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1.
JDR Clin Trans Res ; 7(1): 16-24, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33323035

RESUMO

BACKGROUND: For health care services to address the health care needs of populations and respond to changes in needs over time, workforces must be planned. This requires quantitative models to estimate future workforce requirements that take account of population size, oral health needs, evidence-based approaches to addressing needs, and methods of service provision that maximize productivity. The aim of this scoping review was to assess whether and how these 4 elements contribute to existing models of oral health workforce planning. METHODS: A scoping review was conducted. MEDLINE, Embase, HMIC, and EconLit were searched, all via OVID. Additionally, gray literature databases were searched and key bodies and policy makers contacted. Workforce planning models were included if they projected workforce numbers and were specific to oral health. No limits were placed on country. A single reviewer completed initial screening of abstracts; 2 independent reviewers completed secondary screening and data extraction. A narrative synthesis was conducted. RESULTS: A total of 4,009 records were screened, resulting in 42 included articles detailing 47 models. The workforce planning models varied significantly in their use of data on oral health needs, evidence-based services, and provider productivity, with most models relying on observed levels of service utilization and demand. CONCLUSIONS: This review has identified quantitative workforce planning models that aim to estimate future workforce requirements. Approaches to planning the oral health workforce are not always based on deriving workforce requirements from population oral health needs. In many cases, requirements are not linked to population needs, while in models where needs are included, they are constrained by the existence and availability of the required data. It is critical that information systems be developed to effectively capture data necessary to plan future oral health care workforces in ways that relate directly to the needs of the populations being served. KNOWLEDGE TRANSFER STATEMENT: Policy makers can use the results of this study when making decisions about the planning of oral health care workforces and about the data to routinely collect within health services. Collection of suitable data will allow for the continual improvement of workforce planning, leading to a responsive health service and likely future cost savings.


Assuntos
Mão de Obra em Saúde , Saúde Bucal , Atenção à Saúde , Planejamento em Saúde , Recursos Humanos
2.
BMC Oral Health ; 19(1): 88, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31126270

RESUMO

BACKGROUND: Dental caries in the expanding elderly, predominantly-dentate population is an emerging public health concern. Elderly individuals with heavily restored dentitions represent a clinical challenge and significant financial burden for healthcare systems, especially when their physical and cognitive abilities are in decline. Prescription of higher concentration fluoride toothpaste to prevent caries in older populations is expanding in the UK, significantly increasing costs for the National Health Services (NHS) but the effectiveness and cost benefit of this intervention are uncertain. The Reflect trial will evaluate the effectiveness and cost benefit of General Dental Practitioner (GDP) prescribing of 5000 ppm fluoride toothpaste and usual care compared to usual care alone in individuals 50 years and over with high-risk of caries. METHODS/DESIGN: A pragmatic, open-label, randomised controlled trial involving adults aged 50 years and above attending NHS dental practices identified by their dentist as having high risk of dental caries. Participants will be randomised to prescription of 5000 ppm fluoride toothpaste (frequency, amount and duration decided by GDP) and usual care only. 1200 participants will be recruited from approximately 60 dental practices in England, Scotland and Northern Ireland and followed up for 3 years. The primary outcome will be the proportion of participants receiving any dental treatment due to caries. Secondary outcomes will include coronal and root caries increments measured by independent, blinded examiners, patient reported quality of life measures, and economic outcomes; NHS and patient perspective costs, willingness to pay, net benefit (analysed over the trial follow-up period and modelled lifetime horizon). A parallel qualitative study will investigate GDPs' practises of and beliefs about prescribing the toothpaste and patients' beliefs and experiences of the toothpaste and perceived impacts on their oral health-related behaviours. DISCUSSION: The Reflect trial will provide valuable information to patients, policy makers and clinicians on the costs and benefits of an expensive, but evidence-deficient caries prevention intervention delivered to older adults in general dental practice. TRIAL REGISTRATION: ISRCTN: 2017-002402-13 registered 02/06/2017, first participant recruited 03/05/2018. Ethics Reference No: 17/NE/0329/233335. Funding Body: Health Technology Assessment funding stream of National Institute for Health Research. Funder number: HTA project 16/23/01. Trial Sponsor: Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL. The Trial was prospectively registered.


