Publications by authors named "Tessa J Campbell"

6 Publications

  • Page 1 of 1

Operative Management of Abdominal Wound Dehiscence: Outcomes and Factors Influencing Time to Healing in Patients Undergoing Surgical Debridement With Primary Closure.

Wounds 2018 Nov 23;30(11):317-323. Epub 2018 Aug 23.

Department of Plastic Surgery, Georgetown University Hospital, Washington, DC.

Introduction: Plastic surgeons are often consulted by other surgical teams for management of wound dehiscence following abdominopelvic surgery.

Objective: The purpose of this study is to determine whether operative debridement and primary closure of abdominopelvic wounds are safe and expeditious for patients.

Materials And Methods: A retrospective analysis was conducted on a database of patients who underwent operative debridement and closure at a single institution between January 2011 and December 2015 for dehisced abdominal or pelvic wounds acquired from prior obstetric, gynecologic, transplant, plastic, or general surgery procedures.

Results: Of the 163 patient records identified, 43 patients met inclusion criteria. The median time from final debridement and primary surgical closure to complete wound healing was 27 days. Time to healing differed significantly by index procedure type (P = .004), with obstetric procedures requiring the shortest median time (12.0 days) and general surgery procedures requiring the longest (39.5 days). Wound healing took 3.6 times longer for patients with diabetes (P = .046) and 11.4 times longer for patients who experienced delayed superficial wound healing or redehiscence (P = .003). Nevertheless, with the exception of 4 patients who died of other causes, all wounds (39/39; 100%) achieved complete wound closure.

Conclusions: Operative debridement and closure of abdominopelvic wound dehiscence through a multidisciplinary team approach with plastic surgery results in expeditious wound healing with minimal complications, and it may be safer and more cost effective than healing by secondary intention.
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November 2018

Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis.

Nature 2014 Oct 20;514(7523):494-7. Epub 2014 Aug 20.

1] Department of Archaeological Sciences, University of Tübingen, Ruemelinstraße 23, 72070 Tübingen, Germany [2] Senckenberg Centre for Human Evolution and Palaeoenvironment, University of Tübingen, Tübingen 72070, Germany [3] Max Planck Institute for Science and History, Khalaische Straße 10, 07745 Jena, Germany.

Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact. This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch, although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean.
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http://dx.doi.org/10.1038/nature13591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550673PMC
October 2014

Epidithiodiketopiperazines (ETPs) exhibit in vitro antiangiogenic and in vivo antitumor activity by disrupting the HIF-1α/p300 complex in a preclinical model of prostate cancer.

Mol Cancer 2014 Apr 28;13:91. Epub 2014 Apr 28.

Molecular Pharmacology Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

The downstream targets of hypoxia inducible factor-1 alpha (HIF-1α) play an important role in tumor progression and angiogenesis. Therefore, inhibition of HIF-mediated transcription has potential in the treatment of cancer. One attractive strategy for inhibiting HIF activity is the disruption of the HIF-1α/p300 complex, as p300 is a crucial coactivator of hypoxia-inducible transcription. Several members of the epidithiodiketopiperazine (ETP) family of natural products have been shown to disrupt the HIF-1α/p300 complex in vitro; namely, gliotoxin, chaetocin, and chetomin. Here, we further characterized the molecular mechanisms underlying the antiangiogenic and antitumor effects of these ETPs using a preclinical model of prostate cancer. In the rat aortic ring angiogenesis assay, gliotoxin, chaetocin, and chetomin significantly inhibited microvessel outgrowth at a GI50 of 151, 8, and 20 nM, respectively. In vitro co-immunoprecipitation studies in prostate cancer cell extracts demonstrated that these compounds disrupted the HIF-1α/p300 complex. The downstream effects of inhibiting the HIF-1α/p300 interaction were evaluated by determining HIF-1α target gene expression at the mRNA and protein levels. Dose-dependent decreases in levels of secreted VEGF were detected by ELISA in the culture media of treated cells, and the subsequent downregulation of VEGFA, LDHA, and ENO1 HIF-1α target genes were confirmed by semi-quantitative real-time PCR. Finally, treatment with ETPs in mice bearing prostate tumor xenografts resulted in significant inhibition of tumor growth. These results suggest that directly targeting the HIF-1α/p300 complex with ETPs may be an effective approach for inhibiting angiogenesis and tumor growth.
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http://dx.doi.org/10.1186/1476-4598-13-91DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113146PMC
April 2014

Dihydrotestosterone synthesis from adrenal precursors does not involve testosterone in castration-resistant prostate cancer.

