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1.
BMC Oral Health ; 24(1): 232, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38350886

ABSTRACT

BACKGROUND: Dentists serve a crucial role in managing treatment complications for patients with head and neck cancer, including post-radiation caries and oral infection. To date, dental services for head and neck cancer patients in Ontario, Canada have not been well characterized and considerable disparities in allocation, availability, and funding are thought to exist. The current study aims to describe and assess the provision of dental services for head and neck cancer patients in Ontario. METHODS: A mixed methods scoping assessment was conducted. A purposive sample of dentist-in-chiefs at each of Ontario's 9 designated head and neck cancer centres (tertiary centres which meet provincially-set quality and safety standards) was invited to participate. Participants completed a 36-item online survey and 60-minute semi-structured interview which explored perceptions of dental services for head and neck cancer patients at their respective centres, including strengths, gaps, and inequities. If a centre did not have a dentist-in-chief, an alternative stakeholder who was knowledgeable on that centre's dental services participated instead. Thematic analysis of the interview data was completed using a mixed deductive-inductive approach. RESULTS: Survey questionnaires were completed at 7 of 9 designated centres. A publicly funded dental clinic was present at 5 centres, but only 2 centres provided automatic dental assessment for all patients. Survey data from 2 centres were not captured due to these centres' lack of active dental services. Qualitative interviews were conducted at 9 of 9 designated centres and elicited 3 themes: (1) lack of financial resources; (2) heterogeneity in dentistry care provision; and (3) gaps in the continuity of care. Participants noted concerning under-resourcing and limitations/restrictions in funding for dental services across Ontario, resulting in worse health outcomes for vulnerable patients. Extensive advocacy efforts by champions of dental services who have sought to mitigate current disparities in dentistry care were also described. CONCLUSIONS: Inequities exist in the provision of dental services for head and neck cancer patients in Ontario. Data from the current study will broaden the foundation for evidence-based decision-making on the allocation and funding of dental services by government health care agencies.


Subject(s)
Dental Caries , Head and Neck Neoplasms , Mouth Diseases , Humans , Ontario , Delivery of Health Care , Dental Caries/therapy , Dental Care
2.
BMC Oral Health ; 23(1): 343, 2023 05 31.
Article in English | MEDLINE | ID: mdl-37254183

ABSTRACT

INTRODUCTION: Opportunistic oral cancer screening during visits to the dentist is a non-invasive and accessible option for detection of pre-malignant lesions and early-stage malignancies. The objective of this study was to investigate the knowledge, practices, and attitudes towards oral cancer screening among dentists. METHODS: A 42-item survey was sent to 650 dental professionals affiliated with the University of Toronto. Data regarding training/practice characteristics, knowledge of oral cavity cancer, current screening practices, attitudes towards screening, and remuneration were collected. RESULTS: Ninety-one dentists responded. Most obtained their dental degree from Canada (71.4%) and were practicing in large urban centers (87.9%). Most dentists correctly identified the oral tongue (87.8%) and floor of mouth (80%) as the two of most common sites of oral cavity cancer but only 56% correctly identified the most common presentation. 91% performed intra/extra oral examinations at every patient visit. Only 9.9% of dentists discussed the risk factors of oral cancer and 33% were not familiar with resources for smoking cessation and alcohol abuse. International medical graduates were more likely to discuss risk factor management than Canadian medical graduates (p < 0.01). Over 80% of dentists referred to a specialist when a suspected lesion was found. The greatest barrier for oral cancer screening was lack of time. Almost all dentists (98.8%) reported that their screening practices do not differ depending on the patient's insurance status and 63.8% reported compensation would not influence their decision to perform oral examinations. CONCLUSION: Most dentists have a good knowledge of the presentation and risk factors associated with oral cavity cancer. Most dentists perform screening with every patient, with no influence from compensation and insurance status. Dentists are therefore an excellent first contact for oral cavity cancer screening for the general public and for high-risk populations.


