated with the Parkinsonian animal model toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Accordingly, the DAT serves as a critical component in regulating dopaminergic function in health and disease states. We have been working with a novel cage compound,
Geldenhuys Werner J; Bezuidenhout Lois-May; Dluzen Dean E
European journal of pharmacology
2009
2009-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.ejphar.2009.08.012" target="_blank" rel="noreferrer noopener">10.1016/j.ejphar.2009.08.012</a>
A disease model descriptive of progression between chronic obstructive pulmonary disease exacerbations and community-acquired pneumonia: roles for underlying lung disease and the pharmacokinetics/pharmacodynamics of the antibiotic.
*Anti-Bacterial Agents/pharmacokinetics/therapeutic use; *Community-Acquired Infections/drug therapy/microbiology/physiopathology/prevention & control; *Models; *Pneumonia; Aged; Area Under Curve; Bacterial/drug therapy/microbiology/physiopathology/prevention & control; Biological; Bronchitis; Chronic Obstructive/drug therapy/microbiology/*physiopathology; Chronic/drug therapy/microbiology/physiopathology; Disease Progression; Female; Humans; Lung Diseases/complications/drug therapy/microbiology; Lung/microbiology; Male; Microbial Sensitivity Tests; Middle Aged; Pneumococcal/drug therapy/microbiology/physiopathology/prevention & control; Pneumonia; Pulmonary Disease; Severity of Illness Index; Streptococcus pneumoniae/*drug effects
Patients with chronic obstructive pulmonary disease (COPD) may progress to community-acquired pneumonia (CAP), but there has been no formal study of the factors responsible. We studied the influence of severity of underlying lung disease, pathogen characteristics and the ratio of the area under the concentration-time curve from 0-24h to minimum inhibitory concentration (AUC24/MIC), i.e. the area under the inhibitory curve (AUIC), during the progression from acute exacerbation of chronic bronchitis (AECB) in COPD to CAP. The model parameters were derived from a multinational database of 3885 patients with AECB or CAP (April 1996 to July 2006). Patients with underlying COPD were evaluated in two separate analyses: infection progression between COPD and CAP within Global Initiative for Chronic Obstructive Lung Disease (GOLD)-like grouping (GLG); and distribution of pathogen by GLG, CAP and AECB. Secondary analyses examined the impact of target AUIC attainment on progression to CAP for Streptococcus pneumoniae. The relative impact of GLG and AUIC were modelled in multivariate logistic regression for S. pneumoniae. Progression to CAP linked directly with GLG I/II, III and IV (18.3%, 31.7% and 48.9%, respectively; P \textless 0.001). Progression to CAP was strongly associated with S. pneumoniae (57.3%), whilst other pathogens were predominant in AECB that did not progress to CAP (61.7%) (P = 0.002). AUIC \textgreater or = 100 was associated with AECB (65.1%) and AUIC \textless 100 with CAP (91.7%) (P \textless 0.001). In conclusion, the frequency of progression to CAP increases directly with GLG. For S. pneumoniae, achieving an AUIC \textgreater or =100 can attenuate progression, regardless of GLG. Thus, AUIC \textgreater or = 100 appears to be a viable antibiotic selection strategy to protect patients with S. pneumoniae from developing CAP.
File Thomas M Jr; Monte Scott V; Schentag Jerome J; Paladino Joseph A; Klugman Keith P; Lavin Bruce; Yu Victor L; Singer Mendel E; Adelman Martin H
International journal of antimicrobial agents
2009
2009-01
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<a href="http://doi.org/10.1016/j.ijantimicag.2008.07.019" target="_blank" rel="noreferrer noopener">10.1016/j.ijantimicag.2008.07.019</a>
The dermatology work force: a focus on urban versus rural wait times.
*Dermatology; *Waiting Lists; Appointments and Schedules; Dermatology – Manpower; Human; Humans; Ohio; Rural Population; Skin Diseases – Diagnosis; Skin Diseases/diagnosis; Urban Population; Waiting Lists; Workforce
BACKGROUND: Recent studies suggest a shortage of dermatologists with an average wait time of 36 days in the United States and 40 days in Ohio for a routine dermatology visit. To date, no previous studies have examined supply and demand of dermatology services in rural versus urban populations. OBJECTIVE: We sought to determine the average wait time for a dermatology appointment for new and established patients in both urban and rural areas. METHODS: The offices of 250 dermatologists in Ohio were contacted by telephone to determine the wait time for the next available appointment for new and established patients with a changing mole. RESULTS: The average wait time for new (4.5 weeks) and established (3.1 weeks) patients was similar to times reported in previous studies. A greater density of all dermatologists and medical (general) dermatologists practice in cities, but wait times were not statistically different in rural versus urban settings. LIMITATIONS: Neither insurance status or use of physician extenders were considered. The findings may not be applicable to areas outside Ohio. CONCLUSION: There is a shortage of medical dermatologists throughout Ohio. Training more medical dermatologists or adding physician extenders to dermatology practices would be expected to decrease the waiting time for dermatology appointments. Providing incentives for dermatologists to practice in underserved rural areas may not be necessary judging by the similarities in wait times between rural and urban settings.
Uhlenhake Elizabeth; Brodell Robert; Mostow Eliot
Journal of the American Academy of Dermatology
2009
2009-07
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<a href="http://doi.org/10.1016/j.jaad.2008.09.008" target="_blank" rel="noreferrer noopener">10.1016/j.jaad.2008.09.008</a>
Cardiac magnetic resonance imaging and coronary computed tomography angiography in the diagnosis of anomalous coronary artery.
