23 results on '"Hughes, Duncan"'
Search Results
2. Limited Panniculectomy for Adult Buried Penis Repair.
- Author
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Pestana IA, Hughes DB, and Erdmann D
- Subjects
- Adult, Humans, Male, Penis surgery, Abdominoplasty, Lipectomy
- Published
- 2016
- Full Text
- View/download PDF
3. Sexual and Overall Quality of Life Improvements After Surgical Correction of "Buried Penis".
- Author
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Hughes DB, Perez E, Garcia RM, Aragón OR, and Erdmann D
- Subjects
- Adult, Aged, Follow-Up Studies, Humans, Male, Middle Aged, Patient Satisfaction, Penile Diseases complications, Penile Diseases psychology, Retrospective Studies, Sexual Dysfunction, Physiological diagnosis, Sexual Dysfunctions, Psychological diagnosis, Surveys and Questionnaires, Treatment Outcome, Penile Diseases surgery, Penis surgery, Quality of Life, Plastic Surgery Procedures, Sexual Dysfunction, Physiological etiology, Sexual Dysfunctions, Psychological etiology
- Abstract
Background: "Buried penis" is an increasing burden in our population with many possible etiologies. Although surgical correction of buried penis can be rewarding and successful for the surgeon, the psychological and functional impact of buried penis on the patient is less understood., Methods: The study's aim was to evaluate the sexual satisfaction and overall quality of life before and after buried penis surgery in a single-surgeon's patient population using a validated questionnaire (Changes in Sexual Functioning Questionnaire short-form)., Results: Using Likert scales generated from the questionnaire and 1-tailed paired t test analysis, we found that there was significantly improved sexual function after correction of a buried penis. Variables individually showed that there was significant improvement with sexual pleasure, urinating, and with genital hygiene postoperatively. There were no significant differences concerning frequency of pain with orgasms., Conclusions: Surgical correction of buried penis significantly improves the functional, sexual, and psychological aspects of patient's lives.
- Published
- 2016
- Full Text
- View/download PDF
4. Evolving Trends in Autologous Breast Reconstruction: Is the Deep Inferior Epigastric Artery Perforator Flap Taking Over?
- Author
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Pien I, Caccavale S, Cheung MC, Butala P, Hughes DB, Ligh C, Zenn MR, and Hollenbeck ST
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Databases, Factual, Female, Hospital Charges statistics & numerical data, Hospital Charges trends, Hospital Costs statistics & numerical data, Hospital Costs trends, Humans, Insurance, Health statistics & numerical data, Linear Models, Mammaplasty economics, Mammaplasty trends, Middle Aged, Perforator Flap blood supply, Perforator Flap economics, Practice Patterns, Physicians' economics, Practice Patterns, Physicians' statistics & numerical data, United States, Young Adult, Epigastric Arteries surgery, Mammaplasty methods, Perforator Flap statistics & numerical data, Perforator Flap trends, Practice Patterns, Physicians' trends
- Abstract
Background: Enthusiasm for the deep inferior epigastric artery perforator (DIEP) flap for autologous breast reconstruction has grown in recent years. However, this flap is not performed at all centers or by all plastic surgeons for breast reconstruction, and it is unclear whether practice patterns have measurably changed. This study aimed to (1) evaluate changing trends in breast flap use in the United States in recent years and (2) identify how these trends have affected charges and costs associated with autologous breast reconstruction., Methods: Patients undergoing autologous breast reconstruction [latissimus dorsi (LD), pedicled transverse rectus abdominus myocutaneous (pTRAM), free TRAM (fTRAM), and DIEP] were identified using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database (2009-2011). A total of 19,182 hospital discharges were reviewed. Patient demographics, hospital teaching center status, payer status, length of stay, total charges, and total costs per discharge were reviewed. Statistical analysis was performed using linear regression, t test, and analysis of variance models., Results: Between 2009 and 2011, the total number of discharges did not change significantly. Patient age distribution was similar for all flap groups. For individual flaps, there was a significant increase in DIEP flaps (P = 0.03), with a decreasing trend for other abdominal-based flaps. The patients receiving DIEP flap breast reconstruction were covered by private insurance at a higher rate than all other flap procedures (P = 0.03), whereas other potential cost determinants did not differ significantly between the groups. The mean charge per flap was $40,704 for LD, $51,933 for pTRAM, $69,909 for fTRAM, and $82,320 for DIEP. The mean cost per flap was $12,017 for LD, $15,538 for pTRAM, $20,756 for fTRAM, and $23,616 for DIEP., Conclusions: Between 2009 and 2011, the total amount of autologous breast reconstruction discharges was relatively stable, but the number of DIEP flaps increased significantly. Review of the Healthcare Cost and Utilization Project Nationwide Inpatient Sample data shows that, compared with LD, pTRAM, and fTRAM flaps, the DIEP flap is associated with higher charges and costs.
