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1.
Front Oral Health ; 4: 1188443, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37288425

RESUMO

Pycnodysostosis is a skeletal dysplasia characterized by short stature, generalized osteosclerosis, acro-osteolysis, and recognizable facial features. Oral manifestations are commonly described and include a high-arched palate with dental crowding and malocclusion, hypoplastic enamel, and retained deciduous teeth with impacted permanent teeth, and there is an increased risk of developing osteomyelitis of the jaw. We report here the history of a 9-year-old male with the typical facial and skeletal phenotype of pycnodysostosis but novel oral features. He presented with bilateral progressive facial swelling, which caused functional impairment with chewing and contributed to his severe obstructive sleep apnea (OSA). The severity of his OSA required surgical intervention, and the lesions were resected. Extensive bone remodeling and replacement by fibrous tissue were noted on submucosal dissection, and bilateral subtotal maxillectomies were required. The histopathology of the biopsied lesion was consistent with a giant cell-rich lesion. Genetic testing identified a pathogenic homozygous variant in the CTSK gene, c.953G > A, p. (Cys318Tyr). The proband had a good postsurgical response with sustained improvement in his sleep OSA. We present here the history and clinical characteristics of a patient with typical features of pycnodysostosis and an unusual presentation and histopathology of gnathic bone lesions. This report adds to the body of literature on this rare condition and also highlights the finding of giant cell-rich lesions of the gnathic bones. Giant cell-rich lesions in pycnodysostosis have previously been reported in two cases in the literature. While there is not enough evidence to support a certain association with pycnodysostosis, it is prudent to consider regular oral dental reviews in affected individuals to identify pathology early and avoid such life-threatening complications.

2.
Int J Pediatr Otorhinolaryngol ; 165: 111423, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36681046

RESUMO

INTRODUCTION: Recurrent respiratory papillomatosis (RRP) is a chronic condition caused by Human papillomavirus six (HPV-6) and HPV-11 that involves the respiratory tract. Disease severity ranges from mild (hoarseness), through to severe (stridor, respiratory distress and airway emergencies). Africa has the fastest growing and youngest population of all the continents. It also has the greatest burden of cervical cancer. There is an association with infection of the oncogenic HPV strains and the strains responsible for RRP. It is reasonable to conclude that although RRP may be underestimated in low-to-middle-income countries, it poses a considerable health risk to Africa. The primary aim of this project was to assess the suitability of HPV vaccination coverage on the African continent. METHODS: A prospective study was designed to consist of an online survey. It was distributed to 135 African otolaryngologists. Questions focussed on HPV vaccination programmes; whether they were government directed; and their rollout. Information from countries that had multiple otolaryngologists respond to the survey were compared. Additionally, data review and corroboration were performed. RESULTS: There were 58 (43%) participants from 19 countries. Nine countries reported a national vaccination programme (NVP), five used Cervarix; four used quadrivalent Gardasil. Collateral data revealed 18 of 54 countries had NVP in Africa and 26 countries had completed HPV vaccine pilot or demonstration projects. CONCLUSIONS: HPV vaccination in Africa should be urgently re-evaluated to include the HPV-6 and HPV-11 strains that cause JORRP, which have not been recognised during national vaccination programme planning.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Humanos , Infecções por Papillomavirus/epidemiologia , Papillomavirus Humano , Estudos Prospectivos , Vacinação , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Sistema Respiratório , África/epidemiologia , Papillomavirus Humano 11 , Papillomavirus Humano 6
3.
J Laryngol Otol ; 134(12): 1069-1072, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33243316

RESUMO

BACKGROUND: Thyroid lobectomy is recommended with total laryngectomy for laryngeal cancer in the National Comprehensive Cancer Network ('NCCN') guidelines. However, it is associated with a 32-89 per cent risk of hypothyroidism, with or without adjuvant radiotherapy. OBJECTIVE: The study aimed to determine whether preserving the whole thyroid, compared to a single lobe, does indeed significantly lower the incidence of hypothyroidism in the setting of total laryngectomy. METHOD: A retrospective study was conducted at Groote Schuur Hospital in Cape Town, South Africa. RESULTS: Eighty-four patients met the inclusion criteria. The overall incidence of hypothyroidism was 45.2 per cent. The incidence of hypothyroidism was significantly reduced in patients who underwent thyroid-sparing total laryngectomy compared to hemithyroidectomy (p = 0.037). Adjuvant radiotherapy was associated with a higher incidence of hypothyroidism (p = 0.001). CONCLUSION: Thyroid-preserving laryngectomy should be advocated in carefully selected patients with advanced laryngeal carcinoma, as it reduces the incidence of hypothyroidism.


