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1.
BMC Oral Health ; 24(1): 630, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811865

RESUMO

INTRODUCTION: This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and neck tumours treated with intensity-modulated-radiotherapy (IMRT). METHODS: Saliva samples/clinical data were obtained from 40 head and neck cancer patients treated at Guy's Hospital before -IMRT(T0) and after-IMRT (T1 = 6 m, T2 = 12 m) (ethics approval/consent). Salivary flow rate, total protein concentration, and secretion rate were determined from saliva samples and compared with pre-treatment values. OM was assessed, total/specific salivary proteins, including mucin 5B and 7, IgA, cystatin-S, albumin, and α-amylase, were quantified. RESULTS: 95% patients experienced OM during IMRT, with 33 subjects reaching grade 2&3. At T1, there was a significant reduction in salivary flow rate, total protein secretion rate, α-amylase and cystatin-S compared to baseline. Remarkably IMRT did not significantly alter mucin 5B and 7, or the IgA secretion rate at any time point. At T1, all the analyzed proteins were associated with the OM outcomes. In addition, there was a significant inverse correlation between IgA concentration at T0 and the severity of OM during IMRT. CONCLUSION: This study revealed significant associations between several salivary proteins and OM in patients with head and neck cancer undergoing IMRT. Further longitudinal studies are needed to confirm these results. CLINICAL SIGNIFICANCE: The study contributes to the understanding of certain salivary proteins association with OM. This could be the first step towards identifying potential salivary markers that could offer perspectives for personalized medicine approaches to improve their quality of life (QoL). RESEARCH QUESTION: What is the association between salivary proteins and the occurrence and severity of OM in head and neck cancer patients? AIM: To assess the association between salivary protein composition with the clinical onset/severity of oral mucositis (OM) in head and neck cancer patients treated with intensity modulated radiotherapy. NULL HYPOTHESIS: There is no association between salivary proteins and onset/severity of OM in HNC patients.


Assuntos
Neoplasias de Cabeça e Pescoço , Radioterapia de Intensidade Modulada , Proteínas e Peptídeos Salivares , Estomatite , Humanos , Estudos Longitudinais , Neoplasias de Cabeça e Pescoço/radioterapia , Estomatite/etiologia , Estomatite/metabolismo , Masculino , Proteínas e Peptídeos Salivares/análise , Feminino , Pessoa de Meia-Idade , Radioterapia de Intensidade Modulada/efeitos adversos , Idoso , Saliva/metabolismo , Adulto , alfa-Amilases/análise , alfa-Amilases/metabolismo
2.
Pediatr Surg Int ; 38(2): 193-199, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34854975

RESUMO

PURPOSE: The purpose of this study was to investigate factors impacting transplant-free survival among infants with biliary atresia. METHODS: A multi-institutional, retrospective cohort study was performed at nine tertiary-level children's hospitals in the United States. Infants who underwent Kasai portoenterostomy (KP) from January 2009 to May 2017 were identified. Clinical characteristics included age at time of KP, steroid use, surgical approach, liver pathology, and surgeon experience. Likelihood of transplant-free survival (TFS) was evaluated using logistic regression, adjusting for patient and surgeon-level factors. Secondary outcomes at 1 year included readmission, cholangitis, reoperation, mortality, and biliary clearance. RESULTS: Overall, 223 infants underwent KP, and 91 (40.8%) survived with their native liver. Mean age at surgery was 63.9 days (± 24.7 days). At 1 year, 78.5% experienced readmission, 56.9% developed cholangitis, 3.8% had a surgical revision, and 5 died. Biliary clearance at 3 months was achieved in 76.6%. Controlling for patient and surgeon-level factors, each additional day of age toward operation was associated with a 2% decrease in likelihood of TFS (OR 0.98, 95% CI 0.97-0.99). CONCLUSION: Earlier surgical intervention by Kasai portoenterostomy at tertiary-level centers significantly increases likelihood for TFS. Policy-level interventions to facilitate early screening and surgical referral for infants with biliary atresia are warranted to improve outcomes.


