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1.
Mod Pathol ; 36(5): 100122, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36841178

RESUMO

Olfactory neuroblastoma (ONB, esthesioneuroblastoma) is a sinonasal cancer with an underdeveloped diagnostic toolkit, and is the subject of many incidents of tumor misclassification throughout the literature. Despite its name, connections between the cancer and normal cells of the olfactory epithelium have not been systematically explored and markers of olfactory epithelial cell types are not deployed in clinical practice. Here, we utilize an integrated human-mouse single-cell atlas of the nasal mucosa, including the olfactory epithelium, to identify transcriptomic programs that link ONB to a specific population of stem/progenitor cells known as olfactory epithelial globose basal cells (GBCs). Expression of a GBC transcription factor NEUROD1 distinguishes both low- and high-grade ONB from sinonasal undifferentiated carcinoma, a potential histologic mimic with a distinctly unfavorable prognosis. Furthermore, we identify a reproducible subpopulation of highly proliferative ONB cells expressing the GBC stemness marker EZH2, suggesting that EZH2 inhibition may play a role in the targeted treatment of ONB. Finally, we study the cellular states comprising ONB parenchyma using single-cell transcriptomics and identify evidence of a conserved GBC transcriptional regulatory circuit that governs divergent neuronal-versus-sustentacular differentiation. These results link ONB to a specific cell type for the first time and identify conserved developmental pathways within ONB that inform diagnostic, prognostic, and mechanistic investigation.


Assuntos
Estesioneuroblastoma Olfatório , Neoplasias Nasais , Neoplasias dos Seios Paranasais , Humanos , Camundongos , Animais , Estesioneuroblastoma Olfatório/diagnóstico , Estesioneuroblastoma Olfatório/metabolismo , Estesioneuroblastoma Olfatório/patologia , Neoplasias dos Seios Paranasais/patologia , Neurônios/patologia , Neoplasias Nasais/genética , Neoplasias Nasais/diagnóstico , Cavidade Nasal/metabolismo , Cavidade Nasal/patologia
2.
ORL J Otorhinolaryngol Relat Spec ; 85(6): 312-320, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37062268

RESUMO

BACKGROUND: Definitions are essential for effective communication and discourse, particularly in science. They allow the shared understanding of a thought or idea, generalization of knowledge, and comparison across scientific investigation. The current terms describing olfactory dysfunction are vague and overlapping. SUMMARY: As a group of clinical olfactory researchers, we propose the standardization of the terms "dysosmia," "anosmia," "hyposmia," "normosmia," "hyperosmia," "olfactory intolerance," "parosmia," and "phantosmia" (or "olfactory hallucination") in olfaction-related communication, with specific definitions in this text. KEY MESSAGES: The words included in this paper were determined as those which are most frequently used in the context of olfactory function and dysfunction, in both clinical and research settings. Despite widespread use in publications, however, there still exists some disagreement in the literature regarding the definitions of terms related to olfaction. Multiple overlapping and imprecise terms that are currently in use are confusing and hinder clarity and universal understanding of these concepts. There is a pressing need to have a unified agreement on the definitions of these olfactory terms by researchers working in the field of chemosensory sciences. With the increased interest in olfaction, precise use of these terms will improve the ability to integrate and advance knowledge in this field.


Assuntos
Transtornos do Olfato , Olfato , Humanos , Anosmia , Transtornos do Olfato/diagnóstico , Alucinações
3.
Curr Allergy Asthma Rep ; 22(3): 21-28, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35072929

RESUMO

PURPOSE OF REVIEW: Olfactory dysfunction is a prevalent condition affecting 5-15% of the general population, with significant impact on quality of life. This review summarizes the most recent and relevant literature in the treatment of olfactory dysfunction. RECENT FINDINGS: Current evidence supports the short-term use of topical corticosteroids and systemic therapy. These treatments may occur in conjunction with olfactory training, which is well supported by the literature. While there are several additional treatments currently under investigation, meaningful conclusions are not yet able to be made regarding their efficacy. The treatment of olfactory dysfunction is targeted at the suspected etiology when possible. After normal aging, chronic rhinosinusitis, post-infectious sequelae including as a result SARS-CoV-2 infection (COVID-19), and head trauma are the most common causes. Current evidence supports the short-term use of topical corticosteroids and systemic therapy. Several additional treatments are under investigation but recommendations for their use cannot currently be made.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Transtornos do Olfato , COVID-19/complicações , Humanos , Transtornos do Olfato/tratamento farmacológico , Transtornos do Olfato/etiologia , Qualidade de Vida , SARS-CoV-2 , Olfato
4.
Ophthalmic Plast Reconstr Surg ; 38(5): e141-e144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35470323