Assuntos
Cárie Dentária , Fluoretos , Cremes Dentais , Idoso , Análise Custo-Benefício , Inglaterra , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Escócia
3.
Br J Oral Maxillofac Surg ; 57(6): 505-514, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31128951

RESUMO

We conducted a systematic review of epidemiological studies to assess the prevalence of distal surface caries (DSC) in second molars adjacent to third molars. We searched the Cochrane Library, Lilacs, Embase, and Medline through Ovid® (Wolters Kluwer) to retrieve English and non-English papers from inception to June 2016, and supplemented this with a search of the references and by tracking citations. Three reviewers contributed: one reviewed all the papers, and the other two divided the rest between them. They extracted data, completed structured quality assessments with a validated risk of bias tool for observational studies, and categorised the summary scores. The search yielded 81 records and 11 studies were analysed. The considerable methodological diversity meant that five were not eligible for inclusion in the quantitative synthesis. A meta-analysis of six studies on the prevalence of DSC and a subgroup analysis of three on various third-molar angulations were indicated. The overall pooled prevalence estimate calculated with a random-effects model was 23% (95% CI 2% to 44%) among patients. Prevalence subtotals were 20% (95% CI 5% to 36%) for prospective, and 15% (95% CI 5% to 36%) for retrospective studies among teeth. A subgroup analysis of three studies with 1296 patients (1666 molars) yielded a prevalence of DSC of 36% (95% CI 5% to 67%) for mesial impactions and 22% (95% CI 1% to 42%) for horizontal impactions. DSC was present in 3% of distally-inclined impactions, (95% CI 1% to 5%) and in 7% (95% CI 1% to 13%) of vertical third molars. The studies varied. The risk of bias was low in one and moderate in two. European studies suggested that DSC may be present in about one in four referrals for the assessment of third molars, and that the risk is considerably higher in those with convergent third molar impactions.


Assuntos
Cárie Dentária , Dente Serotino , Cárie Dentária/diagnóstico , Cárie Dentária/terapia , Humanos , Dente Molar , Dente Serotino/patologia , Prevalência , Estudos Prospectivos , Encaminhamento e Consulta , Estudos Retrospectivos
4.
Br Dent J ; 222(7): 519-526, 2017 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-28387272

RESUMO

Objectives To identify guidelines on when and how frequently bitewing radiographs should be used in dentistry for the diagnosis of caries, and to provide an objective appraisal of their quality.Data sources MEDLINE (OVID), US National Guideline Clearinghouse (www.guideline.gov) and the Royal College of Surgeons of England (https://www.rcseng.ac.uk/fds/publications-clinical-guidelines/clinical_guidelines) websites were searched using a variety of relevant search terms (2 August 2016).Data selection Publications were included if they made recommendations on the issue of when and how frequently radiographs should be used in any dentally-related specialty pertaining to the diagnosis of caries; and/or if they were aimed at the individual practitioner (any health professional working within dentistry) and/or patients.Data analysis Thirteen published guidelines were included and assessed using the AGREE II instrument.Conclusions There was a significant variation amongst the guidelines in the recommendations at what age radiography should be undertaken. There was also disagreement on the frequency of repeat radiographs and how this is influenced by the age of the patient and their caries risk.


Assuntos
Guias de Prática Clínica como Assunto , Radiografia Interproximal/normas , Humanos , Radiografia Interproximal/estatística & dados numéricos , Fatores de Tempo
5.
Br Dent J ; 219(3): E1, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-26271885