Subject(s)
Early Detection of Cancer , Mouth Neoplasms , Humans , Dentists , Canada , Mouth Neoplasms/diagnosis , Mouth Neoplasms/prevention & control , Risk Factors , Surveys and Questionnaires , Practice Patterns, Dentists' , Attitude of Health Personnel , Health Knowledge, Attitudes, Practice
3.
Otol Neurotol ; 44(1): e8-e12, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36509436

ABSTRACT

HYPOTHESIS: Electrical tinnitus suppression by cochlear implants requires stimulation of a subset of neural elements in the cochlea. BACKGROUND: Tinnitus is the phantom perception of sound in the ears and is a known correlate of hearing loss. Cochlear implants restore hearing and are known to lessen or extinguish tinnitus. The amount of electrical charge required and the number and location of electrodes required to extinguish tinnitus with a cochlear implant are factors that remain poorly understood. METHODS: In a subject with single-sided deafness, with tinnitus in the deaf ear, we enabled single electrodes and groups of electrodes along the cochlea and increased the current until tinnitus was diminished or extinguished. We recorded the subject's perception of these changes using loudness scaling of both the electrical stimuli and the tinnitus. RESULTS: Tinnitus could be extinguished with individual electrodes and more effectively extinguished by activating a greater number of electrodes. Tinnitus suppression and loudness growth of the electrical stimuli were imperfectly correlated. CONCLUSION: Tinnitus suppression in this cochlear implant patient was achieved by electrically stimulating multiple distinct portions of the cochlea, and the cochlear neural substrate for tinnitus suppression may be distinct from that for auditory perception.


Subject(s)
Cochlear Implantation , Cochlear Implants , Tinnitus , Humans , Tinnitus/surgery , Cochlea/surgery , Hearing
4.
Ear Hear ; 43(3): 862-873, 2022.
Article in English | MEDLINE | ID: mdl-34812791

ABSTRACT

OBJECTIVES: Variations in loudness are a fundamental component of the music listening experience. Cochlear implant (CI) processing, including amplitude compression, and a degraded auditory system may further degrade these loudness cues and decrease the enjoyment of music listening. This study aimed to identify optimal CI sound processor compression settings to improve music sound quality for CI users. DESIGN: Fourteen adult MED-EL CI recipients participated (Experiment No. 1: n = 17 ears; Experiment No. 2: n = 11 ears) in the study. A software application using a modified comparison category rating (CCR) test method allowed participants to compare and rate the sound quality of various CI compression settings while listening to 25 real-world music clips. The two compression settings studied were (1) Maplaw, which informs audibility and compression of soft level sounds, and (2) automatic gain control (AGC), which applies compression to loud sounds. For each experiment, one compression setting (Maplaw or AGC) was held at the default, while the other was varied according to the values available in the clinical CI programming software. Experiment No. 1 compared Maplaw settings of 500, 1000 (default), and 2000. Experiment No. 2 compared AGC settings of 2.5:1, 3:1 (default), and 3.5:1. RESULTS: In Experiment No. 1, the group preferred a higher Maplaw setting of 2000 over the default Maplaw setting of 1000 (p = 0.003) for music listening. There was no significant difference in music sound quality between the Maplaw setting of 500 and the default setting (p = 0.278). In Experiment No. 2, a main effect of AGC setting was found; however, no significant difference in sound quality ratings for pairwise comparisons were found between the experimental settings and the default setting (2.5:1 versus 3:1 at p = 0.546; 3.5:1 versus 3:1 at p = 0.059). CONCLUSIONS: CI users reported improvements in music sound quality with higher than default Maplaw or AGC settings. Thus, participants preferred slightly higher compression for music listening, with results having clinical implications for improving music perception in CI users.


