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1.
Surgeon ; 2024 Jul 06.
Article de Anglais | MEDLINE | ID: mdl-38972805

RÉSUMÉ

BACKGROUND: Climate change has been identified by the World Health Organization (WHO) as the greatest existing threat to human health. Given the direct exposure of the upper aerodigestive system to pollutants, patients in otolaryngology are at high risk for increased disease burden in the setting of climate change and worsening air quality. Given this and the environmental impact of surgical care, it is essential for surgeons to understand their role in addressing climate health through quality-driven clinical initiatives, education, advocacy, and research. METHODS: A state-of-the-art review was performed of the existing literature on the otolaryngologic health impacts of climate change and environmental sustainability efforts in surgery with specific attention to studies in otolaryngology - head and neck surgery. FINDINGS: Climate variables including heat and air pollution are associated with increased incidence of allergic rhinitis, chronic rhinosinusitis and head and neck cancer. A number of studies have shown that sustainability initiatives in otolaryngology are safe and provide direct cost benefit. CONCLUSION: Surgeons have the opportunity to lead on climate health and sustainability to address the public health burden of climate change.

2.
Laryngoscope ; 134(2): 622-628, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-37421241

RÉSUMÉ

OBJECTIVES: To quantify and compare the cost and environmental impact of different techniques for adult tonsillectomy surgery, and to identify target areas for impact reduction. METHODS: Fifteen consecutive adult tonsillectomy surgeries were prospectively randomized to one of three tonsillectomy techniques: cold, monopolar electrocautery, or low-temperature radiofrequency ablation (Coblation). Life cycle assessment was used to comprehensively evaluate the environmental impact of study surgeries. Outcomes assessed included multiple measures of environmental impact, including greenhouse gas (GHG) emissions, and cost. Environmental impact measures were analyzed to identify highest-yield areas for improvement, and outcomes were compared between surgical techniques using statistical analysis. RESULTS: GHG emissions for cold, monopolar electrocautery, and Coblation techniques were 157.6, 184.5, and 204.7 kilograms of carbon dioxide equivalents (kgCO2 -eq) per surgery, respectively, with costs totaling $472.51, $619.10, and $715.53 per surgery, respectively. Regardless of surgery technique, anesthesia medications and disposable equipment contributed most to environmental harm. Cold technique demonstrated reduced environmental impact related to disposable surgical equipment in the categories of greenhouse gas emissions, acidification of soil and water, eutrophication of air, ozone depletion, release of carcinogenic, and non-carcinogenic toxic substances, and respiratory pollutant production (p < 0.05 for all comparisons with other techniques). CONCLUSION: Within the boundaries of operating room processes, cold technique minimizes cost and environmental impact of adult tonsillectomy surgery, with statistical significance noted in the impact of disposable surgical equipment. Areas of highest potential for improvement identified include reducing use of disposable equipment and collaboration with the Anesthesiology care team to streamline medication use. LEVEL OF EVIDENCE: 2, randomized trial Laryngoscope, 134:622-628, 2024.


Sujet(s)
Gaz à effet de serre , Amygdalectomie , Humains , Adulte , Animaux , Amygdalectomie/méthodes , Environnement , Coûts et analyse des coûts , Étapes du cycle de vie
3.
Otolaryngol Clin North Am ; 56(6): 1039-1053, 2023 Dec.
Article de Anglais | MEDLINE | ID: mdl-37442662

RÉSUMÉ

Laryngeal trauma is rare but potentially fatal. Initial evaluation includes efficient history and physical examination, imaging, bedside flexible laryngoscopy, and if necessary, operative endoscopic evaluation. Multiple classification systems exist for laryngeal trauma, and each has its merits. We recommend a patient-centered approach, rather than using the classification alone. Secure airways are the primary goal of acute management, with awake tracheostomy more often indicated over oral intubation compared with traumas not involving the larynx. More severe injuries typically require surgical intervention. Early intervention results in optimal voice and airway outcomes.