Adult; Congenital – Diagnosis; Coronary Angiography; Coronary Vessel Anomalies/*diagnosis; Female; Heart Defects; Humans; Magnetic Resonance Imaging; Tomography; X-Ray Computed
Mikolich J Ronald
Journal of the American College of Cardiology
2009
2009-02
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<a href="http://doi.org/10.1016/j.jacc.2008.10.029" target="_blank" rel="noreferrer noopener">10.1016/j.jacc.2008.10.029</a>
Factors influencing subspecialty choice among radiology residents: a case study of pediatric radiology.
*Career Choice; Career Planning and Development; Decision Making; Internship and Residency – Manpower; Internship and Residency – Statistics and Numerical Data; Internship and Residency/*statistics & numerical data; Medical – Manpower; Medical – Statistics and Numerical Data; Pediatrics – Manpower; Pediatrics – Statistics and Numerical Data; Pediatrics/*statistics & numerical data; Radiology/*statistics & numerical data; Specialties; United States; Workforce
PURPOSE: Persistent workforce shortages exist in some radiology subspecialties. Residents' motivations for selecting particular fellowships, as well as their perceptions of the subspecialty fields, heavily influence the supply of new radiologists to these areas. The authors investigated the factors residents consider most important in subspecialty choice, fellowship choice patterns between 1999 and 2008, and changes that might attract residents to one particular shortage field: pediatric radiology. MATERIALS AND METHODS: An online questionnaire was developed and sent to 1,000 radiology trainees in the United States using contact information from the ACR's national resident database. Anonymized responses were evaluated using analysis of variance and logistic regression models. RESULTS: Leading factors for fellowship selection were "area of strong personal interest," "advanced/multimodality imaging," and "intellectual challenge." Compensation ranked low, 13th among 20 factors. Large shifts in subspecialty preference were seen between 1999 and 2008. Those with a pediatric radiology preference ranked "physician-physician interaction," "physician-patient contact," and "altruism" higher than respondents selecting other subspecialties. Respondents believed that pediatric radiologists make less money than other subspecialists ($325,000 vs $385,000 per year). There was no association between choosing pediatric radiology and gender, age, research plans, or parental status. CONCLUSIONS: Multiple factors account for subspecialty selection among residents, and it is useful to understand these factors when attempting to recruit residents to specific subspecialties. To ease the workforce shortage in pediatric radiology, advanced and varied imaging modalities, numerous job opportunities, and well-paid private practice positions should be emphasized to residents.
Arnold Ryan W; Goske Marilyn J; Bulas Dorothy I; Benya Ellen C; Ying Jun; Sunshine Jonathan H
Journal of the American College of Radiology : JACR
2009
2009-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.jacr.2009.05.005" target="_blank" rel="noreferrer noopener">10.1016/j.jacr.2009.05.005</a>
Projections to the inferior colliculus from layer VI cells of auditory cortex.
Amidines/metabolism; Animals; Auditory Cortex/*cytology/*physiology; Cholera Toxin/metabolism; Efferent Pathways/physiology; Fluorescent Dyes/metabolism; Functional Laterality; Guinea Pigs; Inferior Colliculi/*physiology; NADPH Dehydrogenase/metabolism; Neurons/classification/*physiology; Nitric Oxide Synthase Type I/metabolism
A large injection of a retrograde tracer into the inferior colliculus of guinea pigs labeled two bands of cells in the ipsilateral auditory cortex: a dense band of cells in layer V and a second band of cells in layer VI. On the contralateral side, labeled cells were restricted to layer V. The ipsilateral layer VI cells were distributed throughout temporal cortex, suggesting projections from multiple auditory areas. The layer VI cells included pyramidal cells as well as several varieties of non-pyramidal cells. Small tracer injections restricted to the dorsal cortex or external cortex of the inferior colliculus consistently labeled cells in layer VI. Injections restricted to the central nucleus of the inferior colliculus labeled layer VI cells only rarely. Overall, 10% of the cells in temporal cortex that project to the ipsilateral inferior colliculus were located in layer VI, suggesting that layer VI cells make a significant contribution to the corticocollicular pathway.
Schofield B R
Neuroscience
2009
2009-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuroscience.2008.11.013" target="_blank" rel="noreferrer noopener">10.1016/j.neuroscience.2008.11.013</a>
Sources of cholinergic input to the inferior colliculus.
Acetylcholine/*metabolism; Animals; Choline O-Acetyltransferase/metabolism; Female; Guinea Pigs; Immunohistochemistry; Inferior Colliculi/*anatomy & histology; Male; Neural Pathways/anatomy & histology/metabolism; Pedunculopontine Tegmental Nucleus/anatomy & histology/metabolism; Photomicrography; Tegmentum Mesencephali/*anatomy & histology/*metabolism
We combined retrograde tracing with immunohistochemistry for choline acetyltransferase to identify the source of cholinergic input to the inferior colliculus (IC) in guinea pigs. Injection of a retrograde tracer into one IC labeled cells in many brainstem nuclei. Retrogradely-labeled cells that were also immunoreactive for choline acetyltransferase were identified in two nuclei in the midbrain tegmentum: the pedunculopontine tegmental nucleus (PPT) and the laterodorsal tegmental nucleus (LDT). More PPT and LDT cells project ipsilaterally than contralaterally to the IC and, on both sides, there are more projecting cells in the PPT than in the LDT. Double-labeled cells were not found in any other brainstem nucleus. A common feature of cholinergic cells in PPT and LDT is collateral projections to multiple targets. We placed different retrograde tracers into each IC to identify cells in PPT and LDT that project to both ICs. In both PPT and LDT, a substantial proportion (up to 57%) of the immunoreactive cells that contained tracer from the contralateral IC also contained tracer from the ipsilateral IC. We conclude that acetylcholine in the IC originates from the midbrain tegmental cholinergic nuclei: PPT and LDT. These nuclei are known to participate in arousal, the sleep/wake cycle and prepulse inhibition of acoustic startle. It is likely that the cholinergic input to the IC is directly associated with these functions.