RESUMO

BACKGROUND: There is a lack of evidence and poor understanding of quality measurement and improvement in dentistry. The aim of this study was to undertake a nationally representative survey of the public in England to explore their views on the meaning of quality in dentistry. METHODS: A cross sectional survey of the adult population (18 years and over) of England was undertaken. A sample size of 500 was set to provide a precision to plus or minus 5% after allowing for item non-response. A quota sampling approach was used, with predetermined quotas set for sex, age, working status and tenure to ensure the sample was nationally representative. Question selection and design were informed by the literature and a series of interviews with the public. Simple content analysis was used to identify themes in the responses to open questions. Dental service use, gender, age, ethnicity and social class were recorded. Frequency distributions were computed and outputs were cross-tabulated with various population sub-group categories. RESULTS: Five hundred and thirteen people were interviewed. Approximately 20% of patients reported that their care was suboptimal; a third thought it was poor value for money and 20% did not trust their dentist. Good interpersonal communication, politeness and being put at ease were the most important factors that elicited positive responses. Negative factors were cost of care and waiting times. In making an assessment of quality, access (40% of all responses), technical quality of care (35%), professionalism (30%), hygiene/cleanliness (30%), staff attitude (27%), pain-free treatment (23%), value for money (22%), and staff putting patients at ease (21%) all emerged as important factors. CONCLUSIONS: Quality in dentistry is multi-dimensional in nature, and includes different elements and emphases to other areas of healthcare. The results will inform the development of a measure of quality in dentistry.


Assuntos
Assistência Odontológica , Garantia da Qualidade dos Cuidados de Saúde/métodos , Feminino , Humanos , Masculino , Inquéritos e Questionários
6.
Dentomaxillofac Radiol ; 44(1): 20140225, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25270063

RESUMO

OBJECTIVES: To identify guidelines on the clinical use of CBCT in dental and maxillofacial radiology, in particular selection criteria, to consider how they were produced, to appraise their quality objectively and to compare their recommendations. METHODS: A literature search using MEDLINE (Ovid(®)) was undertaken prospectively from 1 January 2000 to identify published material classifiable as "guidelines" pertaining to the use of CBCT in dentistry. This was supplemented by searches on websites, an internet search engine, hand searching of theses and by information from personal contacts. Quality assessment of publications was performed using the AGREE II instrument. Publications were examined for areas of agreement and disagreement. RESULTS: 26 publications were identified, 11 of which were specifically written to give guidelines on the clinical use of CBCT and contained sections on selection criteria. The remainder were a heterogeneous mixture of publications that included guidelines relating to CBCT. Two had used a formal evidence-based approach for guideline development and two used consensus methods. The quality of publications was frequently low as assessed using AGREE II, with many lacking evidence of adequate methodology. There was broad agreement between publications on clinical use, apart from treatment planning, in implant dentistry. CONCLUSIONS: Reporting of guideline development is often poorly presented. Guideline development panels should aim to perform and report their work using the AGREE II instrument as a template to raise standards and avoid the risk of suspicions of bias.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Guias de Prática Clínica como Assunto , Radiografia Dentária , Consenso , Odontologia Baseada em Evidências , Humanos
7.
Br Dent J ; 217(9): E17, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25377846

RESUMO

OBJECTIVES: Key reforms in England and Japan have called for greater clinical leadership from general dental practitioners to deliver improvements in the quality of care for patients. In England, the reorganisation of the National Health Service has led to the development of Local Professional Networks to ensure services are clinically led, patient and outcome focused. In Japan, the rapidly changing demographics have led to calls for general dental practitioners to become more active in meeting the emerging population health challenges. Both require engagement at a strategic and a local level. However, little is known about what is meant by clinical leadership in dentistry or what training needs exist. The aim of this study was to develop and pilot a questionnaire to understand what general dental practitioners feel is important about clinical leadership and how they rate themselves. METHODS: A 61-item questionnaire was developed from the literature, an earlier qualitative study and refined through cognitive interviews. Questionnaires were distributed to general dental practitioners across the North West of England and Tokyo, using random sequence generation. For each item, the participant had to record whether they thought the statement was an important component of clinical leadership and how they rated themselves. Both were rated using a seven-point Likert scale. Data reduction was undertaken using principal component analysis to examine for factor loadings within the questionnaire. Differences in mean scores were also used to highlight substantive differences in how general dental practitioners rated the different components of leadership and how they rated themselves. RESULTS: The response rate for the pilot was low (22.9% and 7.5% for North West and Tokyo respectively). The items that were considered to be important in leadership reduced to two components in the North West (accounting for 62.1% of the total variance): 'How to lead' and 'How not to lead'. In Tokyo, 56.4% of the total variance was explained by three components: 'Demonstrating personal qualities', 'Working with others' and 'How not to lead'. When the self-rated items were reduced, three factors were found to be important in the North West: 'Working with others', 'Setting direction' and 'Managing services' (55.1% of the variance). 'Working with others', 'Demonstrating personal qualities', 'Pragmatism', 'Setting direction' and 'Improving services' were found to be important in Tokyo (52.8% of the variance). The questionnaire items relating to integrity, team-working and having a positive attitude during difficult times were rated highly by both groups. Items relating to providing vision for team, being assertive and having a positive attitude had the greatest mean difference, suggesting possible areas of training need. CONCLUSION: The nature of the pilot study and the poor response rate makes any conclusion difficult to infer. Among those that participated, leadership was understood to be more important at a practice level rather than at a strategic level. The questionnaire should be refined further based on the results of the pilot and the data reduction.