RESUMO

Intranasal cocaine abuse can lead to significant sinus and orbital complications, including optic neuropathy. A 46-year-old man with a history of recurrent cocaine-induced sino-orbital inflammation and infection with bony destruction presented with acute, painless, vision loss. Examination revealed no light perception vision. MRI of the orbits demonstrated new restricted diffusion of the right optic nerve on diffusion-weighted imaging and apparent diffusion coefficient sequences, consistent with posterior ischemic optic neuropathy. This is the first among cases of cocaine-induced optic neuropathy in the literature to illustrate ischemic changes on MRI in the optic nerve, highlighting the utility of diffusion-weighted imaging/apparent diffusion coefficient sequences when optic neuropathy is suspected and further suggesting an underlying ischemic etiology in similar cases.


Assuntos
Cocaína , Doenças do Nervo Óptico , Neuropatia Óptica Isquêmica , Cocaína/efeitos adversos , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Nervo Óptico , Doenças do Nervo Óptico/etiologia , Neuropatia Óptica Isquêmica/induzido quimicamente , Neuropatia Óptica Isquêmica/diagnóstico
5.
J Allergy Clin Immunol ; 147(5): 1704-1719, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33453291

RESUMO

BACKGROUND: Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD). OBJECTIVE: Our aim was to provide an evidence-based practical guide to the management of PIOD (including post-coronavirus 2019 cases) for both primary care practitioners and hospital specialists. METHODS: A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD. RESULTS: The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction. CONCLUSIONS: The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin A drops. Further research is needed to confirm the place of other therapeutic options.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Transtornos do Olfato , SARS-CoV-2/imunologia , Esteroides/uso terapêutico , Vitamina A/uso terapêutico , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/imunologia , Consenso , Medicina Baseada em Evidências , Transtornos do Olfato/tratamento farmacológico , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/imunologia , Guias de Prática Clínica como Assunto
6.
Clin Infect Dis ; 72(6): 968-975, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32108231

RESUMO

BACKGROUND: Antibody detection is the main method for diagnosis of coccidioidomycosis, but it has limitations. The Coccidioides antigen enzyme immunoassay is recommended for testing cerebrospinal fluid in suspected meningitis. Reports on urine and serum antigen detection evaluated small numbers of patients who were mostly immunocompromised. The purpose of this study was to assess the accuracy of combined antibody and antigen detection for diagnosis. METHODS: A retrospective study, including all patients in whom Coccidioides antigen detection in serum was performed between January 2013 and May 2017, was conducted at Valleywise Health Medical Center (formerly Maricopa Integrated Health System). Sensitivity and specificity of antigen and antibody were evaluated in 158 cases and 487 controls. RESULTS: The sensitivity of antibody detection by immunodiffusion (ID) was 84.2%. The sensitivity of antigen detection was 57.0% if both urine and serum were tested and 36.7% if urine alone was tested. The sensitivity of combining antigen and ID antibody detection was 93.0%. The sensitivity of urine and serum antigen detection was 55.4% in proven and 58.7% in probable cases, 79.1% in disseminated and 41.6% in pulmonary cases, and 74.7% in immunocompromised and 40.0% in immunocompetent patients. Specificity was 99.4% for antigen detection and 96.5% for ID antibody detection. Diagnostic accuracy was 95.4% for ID antibody and antigen detection, 93.6% for ID antibody alone, and 89.1% for pathology or culture. CONCLUSIONS: These findings support combined antibody and antigen detection for diagnosis of progressive coccidioidomycosis. The diagnosis may have been missed if antigen detection was not performed.