Motts S D; Schofield B R
Neuroscience
2009
2009-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuroscience.2009.02.036" target="_blank" rel="noreferrer noopener">10.1016/j.neuroscience.2009.02.036</a>
Regulation of glutamatergic and GABAergic neurotransmission in the chick nucleus laminaris: role of N-type calcium channels.
Animals; Auditory Pathways/cytology/drug effects/metabolism; Calcium Channel Blockers/pharmacology; Calcium Channels; Chick Embryo; Chickens; Cochlear Nucleus/cytology/drug effects/*metabolism; Excitatory Postsynaptic Potentials/drug effects/physiology; Functional Laterality/drug effects/physiology; gamma-Aminobutyric Acid/*metabolism; Glutamic Acid/*metabolism; N-Type/*metabolism; Neural Inhibition/physiology; Neurons/drug effects/metabolism; omega-Conotoxin GVIA/pharmacology; Organ Culture Techniques; Patch-Clamp Techniques; Rhombencephalon/cytology/*metabolism; Synaptic Transmission/drug effects/*physiology
Neurons in the chicken nucleus laminaris (NL), the third order auditory nucleus involved in azimuth sound localization, receive bilaterally segregated (ipsilateral vs contralateral) glutamatergic excitation from the cochlear nucleus magnocellularis and GABAergic inhibition from the ipsilateral superior olivary nucleus (SON). Here, I investigate the voltage-gated calcium channels (VGCCs) that trigger the excitatory and the inhibitory transmission in the NL. Whole-cell recordings were performed in acute brainstem slices. The excitatory transmission was predominantly mediated by N-type VGCCs, as the specific N-type blocker omega-Conotoxin-GVIA (omega-CTx-GVIA, 1-2.5 microM) inhibited excitatory postsynaptic currents (EPSCs) by approximately 90%. Blockers for P/Q- and L-type VGCCs produced no inhibition, and blockade of R-type VGCCs produced a small inhibition. In individual cells, the effect of each VGCC blocker on the EPSC elicited by activation of the ipsilateral input was the same as that on the EPSC elicited by activation of the contralateral input, and the two EPSCs had similar kinetics, suggesting physiological symmetry between the two glutamatergic inputs to single NL neurons. The inhibitory transmission in NL neurons was almost exclusively mediated by N-type VGCCs, as omega-CTx-GVIA (1 microM) produced a approximately 90% reduction of inhibitory postsynaptic currents, whereas blockers for other VGCCs produced no inhibition. In conclusion, N-type VGCCs play a dominant role in triggering both the excitatory and the inhibitory transmission in the NL, and the presynaptic VGCCs that mediate the two bilaterally segregated glutamatergic inputs to individual NL neurons are identical. These features may play a role in optimizing coincidence detection in NL neurons.
Lu Y
Neuroscience
2009
2009-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuroscience.2009.09.013" target="_blank" rel="noreferrer noopener">10.1016/j.neuroscience.2009.09.013</a>
Polycyclic compounds: ideal drug scaffolds for the design of multiple mechanism drugs?
*Drug Design; Adamantane/chemistry/pharmacology; Animals; Central Nervous System Diseases/*drug therapy; Humans; Molecular Structure; Neuroprotective Agents/chemistry/*pharmacology/therapeutic use; Polycyclic Compounds/*chemistry/pharmacology/therapeutic use; Psychotropic Drugs/chemistry/*pharmacology/therapeutic use; Quantitative Structure-Activity Relationship
Recently there has been a resurging interest in developing multi-functional drugs to treat diseases with complex pathological mechanisms. Such drug molecules simultaneously target multiple etiologies that have been found to be important modulators in specific diseases. This approach has significant promise and may be more effective than using one compound specific for one drug target or, by a polypharmaceutical approach, using a cocktail of two or more drugs. Polycyclic ring structures are useful as starting scaffolds in medicinal chemistry programs to develop multi-functional drugs, and may also be useful moieties added to existing structures to improve the pharmacokinetic properties of drugs currently used in the clinic or under development. This review attempts to provide a synopsis of current published research to exemplify the use of polycyclic compounds as starting molecules to develop multi-functional drugs.
Van der Schyf Cornelis J; Geldenhuys Werner J
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
2009
2009-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.nurt.2008.10.037" target="_blank" rel="noreferrer noopener">10.1016/j.nurt.2008.10.037</a>
Cardiac myofibroblast differentiation is attenuated by alpha(3) integrin blockade: potential role in post-MI remodeling.