Assuntos
Hipotireoidismo/prevenção & controle , Neoplasias Laríngeas/cirurgia , Laringectomia/efeitos adversos , Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Idoso , Estudos Transversais , Feminino , Humanos , Hipotireoidismo/epidemiologia , Incidência , Neoplasias Laríngeas/patologia , Laringectomia/métodos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Comportamento de Redução do Risco , África do Sul/epidemiologia , Tireoidectomia/efeitos adversos , Tireoidectomia/tendências
4.
J Laryngol Otol ; 133(2): 129-134, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30773143

RESUMO

OBJECTIVE: Total laryngectomy is considered the primary treatment modality for advanced laryngeal carcinoma. This study assessed the quality of life in patients after total laryngectomy, and ascertained whether quality of life is affected by socioeconomic status. METHOD: Forty-seven patients (20 state- and 27 private-sector) who underwent total laryngectomy between 1998 and 2014 responded to the University of Washington Quality of Life Questionnaire, the Voice-Related Quality of Life Questionnaire and the Brief Illness Perception Questionnaire. RESULTS: Significant differences were found in socioeconomic status between state- and private-sector patients (p < 0.001). There was no significant difference in overall quality of life between groups (p = 0.210). State-sector patients scored significantly higher Voice-Related Quality of Life Questionnaire scores (p = 0.043). Perception of illness did not differ significantly between groups. CONCLUSION: Overall quality of life after total laryngectomy appears to be similar in patients from different socioeconomic backgrounds. However, patients from lower socioeconomic circumstances have better voice-related quality of life. The results illustrate the importance of including socioeconomic status when reporting voice outcomes in total laryngectomy patients.


Assuntos
Neoplasias Laríngeas/cirurgia , Laringectomia , Qualidade de Vida , Qualidade da Voz , Idoso , Estudos Transversais , Feminino , Humanos , Neoplasias Laríngeas/psicologia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Classe Social , Inquéritos e Questionários
5.
Int J Pediatr Otorhinolaryngol ; 110: 6-11, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29859589

RESUMO

INTRODUCTION: HIV-positive children are possibly more prone to developing cholesteatoma. Chronic inflammation of the middle ear cleft may be more common in patients with HIV and this may predispose HIV-positive children to developing cholesteatoma. There are no studies that describe the radiological morphology of the middle ear cleft in HIV-positive compared to HIV-negative children with cholesteatoma. OBJECTIVES: Compare the radiological differences of the middle ear cleft in HIV-positive and HIV-negative children with cholesteatoma. METHODS: A retrospective, cross-sectional, observational analytical review of patients with cholesteatoma at our institute over a 6 year period. RESULTS: Forty patients were included in the study, 11 of whom had bilateral cholesteatoma and therefore 51 ears were eligible for our evaluation. HIV-positive patients had smaller (p=0.02) mastoid air cell systems (MACS). Forty percent of HIV-positive patients had sclerotic mastoids, whereas the rate was 3% in HIV-negative ears (p<0.02). Eighty-two percent of the HIV-positive patients had bilateral cholesteatoma compared to 7% of the control group (p<0.02). There was no difference between the 2 groups with regards to opacification of the middle ear cleft, bony erosion of middle ear structures, Eustachian tube obstruction or soft tissue occlusion of the post-nasal space. CONCLUSION: HIV-positive paediatric patients with cholesteatoma are more likely to have smaller, sclerotic mastoids compared to HIV-negative patients. They are significantly more likely to have bilateral cholesteatoma. This may have implications in terms of surveillance of HIV-positive children, as well as, an approach to management, recurrence and follow-up. HIV infection should be flagged as a risk factor for developing cholesteatoma.