- Published
- 2016
- Full Text
- View/download PDF
5. Sternal talon offers a solution for secondary sternum osteosynthesis in patients with nonunion.
- Author
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DeLong MR, Hughes DB, Gaca JG, Fischer JP, Bond JE, Hargrove WC, Atluri P, Levin LS, and Erdmann D
- Subjects
- Equipment Design, Female, Humans, Male, Middle Aged, Reoperation methods, Retrospective Studies, Surgical Wound Dehiscence etiology, Surgical Wound Infection surgery, Treatment Outcome, Bone Wires, Sternum surgery, Surgical Wound Dehiscence surgery, Surgical Wound Infection complications, Suture Techniques instrumentation, Thoracic Wall surgery
- Abstract
Background: Median sternotomy may be associated with postoperative complications such as nonunion after conventional metal wire closure. The Sternal Talon device (KLS Martin, Jacksonville, FL) has recently been introduced as an alternative for osteosynthesis after median sternotomy and may also be beneficial for patients with persistent sternal nonunion., Methods: A consecutive series of 24 patients underwent Sternal Talon repair for sternal nonunion or acute mediastinitis, or both, after sternal wire closure. Patient data--including demographics, surgical history, and indication for operation, as well as outcomes--were obtained and analyzed by retrospective chart review., Results: The average patient age was 61.3 years and 23 patients were men (95.8%). The most common median sternotomy procedure was coronary artery bypass grafting (CABG) in 19 patients (79.2%). Secondary closure using the Sternal Talon was indicated for sternal nonunion or infection, or both, in all patients. Eight patients underwent simultaneous muscle flap procedures during the placement of the Sternal Talon (33.3%). Sternal union was eventually achieved in 23 of 24 patients (95.8%). Subsequent reoperation was required in 4 patients (16.7%)., Conclusions: The data presented suggest that the osteosynthesis using the Sternal Talon device is a safe and effective modality for treating symptomatic sternal nonunion or acute dehiscence associated with infection (mediastinitis.)., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
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6. Reply: factors influencing fellowship selection, career trajectory, and academic productivity among plastic surgeons.
- Author
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DeLong MR, Hughes DB, Choi BD, and Zenn MR
- Subjects
- Female, Humans, Male, Career Choice, Efficiency, Fellowships and Scholarships, Surgery, Plastic education
- Published
- 2014
- Full Text
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7. Knowledge of Lynch syndrome among obstetrician/gynecologists and general surgeons.
- Author
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Frey MK, Taylor JS, Pauk SJ, Hughes D, Turbendian HK, Sapra KJ, and Holcomb K
- Subjects
- Counseling, Female, Humans, Clinical Competence, Colorectal Neoplasms, Hereditary Nonpolyposis complications, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Early Detection of Cancer, Endometrial Neoplasms diagnosis, Gynecology, Obstetrics, Surgeons
- Abstract
Objective: To determine comfort and knowledge among obstetrician/gynecologists and general surgeons regarding recommendations for cancer screening for women with Lynch syndrome., Methods: A questionnaire on Lynch syndrome was administered to all obstetrician/gynecologists and general surgeons at a hospital in New York, USA., Results: Fifty obstetrician/gynecologists and 62 general surgeons completed the survey (67% response rate). Physicians were more comfortable counseling on colon cancer than endometrial cancer screening (51% vs 28%; P<0.001). Obstetrician/gynecologists were more comfortable than general surgeons counseling patients on endometrial cancer screening (36% vs 21%; P=0.090) but less comfortable counseling patients on colon cancer screening (36% vs 63%; P=0.008). There was no significant difference between the specialties in the number of knowledge-based questions answered correctly. Furthermore, there was no correlation between a physician's perceived knowledge and number of correct answers., Conclusion: Most physicians did not report being comfortable counseling about recommendations for endometrial cancer screening. While obstetrician/gynecologists reported greater comfort than general surgeons, we found no significant difference in disease knowledge between the groups. Because appropriate cancer screening can improve the outcomes of patients with Lynch syndrome, physicians must be knowledgeable and comfortable with screening recommendations for both endometrial and colon cancer, regardless of clinical specialty., (Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
- Full Text
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8. A detailed evaluation of the anatomical variations of the profunda artery perforator flap using computed tomographic angiograms.