Assuntos
Atresia Biliar , Transplante de Fígado , Atresia Biliar/cirurgia , Humanos , Lactente , Portoenterostomia Hepática , Estudos Retrospectivos , Resultado do Tratamento
3.
Hepatology ; 69(6): 2586-2597, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30723921

RESUMO

In patients with biliary atresia (BA), the extent of intrahepatic biliary fibrosis negatively correlates with successful surgical bypass of the congenital cholangiopathy as well as subsequent transplant-free survival. We recently linked the expansion of a population of prominin-1 (Prom1)-expressing hepatic progenitor cells to biliary fibrogenesis. Herein, we hypothesized that Prom1-expressing progenitor cells play a role in BA-associated fibrosis. Rhesus rotavirus (RRV)-mediated experimental BA was induced in newborn mice homozygous for the transgene Prom1cre-ert2-nlacz , which was knocked in to the Prom1 gene locus, thus creating functional Prom1 knockout (KO) mice, and their wildtype (WT) littermates. Clinical data and tissue samples from BA infants from the Childhood Liver Disease Research Consortium were analyzed. Extrahepatic biliary obliteration was present in both WT and KO mice; there was no difference in serum total bilirubin (TBili) levels. The intrahepatic periportal expansion of the PROM1pos cell population, typically observed in RRV-induced BA, was absent in KO mice. RRV-treated KO mice demonstrated significantly fewer cytokeratin-19 (CK19)-positive ductular reactions (P = 0.0004) and significantly less periportal collagen deposition (P = 0.0001) compared with WT. RRV-treated KO mice expressed significantly less integrin-ß6, which encodes a key biliary-specific subunit of a transforming growth factor (TGF) ß activator (P = 0.0004). Infants with successful biliary drainage (Tbili ≤1.5 mg/dL within 3 months postoperatively), which is highly predictive of increased transplant-free survival, expressed significantly less hepatic PROM1, CK19, and COLLAGEN-1α compared with those with TBili >1.5 (P < 0.05). Conclusion: Prom1 plays an important role in biliary fibrogenesis, in part through integrin-mediated TGF pathway activation.


Assuntos
Antígeno AC133/genética , Doenças dos Ductos Biliares/genética , Doenças dos Ductos Biliares/patologia , Atresia Biliar/genética , Rotavirus/patogenicidade , Animais , Animais Recém-Nascidos , Atresia Biliar/patologia , Biópsia por Agulha , Células Cultivadas , Modelos Animais de Doenças , Fibrose/patologia , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Mutação/genética , Distribuição Aleatória , Medição de Risco , Infecções por Rotavirus/patologia , Sensibilidade e Especificidade , Fatores de Transcrição/metabolismo
4.
J Prosthodont ; 29(3): 193-200, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31913534

RESUMO

PURPOSE: To systematically review the available evidence on screening tools to detect the psychological disturbance in patients with tooth loss and technically successful removable dentures (partial and complete). MATERIALS AND METHODS: The study protocol was registered with the National Institute of Health Research Database (I.D. CRD42017082125). The PICOS tool (patients, intervention, control, outcomes measure, and study design) was used to formulate an effective search strategy. Participants were adults (≥ 18), who were edentulous or had significant tooth loss (< 9 remaining teeth). The intervention included undergoing replacement with technically successful dentures (partial or complete). A control group of adults were either edentulous or had significant tooth loss and without dentures. Outcomes included assessing psychological disturbance due to treatment with dentures or due to no treatment using a validated tool. A structured search strategy was used to complete a standard systematic search of the electronic database without any date limit and/or language restriction. Only quantitative studies using a validated measuring tool to screen for psychological distress in adults with significant tooth loss were included. Two authors independently assessed the risk of bias in the included studies. Data homogeneity was assessed in regards to the screening tools to measure psychological disturbance following the management of tooth loss with dentures. The significant level was set at 0.05, using IBM SPSS Statistics 24.0 (SPSS Inc., New York, NY). The psychometric properties and the validation processes of the screening tools were assessed. RESULTS: From the original 3510 studies identified, only eight studies were found to meet the inclusion criteria. All eight studies used the same questionnaire to screen for the emotional distress of tooth loss. In addition, one study also used the Patient Health Questionnaire-9 (PHQ-9) to screen for the association of depression with tooth loss. Six studies suggested that a significant number of patients have difficulties in accepting tooth loss, were less confident, and had emotional distress related to tooth loss. However, two studies reported no significant link. All studies found a marked impact on functional activities and social interaction. However, four studies had a potentially biased selection process, and the questionnaire used was assessed to be at high-risk of measurement bias, as the development and validation process was not clear. There was also a lack of well-defined control groups in all studies. CONCLUSION: Tooth loss could cause psychological disturbance in some patients. To date, there is a lack of available tools that are suitable to screen and measure psychological disturbance in patients with tooth loss. Additional research is required to develop tools to identify and measure such impact and to recommend suitable interventions when needed.