Assuntos
Colesteatoma da Orelha Média/diagnóstico por imagem , Infecções por HIV/complicações , Adolescente , Criança , Pré-Escolar , Colesteatoma da Orelha Média/virologia , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico por imagem , Humanos , Masculino , Processo Mastoide/diagnóstico por imagem , Radiografia , Estudos Retrospectivos
6.
Clin Oral Investig ; 22(4): 1795-1803, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29151196

RESUMO

OBJECTIVES: The aim of this study is to determine the effects of in vitro and in vivo high-dose radiotherapy on microhardness and associated indentation pattern morphology of enamel. MATERIALS AND METHODS: The inner, middle, and outer microhardness of enamel was evaluated using three experimental groups: control (non-radiated); in vitro irradiated; in vivo irradiated. In vitro specimens were exposed to simulated radiotherapy, and in vivo specimens were extracted teeth from oral cancer patients previously treated with radiotherapy. Indentations were measured via SEM images to calculate microhardness values and to assess the mechanomorphological properties of enamel before and after radiotherapy. RESULTS: Middle and outer regions of enamel demonstrated a significant decrease in microhardness after in vitro and in vivo irradiation compared to the control group (p < 0.05). Two indentation patterns were observed: pattern A-presence of microcracks around indent periphery, which represents local dissipation of deformation energy; pattern B-clean, sharp indents. The percentage of clean microindentation patterns, compared to controls, was significantly higher following in vitro and in vivo irradiation in all enamel regions. The highest percentage of clean microindentations (65%) was observed in the in vivo irradiated group in the inner region of enamel near the dentin-enamel junction. CONCLUSIONS: For the first time, this study shows that in vitro and in vivo irradiation alters enamel microhardness. Likewise, the indentation pattern differences suggest that enamel may become more brittle following in vitro and in vivo irradiation. CLINICAL RELEVANCE: The mechanomorphological property changes of enamel following radiation may be a contributory component of pathologic enamel delamination following oral cancer radiotherapy.


Assuntos
Esmalte Dentário/efeitos da radiação , Neoplasias Bucais/radioterapia , Adolescente , Feminino , Testes de Dureza , Humanos , Masculino , Microscopia Eletrônica de Varredura , Propriedades de Superfície , Adulto Jovem
7.
Pharmacol Res ; 117: 54-64, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27940205

RESUMO

The survival rates for patients with osteosarcoma have remained almost static for the past three decades. Current standard of care therapy includes chemotherapies such as doxorubicin, cisplatin, and methotrexate along with complete surgical resection and surgery with or without ifosfamide and etoposide for relapse, though outcomes are hoped to be improved through clinical trials. Additionally, increased understanding of the genetics, signaling pathways and microenvironmental factors driving the disease have led to the identification of promising agents and potential paths towards translation of an exciting array of novel targeted therapies. Here, we review the mechanism of action of these emerging therapies and how, with clinical translation, they can potentially improve the survival rates for osteosarcoma patients in the near future.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Osteossarcoma/tratamento farmacológico , Animais , Humanos , Osteossarcoma/mortalidade , Transdução de Sinais/efeitos dos fármacos , Taxa de Sobrevida , Microambiente Tumoral/efeitos dos fármacos
8.
Int J Pediatr Otorhinolaryngol ; 80: 69-73, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26746615

RESUMO

OBJECTIVES: To highlight important aspects and paradigms in the management of paediatric cholesteatoma in a developing world setting. METHODS: A retrospective audit was conducted of paediatric cholesteatomas that underwent tympanomastoid surgery between 2008 and 2012 at the Red Cross War Memorial Children's Hospital in Cape Town. The following was audited: initial presentation; cholesteatoma complications; types of surgery, intraoperative findings and outcomes of surgery in terms of hearing, otorrhoea and recidivism; and the reliability of follow-up and how this might influence the type of surgery. RESULTS: Fifty-seven children aged 2-13 years with 61 cholesteatomas (4 bilateral) were reviewed. Fifty-five mastoidectomies were done; 11% presented with complicated cholesteatoma. Referrals from primary care were significantly delayed (>6 months) in 76%. Canal wall down surgery was done in 71%. Forty-five percent had improved hearing (within 15dB of better hearing ear) and a further 15% had no or only mild hearing loss. Ossicular chain involvement and ossicles encased in inflammatory tissue were associated with poorer hearing outcomes. Sixty-four percent of ears remained dry. Forty-five percent of the canal wall up, and 23% of canal wall down mastoidectomies had recidivism. Twenty-six percent of patients were lost to follow-up. CONCLUSIONS: Children are likely to present with advanced cholesteatoma with ossicular chain involvement. The children present with high rates of complications, poor pre-operative hearing and have high recurrence rates post-surgery. Referral from primary health care is delayed. Canal wall down procedures may be appropriate in a setting where patient follow-up is unreliable and access to operating theatre is limited.