Animals; Cell Differentiation/*physiology; Collagen Type VI/*metabolism/physiology; Fibroblasts/*cytology; Immunoblotting; Integrin alpha3/*metabolism; Male; Myocardial Infarction/*metabolism; Myocardium/*cytology; Protein Binding; Rats
Cardiac fibroblasts and myofibroblasts are responsible for post-MI remodeling which occurs via regulation of extracellular matrix (ECM). Accelerated post-MI remodeling leads to excessive ECM deposition and fibrosis, contributing to impaired contractile function, arrhythmias, and heart failure. We have previously reported that type VI collagen induces myofibroblast differentiation in cultured cardiac fibroblasts, and that type VI collagen and myofibroblast content were both elevated in the myocardium 20 weeks post-MI. The purpose of this study was to determine the expression patterns of type VI collagen and myofibroblast content in early post-myocardial infarction (MI) remodeling to gain insight into whether type VI collagen induces in vivo myofibroblast differentiation via specific matrix-receptor interactions. Adult male Sprague-Dawley rats were anesthetized and left coronary arteries were permanently ligated. Histological tissue sections and whole tissue protein lysates were obtained from infarcted and non-infarcted areas of MI hearts and sham operated controls. At 3 days post-MI, we observed a significant increase in alpha(3) integrin expression (2.02+/-0.18 fold); at 7 days post-infarction both type VI collagen (2.27+/-0.18 fold) and myofibroblast (4.65+/-0.6 fold) content increased. By 14 days myofibroblast content returned to sham control levels, although type VI collagen (2.42+/-0.11 fold) was still elevated. In vitro cross-linking confirmed that the alpha(3) integrin interacts with type VI collagen, and alpha(3) integrin function blocking antibodies inhibited the differentiation of isolated cardiac fibroblasts. Collectively, our in vitro results indicate that the alpha(3) integrin receptor interacts with type VI collagen to promote myofibroblast differentiation, and that this interaction may impact in vivo post-MI remodeling.
Bryant Jennifer E; Shamhart Patricia E; Luther Daniel J; Olson Erik R; Koshy John C; Costic Donald J; Mohile Monica V; Dockry Michelle; Doane Kathleen J; Meszaros J Gary
Journal of molecular and cellular cardiology
2009
2009-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.yjmcc.2008.10.022" target="_blank" rel="noreferrer noopener">10.1016/j.yjmcc.2008.10.022</a>
Histochemical analyses of tissue-engineered human menisci.
*Tissue Scaffolds; Animals; Cell Differentiation/physiology; Cell Proliferation; Cell Shape/physiology; Cells; Chondrocytes/*cytology/*metabolism/transplantation; Chondrogenesis/physiology; Collagen/metabolism; Cultured; Fibrocartilage/cytology/metabolism/transplantation; Graft Survival/physiology; Heterologous/methods; Histocytochemistry; Humans; Male; Menisci; Mice; Middle Aged; Nude; Phenotype; Polyglycolic Acid/pharmacology/therapeutic use; Tibial/*cytology/*metabolism/transplantation; Tissue Engineering/*methods; Transplantation
The field of tissue engineering remains one of the least explored areas of current meniscal research but holds great promise. In this investigation, meniscal fibrochondrocytes were isolated from fresh human meniscal tissue and seeded onto synthetic polyglycolic acid (PGA) scaffolds. Constructs were implanted into the dorsal subcutaneous space of athymic nude mice. Control scaffolds, devoid of meniscal cells, were simultaneously implanted in additional mice. Constructs were harvested over 12 weeks and treated with a variety of histochemical stains to analyze general specimen morphology, cellular viability and proliferation, and collagen secretion. Results indicate that meniscal fibrochondrocyte proliferation increased over the time of implantation with cellular consolidation occurring as the PGA scaffolding was progressively hydrolyzed. Collagen production also increased over time. There were favorable similarities between constructs and human meniscal controls in terms of cellular morphology, phenotypic expression, and collagen production. These initial findings demonstrate procedures supporting proliferation of meniscal fibrochondrocytes, expression of fibrochondral phenotype, and the formation of putative meniscal tissue.
Schoenfeld Andrew J; Jacquet Robin; Lowder Elizabeth; Doherty Alison; Leeson Mark C; Landis William J
Connective tissue research
2009
1905-7
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1080/03008200902721887" target="_blank" rel="noreferrer noopener">10.1080/03008200902721887</a>
Conceptualizing disease: unifying the divide between philosophical inquiry and empirical research.
*Bioethical Issues; *Empirical Research; *Ethical Analysis; *Mental Disorders; *Mental Health; Autistic Disorder; Bioethics/*trends; Concept Formation; Decision Making; Education; Empirical Research; Ethical; Ethical Theory; Ethics; Ethics Theory; Humans; Medical; Physician-Patient Relations; Psychiatric Patients; Qualitative Research
Aultman Julie M
The American journal of bioethics : AJOB
2009
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1080/15265160902874387" target="_blank" rel="noreferrer noopener">10.1080/15265160902874387</a>
Redox-dependent mechanisms in coronary collateral growth: the "redox window" hypothesis.
Angiotensin II/physiology; Animals; Coronary Vessels/*growth & development/metabolism; Humans; Oxidation-Reduction; Reactive Oxygen Species/metabolism
This review addresses the complexity of coronary collateral growth from the aspect of redox signaling and introduces the concept of a "redox window" in the context of collateral growth. In essence, the redox window constitutes a range in the redox state of cells, which not only is permissive for the actions of growth factors but also amplifies their actions. The interactions of redox-dependent signaling with growth factors are well established through the actions of many redox-dependent kinases (e.g., Akt and p38 mitogen-activated protein kinase). The initial changes in cellular redox can be induced by a variety of events, from the oxidative burst during reperfusion after ischemia, to recruitment of various types of inflammatory cells capable of producing reactive oxygen species. Any event that "upsets" the normal redox equilibrium is capable of amplifying growth. However, extremes of the redox window, oxidative and reductive stresses, are associated with diminished growth-factor signaling and reduced activation of redox-dependent kinases. This concept of a redox window helps to explain why the clinical trials aimed at stimulating coronary collateral growth, the "therapeutic angiogenesis trials," failed. However, understanding of redox signaling in the context of coronary collateral growth could provide new paradigms for stimulating collateral growth in patients.