Sujet(s)
Larynx , Traumatismes du cou , Humains , Larynx/chirurgie , Laryngoscopie , Trachéostomie
4.
Surg Endosc ; 37(7): 5696-5702, 2023 07.
Article de Anglais | MEDLINE | ID: mdl-37237107

RÉSUMÉ

BACKGROUND: Health care accounts for almost 10% of the United States' greenhouse gas emissions, accounting for a loss of 470,000 disability-adjusted life years based on the health effects of climate change. Telemedicine has the potential to decrease health care's carbon footprint by reducing patient travel and clinic-related emissions. At our institution, telemedicine visits for evaluation of benign foregut disease were implemented for patient care during the COVID-19 pandemic. We aimed to estimate the environmental impact of telemedicine usage for these clinic encounters. METHODS: We used life cycle assessment (LCA) to compare greenhouse gas (GHG) emissions for an in-person and a telemedicine visit. For in-person visits, travel distances to clinic were retrospectively assessed from 2020 visits as a representative sample, and prospective data were gathered on materials and processes related to in-person clinic visits. Prospective data on the length of telemedicine encounters were collected and environmental impact was calculated for equipment and internet usage. Upper and lower bounds scenarios for emissions were generated for each type of visit. RESULTS: For in-person visits, 145 patient travel distances were recorded with a median [IQR] distance travel distance of 29.5 [13.7, 85.1] miles resulting in 38.22-39.61 carbon dioxide equivalents (kgCO2-eq) emitted. For telemedicine visits, the mean (SD) visit time was 40.6 (17.1) min. Telemedicine GHG emissions ranged from 2.26 to 2.99 kgCO2-eq depending on the device used. An in-person visit resulted in 25 times more GHG emissions compared to a telemedicine visit (p < 0.001). CONCLUSION: Telemedicine has the potential to decrease health care's carbon footprint. Policy changes to facilitate telemedicine use are needed, as well as increased awareness of potential disparities of and barriers to telemedicine use. Moving toward telemedicine preoperative evaluations in appropriate surgical populations is a purposeful step toward actively addressing our role in health care's large carbon footprint.


Sujet(s)
COVID-19 , Gaz à effet de serre , Télémédecine , Humains , États-Unis , Animaux , Études rétrospectives , Pandémies , Études prospectives , COVID-19/épidémiologie , Télémédecine/méthodes , Empreinte carbone , Étapes du cycle de vie
5.
Am J Otolaryngol ; 43(3): 103436, 2022.
Article de Anglais | MEDLINE | ID: mdl-35429845

RÉSUMÉ

BACKGROUND: Based on a 2018 American Academy of Otolaryngology - Head and Neck Surgery survey, an average of 37 tablets of opioid medication, or about a week's worth of medication, were prescribed after adult tonsillectomy. Nearly 15% of patients will still be taking opioids one year after an initial weeklong prescription, according to data from the Centers for Disease Control and Prevention. Non-steroidal anti-inflammatory medications have traditionally been avoided in adult tonsillectomy patients due to concern for increased bleeding risk from platelet dysfunction, despite little evidence supporting this claim. This study sought to demonstrate that ibuprofen prescriptions after tonsillectomy could be a safe and effective way to reduce postoperative opioid use. METHODS: This study was a retrospective chart review of patients undergoing tonsillectomy with one surgeon over three years. Half of the patients received a prescription for postoperative opioid medications and were counseled against taking ibuprofen. The other half of patients were prescribed ibuprofen following surgery and only provided with opioid analgesia as a rescue medication. The New Mexico Prescription Monitoring System was used to verify opioid prescriptions. Descriptive statistics and logistic regression were used to analyze the data. RESULTS: Ninety-nine patients were included in analysis, with 53 in the first group that did not receive ibuprofen and 46 in the second group that did receive ibuprofen. There was no difference in the bleeding rate between the two groups. Significantly fewer patients in the ibuprofen group filled postoperative opioid prescriptions when compared to the group that did not receive ibuprofen (40% vs. 96.2%, p < 0.0001, OR = 0.02). CONCLUSION: Ibuprofen is a safe and effective analgesic following adult tonsillectomy and significantly reduces the proportion of patients who must fill a postoperative opioid prescription.