Assuntos
Colesteatoma da Orelha Média/complicações , Colesteatoma da Orelha Média/cirurgia , Países em Desenvolvimento , Ossículos da Orelha , Adolescente , Criança , Pré-Escolar , Feminino , Audição , Perda Auditiva/etiologia , Testes Auditivos , Humanos , Perda de Seguimento , Masculino , Processo Mastoide/cirurgia , Recidiva , Encaminhamento e Consulta , Estudos Retrospectivos , África do Sul , Fatores de Tempo , Resultado do Tratamento
9.
Artigo em Inglês | MEDLINE | ID: mdl-25482548

RESUMO

OBJECTIVE: To compare measures of dry mouth following extended use of an alcohol-based mouthrinse (LISTERINE Antiseptic [LA]) and a non-alcohol-based mouthrinse (Crest Pro-Health Rinse [CPH]) on healthy adults with "normal" salivary flow. METHODS: This single-site, randomized, observer-blinded, parallel study compared unstimulated whole salivary flow and perceived dryness following daily use at weeks 4 and 12 versus baseline. Noninferiority, between-treatment flow comparisons (0.15 mL/min margin), and between-treatment comparisons of the mean Bluestone Mouthfeel Questionnaire (BMQ) visual analog scale scores were made using analysis of covariance. RESULTS: Measures of dry mouth were comparable between mouthrinses, as demonstrated by both noninferiority of LA versus CPH flow (P < .001) and no significant differences between groups in the BMQ measures at 4 or 12 weeks. CONCLUSIONS: Extended use of an alcohol-based mouthrinse is no more likely to cause reduction in salivary flow or perceived dryness in individuals with normal salivary flow compared with a non-alcohol-based mouthrinse (CPH).


Assuntos
Cetilpiridínio/efeitos adversos , Antissépticos Bucais/efeitos adversos , Salicilatos/efeitos adversos , Salivação/efeitos dos fármacos , Terpenos/efeitos adversos , Xerostomia/induzido quimicamente , Adulto , Combinação de Medicamentos , Feminino , Humanos , Masculino , Inquéritos e Questionários
10.
J Dent Res ; 93(10): 1028-34, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25146181

RESUMO

The dental basement membrane (BM) is composed of collagen types IV, VI, VII, and XVII, fibronectin, and laminin and plays an inductive role in epithelial-mesenchymal interactions during tooth development. The BM is degraded and removed during later-stage tooth morphogenesis; however, its original position defines the location of the dentin-enamel junction (DEJ) in mature teeth. We recently demonstrated that type VII collagen is a novel component of the inner enamel organic matrix layer contiguous with the DEJ. Since it is frequently co-expressed with and forms functional complexes with type VII collagen, we hypothesized that type IV collagen should also be localized to the DEJ in mature human teeth. To identify collagen IV, we first evaluated defect-free erupted teeth from various donors. To investigate a possible stabilizing role, we also evaluated extracted teeth exposed to high-dose radiotherapy--teeth that manifest post-radiotherapy DEJ instability. We now show that type IV collagen is a component within the morphological DEJ of posterior and anterior teeth from individuals aged 18 to 80 yr. Confocal microscopy revealed that immunostained type IV collagen was restricted to the 5- to 10-µm-wide optical DEJ, while collagenase treatment or previous in vivo tooth-level exposure to > 60 Gray irradiation severely reduced immunoreactivity. This assignment was confirmed by Western blotting with whole-tooth crown and enamel extracts. Without reduction, type IV collagen contained macromolecular α-chains of 225 and 250 kDa. Compositionally, our results identify type IV collagen as the first macromolecular biomarker of the morphological DEJ of mature teeth. Given its network structure and propensity to stabilize the dermal-epidermal junction, we propose that a collagen-IV-enriched DEJ may, in part, explain its well-known fracture toughness, crack propagation resistance, and stability. In contrast, loss of type IV collagen may represent a biochemical rationale for the DEJ instability observed following oral cancer radiotherapy.