Assuntos
Serviços de Saúde Bucal/organização & administração , Odontólogos , Liderança , Inglaterra , Projetos Piloto , Inquéritos e Questionários , Tóquio
8.
Caries Res ; 47 Suppl 1: 22-39, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24107605

RESUMO

It is widely acknowledged that parental beliefs (self-efficacy) about oral health and parental oral health-related behaviours play a fundamental role in the establishment of preventative behaviours that will mitigate against the development of childhood dental caries. However, little attention has been given to the wider perspective of family functioning and family relationships on child oral health. For oral health researchers, exploration of this association requires the use of reliable, valid and appropriate assessment tools to measure family relationships. In order to promote methodologically sound research in oral health, this systematic review aims to provide a guide on self-report psychometric measures of family functioning that may be suitable to utilize when exploring childhood dental caries. This systematic review has identified 29 self-report measures of family functioning and evaluated them in terms of their psychometric support, constructs measured and potential utility for oral health research. The majority of the measures reported adequate levels of reliability and construct validity. Construct evaluation of the measures identified five core domains of family functioning, namely 'communication', 'cohesion/engagement', 'control', 'involvement' and 'authoritative/rigid parenting style'. The constructs were subsequently evaluated with respect to their potential relevance to child oral health. Herewith this review provides a framework to guide future research to explore family functioning in furthering our understanding of the development of childhood dental caries.


Assuntos
Cárie Dentária/etiologia , Relações Familiares , Criança , Comunicação , Cárie Dentária/psicologia , Saúde da Família , Comportamentos Relacionados com a Saúde , Humanos , Saúde Bucal , Relações Pais-Filho , Poder Familiar
9.
Neurology ; 74(7): 565-71, 2010 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-20157158

RESUMO

OBJECTIVES: To explore a potential expansion of the phenotypic and genotypic characteristics of Finnish variant late-infantile neuronal ceroid lipofuscinosis (NCL), we screened a collection of 47 patients with clinically diagnosed NCL in whom no molecular diagnosis had been made. METHODS: We used PCR amplification of genomic DNA, followed by fluorescent-labeled dideoxy-nucleotide chain termination sequencing and multiplex ligation-dependent probe amplification, to screen our cohort of patients for mutations in CLN5. We collected ethnic background, clinical, and pathologic information, as available, to clarify the breadth of CLN5 disease expression and to explore possible genotype-phenotype correlations. RESULTS: We identified 10 patients with pathogenic CLN5 mutations, including 11 mutations not previously described: 4 missense, 5 out-of-frame insertion/deletion mutations, and 2 large intragenic deletions. We also documented 3 previously reported CLN5 mutations. The age at disease onset in this cohort is predominantly juvenile rather than late infantile. Importantly, we have identified 2 adult-onset patients who share a common pathogenic allele. The majority of patients presented with motor and visual impairments and not seizures. In those patients with available longitudinal data, most had progressed to global neurodevelopmental and visual failure with seizures within 1 to 4 years. CONCLUSIONS: Our study suggests that CLN5 mutations 1) are more common in patients with neuronal ceroid lipofuscinosis (NCL) than previously reported, 2) are found in non-Finnish NCL patients of broad ethnic diversity, and 3) can be identified in NCL patients with disease onset in adult and juvenile epochs. CLN5 genetic testing is warranted in a wider population with clinical and pathologic features suggestive of an NCL disorder.


