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Item Are Adults Over 18 Years of Age with Anaemia More Likely to Develop Chronic Periodontitis Than Adults Without Anaemia? - A Systematic Review and Meta-Analysis(Wolters Kluwer, 2023-08-30) Roberts, Madison; Jimson, Sudha; Srinivasan, Mythily; Oral Pathology, Medicine and Radiology, School of DentistryAims and objectives: Periodontitis is a chronic disease affecting the supporting tissues of the teeth and exhibits bidirectional relation with systemic diseases. This study aims to determine the association between chronic periodontitis and erythrocyte functional measures: total red blood cells (RBCs), hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC) by systematic review and meta-analysis. Materials and methods: A systematic search of the electronic databases PUBMED, OVID, Embase, Web on Science, and Google Scholar was undertaken from inception to July 2022. English language studies that evaluated the erythrocyte functional measures in periodontitis and health were selected. Other review reports, letters/opinion articles, studies without a definition of periodontitis, and the concomitant presence of systemic conditions (diabetes, kidney disease, cancer) were excluded. Two reviewers determined full-text eligibility in a blinded process. Meta-Essentials software was used to generate forest plots and to determine heterogeneity and publication bias. Results: Twenty-six studies involving 1082 patients with chronic periodontitis and 980 healthy controls were analyzed. Pooled results showed lower Hb concentration (Hedges' g = -1.16; 95% confidence intervals [CI], -1.7 to -0.62), RBC counts (Hedges' g = -0.85; 95% CI, -1.31 to -0.38) and packed cell volume (-0.56; 95% CI, -1.02 to -0.11) in patients with chronic periodontitis. Conclusion: This meta-analysis showed a decreasing trend in the hematological parameters, including hemoglobin concentration, number of erythrocytes, and hematocrit in patients with chronic periodontitis compared to healthy controls.Item Assessment of p63 expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and basal cell and canalicular adenomas(2004-05) Edwards, Paul C.; Bhuiya, Tawfiqul; Kelsch, Robert DPurpose The purpose of this study was to determine the extent of p63 immunoreactivity in the malignant salivary gland neoplasms adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) and to compare this to the expression of this marker in the benign salivary gland tumors canalicular adenoma and basal cell adenoma. Few studies on the expression of p63 in head and neck salivary gland tumors have been published to date. P63, a selective immunohistochemical marker of basal/stem cells of stratified epithelium and of myoepithelial cells, is a p53 homologue that plays an essential role in both morphogenesis of epidermis and limb development. P63 immunoreactivity has been demonstrated in squamous cell and urothelial carcinomas. It is generally absent in most nonsquamous cell carcinomas. Study design Formalin-fixed paraffin-embedded sections from 49 salivary gland neoplasms, representing 6 canalicular adenomas, 11 basal cell adenomas, 17 PLGA and 15 ACC accessioned from 1989 to 2002 by the Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, NY, were stained with an anti-p63 monoclonal antibody. Results Nuclear p63 reactivity was uniformly positive in PLGA (17/17, 100%). Positive reactivity was also identified in the majority of cases of ACC (13/15, 87%), primarily in the nonluminal myoepithelial-like cells surrounding luminal cells. Canalicular adenoma did not exhibit any p63 immunoreactivity. All basal cell adenomas of parotid origin stained strongly for p63, with staining localized to the peripheral tumor cells situated adjacent to the connective tissue stroma. None of the basal cell adenomas originating in the upper lip stained with p63. In native adjacent salivary gland tissue, p63 reactivity was identified focally in the nuclei of myoepithelial and basal duct cells. Conclusions P63 is strongly expressed in basal cell adenoma of parotid origin, and in ACC and PLGA. Canalicular adenoma did not demonstrate p63 staining, consistent with this tumor's putative luminal ductal cell differentiation. Our results suggest that the neoplastic cells in PLGA may represent either a population of p63-positive epithelial stem/reserve cells similar to the basal cells of stratified epithelium, or modified myoepithelial