Assuntos
Colágeno Tipo IV/análise , Esmalte Dentário/química , Dentina/química , Radioterapia de Alta Energia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Basal/química , Biomarcadores/análise , Colágeno Tipo IV/efeitos dos fármacos , Colágeno Tipo IV/efeitos da radiação , Colágeno Tipo VII/análise , Colagenases/farmacologia , Esmalte Dentário/efeitos dos fármacos , Esmalte Dentário/efeitos da radiação , Proteínas do Esmalte Dentário/análise , Proteínas do Esmalte Dentário/efeitos da radiação , Dentina/efeitos dos fármacos , Dentina/efeitos da radiação , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Pessoa de Meia-Idade , Odontogênese/fisiologia , Dosagem Radioterapêutica , Coroa do Dente/química , Coroa do Dente/efeitos da radiação , Adulto Jovem
11.
J Dent ; 42(5): 626-35, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24607847

RESUMO

OBJECTIVES: We recently demonstrated a significant correlation between enamel delamination and tooth-level radiation dose in oral cancer patients. Since radiation can induce the synthesis and activation of matrix metalloproteinases, we hypothesized that irradiated teeth may contain active matrix metalloproteinases. MATERIALS AND METHODS: Extracted teeth from oral cancer patients treated with radiotherapy and from healthy subjects were compared. Extracted mature third molars from healthy subjects were irradiated in vitro and/or incubated for 0-6 months at 37°C. All teeth were then pulverized, extracted, and extracts subjected to proteomic and enzymatic analyses. RESULTS: Screening of irradiated crown extracts using mass spectrometry identified MMP-20 (enamelysin) which is expressed developmentally in dentine and enamel but believed to be removed prior to tooth eruption. MMP-20 was composed of catalytically active forms at Mr=43, 41, 24 and 22kDa and was immunolocalized predominantly to the morphological dentine enamel junction. The proportion of different sized MMP-20 forms changed with incubation and irradiation. While the pattern was not altered directly by irradiation of healthy teeth with 70Gy, subsequent incubation at 37°C for 3-6 months with or without prior irradiation caused the proportion of Mr=24-22kDa MMP-20 bands to increase dramatically. Extracts of teeth from oral cancer patients who received >70Gy radiation also contained relatively more 24 and 22kDa MMP-20 than those of healthy age-related teeth. CONCLUSION: MMP-20 is a radiation-resistant component of mature tooth crowns enriched in the dentine-enamel. We speculate that MMP-20 catalyzed degradation of organic matrix at this site could lead to enamel delamination associated with oral cancer radiotherapy.


Assuntos
Metaloproteinase 20 da Matriz/análise , Coroa do Dente/efeitos da radiação , Idoso , Western Blotting , Esmalte Dentário/enzimologia , Esmalte Dentário/efeitos da radiação , Dentina/enzimologia , Dentina/efeitos da radiação , Eletroforese , Humanos , Espectrometria de Massas/métodos , Metaloproteinase 20 da Matriz/efeitos da radiação , Microscopia Confocal , Pessoa de Meia-Idade , Dente Serotino/enzimologia , Dente Serotino/efeitos da radiação , Dosagem Radioterapêutica , Espectrometria de Massas em Tandem , Coroa do Dente/enzimologia , Adulto Jovem
12.
Gen Dent ; 61(1): 23-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23302358

RESUMO

This randomized, observer-blind, parallel, controlled study determined the efficacy of an essential oils-containing (EO) antiseptic mouthrinse (in conjunction with toothbrushing) in reducing and/or controlling existing plaque or gingivitis over 6 months. Toothbrushing, combined with placebo rinsing, served as the control (C). Following ethics board approval (Biosci Research Canada, Ltd. Institutional Review Board), 139 healthy adults with mild to moderate plaque and gingivitis were randomized into EO or C groups. All subjects received oral/written instructions, monthly monitoring, and assigned unsupervised rinses. Efficacy variables were whole-mouth mean modified gingival index (MGI), Turesky modification of the Quigley Hein plaque index (PI), bleeding index (BI) at 6, 12, and 24 weeks, and data analysis through an analysis of covariance (ANCOVA) model. The EO group provided greater and increasing MGI, PI, and BI reductions than did C group over all examination periods. Compared to the C group, at 6, 12, and 24 weeks, MGI reductions for the EO group were 4.7%, 9.1%, and 20.4%, and PI reductions were 7.6%, 12.6%, and 26.3%, respectively. BI scores decreased over time and were significant compared to those for the C group (P < 0.001). Additionally, the percentages of sites improved versus baseline MGI over time for EO were 14.1%, 26.4%, and 43.3%, respectively. This study demonstrated that an EO-containing mouthrinse can provide an increasing benefit over a period of 6 months with twice daily use. This study also confirmed that an antiseptic EO rinse can provide a clinically significant benefit in reducing existing plaque and gingivitis.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Placa Dentária/tratamento farmacológico , Gengivite/tratamento farmacológico , Antissépticos Bucais/uso terapêutico , Óleos Voláteis/uso terapêutico , Adulto , Análise de Variância , Índice de Placa Dentária , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Escovação Dentária , Resultado do Tratamento
13.
Int J Proteomics ; 2012: 824024, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22701795