Assuntos
Proteínas de Membrana/genética , Lipofuscinoses Ceroides Neuronais/genética , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Etnicidade/genética , Finlândia , Humanos , Proteínas de Membrana Lisossomal , Mutação , Lipofuscinoses Ceroides Neuronais/etnologia , Polimorfismo Genético , Análise de Sequência de DNA , Adulto Jovem
10.
J Appl Microbiol ; 103(4): 1158-69, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17897221

RESUMO

AIMS: To isolate micro-organisms capable of utilizing polyhexamethylene biguanide (PHMB) as a sole source of nitrogen, and to demonstrate biodegradation of the biocide. METHODS AND RESULTS: Two consortia of bacteria were successfully enriched at the expense of PHMB, using sand from PHMB-treated swimming pools as inoculum. Both consortia were shown to contain bacteria belonging to the genera Sphingomonas, Azospirillum and Mesorhizobium. It was shown that the presence of both Sphingomonas and Azospirillum spp. was required for extensive growth of the consortia. In addition, the Sphingomonads were the only isolates capable of growth in axenic cultures dosed with PHMB. Using a stable isotope (15N)-labelled PHMB, metabolism of the biocide by both consortia was demonstrated. By comparing the level of 15N atom incorporation into bacterial DNA after growth on either 15N-PHMB or 15N-labelled NH4Cl, it was possible to estimate the percentage of PHMB biodegradation. CONCLUSIONS: The microbial metabolism of nitrogen from the biguanide moiety of PHMB has been demonstrated. It was revealed that Sphingomonas and Azospirillum spp. are the principal organisms responsible for growth at the expense of PHMB. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to demonstrate the microbial metabolism of PHMB.


Assuntos
Bactérias/metabolismo , Biguanidas/metabolismo , Desinfetantes/metabolismo , Microbiologia Industrial/métodos , Azospirillum/genética , Azospirillum/crescimento & desenvolvimento , Azospirillum/isolamento & purificação , Azospirillum/metabolismo , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Técnicas de Tipagem Bacteriana/métodos , Biodegradação Ambiental , Meios de Cultura , DNA Bacteriano/metabolismo , Radioisótopos de Nitrogênio/farmacocinética , Filogenia , Sphingomonas/genética , Sphingomonas/crescimento & desenvolvimento , Sphingomonas/isolamento & purificação , Sphingomonas/metabolismo
11.
Phys Rev E Stat Nonlin Soft Matter Phys ; 74(4 Pt 1): 041116, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17155031

RESUMO

We study front propagation when an invading species competes with a resident; we assume nearest-neighbor preemptive competition for resources in an individual-based, two-dimensional lattice model. The asymptotic front velocity exhibits an effective power-law dependence on the difference between the two species' clonal propagation rates (key ecological parameters). The mean-field approximation behaves similarly, but the power law's exponent slightly differs from the individual-based model's result. We also study roughening of the front, using the framework of nonequilibrium interface growth. Our analysis indicates that initially flat, linear invading fronts exhibit Kardar-Parisi-Zhang (KPZ) roughening in one transverse dimension. Further, this finding implies, and is also confirmed by simulations, that the temporal correction to the asymptotic front velocity is of O(t(-2/3)).


Assuntos
Comportamento Competitivo/fisiologia , Ecossistema , Teoria dos Jogos , Interações Hospedeiro-Parasita/fisiologia , Modelos Biológicos , Dinâmica Populacional , Comportamento Predatório/fisiologia , Adaptação Fisiológica , Animais , Simulação por Computador , Comportamento Cooperativo , Humanos , Simbiose
12.
JAMA ; 281(24): 2316-20, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10386556

