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1.
Eur J Prosthodont Restor Dent ; 26(1): 2-15, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29461745

RESUMO

BACKGROUND: This systematic review aims to evaluate the survival of retaining or replacing deciduous teeth in hypodontia patients with a variety of prosthetic tooth replacement options, to evaluate prognostic factors associated with retaining deciduous teeth, and report on patient based outcomes with these treatment modalities. METHODS: MEDLINE, The Cochrane Central Register of Controlled Trials and Science Direct databases were searched (01/1980 - 08/2017) for studies reporting outcomes associated with retaining or replacing deciduous teeth via prosthetic means in adult hypodontia patients. RESULTS: Twenty-one articles were included. The following survival figures were reported; retaining deciduous tooth/teeth (83%-93%), resin-bonded bridgework (59-96.9%) and implants (86-100%). No survival data was reported for fixed or removable partial dentures. Prognostic factors for deciduous tooth survival, quality of life and patient satisfaction data were also reported. CONCLUSION: Within the limits of this review, retaining deciduous teeth have reasonable survival; however, studies beyond the third decade of life are lacking. Dental implants appear to be a highly successful long-term tooth replacement option with high patient satisfaction within this patient group, as have resin-bonded bridgework, albeit over the short to medium term. Tooth replacement options in the form of fixed and removable partial dentures were poorly reported upon.


Assuntos
Anodontia/terapia , Implantes Dentários , Prótese Parcial Fixa , Dente Decíduo/anormalidades , Adulto , Odontologia Baseada em Evidências , Humanos , Satisfação do Paciente , Qualidade de Vida
2.
J Dent ; 36(7): 494-9, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18513848

RESUMO

OBJECTIVES: The current study aimed to reach a greater understanding of psychosocial variables in patients who gag, and is a recognised gap within current literature. Obtaining a profile of patients who gag could provide valuable information in relation to future treatment planning and management of this type of difficulty. METHODS: All new patients aged > or =18 years, identified as having a difficulty with retching, and who attended the Anxiety Management Clinic, Department of Restorative Dentistry, Birmingham Dental Hospital, were invited to complete a brief questionnaire with questions related to general demographic data; difficulties with retching; and an oral health status measurement. This study has reported on 48 patients who attended the dental anxiety management clinic at Birmingham Dental Hospital and who presented with retching difficulties. One patient did not wish to take part in the study, leaving a final sample size of 47. The sample comprised 57% male (n=27) and 43% female (n=20) patients. RESULTS: Retching was more commonly seen in the 40-49-year age group. Onset was frequently related to an earlier dental experience and over half the sample studied had experienced previous psychological difficulties. A fear of choking or suffocation was frequently expressed, supporting a cognitive model in terms of assessment and treatment. CONCLUSION: A number of themes were identified which would be worthy of further exploration. For example, the impact of previous or existing physical health problems such as respiratory complaints, family history of retching, and prevalence of other psychological difficulties. Through participation in this study, patients were able to reach a greater awareness of this commonly encountered difficulty within dentistry.


Assuntos
Engasgo/fisiologia , Vômito/psicologia , Adaptação Psicológica , Adolescente , Adulto , Fatores Etários , Obstrução das Vias Respiratórias/psicologia , Asfixia/psicologia , Ansiedade ao Tratamento Odontológico/psicologia , Assistência Odontológica/psicologia , Medo/psicologia , Feminino , Humanos , Masculino , Anamnese , Pessoa de Meia-Idade , Odorantes , Qualidade de Vida , Paladar/fisiologia , Escovação Dentária/efeitos adversos , Tato/fisiologia , Vômito/fisiopatologia
3.
Br Dent J ; 204(8): E13; discussion 442-3, 2008 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-18425075