Sujet(s)
Analgésiques non narcotiques , Troubles liés aux opiacés , Amygdalectomie , Acétaminophène , Adulte , Analgésiques non narcotiques/usage thérapeutique , Analgésiques morphiniques/usage thérapeutique , Humains , Ibuprofène/usage thérapeutique , Troubles liés aux opiacés/étiologie , Douleur postopératoire/traitement médicamenteux , Douleur postopératoire/prévention et contrôle , Ordonnances , Études rétrospectives , Amygdalectomie/effets indésirables
6.
Ophthalmic Plast Reconstr Surg ; 37(5): 462-464, 2021.
Article de Anglais | MEDLINE | ID: mdl-33481535

RÉSUMÉ

PURPOSE: The use of antibiotic prophylaxis for the prevention of infection in nonoperative orbital fractures is controversial, with limited high-quality evidence and inconsistent recommendations in the current scientific literature. Our primary study objective was to identify the prophylactic antibiotic prescribing pattern at our institution for nonoperative orbital fractures and to determine the effect of antibiotic prophylaxis. METHODS: We retrospectively reviewed 16 years of data from a single institution on patients with acute traumatic fractures of the orbital floor or medial orbital wall. Prophylactic administration of antibiotics and complication rates were evaluated, and complication rates and patient characteristics analyzed. RESULTS: Of 154 patients with nonoperative orbital fractures, 17 patients (group 1) received IV or oral antibiotics and 137 patients (group 2) did not. No patient in either group had documented infectious orbital complications following their orbital injury. Patients receiving antibiotics were more likely to have a concurrent periorbital laceration (58.8% ± 11.9% vs. 28.5% ± 3.9%; P = 0.01). CONCLUSION: We present the largest cohort yet reported of patients managed without antibiotic prophylaxis for nonoperative orbital fractures, with no infectious complications identified. Currently there is no evidence of utility to prophylactic antibiotics in the setting of nonoperative traumatic orbital fractures. Rather than prescribing antibiotics, we recommend clinicians educate patients on return precautions and offer close follow up for the rare, but potentially severe infectious complications of orbital trauma.


Sujet(s)
Antibioprophylaxie , Fractures orbitaires , Antibactériens/usage thérapeutique , Études de cohortes , Humains , Fractures orbitaires/complications , Études rétrospectives
7.
Ear Nose Throat J ; 100(5_suppl): 427S-430S, 2021 Sep.
Article de Anglais | MEDLINE | ID: mdl-31631678

RÉSUMÉ

OBJECTIVES: To quantify differences in waste and cost of disposable equipment between different tonsillectomy techniques. METHODS: Prospective study of waste attributable to disposable waste produced by tonsillectomy surgery. Disposable equipment required for tonsillectomy using cold, monopolar electrocautery (ME), and coblation techniques was measured; and differences in mass, volume, and cost of equipment between the 3 techniques were quantified. RESULTS: Cold technique was found to produce the least waste and have the lowest cost attributable to disposable surgical equipment. Projected single-case savings in mass and volume of waste resulting from using cold technique compared to ME were 1.272 kg and 1.013 L, respectively, and 1.043 kg and 1.723 L compared to coblation. Projected single-case savings in cost of disposable equipment for cold technique compared to ME were US$9.35 and US$185.05 compared to coblation. DISCUSSION: Using cold technique for adult tonsillectomy reduces waste and cost of disposable equipment compared to ME and coblation. Implications for Practice: Surgeons desiring to reduce cost and waste associated with tonsillectomy surgery may consider transitioning to cold technique.