Cancer Biol Ther 2012 Mar 1;13(5):237-8. Epub 2012 Mar 1.

Molecular Pharmacology Section, Medical Oncology Branch, National Cancer Institute, Bethesda, MD, USA.

Androgen deprivation therapy is the frontline treatment for metastatic prostate cancer; however, because the majority of cases of advanced prostate cancer progress to castration-resistant prostate cancer (CRPC), there is a considerable need to better understand the synthesis of intratumoral concentrations of the androgen receptor (AR) agonist, 5α-dihydrotestosterone (DHT) in CRPC. In a recent article in the Proceedings of the National Academy of Sciences, Chang et al. show that, contrary to widely held assumptions, the dominant pathway to DHT synthesis does not involve testosterone as a precursor to DHT, but instead involves the conversion of Δ ( 4) -androstenedione (AD) to 5α-dione (AD→5α-dione→DHT) by the steroid-5α-reductase isoenzyme 1 (SRD5A1). The authors show that it is this alternative pathway that drives the progression of CRPC, and they confirm these findings in six established human prostate cancer cell lines as well as in the metastatic tumors from two patients with CRPC. Such findings open the door to new areas of research and to the development of new therapeutic targets in CRPC.
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http://dx.doi.org/10.4161/cbt.19608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367713PMC
March 2012

Transporter pharmacogenetics: transporter polymorphisms affect normal physiology, diseases, and pharmacotherapy.

Discov Med 2012 Jan;13(68):19-34

Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Drug transporters mediate the movement of endobiotics and xenobiotics across biological membranes in multiple organs and in most tissues. As such, they are involved in physiology, development of disease, drug pharmacokinetics, and ultimately the clinical response to a myriad of medications. Genetic variants in transporters cause population-specific differences in drug transport and are responsible for considerable inter-individual variation in physiology and pharmacotherapy. The purpose of this review is to provide a broad overview of how inherited variants in transporters are associated with disease etiology, disease state, and the pharmacological treatment of diseases. Given that there are thousands of published papers related to the interplay between transporter genetics and medicine, this review will provide examples that exemplify the broader focus of the literature.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006110PMC
January 2012

A novel predicted bromodomain-related protein affects coordination between meiosis and spermiogenesis in Drosophila and is required for male meiotic cytokinesis.

DNA Cell Biol 2010 Sep;29(9):487-98

Department of Biology, Davidson College , Davidson, NC 28035, USA.

Temporal coordination of meiosis with spermatid morphogenesis is crucial for successful generation of mature sperm cells. We identified a recessive male sterile Drosophila melanogaster mutant, mitoshell, in which events of spermatid morphogenesis are initiated too early, before meiotic onset. Premature mitochondrial aggregation and fusion lead to an aberrant mitochondrial shell around premeiotic nuclei. Despite successful meiotic karyokinesis, improper mitochondrial localization in mitoshell testes is associated with defective astral central spindles and a lack of contractile rings, leading to meiotic cytokinesis failure. We mapped and cloned the mitoshell gene and found that it encodes a novel protein with a bromodomain-related region. It is conserved in some insect lineages. Bromodomains typically bind to histone acetyl-lysine residues and therefore are often associated with chromatin. The Mitoshell bromodomain-related region is predicted to have an alpha helical structure similar to that of bromodomains, but not all the crucial residues in the ligand-binding loops are conserved. We speculate that Mitoshell may participate in transcriptional regulation of spermatogenesis-specific genes, though perhaps with different ligand specificity compared to traditional bromodomains.
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http://dx.doi.org/10.1089/dna.2009.0989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931543PMC
September 2010