RESUMO

BACKGROUND: With regard to the management of dental anxiety in general dental practice, it has been considered that general dental practitioners (GDPs) are well placed to treat adults with mild forms of dental anxiety. However, little is known about the specific anxiety management techniques being used by GDPs in the UK. Aim To determine the views and experiences of dental practitioners in their current use of anxiety management techniques, their undergraduate and post-graduation training in these techniques and future training needs. METHODS: A postal questionnaire was sent to a sample of GDPs working in the Midlands region (n = 750) in the UK. Dentists were randomly selected using lists provided by the primary care trusts for each locality. RESULTS: The response rate was 73% (n = 550). Of these, 90 were not included in the final analysis due to exclusion criteria set prior to questionnaire release. This left 460 questionnaires for analysis. Eighty-five percent of respondents agreed that dentists had a responsibility to help dentally anxious patients (n = 391). Dentists were asked their reasons for not using anxiety management techniques in practice. Psychological techniques, sedation (oral, inhalation, or intravenous) and hypnosis were reported as not having been used due to the paucity of time available in practice, a shortage of confidence in using these techniques and the lack of fees available under the NHS regulations. Also, 91% reported feeling stressed when treating anxious patients. When asked about the quality of teaching they had received (undergraduate and postgraduate), 65% considered that the teaching was less than adequate in the use of psychological methods, whereas 44% indicated that they would be interested in further training in psychological methods if financial support was available. CONCLUSION: The need for further training in managing the dentally anxious patient is supported by dentists' lack of confidence and inadequate training in treating such patients, as determined from the results of a postal questionnaire to UK GDPs.


Assuntos
Atitude do Pessoal de Saúde , Terapia Comportamental/educação , Ansiedade ao Tratamento Odontológico/terapia , Odontólogos/psicologia , Adulto , Terapia Comportamental/economia , Competência Clínica , Sedação Consciente/estatística & dados numéricos , Educação em Odontologia , Feminino , Odontologia Geral , Humanos , Masculino , Avaliação das Necessidades , Padrões de Prática Odontológica , Odontologia Estatal/economia , Inquéritos e Questionários , Reino Unido
4.
Dent Update ; 32(2): 90-2, 94-6, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15819152

RESUMO

Dental anxiety is a widespread problem and has a significant impact on the provision of dental care for the general population. Anxiety leads to avoidance of dental treatment and increased stress for dental practitioners. Traditionally, dental anxiety has been managed using pharmacological techniques. This article reviews alternative treatment approaches, including psychological and complementary therapies which can be used in managing dental anxiety and facilitating dental treatment. Many of these approaches are currently being used within the dental profession. Others are gaining a wider acceptance as to their usage. Where available, the evidence of their efficacy will be reviewed.


Assuntos
Ansiedade ao Tratamento Odontológico/prevenção & controle , Terapias Complementares , Humanos , Terapia de Relaxamento
5.
Br Dent J ; 192(6): 335-9; discussion 331, 2002 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-15552071

RESUMO

OBJECTIVE: To study the post-operative cognitive and psychomotor recovery from midazolam conscious sedation, after reversal with the benzodiazepine antagonist flumazenil over a prolonged recovery period. DESIGN: A prospective, double-blind, randomised, crossover trial. SETTING: Out-patient Sedation Department, Newcastle Dental Hospital and School METHOD: Eighteen patients, ASA I or II, received midazolam on two separate occasions to undergo equivalent dental treatment. Following treatment patients were reversed with intravenous flumazenil or saline (placebo) at alternate appointments. Assessment of mood and cognitive function was undertaken using a highly sensitive and specific computerised battery of cognitive tests administered by telephone. Cognitive and psychomotor tests were administered prior to sedation and every hour for 6 hours post reversal. RESULTS: Results indicated no significant effect of flumazenil on simple reaction time and choice reaction time but did show a trend of reversing the effects of midazolam on numeric working memory and word recognition. CONCLUSION: The cognitive and psychomotor effects of the sedation were not fully reversed by flumazenil. Cognitive impairments were still present up to 6 hours post-reversal, despite patients appearing clinically more alert. This has important implications for treatment protocols and discharge instructions.