RESUMO

CONTEXT: Germline mutations of the DNA mismatch repair (MMR) genes hMLH1 and hMSH2 have been shown to cosegregate with the colorectal cancer phenotype in multiple hereditary nonpolyposis colorectal cancer (HNPCC) pedigrees. However, the frequency of these mutations among African American patients with colorectal cancer is unknown. OBJECTIVE: To investigate the frequency of germline alterations of the DNA MMR genes hMLH1 and hMSH2 among African Americans affected by HNPCC and early-age onset colorectal cancer. DESIGN, SETTING, AND PATIENTS: Forty unrelated African American HNPCC and early-age onset colorectal cancer patients (8 women, 3 men) were identified from the cancer registry at a National Cancer Institute-designated referral center, 11 of whom were available for and agreed to study participation from January 1997 to February 1998. The mean age of the subjects was 44 years. An additional 50 age- and sex-matched African Americans without personal or family history of colorectal, endometrial, ovarian, urinary tract, or upper gastrointestinal tract malignancy were also studied as a polymorphism control population. In all subjects, genomic DNA was amplified by polymerase chain reaction for all hMLH1 and hMSH2 exons and screened using single-strand conformation polymorphism (SSCP) analysis. Samples demonstrating significant SSCP shifts underwent automated nucleotide sequencing analysis. MAIN OUTCOME MEASURE: Frequency of hMLH1 and hMSH2 germline alterations in the affected and control subjects. RESULTS: Germline hMLH1 and hMSH2 mutations were detected in 3 (27%) of the African American colorectal cancer probands studied. Each mutation was novel. Two hMLH1 (an A-->T transversion at codon 26 and a GG-->AT substitution across codons 177 and 178) mutations and 1 hMSH2 mutation (a C-->T transition at codon 389) were identified in 3 female study subjects. Six other hMLH1 and hMSH2 alterations were detected but were presumed to be polymorphisms. Neither missense mutation (at codons 26 and 389) was detected in the control population. CONCLUSIONS: The results of our analysis support an association between the 3 mutations reported and predisposition to colorectal cancer. Further studies are needed to define DNA MMR gene-associated colorectal cancer in African Americans, an understudied population at increased risk of fatal colorectal cancer.


Assuntos
População Negra/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais/genética , Reparo do DNA , Proteínas de Ligação a DNA , Mutação em Linhagem Germinativa , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Proteínas de Transporte , Neoplasias Colorretais/etnologia , Neoplasias Colorretais Hereditárias sem Polipose/etnologia , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Proteínas Nucleares , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples
14.
Cancer Res ; 57(17): 3798-803, 1997 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-9288790

RESUMO

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome characterized by early age of onset colorectal cancer (mean 45 years) as well as endometrial, urinary tract, and upper gastrointestinal adenocarcinomas. The HNPCC phenotype has been shown to segregate with germline mutations in the human homologues of the DNA mismatch repair genes MSH2, MLH1, PMS1, and PMS2. However, the majority of published DNA mismatch repair gene mutation surveys associated with HNPCC kindreds report multiple levels of preselection, including 2p and 3p chromosomal linkage analysis and the evaluation of microsatellite instability of proband colorectal cancers prior to mutation analysis. For this reason, the concise contribution of each of the known DNA mismatch repair genes to the HNPCC phenotype remains unknown. We report the results of a genomic DNA-based analysis of hMSH2 and hMLH1 germline mutations in 32 unrelated Eastern United States HNPCC kindreds. These families were selected for study on the basis of phenotype only. We identified three hMSH2 and six hMLH1 mutations in eight families, for a positive mutation rate of 25%. Two mutations were identified in one of the families. Four of the mutations detected have not been reported in the literature previously. One of the mutation-positive families is African American; the others were of European-American ancestry. These results provide a clarification of the contribution of hMSH2 and hMLH1 to the HNPCC phenotype and suggest that in the majority of Eastern United States HNPCC kindreds selected by phenotype alone, the molecular genetic basis for the disease remains unknown.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Proteínas de Ligação a DNA , Mutação em Linhagem Germinativa/genética , Proteínas/genética , Proteínas Proto-Oncogênicas/genética , Adulto , Sequência de Bases , Família , Feminino , Testes Genéticos , Genótipo , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteína 2 Homóloga a MutS , Fenótipo , Reação em Cadeia da Polimerase , Estados Unidos
15.
Dis Colon Rectum ; 39(6): 649-53, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8646951