RESUMO

Alzheimer's disease (AD) is the most common form of dementia found in all human populations worldwide, while vascular dementia (VaD) is the second most common form of dementia. New biomarkers for early and specific diagnosis of AD and VaD are needed to achieve greater insight into changes occurring in the brain and direct therapeutic strategies. The objective of this explorative study was to discover candidate protein biomarkers for the differential diagnosis between VaD and AD. Surface-enhanced laser desorption/ionization (SELDI) TOF-MS was used to differentially profile proteins and peptides in CSF samples from 28 AD patients and 21 patients with VaD. A combination of univariate (Kruskal-Wallis) and multivariate (independent component analysis) statistical approaches produced a list of 27 proteins and peptides that could differentiate between VaD and AD. These markers represent various physiological processes, such as protein degradation (ubiquitin), protease inhibition (cystatin C and alpha-1-antichymoptrypsin), and inflammation (C3a and C4a) that are known to be represented in neurodegenerative diseases.

14.
J Anal Toxicol ; 32(1): 57-62, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18269794

RESUMO

A method to detect fluoride ion generated O-ethyl methylphosphonofluoridate (VX-G) in Göttingen minipig red blood cells (RBC) following whole-body exposure to VX vapor utilizing a gas chromatograph-tandem mass spectrometer (GC-MS-MS) has been developed. Dose-response curves for VX exposure were generated after applying the fluoride ion reactivation assay to the RBC fraction of serially collected whole blood samples that were taken after whole-body exposures that varied in both duration and concentration. GC-MS-MS analysis of minipig RBC samples following 180-min exposures at two different concentrations was a more precise indicator for severity of exposure than the analysis of acetylcholinesterase (AChE) inhibition for the same samples. AChE enzyme activity recovered faster than indicated by the apparent elimination rate of VX-G. GC-MS-MS analyses of RBC samples following VX exposure demonstrate this technique has both adequate sensitivity and specificity to indicate the severity of exposure.


Assuntos
Monitoramento Ambiental/métodos , Eritrócitos/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Compostos Organotiofosforados/sangue , Espectrometria de Massas em Tandem/métodos , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Administração por Inalação , Animais , Biomarcadores/sangue , Calibragem , Substâncias para a Guerra Química/análise , Substâncias para a Guerra Química/metabolismo , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/sangue , Inibidores da Colinesterase/metabolismo , Exposição Ambiental/análise , Eritrócitos/enzimologia , Fluoretos/química , Compostos Organotiofosforados/administração & dosagem , Compostos Organotiofosforados/metabolismo , Compostos de Potássio/química , Reprodutibilidade dos Testes , Extração em Fase Sólida/métodos , Suínos , Porco Miniatura
15.
Dement Geriatr Cogn Disord ; 24(6): 434-40, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17971664

RESUMO

BACKGROUND: An early and accurate diagnosis of Alzheimer's disease (AD) is important in order to initiate symptomatic treatment with currently approved drugs and will be of even greater importance with the advent of disease-modifying compounds. METHODS: Protein profiles of human cerebrospinal fluid samples from patients with AD (n = 85), frontotemporal dementia (n = 20), and healthy controls (n = 32) were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to verify previously discovered biomarkers. RESULTS: We verified 15 protein biomarkers that were able to differentiate between AD and controls, and 7 of these 15 markers also differentiated AD from FTD. CONCLUSION: A panel of cerebrospinal fluid protein markers was verified by a proteomics technology which may potentially improve the accuracy of the AD diagnosis.