Yun June; Rocic Petra; Pung Yuh Fen; Belmadani Souad; Carrao Ana Catarina Ribeiro; Ohanyan Vahagn; Chilian William M
Antioxidants & redox signaling
2009
2009-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1089/ars.2009.2476" target="_blank" rel="noreferrer noopener">10.1089/ars.2009.2476</a>
Development of bone and cartilage in tissue-engineered human middle phalanx models.
*Models; Aggrecans/genetics/metabolism; Animals; Biological; Bone Development/drug effects/*physiology; Calcium Phosphates/pharmacology; Cartilage/cytology/drug effects/*growth & development; Cattle; Chondrocytes/cytology/drug effects/metabolism; Collagen Type II/genetics/metabolism; Durapatite/pharmacology; Electron; Experimental; Finger Phalanges/cytology/diagnostic imaging/drug effects/*physiology; Gene Expression Profiling; Gene Expression Regulation/drug effects; Humans; Implants; Integrin-Binding Sialoprotein; Mice; Microscopy; Paraffin Embedding; Periosteum/cytology/drug effects; Polyesters/pharmacology; Radiography; Scanning; Sialoglycoproteins/genetics/metabolism; Tissue Engineering/*methods; Tissue Scaffolds/chemistry
Human middle phalanges were tissue-engineered with midshaft scaffolds of poly(L-lactide-epsilon-caprolactone) [P(LA-CL)], hydroxyapatite-P(LA-CL), or beta-tricalcium phosphate-P(LA-CL) and end plate scaffolds of bovine chondrocyte-seeded polyglycolic acid. Midshafts were either wrapped with bovine periosteum or left uncovered. Constructs implanted in nude mice for up to 20 weeks were examined for cartilage and bone development as well as gene expression and protein secretion, which are important in extracellular matrix (ECM) formation and mineralization. Harvested 10- and 20-week constructs without periosteum maintained end plate cartilage but no growth plate formation. They also consisted of chondrocytes secreting type II collagen and proteoglycan, and they were composed of midshaft regions devoid of bone. In all periosteum-wrapped constructs at like times, end plate scaffolds held chondrocytes elaborating type II collagen and proteoglycan and cartilage growth plates resembling normal tissue. Chondrocyte gene expression of type II collagen, aggrecan, and bone sialoprotein varied depending on midshaft composition, presence of periosteum, and length of implantation time. Periosteum produced additional cells, ECM, and mineral formation within the different midshaft scaffolds. Periosteum thus induces midshaft development and mediates chondrocyte gene expression and growth plate formation in cartilage regions of phalanges. This work is important for understanding developmental principles of tissue-engineered phalanges and by extension those of normal growth plate cartilage and bone.
Wada Yoshitaka; Enjo Mitsuhiro; Isogai Noritaka; Jacquet Robin; Lowder Elizabeth; Landis William J
Tissue engineering. Part A
2009
2009-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1089/ten.TEA.2009.0078" target="_blank" rel="noreferrer noopener">10.1089/ten.TEA.2009.0078</a>
Commentary: Knowing it when we see it: reflections on pornography.
*Erotica; *Ethics; *Internship and Residency; 20th Century; Education; Female; Feminism/*history; Graduate/ethics; History; Humans; Male; Medical; Professional; Professional Competence; Sexual Harassment; Textbooks as Topic/*history; Undergraduate/ethics
This commentary asks, of what contemporary use is the excavation of a specific incident of sexually intimidating and otherwise inappropriate behavior in medical education's history? The question is posed in response to the accompanying article by Halperin detailing the publication and critical reception of an anatomy textbook that adopted a demeaning attitude toward women and featured pinup style photographs of nude women. The author contends that the generational context of feminist response to this incident and others like it is critical in shaping the current discussion. Today's third-generation feminists recognize the injustice of exploitative or offensive behaviors, but because of a fear of retaliation or negative consequence, they may nonetheless decline to respond in an official or whistle-blowing capacity-despite efforts to normalize appropriate faculty-learner interactions and to provide safe reception for those affected by abuses of power or authority. Revisiting an incident such as the one Halperin recounts reminds readers of both genders and all career stages that violations of professional mores between teacher and learner still occur and that the price of speaking up remains high.
Hull Sharon K
Academic medicine : journal of the Association of American Medical Colleges
2009
2009-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/ACM.0b013e3181939222" target="_blank" rel="noreferrer noopener">10.1097/ACM.0b013e3181939222</a>
Hidden in plain sight: the formal, informal, and hidden curricula of a psychiatry clerkship.