Assuntos
Boca Edêntula , Perda de Dente , Adulto , Dentaduras , Depressão , Humanos , Qualidade de Vida
5.
J Prosthodont ; 28(4): 379-386, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30793816

RESUMO

PURPOSE: To determine if stereophotogrammetry could be used to determine the effects of obturators on facial contour in relation to the measurement of facial volumes. MATERIALS AND METHODS: Stereophotogrammetry images were recorded from 20 subjects with and without their obturators in place. These were converted into a stereolithographic format and overlaid. Registrations were made using the tissues on the normal areas of the face. Difference images were created, enabling surface areas and volumes to be calculated. To assess repeatability of measurement, 2 readings were recorded on each of 2 separate registrations. Data analysis between the sets of readings used correlation coefficients and paired t-tests. Coefficients of repeatability were also calculated. RESULTS: A comparison of readings for the surface areas showed the method of measurement was repeatable with no significant differences between the 2 repeated readings for registration 1 (p = 0.977, coefficient of repeatability = 101 mm2 ), registration 2 (p = 0.085, coefficient of repeatability = 106 mm2 ), and the mean of the two readings for registration 1 compared with registration 2 (p = 0.355, coefficient of repeatability = 103 mm2 ). Similar results were found for the volume measurements with no significant differences between the repeated readings for registration 1 (p = 0.862, coefficient of repeatability = 229 mm3 ), registration 2 (p = 0.200, coefficient of repeatability = 209 mm3 ), and the mean of the 2 readings for registration 1 compared with those for registration 2 (p = 0.131, coefficient of repeatability 339 mm3 ). There was a statistically significant range of volumes that appeared to have been restored by the obturators (p < 0.0005). CONCLUSIONS: Stereophotogrammetry is reliable in assessing the effects of obturators on facial form. In the sample of subjects, obturators generally appeared to be effective in supporting facial tissues following surgical resections of the maxilla and therefore contribute in some degree to the restoration of facial appearance.


Assuntos
Neoplasias de Cabeça e Pescoço , Fotogrametria , Face , Humanos , Maxila , Reprodutibilidade dos Testes
6.
J Surg Res ; 228: 228-237, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29907216

RESUMO

BACKGROUND: Biliary atresia (BA) is difficult to distinguish from other causes of cholestasis. We evaluated the use of liquid chromatography-mass spectroscopy (LC-MS) and bile acid profiles in the rapid, noninvasive diagnosis of BA. MATERIALS AND METHODS: Following Institutional Animal Care and Use Committee and Institutional Review Board approval, we used LC-MS to measure 26 bile acids in serum and stool samples from experimental models of BA and in urine, stool, and serum samples from non-cholestatic and cholestatic human infants. RESULTS: We first evaluated the utility of LC-MS to distinguish bile acid profiles between sham, bile duct ligation, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse models of BA. Serum bile acids were significantly higher and stool bile acids were significantly lower in experimental BA. Next, we evaluated samples from non-cholestatic, cholestatic non-BA, and BA infants. There was no significant difference between cholestatic non-BA and BA stool and urine samples. However, primary bile acids were significantly higher in BA versus cholestatic non-BA samples (128.1 ± 14.2 versus 61.2 ± 20.5 µM). In addition, the primary, conjugated bile acids glycochenodeoxycholic acid and taurochenodeoxycholic acid were significantly elevated in BA compared with cholestatic non-BA serum samples. Using a receiver operating characteristic curve, we found that a serum glycochenodeoxycholic acid concentration of 30 µM had a sensitivity of 100%, specificity of 83.3%, positive predictive value of 88.9%, and negative predictive value of 100% in the diagnosis of BA. CONCLUSIONS: Our data indicate that bile acid patterns can be used to distinguish experimental and human BA from non-cholestatic and, more importantly, cholestatic disease. This suggests that LC-MS may be useful in the accurate, rapid, and non-invasive diagnosis of BA.