Assuntos
Coccidioidomicose , Anticorpos Antifúngicos , Antígenos de Fungos , Coccidioides , Coccidioidomicose/diagnóstico , Humanos , Estudos Retrospectivos
7.
J Cutan Pathol ; 48(7): 948-953, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33694261

RESUMO

Melanosis, clinically presenting as a benign macular hyperpigmentation, consists of increased pigmentation (melanotic or melanocytic) either in the mucosal epithelial cells or as subepithelial pigment-laden macrophages. On the other hand, primary sinonasal mucosal melanoma (SNMM) is a rare disease with poor prognosis and high rates of local recurrence and metastasis. We report follow-up on a previously presented case of a 53-year-old man with recurrent clinical melanosis that progressed from histopathological melanocytic hyperplasia to melanoma in situ over a period of 4.8 years (Yao et al. Allergy Rhinol (Providence), 2016;7(3):164-167). The patient experienced multiple recurrences and local spread despite multiple extensive surgeries. We now report that this patient ultimately developed bilateral invasive SNMM and died with metastatic melanoma. Molecular analysis of the invasive melanoma revealed ALK rearrangement, specifically an EML4-ALK fusion, which represents the first report of this particular genetic variant in mucosal melanoma.


Assuntos
Hiperplasia/diagnóstico , Melanócitos/patologia , Melanoma/genética , Melanose/patologia , Neoplasias Cutâneas/genética , Quinase do Linfoma Anaplásico/genética , Progressão da Doença , Evolução Fatal , Humanos , Hiperplasia/complicações , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Mucosa/patologia , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Proteínas de Fusão Oncogênica , Neoplasias dos Seios Paranasais/patologia , Seios Paranasais/patologia , Neoplasias Cutâneas/diagnóstico , Melanoma Maligno Cutâneo
8.
Med Mycol ; 58(6): 774-778, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32277825

RESUMO

Coccidioidomycosis is a common cause of community-acquired pneumonia in endemic areas of the southwestern United States. Clinical presentations range from self-limited disease to severe, disseminated disease. As such, early and accurate diagnosis is essential to ensure appropriate treatment and monitoring. Currently available diagnostic testing has variable accuracy, particularly in certain patient populations, and new tests may offer improved accuracy for the diagnosis of coccidioidomycosis. Serum samples from patients with coccidioidomycosis and controls were tested for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies using the MVista Coccidioides antibody detection EIA and two commonly used commercial enzyme immunoassay (EIA) kits: the IMMY Omega EIA and the Meridian Premier EIA. The sensitivity of the IgG antibody detection was 87.4% using the MVista test compared to 46.6% for IMMY and 70.9% for Meridian. The sensitivity for IgM antibody detection was 61.2% for the MVista test, 22.3% for IMMY and 29.1% for Meridian. For IgG antibody detection, specificity was 90% for the MVista EIA, 94.6% for IMMY, 96.4% for Meridian. For IgM antibody detection, specificity was 95.3% for the MVista test 98.2% for IMMY and 99.1% for Meridian. The MVista Coccidioides antibody EIA offers improved sensitivity, including among high-risk patient populations, for the detection of IgG and IgM antibodies in comparison to other currently available EIAs.


Assuntos
Anticorpos Antifúngicos/sangue , Coccidioides/imunologia , Coccidioidomicose/diagnóstico , Técnicas Imunoenzimáticas/métodos , Kit de Reagentes para Diagnóstico , Coccidioidomicose/sangue , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Sensibilidade e Especificidade
9.
J Neurosci ; 38(31): 6806-6824, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29934351