Assuntos
Período de Recuperação da Anestesia , Antídotos/uso terapêutico , Cognição/efeitos dos fármacos , Flumazenil/uso terapêutico , Hipnóticos e Sedativos/administração & dosagem , Midazolam/administração & dosagem , Desempenho Psicomotor/efeitos dos fármacos , Adolescente , Adulto , Afeto/efeitos dos fármacos , Atenção/efeitos dos fármacos , Comportamento de Escolha/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Hipnóticos e Sedativos/antagonistas & inibidores , Masculino , Memória/efeitos dos fármacos , Midazolam/antagonistas & inibidores , Pessoa de Meia-Idade , Placebos , Estudos Prospectivos , Tempo de Reação/efeitos dos fármacos
6.
J Clin Periodontol ; 27(5): 285-301, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10847531

RESUMO

Most dentifrices and some mouthrinses now contain 1 or more active anticalculus agents to achieve so-called tartar control. The aim of this article is to review the research associated with the development of anticalculus agents and to evaluate in some detail, the efficacy of those agents which are currently available in dentifrice products.


Assuntos
Cálculos Dentários/prevenção & controle , Cálculos Dentários/tratamento farmacológico , Dentifrícios/química , Dentifrícios/uso terapêutico , Humanos , Antissépticos Bucais/química , Antissépticos Bucais/uso terapêutico
7.
J Prosthet Dent ; 83(3): 367-70, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10709048

RESUMO

This article describes a new procedure for producing cross sections of a cast, a denture, or an impression and a method of presenting the results in graphic form to show variance. To test the method, identically colored, duplicate dentures were embedded in plaster blocks formed from a precisely engineered and calibrated brass box. A modified jig and saw allowed the plaster blocks to be positioned, held, and sectioned at any required location with a high degree of accuracy. The sectioned surfaces of the duplicate dentures were scanned. The resultant profiles were registered in location frames on the computer screen, traced by computer to produce outlines, and printed onto transparent film for the purpose of comparison. In vitro results showed the relationship between congruent outer forms and provided clear visual evidence of the accuracy of the procedure used and a way to further in vivo use.


Assuntos
Técnica de Moldagem Odontológica/instrumentação , Dentaduras , Processamento de Imagem Assistida por Computador/métodos , Modelos Dentários , Sulfato de Cálcio , Calibragem , Gráficos por Computador , Terminais de Computador , Engenharia/instrumentação , Humanos , Reprodutibilidade dos Testes , Propriedades de Superfície
8.
Br Dent J ; 188(2): 99-102, 2000 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-10689772

RESUMO

AIM: A major role of the hospital based secondary care service in restorative dentistry is to accept referrals in order to formulate treatment plans. The aim of this survey was to improve service provision at Newcastle Dental Hospital by establishing baseline quality perceptions from referring general dental practitioners (GDPs). METHOD: A postal questionnaire was sent to 393 randomly selected local GDPs, with a response rate of 67%. RESULTS: Results indicated great demand for advice and treatment which was higher than expected for temporomandibular joint problems. 42% of GDPs felt that treatment plans were not helpful and the period of waiting for a response following consultation too long. The reasons for this perception are discussed. CONCLUSIONS: The need for better communication between primary and secondary care was highlighted, as was the distinct preference of GDPs for hospital consultants rather than registered specialist practitioners to carry out specialist treatment.


Assuntos
Atitude do Pessoal de Saúde , Unidade Hospitalar de Odontologia , Odontologia Geral , Comunicação , Consultores , Restauração Dentária Permanente , Inglaterra , Necessidades e Demandas de Serviços de Saúde , Humanos , Relações Interprofissionais , Planejamento de Assistência ao Paciente , Projetos Piloto , Qualidade da Assistência à Saúde , Encaminhamento e Consulta , Especialidades Odontológicas , Inquéritos e Questionários , Transtornos da Articulação Temporomandibular/terapia , Fatores de Tempo
9.
Meat Sci ; 53(4): 227-31, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22063464

RESUMO

Using the polymerase chain reaction (PCR) and DNA extracted from muscle, a single pair of oligonucleotide primers can yield amplification products from several members of the actin multigene family simultaneously. These multiple PCR products form species-specific "fingerprints" on gel electrophoresis which may be useful for meat authentication. However, for analysis of meat mixtures, the presence of a single band unique to a species would have many advantages over a multi-component fingerprint. A procedure is described in which primers amplify at a single actin gene locus, giving a positive band with DNA extracted from chicken and turkey, but no reaction with duck, pheasant, porcine, bovine, ovine or equine DNA. The chicken signal was clearly detectable with DNA from meat admixtures containing 1% chicken/99% lamb and from meat heat-treated at 120°C. For further discrimination, the chicken PCR product could be differentiated from turkey by restriction enzyme digestion.