*Clinical Clerkship; *Curriculum; Attitude of Health Personnel; Clinical Competence; Faculty; Focus Groups; Humans; Internship and Residency; Intuition; Learning; Medical; Mentors; Physician-Patient Relations; Physician's Role; Psychiatry/*education; Students; Teaching; Time Factors; United States
PURPOSE: To examine perceptions of the formal, informal, and hidden curricula in psychiatry as they are observed and experienced by (1) attending physicians who have teaching responsibilities for residents and medical students, (2) residents who are taught by those same physicians and who have teaching responsibilities for medical students, and (3) medical students who are taught by attendings and residents during their psychiatry rotation. METHOD: From June to November 2007, the authors conducted focus groups with attendings, residents, and students in one midwestern academic setting. The sessions were audiotaped, transcribed, and analyzed for themes surrounding the formal, informal, and hidden curricula. RESULTS: All three groups offered a similar belief that the knowledge, skills, and values of the formal curriculum focused on building relationships. Similarly, all three suggested that elements of the informal and hidden curricula were expressed primarily as the values arising from attendings' role modeling, as the nature and amount of time attendings spend with patients, and as attendings' advice arising from experience and intuition versus "textbook learning." Whereas students and residents offered negative values arising from the informal and hidden curricula, attendings did not, offering instead the more positive values they intended to encourage through the informal and hidden curricula. CONCLUSIONS: The process described here has great potential in local settings across all disciplines. Asking teachers and learners in any setting to think about how they experience the educational environment and what sense they make of all curricular efforts can provide a reality check for educators and a values check for learners as they critically reflect on the meanings of what they are learning.
Wear Delese; Skillicorn Jodie
Academic medicine : journal of the Association of American Medical Colleges
2009
2009-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/ACM.0b013e31819a80b7" target="_blank" rel="noreferrer noopener">10.1097/ACM.0b013e31819a80b7</a>
Perspective: A perfect storm: the convergence of bullet points, competencies, and screen reading in medical education.
*Curriculum; *Professional Competence; *Software; *Teaching; Attention; Cognition; Education; Educational; Humans; Medical/*methods; Models; Physician's Role; Reading
Three distinct phenomena are currently at play in medical education: (1) the pervasive use of PowerPoint in teaching, (2) the wholesale application of competency models, and (3) the shift from paper reading to screen reading regardless of course, text, or genre. Finding themselves placed at this intersection, students encounter fewer and fewer opportunities to practice some of the very cognitive and affective habits medical educators say they value in physicians, particularly critical reflection and deliberation, an eye for nuance, context, and ambiguity, and an appreciation that becoming a doctor involves more than learning content or performing skills. This article confronts these phenomena singly and then at their intersection, which may discourage, even dismantle, many of these habits. The author proposes that the rapid shift over the past decade to a technology-driven, competency-oriented environment in medical education is the medical educators' creation, one that sets up conditions for a perfect cognitive storm.
Wear Delese
Academic medicine : journal of the Association of American Medical Colleges
2009
2009-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/ACM.0b013e3181ba9946" target="_blank" rel="noreferrer noopener">10.1097/ACM.0b013e3181ba9946</a>
Cecal volvulus in a multiple-gestation pregnancy.
*Pregnancy; Adult; Cecal Diseases – Diagnosis; Cecal Diseases – Surgery; Cecal Diseases/*diagnosis/surgery; Female; Humans; Intestinal Obstruction – Diagnosis; Intestinal Obstruction – Surgery; Intestinal Volvulus/*diagnosis/surgery; Multiple; Pregnancy; Pregnancy Complications – Diagnosis; Pregnancy Complications – Surgery; Pregnancy Complications/*diagnosis/surgery; Twins
BACKGROUND: Intestinal obstruction during pregnancy is rare, with volvulus being responsible for about 25% of cases. CASE: We present a case in which a woman in the 12th week of a twin gestation presented with abdominal pain and distension. She was initially diagnosed with an ileus, and radiological studies at the time were deferred. The patient's symptoms worsened, and eventually she was taken to surgery for a diagnostic laparoscopy, which revealed a cecal volvulus with ischemic changes. A right hemicolectomy with primary anastomosis was performed. CONCLUSION: Volvulus in pregnancy carries a high mortality rate, often because diagnosis is delayed due to avoidance of radiography and because of similarity of symptoms to other clinical entities. A high index of suspicion for volvulus must be maintained when a pregnant patient presents with obstructive symptoms. Abdominal radiographs may be justified in aiding the diagnosis, and diagnostic laparoscopy is a viable alternative when the patient has an acute abdomen.
Chase Daniel M; Sparks Dorothy A; Dawood Murtaza Y; Perry Earnest
Obstetrics and gynecology
2009
2009-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/AOG.0b013e3181989578" target="_blank" rel="noreferrer noopener">10.1097/AOG.0b013e3181989578</a>
Calcium channel blocker toxicity.
Adult; Assisted Circulation; Calcium Channel Blockers/classification/pharmacokinetics/*poisoning; Calcium Channels; Calcium Chloride/therapeutic use; Cardiovascular Agents/therapeutic use; Cardiovascular Diseases/*chemically induced/drug therapy; Charcoal/therapeutic use; Child; Combined Modality Therapy; Drug Overdose/drug therapy/therapy; Enema; Extracorporeal Circulation; Fat Emulsions; Fluid Therapy; Glucagon/therapeutic use; Heart/drug effects; Humans; Hyperglycemia/*chemically induced/drug therapy; Infant; Intravenous/therapeutic use; L-Type/physiology; Muscle; Plasmapheresis; Poisoning/drug therapy/physiopathology/therapy; Practice Guidelines as Topic; Preschool; Smooth; Vascular/drug effects
Calcium channel blockers continue to be used for the management of a wide variety of adult and pediatric conditions including hypertension, angina pectoris, atrial arrhythmias, Raynaud phenomenon, and migraine headaches. With increased use comes increased potential for misuse and abuse. This article serves as a review of calcium channel blocker physiology with emphasis on presentation and management of the pediatric patient with calcium channel blocker toxicity.