RESUMO

The olfactory epithelium (OE) of vertebrates is a highly regenerative neuroepithelium that is maintained under normal conditions by a population of stem and progenitor cells, globose basal cells (GBCs), which also contribute to epithelial reconstitution after injury. However, aging of the OE often leads to neurogenic exhaustion, the disappearance of both GBCs and olfactory sensory neurons (OSNs). Aneuronal tissue may remain as olfactory, with an uninterrupted sheet of apically arrayed microvillar-capped sustentacular cell, or may undergo respiratory metaplasia. We have generated a transgenic mouse model for neurogenic exhaustion using olfactory marker protein-driven Tet-off regulation of the A subunit of Diphtheria toxin such that the death of mature OSNs is accelerated. At as early as 2 months of age, the epithelium of transgenic mice, regardless of sex, recapitulates what is seen in the aged OE of humans and rodents. Areas of the epithelium completely lack neurons and GBCs; whereas the horizontal basal cells, a reserve stem cell population, show no evidence of activation. Surprisingly, other areas that were olfactory undergo respiratory metaplasia. The impact of accelerated neuronal death and reduced innervation on the olfactory bulb (OB) was also examined. Constant neuronal turnover leaves glomeruli shrunken and affects the dopaminergic interneurons in the periglomerular layer. Moreover, the acceleration of OSN death can be reversed in those areas where some GBCs persist. However, the projection onto the OB recovers incompletely and the reinnervated glomeruli are markedly altered. Therefore, the capacity for OE regeneration is tempered when GBCs disappear.SIGNIFICANCE STATEMENT A large percentage of humans lose or suffer a significant decline in olfactory function as they age. Therefore, quality of life suffers and safety and nutritional status are put at risk. With age, the OE apparently becomes incapable of fully maintaining the neuronal population of the epithelium despite its well known capacity for recovering from most forms of injury when younger. Efforts to identify the mechanism by which olfactory neurogenesis becomes exhausted with age require a powerful model for accelerating age-related tissue pathology. The current OMP-tTA;TetO-DTA transgenic mouse model, in which olfactory neurons die when they reach maturity and accelerated death can be aborted to assess the capacity for structural recovery, satisfies that need.


Assuntos
Envelhecimento/fisiologia , Regeneração Nervosa/fisiologia , Células-Tronco Neurais/citologia , Neurogênese , Mucosa Olfatória/citologia , Neurônios Receptores Olfatórios/citologia , Idoso , Idoso de 80 Anos ou mais , Animais , Toxina Diftérica/genética , Toxina Diftérica/toxicidade , Feminino , Humanos , Inflamação , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Degeneração Neural/induzido quimicamente , Transtornos do Olfato/etiologia , Transtornos do Olfato/patologia , Mucosa Olfatória/crescimento & desenvolvimento , Neurônios Receptores Olfatórios/patologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/toxicidade , Índice de Gravidade de Doença
10.
Med Mycol ; 57(7): 800-806, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649403

RESUMO

The diagnosis of coccidioidomycosis (CM) in dogs is typically based on clinical presentation, serology, and (less frequently) spherule identification. Agar gel immunodiffusion (AGID) is the most commonly employed serological method, but AGID is slow (requiring up to a week for titer). A Coccidioides antigen enzyme immunoassay (EIA) is also available; however, sensitivity is low in CM dogs. An antibody EIA was developed to detect canine immunoglobulin G (IgG) reacting to Coccidioides antigens. Serum was evaluated from dogs with pathology proven CM and/or AGID positive CM, as well as dogs with histoplasmosis, blastomycosis, non-fungal infections, or healthy dogs. A standard curve was used to convert optical density (OD) values into EIA units (EU). Serum and urine samples from CM dogs were also tested in the antigen EIA. Sensitivity and specificity for IgG were 89.2% and 97.2%, respectively, upon evaluation of dogs with proven or probable CM and control dogs. Cross-reactivity was observed in 7.7% and in 6.4% of dogs with histoplasmosis or blastomycosis, respectively. The antigen EIA alone was insensitive (33.8%). Combined IgG and antigen testing increased sensitivity to 93.2%, as three dogs were IgG-negative but had detectable serum or urine antigen. In 22 dogs with proven CM, sensitivity was statistically similar for antibody EIA and AGID (86% and 73%; P = .487). The MiraVista® canine Coccidioides antibody IgG EIA may aid in the diagnosis of CM by improving turnaround time with comparable sensitivity to AGID. Serial or concurrent testing by antibody and antigen EIAs may be beneficial when screening dogs for CM.