10.
Anim Biotechnol ; 9(2): 89-100, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9713675

RESUMO

Actins constitute a family of highly-conserved multifunctional intracellular proteins, best known as myofibrillar components in striated muscle fibres. Most vertebrate genomes contain numerous actin genes with high sequence homology in protein coding regions but considerable variability in intron number and sizes. This genetic diversity can be utilised for livestock speciation purposes. The high sequence conservation has enabled a single pair of oligonucleotides to be used to prime the polymerase chain reaction (PCR) with DNA extracted from all animals so far studied. Multiple amplification products were obtained which on gel electrophoresis constituted characteristic species-specific 'fingerprints'. The patterns were reproducible, did not vary between individuals of the same breed or between different breeds within a species, and could be generated even from heat-processed muscle held at 120 degrees C for one hour. Given the capacity of PCR to amplify relatively short sequences in highly-degraded DNA, this approach may be suitable for authentication of processed meat products.


Assuntos
Actinas/genética , Bovinos/genética , Galinhas/genética , Cavalos/genética , Produtos da Carne/classificação , Família Multigênica , Ovinos/genética , Sequência de Aminoácidos , Animais , Primers do DNA , Sondas de DNA , DNA Complementar , Produtos da Carne/análise , Produtos da Carne/normas , Dados de Sequência Molecular , Reação em Cadeia da Polimerase
11.
Pharmacogenetics ; 8(6): 543-52, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9918138

RESUMO

To investigate whether interindividual variation in CYP2E1 levels can be explained by genetic polymorphism, we analysed DNA samples from 40 healthy individuals by single-strand conformational polymorphism analysis for polymorphisms in the CYP2E1 coding sequence and promoter region. DNA sequencing of samples showing mobility shifts on single-strand conformational polymorphism detected polymorphisms at positions -316 (A to G), -297 (T to A), -35 (G to T), 1107 (G to C; intron 1), 4804 (G to A Val179Ile; exon 4) and 10157 (C to T; exon 8). All individuals positive for either A(-316)G, G(-35)T, G(4804)A or the previously described RsaI polymorphism at -1019 were also positive for T(-297)A, which had the highest allele frequency of the observed polymorphisms (0.20). A(-316)G, G(-35)T and G(4804)A were detected at allele frequencies of 0.022, 0.052 and 0.013, respectively. The functional significance of the upstream polymorphisms was examined by preparing constructs of positions -549 to +3 of CYP2E1 containing the observed combinations of the polymorphisms fused to luciferase reporter genes and transfecting HepG2 cells. For the G(-35)T/T(-297)A construct, a 1.8-fold increase in luciferase activity compared with the wild-type sequence (P = 0.06) and 2.5-fold compared with T(-297)A only (P = 0.025) was observed. No significant difference in activity was observed between the other constructs. The significance of the predicted Val179Ile base change from G(4804)A was determined by expression of the wild-type and mutated full length cDNAs in lymphoblastoid cells. No significant difference in kinetic constants for chlorzoxazone hydroxylation between mutant and wild-type was observed. In summary, this study demonstrated six novel CYP2E1 polymorphisms, including three upstream of the promoter, but with the possible exception of G(-35)T, none appeared to be of functional significance.


Assuntos
Citocromo P-450 CYP2E1/genética , Polimorfismo Conformacional de Fita Simples , Sequência de Bases , Linhagem Celular , Clorzoxazona/metabolismo , Primers do DNA , Frequência do Gene , Ligação Genética , Humanos , Microssomos Hepáticos/enzimologia , Reação em Cadeia da Polimerase , Transcrição Gênica
12.
Toxicol Lett ; 102-103: 143-7, 1998 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-10022246