Assuntos
Ácidos e Sais Biliares/análise , Atresia Biliar/diagnóstico , Colestase/diagnóstico , Hiperbilirrubinemia/sangue , Espectrometria de Massas/métodos , Adolescente , Animais , Atresia Biliar/sangue , Atresia Biliar/complicações , Atresia Biliar/urina , Criança , Pré-Escolar , Colestase/sangue , Colestase/etiologia , Colestase/urina , Cromatografia Líquida de Alta Pressão/métodos , Diagnóstico Diferencial , Modelos Animais de Doenças , Fezes/química , Feminino , Humanos , Hiperbilirrubinemia/etiologia , Hiperbilirrubinemia/urina , Lactente , Recém-Nascido , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos
7.
Oral Health Prev Dent ; 16(5): 425-429, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30460355

RESUMO

PURPOSE: Radiotherapy causes xerostomia in patients treated for head and neck cancer. This study investigated changes in quality and quantity of saliva after radiotherapy and possible associations between these changes and alterations in oral flora. MATERIALS AND METHODS: The study was a prospective cohort study of patients receiving radiotherapy for head and neck cancer. Suitable patients were recruited before treatment commenced, and informed consent was obtained. Patients were examined, and provided unstimulated and stimulated saliva samples. Quantity of saliva, buffering capacity and pH were measured. Oral flora was cultured from the saliva samples. Oral clearance of glucose and of lactose was measured. These interventions were repeated at intervals after radiotherapy had been completed. RESULTS: Eighteen patients were recruited. Stimulated and unstimulated saliva flow rates, glucose clearance, salivary pH and buffering capacity were significantly reduced after radiotherapy. Candida albicans counts were significantly increased. These increases were significantly correlated with reductions in stimulated and unstimulated salivary flow rates. Counts of lactobacilli, Streptococcus mutans and Bifidobacteriaceae increased, but not statistically significantly. CONCLUSIONS: Therapeutic radiotherapy significantly reduced the quality and quantity of saliva in head and neck cancer patients. These reductions were associated with increased C. albicans counts.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Microbiota/efeitos da radiação , Boca/microbiologia , Saliva/efeitos da radiação , Actinobacteria/efeitos da radiação , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Concentração de Íons de Hidrogênio , Lactobacillus/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radioterapia/efeitos adversos , Streptococcus mutans/efeitos da radiação , Xerostomia/etiologia
8.
J Surg Res ; 215: 250-256, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28688656

RESUMO

BACKGROUND: Biliary atresia (BA) is a congenital, progressive, fibro-obliterative disease of the extrahepatic biliary tree and the most common cause of end-stage liver disease in children. BA is characterized by extensive intrahepatic proliferating ductular reactions that may contribute to biliary fibrosis. Lineage tracing during experimental cholestasis indicates that cells within ductular reactions derive from PROM1-expressing hepatic progenitor cells. Given the role of Notch signaling in normal biliary development, we hypothesize that activated Notch signaling promotes the formation of ductular reactions in BA. METHODS: Liver samples collected from BA infants at Kasai portoenterostomy and age-matched controls, as well as from wild-type and Prom1 knockout mice with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced experimental cholestasis were analyzed histologically using immunofluorescence and by quantitative polymerase chain reaction. RESULTS: Increased expression of genes encoding Notch ligand JAG1 and its receptor NOTCH2 was observed in BA livers compared with control by quantitative polymerase chain reaction analyses. Livers of DDC-treated mice, which exhibit cytokeratin-19-positive ductular reactions typical of BA livers, demonstrated significant increases in the expression level of the gene encoding Notch2, as well as downstream Notch target gene Hes1 compared with control. Prom1 knockout mice exhibit diminished ductular reactions and decreased levels of Jag1 and Hes1 compared with littermate controls. CONCLUSIONS: Human BA and cholestasis induced by DDC are associated with Notch signaling activation. Null mutation of Prom1 is associated with decreased ductular reactions and decreased Notch signaling activation during DDC treatment. These data are consistent with Notch signaling promoting ductular reactions of Prom1 expressing progenitor cells in BA.