Sujet(s)
Cryochirurgie/économie , Cryochirurgie/statistiques et données numériques , Coûts des soins de santé/statistiques et données numériques , Déchets médicaux/statistiques et données numériques , Amygdalectomie/méthodes , Adulte , Cryochirurgie/méthodes , Matériel jetable/économie , Matériel jetable/statistiques et données numériques , Électrocoagulation/économie , Électrocoagulation/méthodes , Humains , Déchets médicaux/économie , Études prospectives , Amygdalectomie/économie
8.
Ear Nose Throat J ; 100(9): NP407-NP412, 2021 Nov.
Article de Anglais | MEDLINE | ID: mdl-32383987

RÉSUMÉ

Malignancy of hematopoietic origin comprises a large portion of all pediatric malignancies; however, it is uncommon for patients with this condition to present only with symptoms related to temporal bone involvement. Here, we report a case of Burkitt Lymphoma of the temporal bone in an 8-year-old patient who initially presented with symptoms of acute otitis media. Additionally, we review the current literature on pediatric hematopoietic malignancy with primary temporal bone involvement and discuss the clinical presentation, management, and outcomes of these rare cases.


Sujet(s)
Lymphome de Burkitt/diagnostic , Tumeurs de la tête et du cou/diagnostic , Tumeurs hématologiques/diagnostic , Os temporal/imagerie diagnostique , Lymphome de Burkitt/anatomopathologie , Enfant , Erreurs de diagnostic , Tumeurs de la tête et du cou/anatomopathologie , Humains , Mâle , Invasion tumorale , Otite moyenne/diagnostic , Os temporal/anatomopathologie , Tomodensitométrie
9.
Ann Otol Rhinol Laryngol ; 130(4): 356-362, 2021 Apr.
Article de Anglais | MEDLINE | ID: mdl-32840127

RÉSUMÉ

OBJECTIVE: National pathology guidelines recommend full pathologic analysis for all adult tonsillectomy specimens. We evaluated the available data on occult malignancy in adult tonsillectomy for benign indication, and created a screening system to reduce the risk of missed malignancies if routine histopathologic examination were to be discontinued. STUDY DESIGN: Retrospective chart review and systematic review of the literature. SETTING: Tertiary care academic hospital and multi-hospital private healthcare system. SUBJECTS AND METHODS: A systematic literature review identified case series of adult tonsillectomy. Retrospective chart review at our institutions from 2000 to 2016 produced an additional case series. The pooled rate of occult malignancy was determined, and re-analyzed using criteria based on preoperative risk factors designed to identify patients requiring full pathologic analysis. The predicted effects of prospective application of the proposed criteria were calculated. Pooled occult malignancy prevalence was estimated. RESULTS: Literature review and our own case series yielded 12,094 total cases. Occult malignancy prevalence in the combined data was 0.033%, representing four occult malignancies. Three out of the four would have been selected for full pathology preoperatively with use of the proposed criteria. Statistical analysis indicates that the predicted frequency of occult malignancy incidence in cases negative for the criteria is 0.01%, or 1/10,000. CONCLUSION: Application of the proposed criteria to adults undergoing tonsillectomy for benign indication identifies a subset of patients with an estimated incidence of occult malignancy similar to that reported for pediatric tonsillectomy, and potentially may permit safe elimination of pathologic analysis of their tonsil specimens. LEVEL OF EVIDENCE: Pooled analysis of case series from the literature and a single institution, level 4.