RESUMO

The cytochrome P450 superfamily is known to exhibit a high degree of genetic polymorphism and polymorphisms associated with absent or low enzyme activity in CYP2D6, CYP2C19 and CYP2C9 are particularly well studied. However, despite early reports of strong disease associations for particular CYP2D6 phenotypes, these have not been confirmed in recent, more detailed studies and it now appears that analysis of CYP2D6, CYP2C19 and CYP2C9 genotype is of most value in predicting metabolism of specific drugs. Polymorphisms in other cytochrome P450 genes are less well studied and appear not to be associated with complete absence of enzyme activity. We have recently carried out studies of polymorphism in both CYP1A1 and CYP2E1. The molecular basis of the apparent CYP1A1 'high inducibility' polymorphism was investigated by studying CYP1A1 and Ah receptor polymorphisms in a group of phenotyped individuals who were genotyped both for known and novel CYP1A1 and Ah receptor polymorphisms. Three novel polymorphisms in CYP1A1 (C(-459)T, G(-469)A and C(4151)T) and one in the Ah receptor (G(1768)A; V(570)I) were detected by single strand conformational polymorphism analysis and DNA sequencing. Among both novel and previously known polymorphisms, only the Ah receptor G(1721)A polymorphism, which has an allele frequency of 0.12 in Caucasians and was detected previously in a Japanese population, was significantly associated with high induced CYP1A1 activity. In the case of CYP2E1, we have detected three polymorphisms in the promoter region (A(-316)G, T(-297)A and G(-35)T) and one in the coding sequence (G(4804)A; V(179)I) by screening Caucasian DNA samples. The significance of these alleles has been investigated but only G(-35)T combined with T(-297)A, which has an allele frequency of 0.05, appears to be of functional significance, with an apparent 1.8-fold increase in levels of transcriptional activity compared with the wild-type.


Assuntos
Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2E1/genética , Polimorfismo Genético , Animais , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Humanos
13.
Meat Sci ; 50(1): 105-14, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22060813

RESUMO

Classical DNA fingerprinting is based on separation of DNA restriction fragments by electrophoresis and hybridisation to nucleic acid probes containing repetitive nucleotide sequences. The use of such mini- or micro-satellite probes tends to yield patterns specific to an individual rather than to a species, hence their value in forensic analysis but general unsuitability for meat speciation. In the present study, a cDNA probe based on conserved sequences contained in members of the actin multigene family has been evaluated for potential application in meat speciation. Genomic DNA was extracted from muscle and digested with BamHI before electrophoresis and hybridisation to a murine α-actin cDNA probe. Beef, pork, lamb, horse, chicken and fish DNA restriction fragments formed characteristic 'fingerprints' which were reproducible and varied sufficiently to allow discrimination even between closely-related species. However no major differences were seen between individuals of the same breed or between different breeds within a species. When DNA obtained from fresh tissue and also from meat heated at 120 °C was analysed, the gel patterns were essentially the same. An attractive feature of this approach is that it employs a single cross-reacting probe and set of conditions, and gives different patterns with all species so far studied. This simplicity suggests applications in meat speciation or related areas of biology.

14.
Fogorv Sz ; 90(2): 35-47, 1997 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-9064235

RESUMO

UNLABELLED: A double blind split-pilot study was carried out to test the potential increase in sensitivity of the Quigley and Hein (Turesky modification) plaque index using a six site recording technique against the two site technique in assessing the antiplaque effects of dentifrices. The study also evaluated the impact of asking the subjects not to brush their teeth the morning of the evaluations versus those who where hot given these instruction. The results indicated that the triclosan containing dentifrice had a significant anti-plaque effect over the placebo at 3 weeks when using both two (p = 0.003) and six (p = 0.002) sited plaque assessment methods. However the six-sited index demonstrated the greater efficacy for the active dentifrice. At six weeks no statistically significant difference between the two dentifrices was seen. The instruction of subjects not to brush before the plaque evaluation increased the mean plaque scores as well as the treatment effect at any time. IN CONCLUSION: The six-sited plaque index increased the sensitivity of the index in determining the anti-plaque efficacy of dentifrices, as well as indicating that instructing subjects not to brush preceding their plaque evaluations also increases sensitivity for determining anti-plaque efficacy of dentifrices.