Assuntos
Anticorpos Antifúngicos/sangue , Coccidioidomicose/veterinária , Doenças do Cão/diagnóstico , Técnicas Imunoenzimáticas/métodos , Imunoglobulina G/sangue , Animais , Antígenos de Fungos/imunologia , Blastomicose , Coccidioides/imunologia , Coccidioidomicose/diagnóstico , Reações Cruzadas , Doenças do Cão/imunologia , Doenças do Cão/microbiologia , Cães , Histoplasmose , Imunoglobulina M , Sensibilidade e Especificidade
11.
J Am Soc Nephrol ; 28(11): 3395-3403, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28775001

RESUMO

Patients with CKD suffer from food aversion, anorexia, and malnutrition. Although olfaction has a significant role in determining food flavor, our understanding of olfactory impairment and of the olfaction-nutrition axis in patients with kidney disease is limited. We quantified odor identification, odor threshold, and subjective odor perception in a cohort (n=161) comprising 36 participants with CKD, 100 participants with ESRD, and 25 controls. We investigated olfaction-nutrition associations in these participants and examined a novel intervention to improve olfaction in ESRD. The mean odor identification score was lower in patients with CKD (75.6%±13.1%; P=0.02) and ESRD (66.8%±15.1%; P<0.001) than in controls (83.6%±11.4%). Patients with ESRD exhibited higher odor threshold than the remaining participants exhibited. All groups had similar scores for subjective smell assessment. In multivariable adjusted analyses, kidney disease associated with increased odds of odor identification deficits (odds ratio, 4.80; 95% confidence interval, 1.94 to 11.89). A reduction in odor identification score was associated with higher subjective global assessment score and lower serum total cholesterol, LDL cholesterol, and albumin concentrations. We found no associations between odor threshold and nutritional parameters. In a proof of concept, 6-week, open-label clinical trial, intranasal theophylline (an epithelial membrane transport and proton secretion activator) increased odor identification score in five out of seven (71%) patients with ESRD. In conclusion, patients with kidney disease have olfactory deficits that may influence their nutritional status. Our preliminary results regarding olfactory improvement using intranasal theophylline warrant confirmation in a randomized controlled trial.


Assuntos
Transtornos do Olfato/etiologia , Insuficiência Renal Crônica/complicações , Feminino , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/tratamento farmacológico , Transtornos do Olfato/fisiopatologia , Inibidores de Fosfodiesterase/uso terapêutico , Teofilina/uso terapêutico
12.
Ophthalmic Plast Reconstr Surg ; 34(3): e79-e81, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29342033

RESUMO

A 51-year-old man who had undergone right orbital decompression 5 months earlier developed a meningoencephalocele extending in the right sphenoid sinus through a skull base defect of the right ethmoid, sphenoid, and frontal bones. The authors report the third case to their knowledge of meningoencephalocele with cerebrospinal fluid leak after orbital decompression and discuss its management and measures that can be taken to prevent this rare but serious complication.


Assuntos
Vazamento de Líquido Cefalorraquidiano/etiologia , Descompressão Cirúrgica/efeitos adversos , Oftalmopatia de Graves/cirurgia , Meningomielocele/etiologia , Complicações Pós-Operatórias/etiologia , Humanos , Masculino , Pessoa de Meia-Idade
14.
J Clin Microbiol ; 55(3): 893-901, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28053216

RESUMO

Coccidioidomycosis is a common cause of community-acquired pneumonia in areas of the southwestern United States in which the disease is endemic. Clinical presentations range from self-limited disease to severe disseminated disease. Therefore, early and accurate diagnosis is essential to ensure appropriate treatment and monitoring. Currently available diagnostic tests have variable accuracy, particularly in certain patient populations, and new tests may offer improved accuracy for the diagnosis of coccidioidomycosis. Serum samples from 103 cases of coccidioidomycosis and 373 controls were tested for IgG and IgM antibodies using the MVista anti-Coccidioides antibody enzyme immunoassay. Serum specimens from 170 controls from areas in which the disease is endemic and 44 cases were tested by immunodiffusion at MiraVista Diagnostics. The sensitivity of the MVista antibody assay was 88.3%, and the specificity was 90%. The sensitivity was maintained in the presence of immunocompromising conditions or immunosuppressive therapies. The sensitivity of immunodiffusion was 60.2%, and the specificity was 98.8%. The sensitivity of complement fixation (62 cases) was 66.1%, but the specificity could not be determined. The MVista anti-Coccidioides antibody enzyme immunoassay offers improved sensitivity, compared with immunodiffusion and complement fixation, is not impaired in immunocompromised patients, and permits highly reproducible semiquantification.