Sujet(s)
Biopsie/méthodes , Métastases d'origine inconnue , Tonsille palatine , Tumeurs de l'amygdale , Amygdalectomie , Adulte , Humains , Incidence , Métastases d'origine inconnue/diagnostic , Métastases d'origine inconnue/épidémiologie , Métastases d'origine inconnue/anatomopathologie , Tonsille palatine/anatomopathologie , Tonsille palatine/chirurgie , Tumeurs de l'amygdale/diagnostic , Tumeurs de l'amygdale/épidémiologie , Tumeurs de l'amygdale/anatomopathologie , Amygdalectomie/méthodes , Amygdalectomie/statistiques et données numériques , Amygdalite/chirurgie , Procédures superflues/méthodes
10.
Clin Med Insights Oncol ; 13: 1179554919838254, 2019.
Article de Anglais | MEDLINE | ID: mdl-30983863

RÉSUMÉ

BACKGROUND: Myoepithelial cell carcinoma is a rare malignant neoplasm of salivary gland origin that typically presents in the parotid gland and minor salivary glands. It has been described previously in head and neck sites such as buccal mucosa, alveolar ridge, and base of tongue. METHODS: A 55-year-old man presented with 30 years of right-sided tongue pain and 10 years of gradually worsening ulceration. Physical examination demonstrated a 2.5 cm ulcerative lesion of the anterior right oral tongue. An initial biopsy was consistent with moderately to poorly differentiated squamous cell carcinoma. Imaging included a positron emission tomography (PET)/computed tomography (CT) scan that demonstrated the right tongue lesion as well as hypermetabolic right level II adenopathy. The patient underwent surgical excision of the right tongue, upper aerodigestive tract endoscopy, and a bilateral supraomohyoid neck dissection. The tongue defect was closed primarily. RESULTS: Final pathology of the surgical specimen demonstrated myoepithelial cell carcinoma. All of the margins were free of tumor and no cervical lymph nodes showed metastasis. Immunohistochemistry demonstrated myoepithelial differentiation. The tumor did not show EWSR1 gene rearrangement on genetic testing, suggesting salivary gland origin. Multidisciplinary tumor board evaluation recommended no adjuvant therapy. The patient recovered well after surgery and nearly a year later is without evidence of recurrent or residual disease. CONCLUSIONS: We present the first reported case of myoepithelial cell carcinoma with primary origin in the oral tongue and review the available literature on this unusual tumor. We discuss the clinical, pathological, and immunohistochemical features and treatment of myoepithelial cell carcinoma.

13.
Ear Nose Throat J ; 95(7): E11-3, 2016 Jul.
Article de Anglais | MEDLINE | ID: mdl-27434479

RÉSUMÉ

Subtotal parathyroidectomy may be indicated in patients with chronic renal failure and tertiary hyperparathyroidism, a population at increased risk for central venous stenosis (CVS) due to repeated vascular access. Here we report a case of complete upper airway obstruction precipitated by subtotal parathyroidectomy with ligation of anterior jugular vein collaterals in a patient with occult CVS. This case demonstrates a previously unreported risk of anterior neck surgery in patients with chronic renal failure. We present a review of the literature and discuss elements of the history and physical examination suggestive of occult CVS, with additional workup proposed for appropriate cases. Recommendations are discussed for perioperative and postoperative care in patients at increased risk for CVS.


Sujet(s)
Obstruction des voies aériennes/étiologie , Cathétérisme veineux central/effets indésirables , Circulation collatérale , Hyperparathyroïdie/chirurgie , Veines jugulaires , Défaillance rénale chronique/chirurgie , Parathyroïdectomie/effets indésirables , Cathétérisme veineux central/méthodes , Sténose pathologique/étiologie , Humains , Hyperparathyroïdie/étiologie , Veines jugulaires/chirurgie , Défaillance rénale chronique/complications , Mâle , Adulte d'âge moyen , Cou/chirurgie , Parathyroïdectomie/méthodes
14.
Otol Neurotol ; 36(8): 1383-9, 2015 Sep.
Article de Anglais | MEDLINE | ID: mdl-26164444