Assuntos
Placa Dentária/diagnóstico , Cremes Dentais , Adulto , Placa Dentária/prevenção & controle , Índice de Placa Dentária , Método Duplo-Cego , Feminino , Humanos , Masculino , Índice de Higiene Oral , Índice Periodontal , Projetos Piloto , Placebos , Sensibilidade e Especificidade , Cremes Dentais/normas
15.
J Clin Dent ; 8(2 Spec No): 62-6, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9238875

RESUMO

Three triclosan-containing "multi-benefit" dentifrices were compared for clinical efficacy in reducing supragingival calculus formation following a dental prophylaxis. A total of 544 subjects completed a double-blind parallel-group clinical study using the Volpe-Manhold Index (VMI) to record severity and occurrence of supragingival calculus. The study design included a pre-test period where the calculus formation rate was measured in subjects brushing with a placebo dentifrice. Following a prophylaxis, subjects were stratified for age, gender and VMI scores and assigned to one of four treatments: 1) a dentifrice containing 5.0% soluble pyrophosphate/0.145% fluoride as NaF/silica abrasive/0.28% triclosan (hereafter PPi/TCS-comparable to Crest Complete dentifrice, Procter & Gamble, UK); 2) a commercial dentifrice containing 2.0% Gantrez acid copolymer/ 0.145% fluoride as NaF/silica abrasive/0.30% triclosan (hereafter Gan/TCS-Colgate Total dentifrice, Colgate-Palmolive Company, UK); 3) a commercial dentifrice containing 0.5% zinc citrate trihydrate/0.15% fluoride as sodium monofluorophosphate/silica abrasive/0.20% triclosan (hereafter Zn/TCS-Mentadent P dentifrice, Unilever, UK); and 4) a control dentifrice comprised of 0.145% fluoride as NaF/silica abrasive (hereafter Control). Subjects were instructed to use their assigned dentifrice at least twice per day and to brush as they do normally. Supragingival calculus formation was assesed at two and four months using site-specific and whole-mouth VMI indices for both calculus severity and occurrence. Following four months of use, the PPi/TCS dentifrice provided statistically significant reductions in calculus severity (22-23%) and occurrence (15%) as compared with the Control dentifrice. The Zn/TCS dentifrice also provided significant reductions in calculus severity (17-19%) and occurrence (12-13%) as compared with the Control. The Gan/TCS produced no statistically significant reductions in calculus formation (occurrence or severity) compared with the Control. The PPi/TCS dentifrice provided statistically significant reductions in calculus severity (15-21%) and occurrence (12-16%) as compared with the Gan/TCS dentifrice. These results support the clinical effectiveness of PPi/TCS and Zn/TCS dentifrices for the reduction of supragingival dental calculus formation following a dental prophylaxis.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Cálculos Dentários/prevenção & controle , Dentifrícios/uso terapêutico , Antissépticos Bucais/uso terapêutico , Triclosan/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Dentifrícios/química , Difosfatos/uso terapêutico , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Peróxido de Hidrogênio/uso terapêutico , Masculino , Maleatos/uso terapêutico , Pessoa de Meia-Idade , Índice de Higiene Oral , Polietilenos/uso terapêutico , Bicarbonato de Sódio/uso terapêutico , Fluoreto de Sódio/uso terapêutico , Resultado do Tratamento
16.
Pharmacogenetics ; 6(4): 319-28, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8873218

RESUMO

The majority of humans deficient in the cytochrome P450 CYP2D6 enzyme, so-called poor metabolizers (PMs), can now be identified by genotyping for several different PM-associated mutations. However, additional null alleles remain to be identified as demonstrated by subjects with the PM phenotype in the absence of a corresponding genotype. The rare 11 kb band on Xba I RFLP analysis, which is distinct from the 13 kb CYP2D6D (CYP2D6*5) allele, has been proposed to constitute such a unique non-functional allele. Here we demonstrate that the 11 kb band represents at least two different nine exon CYP2D7P/CYP2D6 hybrids generated by large deletions in the CYP2D gene cluster due to unequal cross-over or looping-out mechanisms. The total allele frequency was approximately 0.001-0.01 in European and North American Caucasians. The most common variant (CYP2D6*16) had breakpoints lying between the end of exon 7 and the start of exon 9 of the respective genes. The "CYP2D7-like' part of the gene was most homologous to the previously described CYP2D7AP and CYP2D7 (44/11.5) sequences. The other chimeric allele consisted of exon 1 of CYP2D7 and exons 2-9 from CYP2D6, and may be similar to a hybrid gene termed CYP2D6*13 recently described in a French individual. Two different routine PCR assays were developed for rapid and sensitive detection of these alleles, namely amplification of a 8 kb fragment from both CYP2D6*13 and CYP2D6*16, together with a CYP2D6*16-specific method which gave a 1.4 kb PCR product. The 8 kb assay for the CYP2D6*13 and CYP2D6*16 alleles also produced a 9.5 kb fragment in samples positive for the 13 kb CYP2D6*5 allele. Therefore, it is now possible to screen for the large CYP2D gene deletions by a single long PCR method.