Subject(s)
Cochlear Implantation , Cochlear Implants , Deafness , Music , Adult , Auditory Perception , Deafness/rehabilitation , Humans , Sound
5.
J Endod ; 47(11): 1801-1807, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34400198

ABSTRACT

Referred orofacial pain as the first symptom of an otherwise silent distant, nonmetastatic cancer has been reported, but there is sparse literature on the subject. Referred pain may not be considered in the orofacial pain differential diagnosis because of its rarity; however, this may delay a cancer diagnosis. The authors present a case report and a review of the English literature. Peer-reviewed publications were identified through a systematic search of MEDLINE, Embase, and Cochrane CENTRAL. Historic cases were reviewed, and available data regarding demographics, pain characteristics, treatment, cancer diagnosis, and outcome were extracted. Thirty-seven cases were identified. All cancers were intrathoracic. The average age was 54.1 years with a slight female predominance (3:2). Common pain characteristics were (1) diffuse location affecting the ear (76%), jaw (46%), and temple (30%); (2) constant duration (65%); (3) aching quality (74%); (4) severe intensity (94%); and (5) associated systemic symptoms (68%) such as weight loss and digital clubbing. The average time from the onset of facial pain to seeking medical attention was 9 months, and the average time from seeking medication attention to cancer diagnosis was 8 months. Orofacial pain was often attributed to odontogenic (35%) or neuropathic (25%) causes, and treatments for these conditions were also common. The impact of referred orofacial pain on the cancer prognosis was not possible because of the nature of the reviewed studies (case reports with no comparison group). Cancer-associated referred orofacial pain as a first symptom is rare but should be considered in cases with intractable pain and associated systemic symptoms.


Subject(s)
Neoplasms , Pain, Referred , Diagnosis, Differential , Facial Pain/diagnosis , Facial Pain/etiology , Female , Humans , Middle Aged , Referral and Consultation
6.
Ann Pharmacother ; 55(11): 1355-1362, 2021 11.
Article in English | MEDLINE | ID: mdl-33703922

ABSTRACT

BACKGROUND: False penicillin allergies lead to increased antimicrobial resistance, adverse effects, and health care costs by promoting the use of broad-spectrum antibiotics. The Infectious Diseases Society of America recommends the implementation of allergy testing. OBJECTIVES: The primary objective of this research was to estimate the number of pharmacist full-time equivalents (FTEs) required for an intervention aimed at determining penicillin allergy in hospitalized patients. Acceptance of pharmacists' suggestions on antibiotic therapy are described. METHODS: A quasi-experimental study was conducted in a 712-bed university hospital involving hospitalized patients with a suspected penicillin allergy and an infection treatable with penicillin. The time required for the intervention, which included a questionnaire, penicillin allergy testing (skin-prick test, intradermal injection, and oral provocation test), and recommendations on antibiotic therapy were measured to calculate the number of pharmacist FTEs. RESULTS: A total of 55 patients were included. Scarification allergy testing was performed on 37, intradermal allergy test on 33, and oral provocation test on 26 patients. The intervention ruled out penicillin allergy in 26 patients, with no serious adverse effects. The intervention was associated with a median weekly pharmacist FTE of 0.15 (interquartile range = 0.12-0.25). The acceptance of pharmacists' suggestions was high and led to 9 patients being switched to an antibiotic with a narrower spectrum of activity. CONCLUSIONS AND RELEVANCE: This study describes penicillin allergy testing and the number of median weekly hospital pharmacist FTEs required, which was approximately 0.15. These data may aid in the implementation of this safe intervention that promotes narrower-spectrum antibiotherapy.


Subject(s)
Drug Hypersensitivity , Penicillins , Anti-Bacterial Agents/adverse effects , Drug Hypersensitivity/diagnosis , Humans , Penicillins/adverse effects , Pharmacists , Skin Tests
7.
Ear Hear ; 42(3): 732-743, 2021.
Article in English | MEDLINE | ID: mdl-33538429