RESUMO

INTRODUCTION: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition characterized by early age of onset colorectal cancer, right-sided predominance, excess of synchronous and metachronous colonic neoplasms, and extracolonic cancers. The purpose of this study is to report clinical characteristics of HNPCC families in our registry. METHODS: This is a retrospective review of medical records of patients with a significant history of colorectal cancer and interviews with their families. RESULTS: Three hundred one people with cancer in 40 HNPCC families were identified. In 284 of 301 (94 percent) people, 363 cancers were identified. Colorectal cancer only was identified in 182 people (64 percent) and, in conjunction with extracolonic tumors, in another 31 people (11 percent). Extracolonic cancer alone was noted in 71 people (25 percent). Median age at diagnosis of colorectal cancer was 48 (range, 17-92) years. In patients with documented pathology, right-sided tumors predominated (55 percent), synchronous and metachronous tumors were noted in 53 percent, and synchronous of metachronous adenomas were documented in 51 percent of people. Generational anticipation was also noted. CONCLUSION: This study demonstrates and confirms characteristics that have been described in HNPCC. Namely, early age of onset of colorectal cancer, right-sided predominance, multiple synchronous and metachronous neoplasms, increased extracolonic cancers, and generational anticipation.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Primárias Múltiplas/genética , Segunda Neoplasia Primária/genética , Sistema de Registros , Adolescente , Adulto , Distribuição por Idade , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Linhagem , Vigilância da População , Estudos Retrospectivos
16.
Am J Physiol ; 242(4): G380-7, 1982 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7065260

RESUMO

The factors that regulate the rate of mucus secretion in intestinal goblet cells are only partially defined. Autoradiographic and ultrastructural studies demonstrated that muscarinic cholinergic agents accelerate the exocytosis of mucus from goblet cells in the crypts throughout the small and large intestine, both in vivo and in mucosal organ culture. The present study seeks to identify other factors that may alter mucous secretory rates. Mucosal explants were exposed to potential secretagogues and inhibitors in the organ-culture system and analyzed by light and electron microscopy, alpha- and beta-Adrenergic agents, gastrointestinal regulatory peptides, serotonin, histamine, and dibutyryl cyclic nucleotides were tested over wide concentration ranges. With the exception of histamine, none of these agents accelerated or inhibited the exocytosis of mucous granules. Histamine was effective at the concentration of 10(-4) M and induced rapid, compound exocytosis by crypt goblet cells in mucosal explants from the colon but not from small intestine. The response to histamine was unaffected by atropine. Goblet cells on the mucosal surface released mucus by compound exocytosis when exposed to mustard oil, a nonspecific chemical irritant, but not when exposed to histamine or cholinergic agents.


Assuntos
Mucosa Intestinal/metabolismo , Acetilcolina/farmacologia , Animais , Atropina/farmacologia , Colo/metabolismo , Duodeno/metabolismo , Hormônios Gastrointestinais/farmacologia , Histamina/farmacologia , Íleo/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Fisostigmina/farmacologia , Coelhos , Serotonina/farmacologia
17.
Diabetes Care ; 3(1): 38-40, 1980.
Artigo em Inglês | MEDLINE | ID: mdl-6250773

RESUMO

High-fiber diets have a beneficial impact on glucose metabolism of selected persons with diabetes mellitus. A major concern is the long-term effects of fiber intake on mineral and vitamin status. We measured serum concentrations of selected minerals and vitamins and also assessed three fat-soluble vitamins in 15 patients fed high-fiber diets for an average of 21 mo. Average values for serum calcium, phosphorus, alkaline phosphatase, iron-binding capacity, magnesium, and hemoglobin values were normal. Vitamin B12 and folic acid concentrations in serum were also normal. Indirect assessment suggested that these patients had adequate intakes of the fat-soluble vitamins A, D, and K. These preliminary observations suggest that high-fiber diets containing a wide variety of natural foods are well tolerated for up to 51 mo; we failed to detect evidence suggesting mineral or vitamin deficiency in these patients.


Assuntos
Celulose/uso terapêutico , Diabetes Mellitus/sangue , Dieta para Diabéticos , Fibras na Dieta/uso terapêutico , Minerais/sangue , Vitaminas/sangue , Glicemia/metabolismo , Diabetes Mellitus/dietoterapia , Feminino , Ácido Fólico/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Vitamina A/sangue , Vitamina B 12/sangue , Vitamina D/sangue , Vitamina K/sangue
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