Assuntos
Alelos , Citocromo P-450 CYP2D6/genética , Sistema Enzimático do Citocromo P-450/genética , Metabolismo/genética , Frequência do Gene , Humanos , Fenótipo , Reação em Cadeia da Polimerase , Mapeamento por Restrição
18.
Cancer Res ; 55(24): 6035-7, 1995 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-8521388

RESUMO

The possible association between lung cancer and a polymorphism of the CYP1A1 gene specific to African-Americans was examined using peripheral blood DNA from 144 incident cases of lung cancer and 230 population controls with detailed data on smoking and other risk factors for the disease. The CYP1A1 variant allele was present in 15.2% of controls and 16.7% of cases. The smoking-adjusted odds ratio for the presence of the variant allele in relation to lung cancer risk overall was 1.3 (95% confidence interval, 0.7-2.4). According to histological type, the strongest association was observed for squamous cell carcinoma (odds ratio, 2.1), but this result was compatible with chance (95% confidence interval, 0.8-5.9). Adenocarcinoma was not materially associated with the presence of the variant allele (odds ratio, 1.3; 95% confidence interval, 0.5-3.2). No important associations were observed upon stratification by several risk factors for lung cancer, including smoking history, occupational exposures to asbestos and motor vehicle exhaust, or low intake of the micronutrient antioxidants beta-carotene, vitamin E, or vitamin C. These results do not confirm an earlier report that this CYP1A1 polymorphism may be an important risk factor for adenocarcinoma of the lung in African-Americans.


Assuntos
População Negra , Sistema Enzimático do Citocromo P-450/genética , Neoplasias Pulmonares/epidemiologia , Idoso , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA/química , Feminino , Humanos , Los Angeles , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo Genético , Fatores de Risco , Fumar
19.
Pharmacogenetics ; 4(2): 73-81, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8081414

RESUMO

DNA from two subjects showing anomalous CYP2D6 phenotype-genotype relationships was analysed for the presence of new CYP2D6 mutations by single strand conformational polymorphism (SSCP) analysis. One of these subjects was homozygous for polymorphisms in exon 1 and exon 9 previously detected in Oriental populations and termed the CYP2D6J allele. The frequency of these polymorphisms and their effect on phenotype was investigated in a European population with a small Chinese population as a control group. Subjects homozygous for both polymorphisms showed impaired metabolism of debrisoquine whereas subjects with the exon 9 mutation only appeared to show similar metabolism to the wild-type. The CYP2D6J allele frequency was 0.05 in the European group compared with 0.47 for the Chinese group. The relationship between the CYP2D6J allele and the exon 9 polymorphism and the presence of insertions upstream of CYP2D6 detectable by RFLP analysis with Xba I was investigated. In the Chinese group the insertion appeared to be associated with the CYP2D6J allele but in the European group no association was detected. Subjects homozygous for the CYP2D6J allele appear to show a similar debrisoquine phenotype to those heterozygous for CYP2D6-inactivating mutations but the exon 9 polymorphism or the presence of an upstream insertion without an associated CYP2D6B or CYP2D6J allele does not appear to affect enzyme activity.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Oxigenases de Função Mista/genética , Alelos , Povo Asiático/genética , China/etnologia , Citocromo P-450 CYP2D6 , Elementos de DNA Transponíveis/genética , Debrisoquina/metabolismo , Inglaterra , Éxons/genética , Frequência do Gene , Homozigoto , Humanos , Polimorfismo Genético , População Branca/genética
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