Assuntos
Anticorpos Antifúngicos/sangue , Coccidioides/imunologia , Coccidioidomicose/diagnóstico , Técnicas Imunoenzimáticas/métodos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Humanos , Pneumonia/diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estados Unidos
15.
Infect Immun ; 82(10): 4414-25, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25114108

RESUMO

The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. We have generated three monoclonal antibodies as tools for characterization and detection of Cfp4 and determined the epitope each recognizes. Through site-directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. To test the function of Cfp4 in Histoplasma pathogenesis, we generated Cfp4-deficient strains by insertional mutagenesis and by RNA interference. Cfp4-deficient strains are not attenuated in virulence in human macrophages or during lung infection in a murine model of histoplasmosis. Coinfection of differentially marked Cfp4-producing and Cfp4-deficient strains demonstrates that production of Cfp4 does not confer a fitness advantage to Histoplasma yeasts during murine lung infection. Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. In addition, human immune sera recognize the Histoplasma Cfp4 protein, confirming Cfp4 production during infection of human hosts. These results suggest the potential utility of Cfp4 as a diagnostic exoantigen for histoplasmosis.


Assuntos
Proteínas Fúngicas/imunologia , Histoplasma/imunologia , Processamento de Proteína Pós-Traducional , Animais , Anticorpos Antifúngicos/imunologia , Anticorpos Monoclonais/imunologia , Células Cultivadas , Análise Mutacional de DNA , Modelos Animais de Doenças , Mapeamento de Epitopos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Técnicas de Silenciamento de Genes , Técnicas de Inativação de Genes , Glicosilação , Histoplasma/genética , Histoplasma/metabolismo , Histoplasmose/microbiologia , Histoplasmose/patologia , Humanos , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Mutagênese Insercional , Interferência de RNA
16.
PLoS Pathog ; 8(5): e1002713, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22615571

RESUMO

In order to establish infections within the mammalian host, pathogens must protect themselves against toxic reactive oxygen species produced by phagocytes of the immune system. The fungal pathogen Histoplasma capsulatum infects both neutrophils and macrophages but the mechanisms enabling Histoplasma yeasts to survive in these phagocytes have not been fully elucidated. We show that Histoplasma yeasts produce a superoxide dismutase (Sod3) and direct it to the extracellular environment via N-terminal and C-terminal signals which promote its secretion and association with the yeast cell surface. This localization permits Sod3 to protect yeasts specifically from exogenous superoxide whereas amelioration of endogenous reactive oxygen depends on intracellular dismutases such as Sod1. While infection of resting macrophages by Histoplasma does not stimulate the phagocyte oxidative burst, interaction with polymorphonuclear leukocytes (PMNs) and cytokine-activated macrophages triggers production of reactive oxygen species (ROS). Histoplasma yeasts producing Sod3 survive co-incubation with these phagocytes but yeasts lacking Sod3 are rapidly eliminated through oxidative killing similar to the effect of phagocytes on Candida albicans yeasts. The protection provided by Sod3 against host-derived ROS extends in vivo. Without Sod3, Histoplasma yeasts are attenuated in their ability to establish respiratory infections and are rapidly cleared with the onset of adaptive immunity. The virulence of Sod3-deficient yeasts is restored in murine hosts unable to produce superoxide due to loss of the NADPH-oxidase function. These results demonstrate that phagocyte-produced ROS contributes to the immune response to Histoplasma and that Sod3 facilitates Histoplasma pathogenesis by detoxifying host-derived reactive oxygen thereby enabling Histoplasma survival.