Assuntos
Atresia Biliar/metabolismo , Atresia Biliar/patologia , Receptor Notch2/metabolismo , Transdução de Sinais , Antígeno AC133/genética , Antígeno AC133/metabolismo , Animais , Biomarcadores/metabolismo , Estudos de Casos e Controles , Humanos , Imuno-Histoquímica , Proteína Jagged-1/metabolismo , Camundongos , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição HES-1/metabolismo , Regulação para Cima
9.
Pediatr Surg Int ; 33(12): 1315-1318, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28983658

RESUMO

Despite advances in our understanding of the pathogenesis of biliary atresia (BA), BA remains the most common cause of end-stage liver disease in children and the leading indication for pediatric liver transplantation. Age at time of Kasai portoenterostomy (KPE), performed to provide bile drainage, strongly correlates with transplant-free survival, mostly due to progression of intrahepatic fibrosis to cirrhosis. Unfortunately, challenges remain in recognizing that a jaundiced infant may have BA. To better diagnose infants with BA at an earlier age, population-based screening programs in countries such as Taiwan, Japan, and China have utilized stool color cards. Early results have been promising demonstrating earlier diagnosis, earlier KPE, and, hence, improved outcomes. Cost-effectiveness studies focused on stool color card screening in North America where the incidence of BA is much lower also project improved transplant-free survival rate with a savings in terms of healthcare expenditure. There is also evidence that postnatal serum bilirubin levels may also be effective as a screening tool given that all infants with BA exhibit hyperbilirubinemia at birth. The American Academy of Pediatrics (AAP) recently advocated studying the implementation of newborn screening for BA in the United States. Further efforts and analyses within the United States are ongoing, but current evidence is supportive of screening for BA even in low incidence countries.


Assuntos
Atresia Biliar/diagnóstico , Atresia Biliar/epidemiologia , Diagnóstico Precoce , Triagem Neonatal/métodos , Humanos , Incidência , Recém-Nascido , Estados Unidos/epidemiologia
10.
J Indian Prosthodont Soc ; 17(2): 207-211, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28584424

RESUMO

This paper describes a method used for the fabrication of a two-piece denture obturator for a patient who had surgical removal of the premaxilla due to squamous cell carcinoma. The patient had been wearing a two-piece obturator but encountered difficulty in inserting the prosthesis. In this case report, a lock-and-key mechanism was used to easily assemble the two-piece prosthesis intraorally. A keyhole was designed on the obturator to act as the lock while the denture was used as the key that fitted into the keyhole. This mechanism facilitated insertion and provided retention for the prosthesis. Heat-cured resilient acrylic material (Molloplast B®), which was used to fabricate the obturator, was a nonirritant, nontoxic, tissue-compatible material. It also did not contain plasticizers, therefore eliminating the problems associated with leaching out of plasticizers. The use of this flexible and resilient material allowed the obturator to engage in the undercuts without causing trauma and irritation to the soft tissues in the region of the defect. To conclude, the "lock-and-key" mechanism used in the fabrication of the two-piece denture obturator provided the patient with a lightweight, comfortable, and user-friendly form of prostheses.

11.
Dent Update ; 39(10): 694-6, 698-700, 702, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23367634

RESUMO

UNLABELLED: The general dental practitioner (GDP) plays a critical role in managing head and neck cancer patients. The first and most important role is to offer preventive services, particularly to smokers and to patients who drink alcohol to excess. It is of critical importance that every patient has a systematic examination of oral soft tissues when seen by a GDP. All patients with suspicious lesions should be referred for urgent attention to a specialist centre. Once oral cancer has been diagnosed, GDPs may be presented with patients requiring urgent dentistry, including extractions before commencement of treatment, requiring palliation of symptoms during treatment, or requiring general dentistry after treatment. Radiotherapy provides increased survival but has serious adverse consequences, which may be lifelong, including dry mouth, radiation caries, limitation of mouth opening and high risk of osteonecrosis after extractions. Extraction of teeth in irradiated bone should be referred to specialist centres. Improving survival rates and an ageing population mean that GDPs will see many more survivors of head and neck cancer in the future, with an increased burden of dental care in the longer-term and an increased need for monitoring and secondary prevention. CLINICAL RELEVANCE: The management of patients with head and neck cancer is complex and involves a multi-disciplinary team, both in the primary treatment but also in the long-term care. This paper reviews the consequences of treatment for head and neck cancer and gives practical advice for GDPs and their team in the long-term care of these patients.