ABSTRACT

OBJECTIVES: To determine the sources of variability for cochlear duct length (CDL) measurements for the purposes of fine-tuning cochlear implants (CI) and to propose a set of standardized landmarks for computed tomography (CT) pitch mapping. DESIGN: This was a retrospective cohort study involving 21 CI users at a tertiary referral center. The intervention involved flat-panel CT image acquisition and secondary reconstructions of CIs in vivo. The main outcome measures were CDL measurements, CI electrode localization measurements, and frequency calculations. RESULTS: Direct CT-based measurements of CI and intracochlear landmarks are methodologically valid, with a percentage of error of 1.0% ± 0.9%. Round window (RW) position markers (anterior edge, center, or posterior edge) and bony canal wall localization markers (medial edge, duct center, or lateral edge) significantly impact CDL calculations [F(2, 78) = 9.9, p < 0.001 and F(2, 78) = 1806, p < 0.001, respectively]. These pitch distortions could be as large as 11 semitones. When using predefined anatomical landmarks, there was still a difference between researchers [F(2, 78) = 12.5; p < 0.001], but the average variability of electrode location was reduced to differences of 1.6 semitones (from 11 semitones. CONCLUSIONS: A lack of standardization regarding RW and bony canal wall landmarks results in great CDL measurement variability and distorted pitch map calculations. We propose using the posterior edge of the RW and lateral bony wall as standardized anatomical parameters for CDL calculations in CI users to improve pitch map calculations. More accurate and precise pitch maps may improve CI-associated pitch outcomes.


Subject(s)
Cochlear Implantation , Cochlear Implants , Cochlear Duct/surgery , Humans , Retrospective Studies , Tomography, X-Ray Computed
8.
Article in English | MEDLINE | ID: mdl-36341037

ABSTRACT

Background: Outcomes associated with physician responses to recommendations from an antimicrobial stewardship program (ASP) at an individual patient level have not yet been assessed. We aimed to compare clinical characteristics and mortality risk among patients for whom recommendations from an ASP were accepted or refused. Methods: A prospective cohort study was performed with hospitalized adults who received intravenous or oral antimicrobials at a 677-bed academic centre in Canada in 2014-2017. We included patients with an alert produced by a clinical decision support system (CDSS) for whom a recommendation was made by the pharmacist to the attending physician. The outcome was 90-day in-hospital all-cause mortality. Results: We identified 3,197 recommendations throughout the study period, of which 2,885 (90.2%) were accepted. The median length of antimicrobial treatment was significantly shorter when a recommendation was accepted (0.26 versus 1.78 d; p < 0.001). Refusal of a recommendation was not associated with mortality (odds ratio 1.32; 95% confidence interval, 0.93 to 1.89; p = 0.12). The independent risk factors associated with in-hospital mortality were age, Charlson Comorbidity Index score, admission to a critical care unit, duration between admission and recommendation, and issuance of a recommendation on a carbapenem. Conclusions: The duration of antimicrobial treatment was significantly shorter when a recommendation originating from a CDSS-assisted ASP program was accepted. Future prospective studies including potential residual confounding variables, such as the source of infection or physiological derangement, might help in understanding whether CDSS-assisted ASP will have a direct impact on patient mortality.


Historique: Les résultats liés aux réponses des médecins aux recommandations du programme de gestion antimicrobienne (PGA) n'ont pas encore été évalués à l'égard de chaque patient. Les chercheurs ont visé à comparer les caractéristiques cliniques et le risque de mortalité chez les patients dont les recommandations provenant d'une PGA ont été acceptées ou refusées. Méthodologie: Les chercheurs ont procédé à une étude de cohorte prospective auprès d'adultes hospitalisés qui avaient reçu des antimicrobiens par voie intraveineuse ou orale à un centre universitaire de 667 lits composé de deux établissements du Canada entre 2014 et 2017. Ils ont inclus les patients pour qui s'était déclenchée une alerte produite par un système d'aide à la décision clinique (SADC) et pour qui le pharmacien avait fait une recommandation au médecin traitant. Le résultat était la mortalité toutes causes confondues après un séjour hospitalier de 90 jours. Résultats: Les chercheurs ont extrait 3 197 recommandations tout au long de l'étude, dont 2 885 (90,2 %) ont été acceptées. La durée médiane du traitement antimicrobien était considérablement plus courte lorsqu'une recommandation était acceptée (0,26 par rapport à 1,78 jour; p < 0,001). Le refus d'une recommandation n'était pas associé à la mortalité (rapport de cotes de 1,32; IC de 95 %, 0,93 à 1,89; p = 0,12). Les facteurs de risque indépendants associés à la mortalité en milieu hospitalier étaient l'âge, l'indice de Charlson, l'admission dans une unité de soins intensifs, la période entre l'admission et la recommandation, et la formulation d'une recommandation sur un carbapénem. Conclusion: La durée du traitement antimicrobien était beaucoup plus courte lorsque la recommandation d'un PGA assisté par un SADC était acceptée. De futures études prospectives incluant de potentielles variables confusionnelles résiduelles, telles que la source de l'infection ou le dérangement physiologique, pourraient contribuer à établir si un PGA assisté par un SADC aura des conséquences directes sur la mortalité des patients.