- Author
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DeLong MR, Hughes DB, Bond JE, Thomas SM, Boll DT, and Zenn MR
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Linear Models, Male, Middle Aged, Multidetector Computed Tomography, Retrospective Studies, Thigh diagnostic imaging, Young Adult, Mammaplasty methods, Perforator Flap blood supply, Thigh blood supply
- Abstract
Background: The profunda artery perforator flap is a new option for breast reconstruction in appropriate patients. While the basic anatomy is known, detailed profunda perforator anatomy has never fully been described and we present new data that will aid dissection., Methods: Fifty consecutive lower extremity computed tomography angiogram scans (100 legs) were retrospectively analyzed to acquire profunda artery perforator measurements. Patient medical records were then examined to ascertain patient information. Data were then analyzed using simple descriptive statistics and bivariate linear regressions with repeated measures., Results: Bilateral thighs from 50 consecutive angiograms were included for a total of 100 thighs. Females comprised 30 (60 percent) of the patients and the cohort average age was 59.1 years old. All thighs had at least two perforators, with 85 percent having three or more. On average, perforators were located 6.2 cm below the gluteal crease, and were evenly distributed between the medial and lateral halves of the thigh. The average perforator diameter at origin off profunda was 2.7 mm. There was significantly greater diameter in vessels in the lateral thigh (p<0.001), in patients with higher Body Mass Index (BMI) (p<0.05), and in patients with decreased age (p<0.05). Males were more likely to have perforators that shared a common trunk off the profunda artery (p<0.05)., Conclusions: At least two profunda perforators exist in each thigh with an average diameter suitable for microvascular transfer, although larger perforators are observed laterally and in younger patients with higher BMI.
- Published
- 2014
- Full Text
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9. Factors influencing fellowship selection, career trajectory, and academic productivity among plastic surgeons.
- Author
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DeLong MR, Hughes DB, Tandon VJ, Choi BD, and Zenn MR
- Subjects
- Biomedical Research, Data Collection, Education, Medical, Graduate, Female, Humans, Male, Mentors, Middle Aged, Career Choice, Efficiency, Fellowships and Scholarships, Surgery, Plastic education
- Abstract
Background: Several factors influence the career trajectory of graduating plastic surgeons, and the authors' study sought to capture characteristics of plastic surgery trainees as they relate to outcomes, including fellowship selection, career choice, and academic productivity., Methods: Anonymous online survey data were obtained from members of the American Society of Plastic Surgeons. Correlative analysis was performed implementing the Pearson chi-square test, the Mann-Whitney test, and the Kendall tau-b correlation to determine significant correlations defined by values of p < 0.05., Results: Of 4543 survey invitations sent, a total of 624 plastic surgeons (13.7 percent) completed the study. Greater numbers of publications on entering residency (p < 0.05) and on graduating from residency (p < 0.0001), stronger perceived mentorship during residency (p < 0.01), graduating from an integrated program (p < 0.01), and fellowship training (p < 0.001) were all correlated with a future career in academia. In addition, fellowship training and number of publications during and before residency were correlated with eventual academic productivity (p < 0.05). Lastly, individual tendency to prioritize economics (p < 0.01) or geographic location (p < 0.05) was associated with eventual private practice, whereas prioritization of research (p < 0.01) and culture of training institute (p < 0.001) predicted academic careers., Conclusions: Graduating plastic surgery residents from integrated programs, with greater numbers of publications, stronger mentor relationships, and fellowship training were more likely to become academic surgeons. Among this academic cohort, fellowship training and greater numbers of publications before and during residency were significantly correlated with increased academic productivity as an attending surgeon.
- Published
- 2014
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10. Abstract 30: the economic implications of changing trends in breast flap reconstruction in the United States.
- Author
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Caccavale S, Pien I, Cheung M, Butala P, Hughes D, Ligh C, Zenn MR, and Hollenbeck ST
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- 2014
- Full Text
- View/download PDF
11. Tension pneumoperitoneum in a child resulting from high-frequency oscillatory ventilation: a case report and review of the literature.