Assuntos
Assistência Odontológica para Doentes Crônicos , Odontologia Geral , Neoplasias de Cabeça e Pescoço , Irradiação Craniana/efeitos adversos , Assistência Odontológica para Doentes Crônicos/efeitos adversos , Cárie Dentária/etiologia , Cárie Dentária/terapia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Mucosite/terapia , Osteorradionecrose/etiologia , Estomatite/terapia , Distúrbios do Paladar/etiologia , Xerostomia/etiologia
12.
Int J Prosthodont ; 35(5): 609­615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35649278

RESUMO

PURPOSE: To investigate the psychologic morbidities associated with tooth loss despite treatment with technically successful dentures. MATERIALS AND METHODS: This cross-sectional questionnaire-based study compared the psychologic disturbance and functional difficulties in two groups: individuals with tooth loss who wore optimal-quality removable dentures (test group), and individuals with tooth loss who did not wear dentures (control group). The questionnaire used was developed and validated previously. The short-form revised Eysenck personality questionnaire was also used to assess the relationship with personality traits. A total of 138 participants were recruited (denture group = 70; control group = 68). RESULTS: There was a significant difference in body image dissatisfaction between the groups (χ2 = 7.72, P value = .005). The denture group had 5.75-times higher probability than the control group of suffering from body image disturbance. Older patients were predicted to have 75% less probability of body image disturbance (OR = 0.25), and men were predicted to have up to 70% less disturbance (OR = 0.3). As for psychologic morbidities, participants in both groups presented with somatic symptoms related to depression or anxiety, which were nearly double that expected in the general population (15.7% and 7.8%, respectively). Furthermore, participants who complained about body image impairment were more likely to have higher scores on the neuroticism scale (OR = 3.64). CONCLUSION: Tooth loss and dentures could be associated with body image dissatisfaction and psychologic morbidity. Planning for patient-centered care is paramount prior to extracting any teeth and providing replacement options.


Assuntos
Perda de Dente , Masculino , Humanos , Perda de Dente/etiologia , Dentaduras , Imagem Corporal , Estudos Transversais , Inquéritos e Questionários
13.
Proc Natl Acad Sci U S A ; 105(49): 19532-7, 2008 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-19033455

RESUMO

Cyclic nucleotide phosphodiesterase (PDE) isoforms can influence disease pathogenesis and be novel therapeutic targets. Because lower cAMP levels may contribute to the decreased apoptosis that occurs in chronic lymphocytic leukemia (CLL), we assessed the expression levels of PDE isoforms in peripheral blood mononuclear cells (PBMC) of healthy adults and patients with CLL. We found a unique PDE mRNA signature in CLL: higher levels than in normal PBMC of PDE7B (increased approximately 23-fold) and lower levels of PDE3B, 4D, 5A, and 9A mRNA (each decreased approximately 30-fold). Increased PDE7B mRNA in CLL correlates with a 10-fold-higher expression of PDE7B protein and results in an increased contribution of PDE7 to total PDE activity. Consistent with the higher level of PDE7B expression, inhibitors of PDE7 (BRL-50481, IR-202) and a dual PDE4/PDE7 inhibitor (IR-284) selectively increase apoptosis in CLL cells compared with normal PBMC or B cells. Apoptosis of CLL cells promoted by inhibitors of PDE7 and PDE4/7 is attenuated by PKA inhibition, occurs via a mitochondrial-dependent process, and is associated with increased cAMP accumulation and down-regulation of the antiapoptotic protein survivin and of PDE7B. The increase in PDE7B expression and PDE7 inhibitor-promoted apoptosis implicates PDE7B as a drug target in CLL. Our findings identify a unique PDE signature in CLL and illustrate the utility of broad analyses of PDE isoform expression in human disease.


Assuntos
Linfócitos B/enzimologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 7/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 7/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/fisiopatologia , 3',5'-AMP Cíclico Fosfodiesterases/genética , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , Apoptose/imunologia , Linfócitos B/citologia , Divisão Celular/imunologia , Células Cultivadas , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 7/antagonistas & inibidores , Ativação Enzimática/imunologia , Regulação Enzimológica da Expressão Gênica , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Potencial da Membrana Mitocondrial , Inibidores da Fosfodiesterase 3 , Inibidores de Fosfodiesterase/farmacologia , RNA Mensageiro/metabolismo
14.
Radiother Oncol ; 164: 232-235, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34624407

RESUMO

Patients due to commence head and neck radiation treatment are expected to undergo a dental assessment and be deemed 'dentally fit'. Though this intervention is welcomed by the dental fraternity it is not without its challenges especially in human papilloma virus (HPV) related oropharyngeal cancer (OPC) which has seen a phenomenal rise over the past decade. This perspective piece presents these challenges and proposes a potential adaption of the dental assessment for HPV OPC patients though not necessarily exclusive to this tumour sub-site.