cells. Given the staining pattern of the tumors examined, p63 does not appear to be an ideal marker for distinguishing between ACC, PLGA, and basal cell adenoma.Item Assessment of Salivary Adipokines Resistin, Visfatin, and Ghrelin as Type 2 Diabetes Mellitus Biomarkers(Hindawi Publishing Corporation, 2018-02-01) Srinivasan, Mythily; Meadows, Melinda L.; Maxwell, Lisa; Oral Pathology, Medicine and Radiology, School of DentistryType 2 diabetes mellitus (T2DM) is emerging as a metabolic epidemic worldwide. Pathologically, dysregulation of many biological pathways precedes hyperglycemia and the clinical diagnosis of T2DM. Changing trajectories along the process of T2DM development necessitates frequent measurement of biomarkers for early identification of at-risk individuals and successful prevention. Increase in circulating inflammatory adipokines has been suggested as predictive of T2DM. Human saliva is an easily accessible biospecimen amenable for painless frequent collection and possesses nearly 50% of serum proteome. In this study, we measured the adipokines resistin, visfatin, TNF-α, and ghrelin as markers for T2DM in unstimulated whole saliva (UWS) using specific assay kits. Resistin and visfatin concentrations were significantly higher in T2DM saliva. Although the concentration of acylated or unacylated ghrelin was lower in diabetic saliva, the decrease was not significant. Since resistin and visfatin are biomarkers integral to T2DM pathology, their salivary assessments may receive clinical acceptance.Item Bilateral Central Giant Cell Granulomas of the Mandible in An Eight Year-Old Girl with Noonan Syndrome (Noonan-Like/Multiple Giant Cell Lesions Syndrome)(2005-03) Edwards, Paul C.; Fox, Joyce; Fantasia, John E; Goldberg, Jeff; Kelsch, Robert DA number of conditions can present with lesions that histologically are indistinguishable from the central giant cell granuloma (CGCG) of bone, including brown tumors of hyperparathyroidism, cherubism, and, less commonly, a number of inherited syndromes. We report a case of an eight-year girl who presented with bilateral CGCGs of the posterior mandible. Characteristic facial features, reported increased post-operative bleeding and history of pulmonary stenosis led us to suspect a diagnosis of Noonan syndrome. A medical geneticist confirmed this on further evaluation. This case report will discuss the salient features of this diagnosis.Item Bisphosphonates Inhibit Expression of p63 by Oral Keratinocytes(2011-07) Scheller, E L; Baldwin, C M; Kuo, S; D'Silva, N J; Feinberg, S E; Krebsbach, P H; Edwards, Paul C.Osteonecrosis of the jaw (ONJ), a side-effect of bisphosphonate therapy, is characterized by exposed bone that fails to heal within eight weeks. Healing time of oral epithelial wounds is decreased in the presence of amino-bisphosphonates; however, the mechanism remains unknown. We examined human tissue from individuals with ONJ and non-bisphosphonate-treated controlindividuals to identify changes in oral epithelium and connective tissue. Oral and intravenous bisphosphonate-treated ONJ sites had reduced numbers of basal epithelial progenitor cells, as demonstrated by a 13.8 ± 1.1% and 31.9 ± 5.8% reduction of p63 expression, respectively. No significant differences in proliferation rates, vessel density, or macrophage number were noted. In vitro treatment of clonal and primary oral keratinocytes with zoledronic acid (ZA) inhibited p63, and expression was rescued by the addition of mevalonate pathway intermediates. In addition, both ZA treatment and p63 shRNA knock-down impaired formation of 3D Ex Vivo Produced Oral Mucosa Equivalents (EVPOME) and closure of an in vitro scratch assay. Analysis of our data suggests that bisphosphonate treatment may delay oral epithelial healing by interfering with p63-positive progenitor cells in the basal layer of the oral epithelium in a mevalonate-pathway-dependent manner. This delay in healing may increase the likelihood of osteonecrosis developing in already-compromised bone.Item C-kit expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and monomorphic adenoma(2003-05) Edwards, Paul C.; Bhuiya, Tawfigul; Kelsch, Robert DObjective. Differentiating between adenoid cystic carcinomas (ACCs), polymorphous low-grade adenocarcinomas (PLGAs), and the monomorphic adenomas (including canalicular adenomas, trabecular adenomas, and basal cell adenomas) can present a diagnostic challenge, especially when