- Author
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Hughes DB, Judge TN, and Spigland NA
- Subjects
- Age of Onset, Bronchopulmonary Dysplasia complications, Bronchopulmonary Dysplasia therapy, Diagnosis, Differential, Ductus Arteriosus, Patent complications, Humans, Hypertension, Pulmonary etiology, Hypoxia therapy, Infant, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases surgery, Infant, Premature, Diseases therapy, Intestinal Perforation diagnosis, Laparotomy, Male, Mediastinal Emphysema etiology, Pneumatosis Cystoides Intestinalis diagnosis, Pneumatosis Cystoides Intestinalis epidemiology, Pneumoperitoneum diagnosis, Pneumoperitoneum physiopathology, Pressure adverse effects, Respiratory Distress Syndrome, Newborn complications, Respiratory Distress Syndrome, Newborn therapy, Retinopathy of Prematurity complications, Rupture, Spontaneous, High-Frequency Ventilation adverse effects, Intra-Abdominal Hypertension etiology, Pneumatosis Cystoides Intestinalis etiology, Pneumoperitoneum etiology
- Abstract
An 18-month-old male infant was placed on high-frequency oscillatory ventilation for profound hypoxemia and subsequently developed tension pneumoperitoneum. He underwent a bedside exploratory laparotomy for suspected perforated viscus. No intestinal perforation was identified, and a diagnosis of tension pneumoperitoneum secondary to pneumatosis cystoides intestinalis was made. To our knowledge, this is the only report of a pediatric patient developing tension pneumoperitoneum from high-frequency oscillatory ventilation. A review of the literature examines the differential diagnosis, physiology, and treatment of tension pneumoperitoneum., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
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12. Surgical management of incidental adrenal schwannomas.
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Kleiman DA, Hughes DB, and Joshi AR
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- Abdominal Pain diagnosis, Abdominal Pain etiology, Adrenal Gland Neoplasms pathology, Adrenalectomy methods, Adult, Appendectomy methods, Appendicitis therapy, Biopsy, Needle, Diagnosis, Differential, Emergency Service, Hospital, Female, Follow-Up Studies, Humans, Immunohistochemistry, Incidental Findings, Laparoscopy methods, Magnetic Resonance Imaging methods, Neurilemmoma pathology, Tomography, X-Ray Computed, Treatment Outcome, Adrenal Gland Neoplasms diagnosis, Adrenal Gland Neoplasms surgery, Appendicitis diagnosis, Neurilemmoma diagnosis, Neurilemmoma surgery
- Published
- 2011
13. You're the flight surgeon. Osteochondritis dissecans.
- Author
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Hughes DG
- Subjects
- Adult, Alaska, Arthralgia pathology, Humans, Knee Injuries pathology, Magnetic Resonance Imaging, Male, Military Personnel, Occupational Health, Osteochondritis Dissecans surgery, Range of Motion, Articular, United States, Aircraft, Arthralgia diagnosis, Knee pathology, Knee Injuries diagnosis, Osteochondritis Dissecans diagnosis
- Published
- 2010
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14. Effects of cigarette smoke on the human oral mucosal transcriptome.
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Boyle JO, Gümüs ZH, Kacker A, Choksi VL, Bocker JM, Zhou XK, Yantiss RK, Hughes DB, Du B, Judson BL, Subbaramaiah K, and Dannenberg AJ
- Subjects
- Biomarkers, Tumor metabolism, Blotting, Western, Bronchi metabolism, Case-Control Studies, Female, Humans, Immunoenzyme Techniques, Langerhans Cells metabolism, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Gene Expression Regulation physiology, Mouth Mucosa metabolism, Smoking genetics
- Abstract
Use of tobacco is responsible for approximately 30% of all cancer-related deaths in the United States, including cancers of the upper aerodigestive tract. In the current study, 40 current and 40 age- and gender-matched never smokers underwent buccal biopsies to evaluate the effects of smoking on the transcriptome. Microarray analyses were carried out using Affymetrix HGU133 Plus 2 arrays. Smoking altered the expression of numerous genes: 32 genes showed increased expression and 9 genes showed reduced expression in the oral mucosa of smokers versus never smokers. Increases were found in genes involved in xenobiotic metabolism, oxidant stress, eicosanoid synthesis, nicotine signaling, and cell adhesion. Increased numbers of Langerhans cells were found in the oral mucosa of smokers. Interestingly, smoking caused greater induction of aldo-keto reductases, enzymes linked to polycyclic aromatic hydrocarbon-induced genotoxicity, in the oral mucosa of women than men. Striking similarities in expression changes were found in oral compared with the bronchial mucosa. The observed changes in gene expression were compared with known chemical signatures using the Connectivity Map database and suggested that geldanamycin, a heat shock protein 90 inhibitor, might be an antimimetic of tobacco smoke. Consistent with this prediction, geldanamycin caused dose-dependent suppression of tobacco smoke extract-mediated induction of CYP1A1 and CYP1B1 in vitro. Collectively, these results provide new insights into the carcinogenic effects of tobacco smoke, support the potential use of oral epithelium as a surrogate tissue in future lung cancer chemoprevention trials, and illustrate the potential of computational biology to identify chemopreventive agents.