Assuntos
Envelhecimento/fisiologia , Doença de Alzheimer , Demência/diagnóstico , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Biomarcadores , Cromogranina A/líquido cefalorraquidiano , Cistatina C , Cistatinas/líquido cefalorraquidiano , Diagnóstico Diferencial , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Ribonuclease Pancreático/líquido cefalorraquidiano
16.
Pediatr Cardiol ; 27(1): 62-66, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16391971

RESUMO

No one set of characteristics has been consistently predictive of perioperative mortality and morbidity associated with the Norwood procedure. The purpose of the current study is to further validate a scoring system shown to be predictive of mortality following the Norwood procedure. We performed a retrospective review of all infants with the diagnosis of hypoplastic left heart syndrome (HLHS) who underwent the Norwood procedure at St. Louis Children's Hospital from July 1, 1994, to December 31, 2002. A weighted score for each of six factors comprised the scoring system. The factors included ventricular function, tricuspid regurgitation, ascending aortic diameter, atrial septal defect blood flow characteristics, blood type, and age. A score of > or = 7 points indicated lower reconstructive mortality risk, and a total score of < 7 points indicated a higher mortality risk. A total of 57 patients were analyzed. Twenty-five infants (44%) had a low risk score. These infants had a significantly greater survival at 48 hours compared to infants with a score of < 7 (92 vs 75%, p < 0.05). Infants with a high risk score had a significantly greater relative risk of mortality at 48 hours [OR = 2.04; confidence interval (CI) 1.04-4.00; p = 0.036]. The area under the receiver operating characteristic (ROC) curve is 0.8534 (95% CI, 0.78-0.922). This suggests that the scoring system has a very good degree of discriminatory power in selecting children who did not survive. Based on the results of the ROC, a cutoff score of >7 gives the best sensitivity and specificity for survival. When applied retrospectively, the survival outcomes predicted by our scoring system significantly correlated with actual outcomes. This supports the conclusion that a specific population of HLHS patients may have a higher mortality risk independent of surgical technique and postoperative care based on factors that can be assessed preoperatively.


Assuntos
Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Complicações Pós-Operatórias/mortalidade , Medição de Risco/estatística & dados numéricos , Fatores Etários , Aorta/fisiopatologia , Peso ao Nascer , Antígenos de Grupos Sanguíneos , Intervalos de Confiança , Feminino , Comunicação Interatrial/mortalidade , Comunicação Interatrial/fisiopatologia , Hemodinâmica/fisiologia , Mortalidade Hospitalar , Humanos , Síndrome do Coração Esquerdo Hipoplásico/fisiopatologia , Lactente , Recém-Nascido , Masculino , Cuidados Paliativos , Complicações Pós-Operatórias/fisiopatologia , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Análise de Sobrevida , Insuficiência da Valva Tricúspide/mortalidade , Insuficiência da Valva Tricúspide/fisiopatologia , Função Ventricular Esquerda/fisiologia
17.
Comput Aided Surg ; 10(1): 45-9, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16199381

RESUMO

The primary aim of computer-assisted knee arthroplasty is to improve the alignment of the implanted prostheses. Accurate component alignment is dependent on the establishment of accurate anatomical reference points. Current techniques for establishing the center of the ankle joint, especially in the coronal plane, rely solely on clinical judgment in relation to the position of the center of the ankle joint. The aim of this study was to determine if an algorithm could be developed, based on establishing the most prominent points on the medial and lateral malleoli on 3D CT scans, to accurately and reproducibly establish the position of the center of the ankle joint. To determine this, images of 20 ankles were obtained and axial, coronal, and sagittal 2D reconstructions were manipulated on a workstation. Two observers independently performed relevant measurements and calculations. The calculated data was found to be reproducible with a very small standard deviation in each plane. This algorithm is able to provide accurate measurements of the ankle joint in knee navigation surgery. Caution must be exercised in anatomically abnormal ankles, as the calculations of the ankle center were found to be significantly different.


Assuntos
Articulação do Tornozelo/diagnóstico por imagem , Artroplastia do Joelho , Imageamento Tridimensional , Cirurgia Assistida por Computador , Tomografia Computadorizada por Raios X , Algoritmos , Humanos , Processamento de Imagem Assistida por Computador
18.
Br J Dermatol ; 151(6): 1266-9, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15606525

RESUMO

We report a woman with recessive dystrophic epidermolysis bullosa (RDEB) in whom there was prolonged sepsis and death at age 22 years. Autopsy revealed multiple epidermolytic skin lesions with chronic ulceration, mesangioproliferative glomerulonephritis and multifocal necrotizing leucoencephalopathy (MNL) of the pons. The latter two conditions may have been mediated by sepsis-associated cytokines. Although mesangioproliferative glomerulonephritis has previously been described in association with RDEB, to our knowledge this is the first report of MNL in a patient with RDEB.