9.
Ear Hear ; 40(6): 1368-1375, 2019.
Article in English | MEDLINE | ID: mdl-30946137

ABSTRACT

OBJECTIVES: Cochlear implant (CI) users frequently report poor sound quality while listening to music, although the specific parameters responsible for this loss of sound quality remain poorly understood. Audio compression, which reduces the dynamic range (DR) for a given sound, is a ubiquitous component of signal processing used by both CI and hearing aid technology. However, the relative impact of compression for acoustic and electric hearing on music perception has not been well studied, an important consideration especially given that most compression algorithms in CIs were developed to optimize speech perception. The authors hypothesized that normal-hearing (NH) listeners would detect increased levels of compression more easily than CI users, but that both groups would perceive a loss of sound quality with increasing compression levels. DESIGN: The present study utilizes the Cochlear Implant-MUltiple Stimulus with Hidden Reference and Anchor to evaluate the listener sensitivity to increasing levels of compression applied to music stimuli. The Cochlear Implant-MUltiple Stimulus with Hidden Reference and Anchor is a tool used to assess relative changes in the perceived sound quality of music across increasingly degraded listening conditions, in both CI and NH subjects. In this study, the authors applied multiple iterations of an aggressive compression algorithm to the music clips using Adobe Audition. The test conditions included 1, 3, 5, and 20 iterations sound tokens, with the 20-iteration samples serving as the Anchor stimuli. The compressed excerpts were 5 sec in length, with five clips for each of the five common musical genres (i.e., Classical, Jazz, Country, Rock, and Hip-Hop). Subjects were also presented with a Reference excerpt, which was the original music clip without any additional compression applied. CI recipients (n = 7, 11 ears) and NH listeners (n = 10) were asked to rate the sound quality of additionally compressed music as compared to the Reference. RESULTS: Although both NH and CI groups could detect sound quality differences as a function of compression level, the discriminatory ability of the CI group was blunted compared to the NH group. The CI group had less variability in their responses and overall demonstrated reduced sensitivity to deterioration caused by excessive levels of compression. On average, the CI group rated the Anchor condition as only "Slightly worse" than the Reference. The music clips that were most affected by the compression were from Jazz and Hip-Hop genres and less so for Rock and Country clips. Corollary to this was a small but statistically significant impact of DR of the music clips on sound quality ratings, with narrower DR showing an association with poorer ratings. CONCLUSIONS: These results indicate that CI users exhibit less sensitivity to sound quality changes in music attributable to high levels of compression. These findings may account for another contributing factor to the generally poor music perception observed in CI users, particularly when listening to commercially recorded music.