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- 2010
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15. MicroRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus: associations with survival.
- Author
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Mathé EA, Nguyen GH, Bowman ED, Zhao Y, Budhu A, Schetter AJ, Braun R, Reimers M, Kumamoto K, Hughes D, Altorki NK, Casson AG, Liu CG, Wang XW, Yanaihara N, Hagiwara N, Dannenberg AJ, Miyashita M, Croce CM, and Harris CC
- Subjects
- Adult, Aged, Aged, 80 and over, Barrett Esophagus genetics, Barrett Esophagus pathology, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Survival Analysis, Adenocarcinoma genetics, Adenocarcinoma mortality, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell mortality, Esophageal Neoplasms genetics, Esophageal Neoplasms mortality, MicroRNAs genetics
- Abstract
Purpose: The dismal outcome of esophageal cancer patients highlights the need for novel prognostic biomarkers, such as microRNAs (miRNA). Although recent studies have established the role of miRNAs in esophageal carcinoma, a comprehensive multicenter study investigating different histologic types, including squamous cell carcinoma (SCC) and adenocarcinoma with or without Barrett's, is still lacking., Experimental Design: miRNA expression was measured in cancerous and adjacent noncancerous tissue pairs collected from 100 adenocarcinoma and 70 SCC patients enrolled at four clinical centers from the United States, Canada, and Japan. Microarray-based expression was measured in a subset of samples in two cohorts and was validated in all available samples., Results: In adenocarcinoma patients, miR-21, miR-223, miR-192, and miR-194 expression was elevated, whereas miR-203 expression was reduced in cancerous compared with noncancerous tissue. In SCC patients, we found elevated miR-21 and reduced miR-375 expression levels in cancerous compared with noncancerous tissue. When comparing cancerous tissue expression between adenocarcinoma and SCC patients, miR-194 and miR-375 were elevated in adenocarcinoma patients. Significantly, elevated miR-21 expression in noncancerous tissue of SCC patients and reduced levels of miR-375 in cancerous tissue of adenocarcinoma patients with Barrett's were strongly associated with worse prognosis. Associations with prognosis were independent of tumor stage or nodal status, cohort type, and chemoradiation therapy., Conclusions: Our multicenter-based results highlight miRNAs involved in major histologic types of esophageal carcinoma and uncover significant associations with prognosis. Elucidating miRNAs relevant to esophageal carcinogenesis is potentially clinically useful for developing prognostic biomarkers and identifying novel drug targets and therapies.
- Published
- 2009
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16. Heat shock protein 90 inhibitors suppress aryl hydrocarbon receptor-mediated activation of CYP1A1 and CYP1B1 transcription and DNA adduct formation.
- Author
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Hughes D, Guttenplan JB, Marcus CB, Subbaramaiah K, and Dannenberg AJ
- Subjects
- Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Aryl Hydrocarbon Hydroxylases metabolism, Benzoquinones therapeutic use, Carcinoma, Squamous Cell enzymology, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell prevention & control, Cells, Cultured, Chemoprevention methods, Cytochrome P-450 CYP1A1 genetics, Cytochrome P-450 CYP1B1, DNA Adducts drug effects, Drug Evaluation, Preclinical, Enzyme Activation drug effects, Gene Expression Regulation, Enzymologic drug effects, Head and Neck Neoplasms enzymology, Head and Neck Neoplasms genetics, Head and Neck Neoplasms prevention & control, Humans, Lactams, Macrocyclic therapeutic use, Models, Biological, Pentacyclic Triterpenes, Precancerous Conditions genetics, Precancerous Conditions metabolism, Precancerous Conditions prevention & control, Receptors, Aryl Hydrocarbon metabolism, Receptors, Aryl Hydrocarbon physiology, Transcription, Genetic drug effects, Triterpenes therapeutic use, Aryl Hydrocarbon Hydroxylases genetics, Benzoquinones pharmacology, Cytochrome P-450 CYP1A1 metabolism, DNA Adducts metabolism, HSP90 Heat-Shock Proteins antagonists & inhibitors, Lactams, Macrocyclic pharmacology, Receptors, Aryl Hydrocarbon antagonists & inhibitors, Triterpenes pharmacology
- Abstract