examining tissue obtained from small incisional or fragmented biopsies. Recent studies have revealed that overexpression of the tyrosine kinase receptor protein c-kit occurs in a narrow subset of malignant neoplasms, including gastrointestinal stromal tumors, myeloid leukemias, seminomas, and ACCs. C-kit reportedly is not expressed in PLGAs. We compared the expression of the c-kit antigen in the malignant salivary gland neoplasms ACC and PLGA with its expression in salivary gland monomorphic adenoma (including canalicular adenoma and basal cell adenoma). Study design. Formalin-fixed paraffin-embedded sections of 49 salivary gland neoplasms (17 monomorphic adenomas, 17 PLGAs, and 15 ACCs) accessioned between 1989 and 2002 were retrieved from the files of the Department of Pathology, Long Island Jewish Medical Center, and were stained with an anti-c-kit polyclonal antibody. Results. C-kit reactivity was uniformly positive in the cytoplasm of luminal neoplastic cells in ACCs (15/15, 100%). Positive reactivity was also identified in the majority of PLGAs (16/17, 94%), with at least 25% of the tumor cells being positive. Similar reactivity was seen in monomorphic adenomas (16/17, 94%). Conclusions. In contrast to previous reports, we find that c-kit expression was not restricted to ACC but was expressed in all 3 tumor types evaluated (ACC, PLGA, and monomorphic adenoma). Therefore, c-kit does not appear to be a useful marker for distinguishing between either ACC and PLGA in equivocal cases, or in benign and malignant salivary gland neoplasms.Item CERE-120 Prevents Irradiation-Induced Hypofunction and Restores Immune Homeostasis in Porcine Salivary Glands(Elsevier, 2020-09-11) Lombaert, Isabelle M. A.; Patel, Vaishali N.; Jones, Christina E.; Villier, Derrick C.; Canada, Ashley E.; Moore, Matthew R.; Berenstein, Elsa; Zheng, Changyu; Goldsmith, Corinne M.; Chorini, John A.; Martin, Daniel; Zourelias, Lee; Trombetta, Mark G.; Edwards, Paul C.; Meyer, Kathleen; Ando, Dale; Passineau, Michael J.; Hoffman, Matthew P.; Oral Pathology, Medicine and Radiology, School of DentistrySalivary gland hypofunction causes significant morbidity and loss of quality of life for head and neck cancer patients treated with radiotherapy. Preventing hypofunction is an unmet therapeutic need. We used an adeno-associated virus serotype 2 (AAV2) vector expressing the human neurotrophic factor neurturin (CERE-120) to treat murine submandibular glands either pre- or post-irradiation (IR). Treatment with CERE-120 pre-IR, not post-IR, prevented hypofunction. RNA sequencing (RNA-seq) analysis showed reduced gene expression associated with fibrosis and the innate and humoral immune responses. We then used a minipig model with CERE-120 treatment pre-IR and also compared outcomes of the contralateral non-IR gland. Analysis of gene expression, morphology, and immunostaining showed reduced IR-related immune responses and improved secretory mechanisms. CERE-120 prevented IR-induced hypofunction and restored immune homeostasis, and there was a coordinated contralateral gland response to either damage or treatment. CERE-120 gene therapy is a potential treatment for head and neck cancer patients to influence communication among neuronal, immune, and epithelial cells to prevent IR-induced salivary hypofunction and restore immune homeostasis.Item Characteristics of Chemosensory Perception in Long COVID and COVID Reinfection(MDPI, 2023-05-22) Jaramillo, Mikki; Thyvalikakath, Thankam P.; Eckert, George; Srinivasan, Mythily; Oral Pathology, Medicine and Radiology, School of DentistryEmerging data suggest an increasing prevalence of persistent symptoms in individuals affected by coronavirus disease-19 (COVID-19). The objective of this study was to determine the relative frequency of altered taste and smell in COVID reinfection (multiple COVID positive tests) and long COVID (one COVID positive test). We sent an electronic survey to patients in the Indiana University Health COVID registry with positive COVID test results, querying if they were experiencing symptoms consistent with long COVID including altered chemosensory perceptions. Among the 225 respondents, a greater long COVID burden and COVID reinfection was observed in women. Joint pain was reported as the most common symptom experienced by 18% of individuals in the long COVID cohort. In the COVID reinfection cohort >20% of individuals reported headache, joint pain, and