Assuntos
Histoplasma/enzimologia , Histoplasma/patogenicidade , Histoplasmose/imunologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Animais , Histoplasmose/metabolismo , Histoplasmose/microbiologia , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Neutrófilos/microbiologia , Fagocitose , Interferência de RNA , RNA Interferente Pequeno , Superóxido Dismutase/biossíntese
17.
Chem Senses ; 39(7): 601-16, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25056730

RESUMO

The capacity of the peripheral olfactory system to recover after injury has not been thoroughly explored. P2-IRES-tauLacZ mice were exposed to methyl bromide, which causes epithelial damage and kills 90% of the P2 neurons. With subsequent neuronal regeneration, P2 neurons recover within their usual territory to equal control numbers by 1 month but then decline sharply to roughly 40% of control by 3 months. At this time, the P2 projection onto the olfactory bulb is erroneous in several respects. Instead of converging onto 1 or 2 glomeruli per surface, small collections of P2 axons innervate multiple glomeruli at roughly the same position in the bulb as in controls. Within these glomeruli, the P2 axons are aggregated near the edge, whereas the remainder of the glomerulus contains olfactory marker protein (+), non-P2 axons, violating the one receptor-one glomerulus rule normally observed. The aggregates are denser than found in control P2-innervated glomeruli, suggesting that the P2 axons may not be synaptically connected. Based on published literature and other data, we hypothesize that P2 neurons lose out in an activity-based competition for synaptic territory within the glomeruli and are not maintained at control numbers due to a lack of trophic support from the bulb.


Assuntos
Hidrocarbonetos Bromados/farmacologia , Mucosa Olfatória/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/patologia , Animais , Hidrocarbonetos Bromados/administração & dosagem , Masculino , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mucosa Olfatória/citologia , Mucosa Olfatória/metabolismo , Mucosa Olfatória/patologia , Células Receptoras Sensoriais/metabolismo
18.
Laryngoscope ; 134(4): 1597-1602, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37772908

RESUMO

OBJECTIVES: The COVID-19 pandemic affected the epidemiology of several diseases. This study aims to compare the incidence of surgically treated odontogenic sinusitis (ODS) before and during the COVID-19 pandemic and identify unique features. METHODS: A retrospective chart review of patients who underwent at least maxillary antrostomy at a tertiary referral center was performed. The patients were divided into two cohorts: "pre-COVID" (March 2018 to February 2020) and "COVID" (March 2020 to February 2022). Data on demographics, comorbidities, and treatment interventions were collected and analyzed. RESULTS: Of the 734 patients who underwent maxillary antrostomy, 370 (50.4%) were operated on during the COVID period, with a mean age of 53.1 ± 15.7 years. ODS was found as the etiology of 22 (6%) and 45 (12.2%) of the pre-COVID and COVID cases, respectively (p = 0.006). Although no difference was found in the incidence of diabetes (p = 0.9) or obesity (p = 0.7) between groups, a trend toward higher incidence of immunosuppression was found in the pre-COVID patients (18.2% vs. 0%, p = 0.06). A higher incidence of sphenoid sinus involvement (31.8% vs. 8.9%, p < 0.05) was identified in the pre-COVID group; however, no differences in ethmoid (86.4% vs. 86.7%, p = 0.999) or frontal sinus involvement (54.5% vs. 37.8%, p = 0.3) were found between the groups. CONCLUSION: There was an increase in the incidence of ODS during the first 2 years of the COVID-19 pandemic compared to the 2 years prior. Similar clinical characteristics were found in both groups. Future studies focusing on specific etiologies to explain ODS preponderance may help determine optimal treatment and prevention strategies. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1597-1602, 2024.


Assuntos
COVID-19 , Sinusite Maxilar , Sinusite , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Seio Maxilar/cirurgia , Estudos Retrospectivos , Incidência , Pandemias , COVID-19/epidemiologia , Sinusite/cirurgia , Sinusite Maxilar/epidemiologia , Sinusite Maxilar/etiologia , Sinusite Maxilar/cirurgia , Endoscopia , Doença Crônica
19.
Laryngoscope ; 134(6): 2592-2601, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38126531