Assuntos
Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Neoplasias Orofaríngeas/radioterapia , Papillomaviridae , Infecções por Papillomavirus/complicações
15.
Br Dent J ; 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34887552

RESUMO

Introduction Patients are often keen to replace their missing teeth after radiotherapy for head and neck cancer (HNC), yet such replacement does not always take place.Aims This study aimed to investigate the influences on dentists' provision of dentures for patients treated with radiotherapy for HNC, including whether risk of osteoradionecrosis (ORN) is a factor influencing intention to provide dentures.Methods An online cross-sectional survey including a case scenario, self-reported behaviour and measures of factors (selected using the theoretical domains framework) that may affect dentists' decisions was completed by general dental practitioners (n = 150) and HNC multidisciplinary team dentists (n = 25) in England.Results Dentists' reluctance to provide dentures for HNC patients post-radiotherapy was often due to concerns about dry mouth and radiation caries rather than risk of ORN. Knowledge of guidelines and beliefs about consequences were independently associated with dentists' intention to replace missing teeth with dentures.Conclusion The likelihood of replacing missing teeth with dentures increased with awareness of clinical guidance on the use of dentures in HNC and that denture provision would have positive consequences that outweigh the costs.

16.
Biotechniques ; 70(2): 72-80, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33467918

RESUMO

Five established clearing protocols were compared with a modified and simplified method to determine an optimal clearing reagent for three-dimensionally visualizing fluorophores in the murine liver, a challenging organ to clear. We report successful clearing of whole liver lobes by modification of an established protocol (UbasM) using only Ub-1, a urea-based amino sugar reagent, in a simpler protocol that requires only a 24-h processing time. With Ub-1 alone, we observed sufficiently preserved liver tissue structure in three dimensions along with excellent preservation of fluorophore emissions from endogenous protein reporters and lipophilic tracer dyes. This streamlined technique can be used for 3D cell lineage tracing and fluoroprobe-based reporter gene expression to compare various experimental conditions.


Assuntos
Amino Açúcares , Corantes Fluorescentes , Fígado/diagnóstico por imagem , Ureia , Animais , Fluorescência , Camundongos
17.
Spec Care Dentist ; 41(3): 319-326, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33576541

RESUMO

OBJECTIVES: This observational study aims to determine individual dental doses in oropharyngeal cancer (OPC) patients managed by intensity modulated radiation treatment (IMRT). MATERIALS AND METHODS: OPC patients treated with IMRT had each tooth individually contoured on post-IMRT CT scans. The mean, maximum and minimum doses were calculated per tooth-based upon patient and tumor demographics (tumor size and nodal status). RESULTS: A total of 160 patients were included in this study. Escalating tumor size and nodal status led to an observed increase in Dmean doses to the dentition on the contralateral tumor side. A significant region in both jaws received >30 Gy in this tumor group. CONCLUSION: Tumor demographics were observed to influence RT doses to the dentition and need to be considered when providing a pre-RT dental assessment. The observed dose of >30 Gy in large spans of the dentition and jaws highlights future risk of dental deterioration and ORN with long term survival.


Assuntos
Neoplasias Orofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Neoplasias Orofaríngeas/radioterapia , Doses de Radiação , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X
18.
Eur J Prosthodont Restor Dent ; 18(1): 33-8, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20397501

RESUMO

The purpose of this study was to measure deformation of mandibular complete denture permanent bases after secondary curing. A cast of a flat mandibular edentulous ridge was duplicated ten times. A wax base was laid on the original cast, two wax sprues were attached and an overcast was made. The overcast was used to produce wax bases similar in outline and thickness on the duplicate casts. These were invested and following manufacturer's instructions ten similar acrylic resin bases were produced. The fitting surface of each denture base was scanned on a contacting scanner with an axis resolution of 1 microm and accurate to 25 microm. Denture teeth were waxed up on the base on the original master cast, an overcast was made to produce wax ups and tooth positions that were similar in outline and thickness to the original. These were processed, removed from the flasks and excess acrylic resin was removed. The denture bases were rescanned in an identical fashion to the first scanning procedure. Using commercially developed metrology software calibrated colour maps were generated for each denture base that illustrates measurements of differences between pairs of surfaces. Histograms showing distributions of distances between points were constructed. 50% of the points were separated by a mean 50 microm or less and that 90% of the points were separated by 160 microm or less. The maximum separation was of 380 microm. Complete denture permanent bases were not found to distort significantly as a result of being subjected to a second heat curing cycle as part of final processing of dentures.