The aryl hydrocarbon receptor (AhR), a client protein of heat shock protein 90 (HSP90), plays a significant role in polycyclic aromatic hydrocarbon (PAH)-induced carcinogenesis. Tobacco smoke, a source of PAHs, activates the AhR, leading to enhanced transcription of CYP1A1 and CYP1B1, which encode proteins that convert PAHs to genotoxic metabolites. The main objectives of this study were to determine whether HSP90 inhibitors suppress PAH-mediated induction of CYP1A1 and CYP1B1 or block benzo(a)pyrene [B(a)P]-induced formation of DNA adducts. Treatment of cell lines derived from oral leukoplakia (MSK-Leuk1) or esophageal squamous cell carcinoma (KYSE450) with a saline extract of tobacco smoke, B(a)P, or dioxin induced CYP1A1 and CYP1B1 transcription, resulting in enhanced levels of message and protein. Inhibitors of HSP90 [17-allylamino-17-demethoxygeldanamycin (17-AAG); celastrol] suppressed these inductive effects of PAHs. Treatment with 17-AAG and celastrol also caused a rapid and marked decrease in amounts of AhR protein without modulating levels of HSP90. The formation of B(a)P-induced DNA adducts in MSK-Leuk1 cells was inhibited by 17-AAG, celastrol, and alpha-naphthoflavone, a known AhR antagonist. The reduction in B(a)P-induced DNA adducts was due, at least in part, to reduced metabolic activation of B(a)P. Collectively, these results suggest that 17-AAG and celastrol, inhibitors of HSP90, suppress the activation of AhR-dependent gene expression, leading, in turn, to reduced formation of B(a)P-induced DNA adducts. Inhibitors of HSP90 may have a role in chemoprevention in addition to cancer therapy.
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- 2008
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17. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase regulates levels of bioactive lipids in non-small cell lung cancer.
- Author
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Hughes D, Otani T, Yang P, Newman RA, Yantiss RK, Altorki NK, Port JL, Yan M, Markowitz SD, Mazumdar M, Tai HH, Subbaramaiah K, and Dannenberg AJ
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- Animals, Carcinoma, Non-Small-Cell Lung enzymology, Carcinoma, Non-Small-Cell Lung metabolism, Cyclooxygenase 2 genetics, Cyclooxygenase 2 metabolism, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Humans, Hydroxyprostaglandin Dehydrogenases genetics, Hydroxyprostaglandin Dehydrogenases metabolism, Intramolecular Oxidoreductases genetics, Intramolecular Oxidoreductases metabolism, Lung Neoplasms enzymology, Lung Neoplasms metabolism, Mice, Mice, Knockout, Prostaglandin-E Synthases, Prostaglandins metabolism, Carcinoma, Non-Small-Cell Lung genetics, Hydroxyprostaglandin Dehydrogenases physiology, Lipid Metabolism genetics, Lung Neoplasms genetics
- Abstract
Elevated levels of procarcinogenic prostaglandins (PG) are found in a variety of human malignancies including non-small cell lung cancer (NSCLC). Overexpression of cyclooxygenase-2 and microsomal prostaglandin synthase 1 occurs in tumors and contributes to increased PG synthesis. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme responsible for metabolic inactivation of PGs, is down-regulated in various malignancies. The main objective of this study was to elucidate the effect of loss of 15-PGDH on levels of bioactive lipids in NSCLC. We found that levels of cyclooxygenase-2 and microsomal prostaglandin synthase 1 were commonly increased whereas the amount of 15-PGDH was frequently decreased in NSCLC compared with adjacent normal lung. Reduced expression of 15-PGDH occurred in tumor cells and was paralleled by decreased 15-PGDH activity in tumors. Amounts of PGE1, PGE2, and PGF(2alpha), known substrates of 15-PGDH, were markedly increased whereas levels of 13,14-dihydro-15-keto-PGE2, a catabolic product of PGE2, were markedly reduced in NSCLC compared with normal lung. Complementary in vitro and in vivo experiments were done to determine whether these changes in PG levels were a consequence of down-regulation of 15-PGDH in NSCLC. Similar to NSCLC, amounts of PGE1, PGE2, and PGF(2alpha) were markedly increased whereas levels of 13,14-dihydro-15-keto-PGE2 were decreased in the lungs of 15-PGDH knockout mice compared with wild-type mice or when 15-PGDH was silenced in A549 lung cancer cells. Collectively, these data indicate that 15-PGDH is commonly down-regulated in NSCLC, an effect that contributes to the accumulation of multiple bioactive lipids in NSCLC.
- Published
- 2008
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18. The contemporary approach to the care of Jehovah's witnesses.