Assuntos
Epidermólise Bolhosa Distrófica/complicações , Glomerulonefrite Membranoproliferativa/etiologia , Leucoencefalopatia Multifocal Progressiva/etiologia , Adulto , Epidermólise Bolhosa Distrófica/patologia , Evolução Fatal , Feminino , Glomerulonefrite Membranoproliferativa/patologia , Humanos , Leucoencefalopatia Multifocal Progressiva/patologia , Ponte/patologia
19.
J Anal Toxicol ; 28(5): 357-63, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15239856

RESUMO

A new method for measuring fluoride ion released isopropyl methylphosphonofluoridate (sarin, GB) in the red blood cell fraction was developed that utilizes an autoinjector, a large-volume injector port (LVI), positive ion ammonia chemical ionization detection in the SIM mode, and a deuterated stable isotope internal standard. This method was applied to red blood cell (RBC) and plasma ethyl acetate extracts from spiked human and animal whole blood samples and from whole blood of minipigs, guinea pigs, and rats exposed by whole-body sarin inhalation. Evidence of nerve agent exposure was detected in plasma and red blood cells at low levels of exposure. The linear method range of quantitation was 10-1000 pg on-column with a detection limit of approximately 2-pg on-column. In the course of method development, several conditions were optimized for the LVI, including type of injector insert, injection volume, initial temperature, pressure, and flow rate. RBC fractions had advantages over the plasma with respect to assessing nerve agent exposure using the fluoride ion method especially in samples with low serum butyrylcholinesterase activity.


Assuntos
Substâncias para a Guerra Química/análise , Eritrócitos/química , Fluoretos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Sarina/análise , Porco Miniatura , Animais , Substâncias para a Guerra Química/farmacocinética , Substâncias para a Guerra Química/intoxicação , Relação Dose-Resposta a Droga , Cobaias , Humanos , Exposição por Inalação , Troca Iônica , Marcação por Isótopo , Ratos , Ratos Sprague-Dawley , Sarina/farmacocinética , Sarina/intoxicação , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Espectrometria de Massas por Ionização por Electrospray/métodos , Suínos
20.
J Am Dent Assoc ; 135(4): 496-504, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15127875

RESUMO

BACKGROUND: Mechanical methods of oral hygiene can be complemented by the use of chemotherapeutic mouthrinses. The authors sought to quantify the additional benefit provided by an essential oil-, or EO-, containing mouthrinse in reducing plaque and gingivitis in patients who brush and floss regularly. METHODS: The authors randomly assigned patients with gingivitis to one of three treatment groups: brushing and rinsing with a control mouthrinse, or BC; brushing, flossing and rinsing with a control mouthrinse, or BFC; or brushing, flossing and rinsing with an EO-containing mouthrinse, or BFEO. Patients received a dental prophylaxis at baseline, and the authors followed them for six months. RESULTS: Of 246 enrolled subjects enrolled in the study, 237 subjects were evaluable at the study's conclusion. After six months, the subjects using the BFEO regimen had statistically and clinically significant lower mean Modified Gingival Index, or MGI, scores and Plaque Index, or PI, scores than did subjects in the BC group (29.9 percent and 56.3 percent, respectively; P < .001). Subjects in the BFC group had statistically significantly lower mean MGI and PI scores than did subjects in the BC group (11.2 percent and 9.3 percent, respectively; P < .001). Subjects in the BFEO group exhibited statistically and clinically significantly lower mean scores for MGI and PI than did subjects in the BFC group (21 percent and 51.9 percent, respectively; P < .001). CONCLUSIONS: This study confirms that for patients with gingivitis who brush and floss routinely, the adjunctive use of an EO-containing mouthrinse provides a clinically significant and meaningful additional benefit in reducing plaque and gingivitis. CLINICAL IMPLICATIONS: An EO-containing mouthrinse is an effective adjunct to regular brushing and flossing. Therefore, the BFEO regimen can be beneficial for patients with gingival inflammation.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Placa Dentária/prevenção & controle , Gengivite/prevenção & controle , Antissépticos Bucais/uso terapêutico , Óleos Voláteis/uso terapêutico , Adolescente , Adulto , Distribuição de Qui-Quadrado , Dispositivos para o Cuidado Bucal Domiciliar , Índice de Placa Dentária , Dentifrícios/uso terapêutico , Combinação de Medicamentos , Feminino , Seguimentos , Hemorragia Gengival/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Índice Periodontal , Salicilatos/uso terapêutico , Método Simples-Cego , Terpenos/uso terapêutico , Escovação Dentária
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