RESUMO

OBJECTIVE: The EuroQol 5-Dimension (EQ-5D) is a general health survey that is quick to administer, widely used, and directly convertible to health utility values (HUV). We aim to describe the five-year EQ-5D outcomes among patients who undergo surgical treatment for chronic rhinosinusitis (CRS). STUDY DESIGN: Prospective observational cohort study. METHODS: Patients with CRS completed the EQ-5D questionnaire preoperatively and annually for five years following endoscopic sinus surgery. Paired t-tests and McNemar's tests were used to compare preoperative and postoperative scores. Mixed-effects modeling was used for multivariate analysis. RESULTS: Among 1296 patients enrolled in our study, 812 (74.7%) completed the postoperative survey at one year and 336 (38.9%) completed it at five years. There was a significant and sustained reduction of patients reporting pain/discomfort (74.9% vs. 58.0%, p < 0.001) and anxiety/depression (49.6% vs. 38.1%, p = 0.01) out to five years. Frequency of problems reported in the usual activity domain decreased at one year and was sustained through year four (30.6% vs 19.7%, p = 0.003). After multivariable modeling, female gender (p = 0.02), prior sinus surgery (p = 0.01), tobacco use (p = 0.038), headaches (p = 0.013), allergies (p = 0.001), diabetes (p = 0.022), hypertension (p = 0.036), higher preoperative SNOT-22 score (p < 0.001), and a lower preoperative Lund-Mackay score (p < 0.001) were associated with significantly worse EQ-5D HUV over time. Similarly, a worse EQ-5D Visual Analog Scale (VAS) over time was associated with allergies (p = 0.03), diabetes (p < 0.001), hypertension (p = 0.04), higher preoperative SNOT-22 score (p < 0.001), and prior sinus surgery (p < 0.001). CONCLUSION: Patients with chronic rhinosinusitis experience significant sustained improvements in health-related quality of life up to five years after ESS as measured by the EQ-5D instrument. LEVEL OF EVIDENCE: Level 2 Laryngoscope, 134:2592-2601, 2024.


Assuntos
Endoscopia , Qualidade de Vida , Rinite , Sinusite , Humanos , Masculino , Feminino , Sinusite/cirurgia , Endoscopia/métodos , Estudos Prospectivos , Rinite/cirurgia , Pessoa de Meia-Idade , Doença Crônica , Adulto , Resultado do Tratamento , Inquéritos e Questionários , Fatores de Tempo , Seguimentos , Idoso
20.
J Clin Neurosci ; 122: 93-102, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492512

RESUMO

OBJECTIVE: Though the endoscopic endonasal approach (EEA) is a widely accepted treatment for skull base tumors, the specific use of EEA for olfactory groove meningiomas (OGMs) is debated, with variable outcomes reported in the literature. We review the surgical results of OGM resections for one surgeon including the operative approach, surgical nuances, and outcomes, with a focus on factors relating to patient selection which favor EEA over transcranial approaches. METHODS: We retrospectively reviewed thirteen cases of endoscopic endonasal resection of olfactory groove meningiomas. Patient characteristics, clinical characteristics, surgical outcomes, and complications were analyzed. Extent of resection was determined based on volumetric analysis of pre- and postoperative MRI. RESULTS: Anatomic characteristics that render a tumor difficult to access fully are lateral extension beyond the mid-orbit and anterior extension to the falx. Simpson Grade I resection was achieved in 11/13 (84.6 %) cases. Mean pre-operative tumor volume was 8.99 cm3 (range 2.19-16.79 cm3), and 92 % of tumors were WHO grade I. We demonstrate 2 cases of smell preservation, possible with small unilateral tumors and tumors that are confined to either the anterior or posterior portion of the cribriform plate. The post-operative CSF leak rate was 7.7 %, without prophylactic lumbar CSF drainage. The mortality rate was 7.7 % (n = 1) after infectious complications following CSF leak. CONCLUSIONS: Endoscopic endonasal resection of olfactory groove meningiomas is an effective and safe operative method with outcomes and complication rates comparable to transcranial approaches. Key considerations include careful patient selection and familiarity with technical nuances of endoscopic endonasal approach for this specific tumor type.


Assuntos
Neoplasias Meníngeas , Meningioma , Neoplasias da Base do Crânio , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Meningioma/patologia , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/cirurgia , Nariz/cirurgia , Nariz/patologia , Estudos Retrospectivos , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/cirurgia , Resultado do Tratamento
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