Subject(s)
Cochlear Implants , Data Compression , Deafness/rehabilitation , Music , Signal Processing, Computer-Assisted , Acoustics , Adult , Aged , Case-Control Studies , Cochlear Implantation , Female , Humans , Male , Middle Aged
10.
JAMA Otolaryngol Head Neck Surg ; 145(2): 109-116, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30477013

ABSTRACT

Importance: Cochlear implant users generally display poor pitch perception. Flat-panel computed tomography (FPCT) has recently emerged as a modality capable of localizing individual electrode contacts within the cochlea in vivo. Significant place-pitch mismatch between the clinical implant processing settings given to patients and the theoretical maps based on FPCT imaging has previously been noted. Objective: To assess whether place-pitch mismatch is associated with poor cochlear implant-mediated pitch perception through evaluation of an individualized, image-guided approach toward cochlear implant programming on speech and music perception among cochlear implant users. Design, Setting, and Participants: A prospective cohort study of 17 cochlear implant users with MED-EL electrode arrays was performed at a tertiary referral center. The study was conducted from June 2016 to July 2017. Interventions: Theoretical place-pitch maps using FPCT secondary reconstructions and 3-dimensional curved planar re-formation software were developed. The clinical map settings (eg, strategy, rate, volume, frequency band range) were modified to keep factors constant between the 2 maps and minimize confounding. The acclimation period to the maps was 30 minutes. Main Outcomes and Measures: Participants performed speech perception tasks (eg, consonant-nucleus-consonant, Bamford-Kowal-Bench Speech-in-Noise, vowel identification) and a pitch-scaling task while using the image-guided place-pitch map (intervention) and the modified clinical map (control). Performance scores between the 2 interventions were measured. Results: Of the 17 participants, 10 (58.8%) were women; mean (SD) was 59 (11.3) years. A significant median increase in pitch scaling accuracy was noted when using the experimental map compared with the control map (4 more correct answers; 95% CI, 0-8). Specifically, the number of pitch-scaling reversals for notes spaced at 1.65 semitones or greater decreased when an image-based approach to cochlear implant programming was used vs the modified clinical map (4 mistakes; 95% CI, 0.5-7). Although there was no observable median improvement in speech perception during use of an image-based map, the acute changes in frequency allocation and electrode channel deactivations used with the image-guided maps did not worsen consonant-nucleus-consonant (-1% correct phonemes, 95% CI, -2.5% to 6%) and Bamford-Kowal-Bench Speech-in-Noise (0.5-dB difference; 95% CI, -0.75 to 2.25 dB) median performance results relative to the clinical maps used by the patients. Conclusions and Relevance: An image-based approach toward ochlear implant mapping may improve pitch perception outcomes by reducing place-pitch mismatch. Studies using a longer acclimation period with chronic stimulation over months may help assess the full range of the benefits associated with personalized image-guided cochlear implant mapping.


Subject(s)
Cochlear Implantation , Cochlear Implants , Hearing Loss/diagnostic imaging , Pitch Perception , Surgery, Computer-Assisted , Tomography, X-Ray Computed , Aged , Female , Hearing Loss/surgery , Humans , Male , Middle Aged , Prospective Studies , Speech Perception
11.
Ear Hear ; 38(2): 255-261, 2017.
Article in English | MEDLINE | ID: mdl-27941405

ABSTRACT

OBJECTIVE: The electrically-evoked stapedial reflex threshold (eSRT) has proven to be useful in setting upper stimulation levels of cochlear implant recipients. However, the literature suggests that the reflex can be difficult to observe in a significant percentage of the population. The primary goal of this investigation was to assess the difference in eSRT levels obtained with alternative acoustic admittance probe tone frequencies. DESIGN: A repeated-measures design was used to examine the effect of 3 probe tone frequencies (226, 678, and 1000 Hz) on eSRT in 23 adults with cochlear implants. RESULTS: The mean eSRT measured using the conventional probe tone of 226 Hz was significantly higher than the mean eSRT measured with use of 678 and 1000 Hz probe tones. The mean eSRT were 174, 167, and 165 charge units with use of 226, 678, and 1000 Hz probe tones, respectively. There was not a statistically significant difference between the average eSRTs for probe tones 678 and 1000 Hz. Twenty of 23 participants had eSRT at lower charge unit levels with use of either a 678 or 1000 Hz probe tone when compared with the 226 Hz probe tone. Two participants had eSRT measured with 678 or 1000 Hz probe tones that were equal in level to the eSRT measured with a 226 Hz probe tone. Only 1 participant had an eSRT that was obtained at a lower charge unit level with a 226 Hz probe tone relative to the eSRT obtained with a 678 and 1000 Hz probe tone. CONCLUSIONS: The results of this investigation demonstrate that the use of a standard 226 Hz probe tone is not ideal for measurement of the eSRT. The use of higher probe tone frequencies (i.e., 678 or 1000 Hz) resulted in lower eSRT levels when compared with the eSRT levels obtained with use of a 226 probe tone. In addition, 4 of the 23 participants included in this study did not have a measureable eSRT with use of a 226 Hz probe tone, but all of the participants had measureable eSRT with use of both the 678 and 1000 Hz probe tones. Additional work is required to understand the clinical implication of these changes in the context of cochlear implant programming.