RÉSUMÉ

OBJECTIVES: To determine the prevalence of radiographic and histologic superior semicircular canal dehiscence (SSCD) and posterior semicircular canal dehiscence (PSCD) and associated changes in temporal bone thickness in children aged 0 to 7 years. STUDY DESIGN: Retrospective chart review and histopathologic review of cadaveric bone specimens. SETTING: Two tertiary referral centers. PATIENTS: Children younger than 7 years who underwent high-resolution computed tomography scan including the temporal bones between 1998 and 2013 and temporal bones harvested from children younger than 7 years. INTERVENTION(S): Two hundred twenty-eight computed tomography studies and 58 temporal bone specimens were reviewed. Available patient demographics were tabulated. MAIN OUTCOME MEASURE(S): Prevalence of SSCD and PSCD and bone thickness over semicircular canals, with comparison across age groups. Clinical data were extracted for patients with radiographic dehiscence. RESULTS: Prevalence by ear of SSCD was 11.9%, 4.9%, 2.8%, and 0% and of PSCD was 16.7%, 2.4%, 1.4%, and 0% in children aged less than 6 months, 6 to 11 months, 12 to 35 months, and 3 to 7 years, respectively. SSCD was statistically more common before 1 year of age and PSCD before 6 months of age. Bone thickness overlying both the SSC and the PSC increased with age. Radiographic PSC bone was significantly thicker than SSC bone in patients older than 12 months. No dehiscences were found in the histologic specimens. CONCLUSION: Radiographic dehiscence of the canals is common in the first 6 months of life, with thin bone seen histologically. Prevalence decreases with increasing age as the bone overlying the canals increases in thickness.


Sujet(s)
Maladies labyrinthiques/épidémiologie , Canaux semicirculaires osseux/imagerie diagnostique , Os temporal/imagerie diagnostique , Répartition par âge , Enfant , Enfant d'âge préscolaire , Études de cohortes , Femelle , Humains , Nourrisson , Maladies labyrinthiques/imagerie diagnostique , Maladies labyrinthiques/anatomopathologie , Mâle , Prévalence , Plan de recherche , Études rétrospectives , Canaux semicirculaires osseux/anatomopathologie , Os temporal/anatomopathologie , Tomodensitométrie
15.
J Virol ; 87(24): 13307-20, 2013 Dec.
Article de Anglais | MEDLINE | ID: mdl-24089548

RÉSUMÉ

Type 1 long-interspersed nuclear elements (L1s) are autonomous retrotransposable elements that retain the potential for activity in the human genome but are suppressed by host factors. Retrotransposition of L1s into chromosomal DNA can lead to genomic instability, whereas reverse transcription of L1 in the cytosol has the potential to activate innate immune sensors. We hypothesized that HIV-1 infection would compromise cellular control of L1 elements, resulting in the induction of retrotransposition events. Here, we show that HIV-1 infection enhances L1 retrotransposition in Jurkat cells in a Vif- and Vpr-dependent manner. In primary CD4(+) cells, HIV-1 infection results in the accumulation of L1 DNA, at least the majority of which is extrachromosomal. These data expose an unrecognized interaction between HIV-1 and endogenous retrotransposable elements, which may have implications for the innate immune response to HIV-1 infection, as well as for HIV-1-induced genomic instability and cytopathicity.


Sujet(s)
ADN viral/métabolisme , Rétrovirus endogènes/génétique , Infections à VIH/virologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/génétique , Éléments LINE , Lymphocytes T CD4+/virologie , Lignée cellulaire , ADN viral/génétique , Rétrovirus endogènes/métabolisme , Infections à VIH/génétique , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/métabolisme , Humains , Produits du gène vif du virus de l'immunodéficience humaine/génétique , Produits du gène vif du virus de l'immunodéficience humaine/métabolisme , Produits du gène vpr du virus de l'immunodéficience humaine/génétique , Produits du gène vpr du virus de l'immunodéficience humaine/métabolisme
16.
Skull Base Rep ; 1(2): 89-94, 2011 Nov.
Article de Anglais | MEDLINE | ID: mdl-23984208

RÉSUMÉ

In most series, 90% of cerebellopontine angle tumors are vestibular schwannomas. Meningiomas and epidermoid tumors follow with decreased frequency. Ganglioneuroma is a benign tumor usually found in the retroperitoneum and posterior mediastinum. We report a case of a 21-year-old man with gradual sensorineural hearing loss and a minimally enhancing lesion of the internal auditory canal, which was excised through a middle fossa approach and found histologically to be a ganglioneuroma. Like vestibular schwannomas, these lesions are benign in nature and may be managed in a similar fashion, although the possibility of malignant transformation may support surgical resection over conservative management or radiosurgery. Ganglioneuromas should be considered in patients with atypical radiographic findings for vestibular schwannomas.

