Zinc Gluconate Induces Potentially Cancer Chemopreventive Activity in Barrett's Esophagus: A Phase 1 Pilot Study.

BACKGROUND: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. AIMS: To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. METHODS: Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. RESULTS: Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1ß, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. CONCLUSIONS: When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists.

Prevalence of pelvic organ prolapse detected at dynamic MRI in women without history of pelvic floor dysfunction: comparison of two reference lines.

AIM: To retrospectively evaluate the prevalence of pelvic organ prolapse as an incidental finding on dynamic magnetic resonance imaging (MRI) using two different references lines. MATERIALS AND METHODS: Sixty women with symptoms unrelated to pelvic floor dysfunction who underwent MRI including a dynamic sagittal true fast imaging with steady-state free precession (TrueFISP) sequence during straining were identified. Two radiologists in consensus used the pubococcygeal line (PCL) and mid-pubic line (MPL) to diagnose and grade prolapse in all three pelvic compartments. RESULTS: Cystocele was absent, mild, moderate, and severe in 88% (53/60), 7% (4/60), 5% (3/60), and 0% (0/60) of patients, respectively, using PCL, versus 78% (47/60), 13% (8/60), 5% (3/60), and 3% (2/60) of patients, respectively, using MPL. Vaginal prolapse was absent, mild, moderate, and severe in 95% (57/60), 5% (3/60), 0% (0/60), and 0% (0/60) of patients, respectively, using PCL, versus 80% (48/60), 17% (10/60), 3% (2/60), and 0% (0/60) of patients, respectively, using MPL. Rectal descent was absent, mild, moderate, and severe in 63% (38/60), 10% (6/60), 23% (14/60), and 3% (2/60) of patients, respectively, using PCL, versus 43% (26/60), 27% (16/60), 27% (16/60), and 3% (2/60) of patients, respectively, using MPL. No enterocele, peritoneocele, or muscular defect was identified. Two percent (1/60) of patients had mild rectocele, 8% (5/60) had abnormal vesico-urethral angle, and 25% (15/60) had abnormal levator plate angle. CONCLUSION: In asymptomatic women, dynamic MRI identified the greatest degrees of prolapse in the posterior compartment. The MPL consistently yielded greater frequency of prolapse than the PCL. Findings of pelvic organ prolapse may be observed in asymptomatic patients and are of uncertain significance, requiring correlation with clinical and physical examination findings.

Optic neuritis.

AIMS: The aim of this study is to provide a clinical update on optic neuritis (ON), its association with multiple sclerosis (MS), and neuromyelitis optica (NMO). METHODS: This study included a PubMed review of the literature written in the English language. RESULTS: ON in adults is typically idiopathic or demyelinating, and is characterised by unilateral, subacute, painful loss of vision that is not associated with any systemic or other neurological symptoms. Demyelinating ON is associated with MS, and we review the key studies of ON including the ON treatment trial and several other MS treatment trials and NMO. CONCLUSION: Acute demyelinating ON can occur in isolation or be associated with MS. Typical ON does not require additional evaluation other than cranial magnetic resonance imaging. NMO is likely a separate disorder from MS and the ON in NMO has a different treatment and prognosis. METHODOLOGY: The authors conducted an English language search using Pubmed from the years 1964 to 2010 using the search terms 'ON', 'MS' and 'NMO'. The authors included original articles, review articles, and case reports, which revealed new aspects as far as epidemiology, histopathology, clinical manifestations, imaging, genetics, and treatment of ON. Titles were reviewed for topicality and full references were obtained. Letters to the editor, unpublished work, and abstracts were not included in this review.

Why should disorders of the ear, nose and throat be treated by the same specialty? Can this situation persist?

The surgical specialty of otorhinolaryngology has its origins in the nineteenth century. Subsequently, the specialty also incorporated allied disciplines such as plastics and head and neck surgery. Following World War II, the survival of the specialty was threatened by the advent of antibiotics and the rise of the general surgeon. Despite this, the specialty of ENT was strengthened by strong post-war leadership and robust training.Today, with ENT knowledge ever increasing, the subspecialties have again begun to subdivide. Specialisation brings improved efficiency and outcomes; however, there remains a great need for the ENT generalist. Not all cases require subspecialist attention, and the generalist remains the basis of competent emergency cover. The natural development of otorhinolaryngology has brought the invaluable synergistic knowledge required to comprehensively treat disorders of the ear, nose and throat, knowledge that must not be overlooked when shaping the future of the specialty.