Subject(s)
Cochlear Implantation , Cochlear Implants , Deafness/rehabilitation , Reflex, Acoustic/physiology , Action Potentials/physiology , Adult , Aged , Aged, 80 and over , Deafness/physiopathology , Electric Stimulation , Female , Humans , Male , Middle Aged , Young Adult
12.
Infect Immun ; 83(2): 730-42, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25452551

ABSTRACT

A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human proteins, we immunized mice with recombinant truncated type I rMIP proteins that lacked the globular domain and the signal leader peptide (LP) signal sequence (amino acids 1 to 22) and contained the His purification tag at either the N or C terminus (C-term). The immunogenicity of truncated rMIP proteins was compared to that of full (i.e., full-length) rMIP proteins (containing the globular domain) with either an N- or C-terminal His tag and with or without the LP sequence. By comparing the functional murine antibody responses to these various constructs, we determined that C-term His truncated rMIP (-LP) delivered in liposomes induced high levels of antibodies that bound to the surface of wild-type but not Δmip mutant meningococci and showed bactericidal activity against homologous type I MIP (median titers of 128 to 256) and heterologous type II and III (median titers of 256 to 512) strains, thereby providing at least 82% serogroup B strain coverage. In contrast, in constructs lacking the LP, placement of the His tag at the N terminus appeared to abrogate bactericidal activity. The strategy used in this study would obviate any potential concerns regarding the use of MIP antigens for inclusion in bacterial vaccines.


Subject(s)
Antibodies, Bacterial/immunology , Bacterial Proteins/immunology , Meningitis, Meningococcal/immunology , Meningococcal Vaccines/immunology , Neisseria meningitidis/immunology , Tacrolimus Binding Proteins/immunology , Amino Acid Sequence , Animals , Bacterial Proteins/genetics , Cloning, Molecular , Cross Reactions/immunology , Humans , Meningitis, Meningococcal/prevention & control , Mice , Mice, Inbred BALB C , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Sequence Alignment , Vaccination
15.
Dermatol Online J ; 17(5): 4, 2011 May 15.
Article in English | MEDLINE | ID: mdl-21635826

ABSTRACT

Dermatologic manifestations from therapy with imatinib are well known and frequently include hypopigmentation, and less commonly, hyperpigmentation. There have been few reports of oral hyperpigmentation. We present a case of palatal melanosis related to imatinib therapy for chronic myelogenous leukemia. This case is reported to add to the sparse literature concerning mucosal reactions related to this medication.


Subject(s)
Antineoplastic Agents/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Melanosis/chemically induced , Mouth Diseases/chemically induced , Palate, Hard/pathology , Piperazines/adverse effects , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Adult , Antineoplastic Agents/therapeutic use , Benzamides , Female , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications , Melanins/analysis , Melanosis/pathology , Mouth Diseases/pathology , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use
16.
Clin Pract ; 1(1): e17, 2011 Mar 29.
Article in English | MEDLINE | ID: mdl-24765271

ABSTRACT

Oral pigmented lesions are uncommon and congenital melanocytic nevi are especially rare. We report a case of a patient with multiple congenital melanocytic nevi including a palatal lesion. This is reported to add to the scant literature that exists on this subject. Prognosis and management are discussed.

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