17.
PLoS One ; 5(4): e10249, 2010 04 21.
Article de Anglais | MEDLINE | ID: mdl-20422053

RÉSUMÉ

BACKGROUND: The HLA-B*35-Px allele has been associated with rapid disease progression in HIV-1 infection, in contrast to the HLA-B*35-Py allele. METHODOLOGY/PRINCIPAL FINDINGS: Immune responses to two HLA-B*35 restricted HIV-1 specific CTL epitopes and their variants were followed longitudinally during early HIV-1 infection in 16 HLA-B*35+ individuals. Subjects expressing HLA-B*35-Px alleles showed no difference in response to the consensus epitopes compared to individuals with HLA-B*35-Py alleles. Surprisingly, all the HLA-B*35-Px+ individuals responded to epitope-variants even in the absence of a consensus response. Sequencing of the viral population revealed no evidence of variant virus in any of the individuals. CONCLUSIONS/SIGNIFICANCE: This demonstrates a novel phenomenon that distinguishes individuals with the HLA-B*35-Px rapid progressing allele and those with the HLA-B*35-Py slower progressing allele.


Sujet(s)
Allèles , Lymphocytes T CD8+/immunologie , Déterminants antigéniques des lymphocytes T/immunologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/immunologie , Antigène HLA-B35/génétique , Lymphocytes T cytotoxiques/immunologie , Numération des lymphocytes CD4 , Évolution de la maladie , Déterminants antigéniques des lymphocytes T/génétique , Variation génétique , Infections à VIH/sang , Infections à VIH/diagnostic , Infections à VIH/immunologie , Humains , Études longitudinales , Spécificité antigénique des récepteurs des lymphocytes T , Charge virale
18.
J Acquir Immune Defic Syndr ; 53(1): 36-46, 2010 Jan.
Article de Anglais | MEDLINE | ID: mdl-19910798

RÉSUMÉ

We analyzed immune responses in chronically HIV-infected individuals who took part in a treatment interruption (TI) trial designed for patients who initiated antiretroviral therapy within 6 months of seroconversion. In the 2 subjects who exhibited the best viral control, we detected CD8(+) T-cell responses against 1-2 Gag epitopes during the early weeks of TI and a subsequent increase in the number of epitopes recognized by the later time points. Each of these subjects developed mutations within the epitopes targeted by the highest magnitude responses. In the subject with the worst viral control, we detected responses against 2 Gag epitopes throughout the entire TI and no Gag mutations. The magnitude of these responses increased dramatically with time, greatly exceeding those detected in the virologic controllers. The highest levels of contemporaneous autologous neutralizing antibody activity were detected in the virologic controllers, and a subsequent escape mutation developed within the envelope gene of one controller that abrogated the response. These data suggest that immune escape mutations are a sign of viral control during TI, and that the absence of immune escape mutations in the presence of high levels of viral replication indicates the lack of an effective host immune response.