Arroyo Anna Maria; Kao Louise W
Pediatric emergency care
2009
2009-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/PEC.0b013e3181b0a504" target="_blank" rel="noreferrer noopener">10.1097/PEC.0b013e3181b0a504</a>
Disorders of the female breast in the pediatric age group.
Breast Neoplasms/epidemiology; Breast/*abnormalities/embryology/injuries/surgery; Burns/surgery; Child; Female; Fibroadenoma/epidemiology; Humans; Hyperplasia; Nipples/abnormalities; Poland Syndrome/physiopathology; Reconstructive Surgical Procedures; Tissue Expansion
SUMMARY: Disorders of the female breast in the pediatric age group are a relatively common finding; however, there is limited information in the current literature. The plastic surgeon treating these patients is faced with a wide range of reconstructive problems. By understanding the various breast disorders, the plastic surgeon can better diagnose and treat this patient population appropriately.
Pryor Landon S; Lehman James A Jr; Workman Meredith C
Plastic and reconstructive surgery
2009
2009-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/PRS.0b013e3181aa0ef9" target="_blank" rel="noreferrer noopener">10.1097/PRS.0b013e3181aa0ef9</a>
Dynamic automatic ultrasound optimization: time savings, keystroke savings, and image quality.
Abdomen/*diagnostic imaging; Adult; Automation; Computer-Assisted; Ergonomics; Female; Human; Humans; Image Enhancement; Image Processing; Imaging; Job Experience; Middle Aged; Occupational Diseases/diagnosis; Pain/diagnosis; Phantoms; Treatment Duration; Ultrasonography; Ultrasonography – Methods; Ultrasonography/*methods; Young Adult
PURPOSE: The aims of this study were to evaluate if a dynamic automatic image optimization technique decreases examination time and number of keystrokes while maintaining or improving image quality and to determine if these variables vary with sonographer experience. MATERIALS AND METHODS: Five sonographers of varying experience performed a randomized standard abdominal ultrasonography using manual and automatic techniques on 5 healthy volunteers. The time to perform the examinations and the number of images obtained were recorded, and a keystroke log was maintained for all examinations. Images were stored digitally for review and image analysis. The sonographers graded their pain during the examinations on a
Barr Richard G; Grajo Joseph R
Ultrasound quarterly
2009
2009-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/RUQ.0b013e3181a424e2" target="_blank" rel="noreferrer noopener">10.1097/RUQ.0b013e3181a424e2</a>
Contrast-enhanced ultrasound detection and treatment guidance in a renal transplant patient with renal cell carcinoma.
*Fluorocarbons; Aged; Angiography; Biopsy; Carcinoma; Catheter Ablation; Catheter Ablation/*methods; Computer-Assisted/methods; Contrast Media; Equipment and Supplies; Humans; Kidney Neoplasms/*diagnostic imaging/*surgery; Magnetic Resonance Imaging; Male; Renal Cell – Diagnosis; Renal Cell – Epidemiology; Renal Cell/*diagnostic imaging/*surgery; Surgery; Tomography; Treatment Outcome; Ultrasonography; Ultrasonography/*methods
Contrast-enhanced ultrasonography (CEUS) is an imaging modality that shows promise in the detection and characterization of renal masses, as well as treatment through CEUS-guided percutaneous radiofrequency ablation. These techniques may be especially valuable in challenging patients who cannot tolerate traditional contrast agents, such as those with diminished renal function, and those who cannot tolerate more invasive surgical treatment. The following case report details an incidence of renal cell carcinoma in a renal transplant patient whose tumor was diagnosed with CEU and successfully treated with CEUS-guided percutaneous RFA.
Sanchez Kimberly; Barr Richard G
Ultrasound quarterly
2009
2009-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/RUQ.0b013e3181b4f9cf" target="_blank" rel="noreferrer noopener">10.1097/RUQ.0b013e3181b4f9cf</a>
Speed of sound imaging: improved image quality in breast sonography.
*Artifacts; Breast Diseases – Classification; Breast Diseases – Diagnosis; Continuing (Credit); Education; Equipment and Supplies; Female; Funding Source; Human; Humans; Image Enhancement/*methods; Mammary/*methods; Middle Aged; Observer Variation; Quality of Health Care; Reproducibility of Results; Sensitivity and Specificity; Ultrasonography; Ultrasonography – Methods
PURPOSE: The purpose of this study was to evaluate blindly breast ultrasound images corrected for the speed of sound in breast tissue compared with conventional images. MATERIALS AND METHODS: In this study, 409 images from 153 patients were obtained on an Antares Ultrasound system. The system was modified to process the radiofrequency data with the standard 1540 m/s as the speed of sound and at a corrected speed of sound for breast tissue. An offline
Barr Richard G; Rim Alice; Graham Ruffin; Berg Wendie; Grajo Joseph R
Ultrasound quarterly
2009
2009-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/RUQ.0b013e3181b789aa" target="_blank" rel="noreferrer noopener">10.1097/RUQ.0b013e3181b789aa</a>
Derogatory and cynical humour directed towards patients: views of residents and attending doctors.