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Hughes DB, Ullery BW, and Barie PS
- Subjects
- Blood Transfusion, Humans, Critical Care, Hematologic Agents therapeutic use, Jehovah's Witnesses, Wounds and Injuries therapy
- Abstract
Background: Jehovah's Witnesses are widely known for their prohibition on the acceptance of blood transfusion. Such refusal serves as a potential obstacle to optimal therapeutic intervention among critically injured Jehovah's Witnesses. As such, care of these patients requires an aggressive and multidisciplinary approach to therapy., Methods: A review of the pertinent English language literature., Results: Jehovah's Witnesses exercise the right of any adult with capacity to refuse medical treatment and often carry advance directive cards indicating their incontrovertible refusal of blood. Despite their belief regarding transfusion, Jehovah's Witnesses do not have a higher mortality rate after traumatic injury or surgery. Transfusion requirements are often overestimated. Increased morbidity and mortality is rarely observed in patients with a hemoglobin concentration >7 g/dL, and the acute hemoglobin threshold for cardiovascular collapse may be as low as 3 g/dL to 5 g/dL. There are many modalities to treat the Jehovah's Witness patient with acute blood loss. Treatment with recombinant human erythropoietin, albumin, and recombinant activated Factor VIIa have all been used with success. Autologous autotransfusion and isovolemic hemodilution can also be used to treat patients who refuse transfusion. Hemoglobin-based oxygen carriers may play a future role as intravascular volume expanders in lieu of transfusion of red blood cell concentrates., Conclusion: There are many treatment modalities available to assist in the care of Jehovah's Witness patients, especially since their beliefs on the intricacies of the Blood Ban appear to be in flux.
- Published
- 2008
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19. Formation of a calcified "cast" in a long-term indwelling central venous catheter: a case report.
- Author
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Hughes DB, Ullery BW, and Spigland N
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- Antineoplastic Combined Chemotherapy Protocols administration & dosage, Catheters, Indwelling adverse effects, Child, Preschool, Device Removal, Female, Humans, Jugular Veins, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Sepsis etiology, Vascular Surgical Procedures, Venous Thrombosis surgery, Calcinosis etiology, Catheterization, Central Venous adverse effects, Venous Thrombosis etiology
- Abstract
Catheter-related central venous thrombosis is a complication seen with long-term indwelling central venous catheters. The uses of total parenteral nutrition, catheter location, and duration of catheter use have been shown to increase the risk of thrombus formation. However, organized calcification of such a thrombus is a rare occurrence and, to our knowledge, has never been reported in a patient unexposed to total parenteral nutrition. We report a patient with an extensive, organized, calcified "cast" surrounding a central venous catheter used solely for chemotherapy administration.
- Published
- 2006
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20. Implant reconstruction in breast cancer patients treated with radiation therapy.
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Ascherman JA, Hanasono MM, Newman MI, and Hughes DB
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- Adult, Aged, Breast Neoplasms drug therapy, Breast Neoplasms epidemiology, Combined Modality Therapy, Confounding Factors, Epidemiologic, Diabetes Mellitus epidemiology, Female, Humans, Middle Aged, Retrospective Studies, Smoking, Breast Implantation, Breast Neoplasms radiotherapy, Breast Neoplasms surgery, Tissue Expansion methods
- Abstract
Background: Implant reconstruction in breast cancer patients treated with radiation therapy is controversial. Prior studies are limited by older prosthetic devices, reconstructive techniques, and radiation therapy protocols., Methods: A retrospective review was performed of patients who underwent tissue expansion and implant breast reconstruction performed by a single surgeon after mastectomy for breast cancer from 1996 to 2003. Complications and aesthetic results were compared between patients who received radiation therapy and those who did not., Results: A total of 104 patients (123 breasts) who underwent mastectomy and implant breast reconstruction were included in the study. Twenty-seven patients (27 breasts) received either premastectomy or postmastectomy radiation therapy for breast cancer. All patients who received radiation therapy did so before completion of their implant reconstruction. Complications ultimately requiring prosthetic device removal or replacement, as well as total complications (those requiring prosthetic removal or replacement and those not requiring prosthetic removal or replacement), were more frequent in breasts that received radiation than breasts that did not (18.5 percent versus 4.2 percent for complications requiring prosthetic removal or replacement, p < or = 0.025, and 40.7 percent versus 16.7 percent for total complications, p < or = 0.01). Breast symmetry was significantly better in patients who did not receive radiation compared with those who did (p < 0.01)., Conclusions: Implant breast reconstruction in patients who receive radiation therapy is possible but associated with more frequent complications and decreased aesthetic results. However, the present results compare favorably to those reported in prior studies. Improved results in the present study may be attributable to the use of newer prostheses, staged breast reconstruction with initial tissue expansion, total muscular coverage of the implant, and modern radiation therapy protocols.