Sujet(s)
Lymphocytes T CD8+/immunologie , Épitopes/immunologie , Infections à VIH/immunologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/génétique , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/immunologie , Abstention thérapeutique , Anticorps neutralisants/sang , Thérapie antirétrovirale hautement active , Numération des lymphocytes CD4 , Lymphocytes T CD8+/métabolisme , Lymphocytes T CD8+/virologie , Épitopes/génétique , Protéine d'enveloppe gp160 du VIH/immunologie , Infections à VIH/traitement médicamenteux , Infections à VIH/virologie , Humains , Interféron gamma/biosynthèse , Interféron gamma/immunologie , Études longitudinales , Mutation , Tests de neutralisation , Charge virale , Réplication virale/génétique , Réplication virale/immunologie , Produits du gène gag du virus de l'immunodéficience humaine/immunologie
19.
PLoS Pathog ; 3(11): e165, 2007 Nov.
Article de Anglais | MEDLINE | ID: mdl-17997601

RÉSUMÉ

Human endogenous retroviruses (HERVs) are remnants of ancient infectious agents that have integrated into the human genome. Under normal circumstances, HERVs are functionally defective or controlled by host factors. In HIV-1-infected individuals, intracellular defense mechanisms are compromised. We hypothesized that HIV-1 infection would remove or alter controls on HERV activity. Expression of HERV could potentially stimulate a T cell response to HERV antigens, and in regions of HIV-1/HERV similarity, these T cells could be cross-reactive. We determined that the levels of HERV production in HIV-1-positive individuals exceed those of HIV-1-negative controls. To investigate the impact of HERV activity on specific immunity, we examined T cell responses to HERV peptides in 29 HIV-1-positive and 13 HIV-1-negative study participants. We report T cell responses to peptides derived from regions of HERV detected by ELISPOT analysis in the HIV-1-positive study participants. We show an inverse correlation between anti-HERV T cell responses and HIV-1 plasma viral load. In HIV-1-positive individuals, we demonstrate that HERV-specific T cells are capable of killing cells presenting their cognate peptide. These data indicate that HIV-1 infection leads to HERV expression and stimulation of a HERV-specific CD8+ T cell response. HERV-specific CD8+ T cells have characteristics consistent with an important role in the response to HIV-1 infection: a phenotype similar to that of T cells responding to an effectively controlled virus (cytomegalovirus), an inverse correlation with HIV-1 plasma viral load, and the ability to lyse cells presenting their target peptide. These characteristics suggest that elicitation of anti-HERV-specific immune responses is a novel approach to immunotherapeutic vaccination. As endogenous retroviral sequences are fixed in the human genome, they provide a stable target, and HERV-specific T cells could recognize a cell infected by any HIV-1 viral variant. HERV-specific immunity is an important new avenue for investigation in HIV-1 pathogenesis and vaccine design.


Sujet(s)
Antigènes viraux/immunologie , Lymphocytes T CD8+/immunologie , Lymphocytes T CD8+/virologie , Rétrovirus endogènes/immunologie , Infections à VIH/virologie , Études de cohortes , Études transversales , Cytométrie en flux , Infections à VIH/immunologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1) , Humains , ARN viral/sang , RT-PCR , Charge virale
20.
J Infect Dis ; 195(9): 1361-4, 2007 May 01.
Article de Anglais | MEDLINE | ID: mdl-17397008

RÉSUMÉ

Mycobacterium tuberculosis (MTB) is a leading cause of mortality worldwide from an infectious agent. Natural killer T (NKT) cells recognize mycobacterial antigens and contribute to anti-MTB immunity in mouse models. NKT cells were measured in subjects with pulmonary tuberculosis, MTB-exposed individuals, and healthy controls. NKT cell levels are selectively lower in peripheral blood mononuclear cells from individuals with pulmonary tuberculosis than in both MTB-exposed subjects and healthy control subjects. This apparent loss of NKT cells from the peripheral blood is sustained during the 6 months after the initiation of MTB treatment. These findings indicate that NKT cells may be an important component of antituberculosis immunity.


Sujet(s)
Antigènes CD1/analyse , Cellules tueuses naturelles/immunologie , Mycobacterium tuberculosis/immunologie , Tuberculose pulmonaire/immunologie , Adulte , Antigène CD1d , Études cas-témoins , Femelle , Cytométrie en flux , Humains , Agranulocytes/cytologie , Mâle
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