cough. Taste perception worse than pre-COVID was reported by 29% and 42% of individuals in the long COVID and COVID reinfection cohorts, respectively. Smell perception worse than pre-COVID was reported by 37% and 46% of individuals in long COVID and COVID reinfection cohorts, respectively. Further, Chi-square test suggested significant association between pre-COVID severity of taste/smell perception and headache in both cohorts. Our findings highlight the prevalence of persistent chemosensory dysfunction for two years and longer in long COVID and COVID reinfection.Item Chronic fibrosing osteomyelitis of the jaws: an important cause of recalcitrant facial pain. A clinicopathologic study of 331 cases in 227 patients(Elsevier, 2017) Goldblatt, Lawrence I.; Adams, William R.; Spolnik, Kenneth J.; Deardorf, Kevin A.; Parks, Edwin T.; Department of Oral Pathology, Medicine and Radiology, School of DentistryObjective This was a retrospective and follow-up analysis of 331 cases of chronic fibrosing osteomyelitis of the jaws (CFOJ) in 227 patients. Study Design Demographic, clinical, surgical, and microscopic characteristics were tabulated for all patients. A follow-up mail survey was used to determine the degree of symptom relief experienced after surgery. Results The female to male ratio approached 7:1, and mean age of patients was 53 years. The most common sites were the mandibular posterior region, followed by the maxillary posterior region. Consistent clinical findings included intractable jaw pain mimicking that of odontogenic origin but unresponsive to usual therapies, minimal or undetectable radiographic abnormalities on plain films but dramatic radiolucencies detected on cone beam computed tomography, and large cavities that were either empty or filled with blood mixed with lipid globules encountered at surgery. The most common histomorphologic findings were vital lamellar bone, prominent resting and reversal lines, microshards and splaying of trabeculae, rounded trabeculae, marrow fibrosis, and pools of erythrocytes and lipid globules, often together. Moderate to complete relief of symptoms for periods up to 108 months after surgery were reported by 83% of the 70 patients who returned the survey. Conclusions On the basis of the findings of this study, CFOJ can be considered a unique entity with consistent clinicopathologic features. Its features suggest a pathogenesis based on bone marrow ischemia. CFOJ can be treated on a rational basis with a justifiable expectation of success and probable cure.Item Clinically aggressive central giant cell granulomas in two patients with neurofibromatosis 1(2006-12) Edwards, Paul C.; Fantasia, John E; Saini, Tamjit; Rosenberg, Tracey J; Sachs, Stephen A; Ruggiero, SalvatoreBackground Neurofibromatosis 1 (NF1) is an autosomal dominantly inherited disorder caused by a spectrum of mutations affecting the Nf1 gene. Affected patients develop benign and malignant tumors at an increased frequency. Clinical findings include multiple cutaneous café-au-lait pigmentations, neurofibromas, axillary freckling, optic gliomas, benign iris hamartomas (Lisch nodules), scoliosis, and poorly defined soft tissue lesions of the skeleton. Kerl first reported an association of NF1 with multiple central giant cell granulomas (CGCGs) of the jaws. There have since been 4 additional published cases of NF1 patients with CGCGs of the jaws. Clinical cases We report on 2 patients who presented with NF1 and aggressive CGCGs of the jaws. In both cases, the clinical course was characterized by numerous recurrences despite mechanical curettage and surgical resection. Conclusions We review proposed mechanisms to explain the apparent association between NF1 and an increased incidence of CGCGs of the jaws. While the presence of CGCGs of the jaws in patients with NF1 could represent either a coincidental association or a true genetic linkage, we propose that this phenomenon is most likely related to NF1-mediated osseous dysplasia. Compared to normal bone, the Nf1-haploinsufficient bone in a patient with NF1 may be less able to remodel in response to as of yet unidentified stimuli (e.g. excessive mechanical stress and/or vascular fragility), and consequently may be more susceptible to developing CGCG-like lesions. Alternatively, the CGCG in NF1 patients could represent a true neoplasm, resulting from additional, as of yet unidentified, genetic alterations to Nf1-haploinsufficient bone.