- Published
- 2006
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21. Juvenile xanthogranuloma of the finger.
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Hughes DB, Hanasono MM, and Nolan WB 3rd
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- Biopsy, Needle, Child, Preschool, Female, Follow-Up Studies, Humans, Immunohistochemistry, Magnetic Resonance Imaging, Rare Diseases, Risk Assessment, Treatment Outcome, Fingers, Xanthogranuloma, Juvenile diagnosis, Xanthogranuloma, Juvenile surgery
- Abstract
We present an unusual instance of juvenile xanthogranuloma occurring in the hand. A 23-month-old girl had a mass on the radial aspect of the right third finger at the distal interphalangeal joint that extended to the collateral ligament. The lesion was histologically diagnosed as a juvenile xanthogranuloma after resection of the mass. Juvenile xanthogranuloma is uncommon in the hand, and only three patients with this condition occurring in the digits have been reported in the English language literature. The clinical presentation, diagnosis, and treatment are discussed.
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- 2006
- Full Text
- View/download PDF
22. Preventing pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis: cost effectiveness of IgG4.
- Author
-
Hughes DB, Grobmyer SR, and Brennan MF
- Subjects
- Autoimmune Diseases blood, Autoimmune Diseases economics, Autoimmune Diseases immunology, Autoimmune Diseases surgery, Biomarkers, Carcinoma, Pancreatic Ductal blood, Carcinoma, Pancreatic Ductal immunology, Cost-Benefit Analysis, Costs and Cost Analysis, Diagnosis, Differential, Humans, Pancreatic Neoplasms blood, Pancreatic Neoplasms immunology, Pancreatitis blood, Pancreatitis economics, Pancreatitis immunology, Pancreatitis surgery, Preoperative Care, Unnecessary Procedures, Autoimmune Diseases diagnosis, Carcinoma, Pancreatic Ductal diagnosis, Immunoglobulin G blood, Pancreatic Neoplasms diagnosis, Pancreaticoduodenectomy economics, Pancreatitis diagnosis
- Published
- 2004
- Full Text
- View/download PDF
23. Huntington's disease of the endocrine pancreas: insulin deficiency and diabetes mellitus due to impaired insulin gene expression.
- Author
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Andreassen OA, Dedeoglu A, Stanojevic V, Hughes DB, Browne SE, Leech CA, Ferrante RJ, Habener JF, Beal MF, and Thomas MK
- Subjects
- Aging, Animals, Blood Glucose metabolism, Blotting, Northern, Blotting, Western, Calcium metabolism, Diabetes Mellitus metabolism, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Glucagon metabolism, Glucose Intolerance etiology, Huntingtin Protein, Huntington Disease metabolism, Immunohistochemistry, Insulin blood, Insulin deficiency, Insulin genetics, Mice, Mice, Transgenic, RNA, Messenger metabolism, Somatostatin metabolism, Transcription Factors genetics, Transcription Factors metabolism, Diabetes Mellitus etiology, Gene Expression Regulation, Huntington Disease complications, Insulin metabolism, Islets of Langerhans metabolism, Nerve Tissue Proteins metabolism, Nuclear Proteins metabolism
- Abstract
In a transgenic mouse model of the neurodegenerative disorder Huntington's disease (HD), age-dependent neurologic defects are accompanied by progressive alterations in glucose tolerance that culminate in the development of diabetes mellitus and insulin deficiency. Pancreatic islets from HD transgenic mice express reduced levels of the pancreatic islet hormones insulin, somatostatin, and glucagon and exhibit intrinsic defects in insulin production. Intranuclear inclusions accumulate with aging in transgenic pancreatic islets, concomitant with the decline in glucose tolerance. HD transgenic mice develop an age-dependent reduction of insulin mRNA expression and diminished expression of key regulators of insulin gene transcription, including the pancreatic homeoprotein PDX-1, E2A proteins, and the coactivators CBP and p300. Disrupted expression of a subset of transcription factors in pancreatic beta cells by a polyglutamine expansion tract in the huntingtin protein selectively impairs insulin gene expression to result in insulin deficiency and diabetes. Selective dysregulation of gene expression in triplet repeat disorders provides a mechanism for pleiotropic cellular dysfunction that restricts the toxicity of ubiquitously expressed proteins to highly specialized subpopulations of cells.
- Published
- 2002
- Full Text
- View/download PDF
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