*Attitude of Health Personnel; *Social Identification; *Wit and Humor as Topic; Culture; Education; ETHICS; Hospital/*psychology; Humans; HUMOR in the workplace; MEDICAL personnel & patient; Medical Staff; Medical/methods; Medical/psychology; Physician-Patient Relations; PROFESSIONALISM; Social Perception; Students; WIT & humor; WIT & humor in medicine
CONTEXT: A study of medical students' perspectives on derogatory and cynical humour was published in 2006. The current study examines residents' and attending doctors' perspectives on the same phenomenon in three clinical departments of psychiatry, internal medicine and surgery. METHODS: Two focus groups were conducted in each of the three clinical departments, one with residents and one with attending doctors,during the 2006-07 academic year. Seventy doctors participated, including 49 residents and 21 attendings. The same semi-structured format was used in each group. Questions focused on characterisations of derogatory and cynical humour along with motives and rules for its use.All focus groups were audiotaped and the tapes transcribed. Each transcript was read independently by each researcher as part of an inductive process to discover the categories that describe and explain the uses, motives and effects of such humour. RESULTS: Three categories that appeared in the first study with medical students - locations for humour, the humour game, and not-funny humour - emerged as virtually identical,whereas two others–objects of humour and motives for humour - were more fully elaborated. DISCUSSION: Discussions of derogatory and cynical humour should occur in any department where teaching and role modelling are priorities. In addition, the tenets of appreciative inquiry and the complex responsive process,particularly as they are used at the Indiana University School of Medicine, offer medical educators valuable tools for addressing this phenomenon.
Wear Delese; Aultman Julie M; Zarconi Joseph; Varley Joseph D
Medical education
2009
2009-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/j.1365-2923.2008.03171.x" target="_blank" rel="noreferrer noopener">10.1111/j.1365-2923.2008.03171.x</a>
Obstetrics and gynaecology chief resident attitudes toward teaching junior residents under normal working conditions.
*Attitude of Health Personnel; *Internship and Residency; Clinical Competence; Education; Graduate/*methods; Gynecology/*education; Hospital/education/psychology/standards; Humans; Medical; Medical Staff; Mentors/psychology; Obstetrics/*education; Ohio; Teaching/methods
OBJECTIVES: This study aimed to identify factors that chief residents believe impact the teaching of junior residents under normal working conditions and the areas in which they believe education on the role of resident as teacher would be beneficial. METHODS: Obstetrics and gynaecology (O&G) chief residents were asked to rate the importance of teaching various skills, how often conflict situations arose, and to identify training that would be helpful through a national web-based survey. An e-mail was sent to coordinators of the Residency Review Committee (RRC) O&G residency programmes with a request that they forward the link to their chief residents three times from January through March 2006. RESULTS: Responses were received from 204 postgraduate Year 4 (PGY4) residents (18% of all PGY4 residents) from 133 programmes (54% of all residency programmes) and 33 states. Teaching junior residents how to prioritise patient care and obtain critical information in an emergent situation was considered very to extremely important by 97%. Conflict situations with junior residents were reported to occur between one and five times by 41-58%; an additional 26-28% reported that these situations occurred six or more times. Residents felt it would be helpful to extremely helpful to have training in resolving conflicts that involved patient care (48-59%), as well as in resolving conflict among junior residents, communicating effectively with them and becoming an effective leader (65-78%). CONCLUSIONS: The skills that chief residents considered most important to teach junior residents involved direct patient care. Chief residents would like training in how to resolve conflict with, and among, junior residents, and in how to become an effective leader.
Gil Karen M; Savitski Jennifer L; Bazan Sara; Patterson Laurene R; Kirven Melissa
Medical education
2009
2009-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/j.1365-2923.2009.03422.x" target="_blank" rel="noreferrer noopener">10.1111/j.1365-2923.2009.03422.x</a>
A genethics debate within an interdisciplinary curriculum.
AULTMAN; Curriculum; Education; Ethics; GENETICS; Genetics – Education; Genetics/education/*ethics; Humans; Julie M.; Medical; Medical – Education; Medical/*education; Medical/psychology; Molecular Biology/education; Ohio; Pharmacy/*methods/standards; Pharmacy/psychology; Students; Teaching Methods – Evaluation; Undergraduate/*methods/standards
Aultman Julie M
Medical education
2009
2009-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/j.1365-2923.2009.03504.x" target="_blank" rel="noreferrer noopener">10.1111/j.1365-2923.2009.03504.x</a>
Iron localization in superficial siderosis of the central nervous system.
Astrocytes/chemistry/ultrastructure; Brain Chemistry; Brain Diseases/metabolism/*pathology; Brain/pathology/ultrastructure; Confocal; Electron; Female; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Iron/*analysis; Macrophages/chemistry; Magnetic Resonance Imaging; Microscopy; Middle Aged; Mitochondria/chemistry/ultrastructure; Neurons/chemistry; Oligodendroglia/chemistry/ultrastructure; Siderosis/*metabolism/*pathology; Spinal Cord Diseases/*pathology/physiopathology; Spinal Cord/chemistry/pathology/ultrastructure; Transmission
Originally conceived as an uncommon disorder, with the advent of MRI, CNS superficial siderosis has been observed more frequently. We present histologic, histochemical, immunohistochemical, immunofluorescent and ultrastructural evaluation of a 56-year-old woman with superficial siderosis. Iron was concentrated in macrophages, superficial astrocytes and gray matter oligodendroglia deep within the cord. While spatially associated with dystrophic glial and neuronal spheroids, iron did not colocalize with mitochondria. Neurotoxic effects were observed despite selective iron localization only within a variety of non-neuronal cell types.
Kellermier Harry; Wang Guoji; Wiley Clayton
Neuropathology : official journal of the Japanese Society of Neuropathology
2009
2009-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/j.1440-1789.2008.00943.x" target="_blank" rel="noreferrer noopener">10.1111/j.1440-1789.2008.00943.x</a>