Assuntos
Resinas Acrílicas/química , Materiais Dentários/química , Bases de Dentadura , Prótese Total Inferior , Sulfato de Cálcio/química , Técnica de Fundição Odontológica , Materiais para Moldagem Odontológica/química , Técnica de Moldagem Odontológica , Planejamento de Dentadura , Humanos , Processamento de Imagem Assistida por Computador , Teste de Materiais , Polivinil/química , Siloxanas/química , Software , Propriedades de Superfície , Dente Artificial
19.
J Dent ; 98: 103373, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32389732

RESUMO

OBJECTIVES: To investigate the effect of complete denture wearing on residual ridge resorption in edentulous patient compared with edentulous patient who never wore dentures. METHODS: Patients who had been edentulous for at least five year who had never worn dentures successfully were matched to edentulous denture wearing control patients. To control for factors possibly associated with alveolar ridge resorption patients who had been rendered edentulous in one arch before the other, smokers, those taking steroids, bisphosphonates, with histories of autoimmune diseases, diabetes mellitus or osteoporosis at any time during their period of edentulousness were excluded. Case and control groups were matched for age, sex and time since being rendered edentulous. Statistical analyses were undertaken using Person's Chi squared (X2) test and Fisher's exact test. RESULTS: 30 edentulous patients who had not worn dentures for at least five years were identified and matched with 30 controls. All control patients were the same age ± 2 years and had been edentulous for the same number of years ± 2 years of their respective controls. There was no significant difference between age and time since being rendered edentulous between case and control. Denture wearers had significantly more maxillary and mandibular residual alveolar ridge resorption than did non denture wearers. Severe ridge resorption was mostly confined to the denture wearing group. CONCLUSION: Patients wearing complete dentures for more than 5 years had significantly more residual alveolar ridge resorption than was found in non-denture wearing edentulous patients.


Assuntos
Perda do Osso Alveolar , Arcada Edêntula , Perda do Osso Alveolar/etiologia , Processo Alveolar , Estudos de Casos e Controles , Desgaste de Restauração Dentária , Prótese Total , Humanos , Mandíbula
20.
J Dent ; 98: 103353, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32360321

RESUMO

OBJECTIVES: To develop and validate a self-reporting measure to assess the psychological disturbance in adult patients with tooth loss and dentures Methods: Ethical approval obtained from the Health Research Authority NHS England (Ref:17/NI/0098). 128 participants (100 patients - 28 clinicians) were recruited to participate in the development and validation of the questionnaire. Inclusion criteria included adults (age ≥18) with tooth loss/dentures. Exclusion criteria included patients with a history of psychotic mental illness or patients who had treatment with dental implants. The development processes included: Phase 1. Development of questionnaire: describing the aims/target population of the questionnaire, generating a pool of items, defining the constructs to be measured, adapting psychological morbidity screening tools, Items reduction and producing a preliminary questionnaire. Phase 2. Validation of questionnaire: content validation, face validation, establishing construct validity, pilot testing and establishing reliability. RESULTS: Face and content validation indicated that the questionnaire was an appropriate tool to measure the impact of tooth loss and related psychological morbidities. Reliability analysis (Test re-test reliability/internal consistency) indicated the questionnaire has satisfactory reliability (correlation >0.7). Testing the theoretical hypothesis structure of the impact of tooth loss has also enhanced the construct validity of the questionnaire (domains correlated mildly (r>5 & <3) to strongly (r>5). Pilot testing confirmed the scale adequacy and wording clarity (>90 % of respondents). Results indicated that the developed questionnaire has adequate psychometric properties. CONCLUSION: A disease-specific measure that assesses the psychological impact of tooth loss and the effectiveness of interventions (i.e. dentures) has been developed and validated. CLINICAL SIGNIFICANT: A patient outcome measure was developed which could be used to assess the psychological impact of tooth loss and compare the effectiveness of various interventions like dentures and implants.


Assuntos
Perda de Dente , Adulto , Humanos , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários
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