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1.
Int J Oral Maxillofac Surg ; 51(9): 1211-1225, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35339331

RESUMEN

Temporomandibular disorders (TMD) impact a significant proportion of the population. Given the range of management strategies, contemporary care should be evidence-informed for different TMD types. A knowledge-to-action rapid review of systematic reviews published in the past 5 years and guidelines published in the past 10 years concerning the management of TMD was conducted. The Cochrane, Embase, MEDLINE, PEDro, and PubMed databases were searched. A qualitative data analysis was undertaken, with quality assessment completed using the AMSTAR 2 checklist. In total, 62 systematic reviews and nine guidelines considering a range of treatment modalities were included. In concordance with current guidelines, moderate evidence supports a multi-modal conservative approach towards initial management. Contrary to existing guidelines, occlusal splint therapy is not recommended due to a lack of supporting evidence. The evidence surrounding oral and topical pharmacotherapeutics for chronic TMD is low, whilst the evidence supporting injected pharmacotherapeutics is low to moderate. In concordance with current guidelines, moderate quality evidence supports the use of arthrocentesis or arthroscopy for arthrogenous TMD insufficiently managed by conservative measures, and open joint surgery for severe arthrogenous disease. Based on this, a management pathway showing escalation of treatment from conservative to invasive is proposed.


Asunto(s)
Trastornos de la Articulación Temporomandibular , Artrocentesis , Humanos , Ferulas Oclusales , Revisiones Sistemáticas como Asunto , Trastornos de la Articulación Temporomandibular/terapia
2.
J Dent ; 105: 103556, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33359043

RESUMEN

OBJECTIVES: This review aimed to identify which dental procedures generate droplets and aerosols with subsequent contamination, and for these, characterise their pattern, spread and settle. DATA RESOURCES: Medline(OVID), Embase(OVID), Cochrane Central Register of Controlled Trials, Scopus, Web of Science and LILACS databases were searched for eligible studies from each database's inception to May 2020 (search updated 11/08/20). Studies investigating clinical dental activities that generate aerosol using duplicate independent screening. Data extraction by one reviewer and verified by another. Risk of bias assessed through contamination measurement tool sensitivity assessment. STUDY SELECTION: A total eighty-three studies met the inclusion criteria and covered: ultrasonic scaling (USS, n = 44), highspeed air-rotor (HSAR, n = 31); oral surgery (n = 11), slow-speed handpiece (n = 4); air-water (triple) syringe (n = 4), air-polishing (n = 4), prophylaxis (n = 2) and hand-scaling (n = 2). Although no studies investigated respiratory viruses, those on bacteria, blood-splatter and aerosol showed activities using powered devices produced greatest contamination. Contamination was found for all activities, and at the furthest points studied. The operator's torso, operator's arm and patient's body were especially affected. Heterogeneity precluded inter-study comparisons but intra-study comparisons allowed construction of a proposed hierarchy of procedure contamination risk: higher (USS, HSAR, air-water syringe, air polishing, extractions using motorised handpieces); moderate (slow-speed handpieces, prophylaxis, extractions) and lower (air-water syringe [water only] and hand scaling). CONCLUSION: Gaps in evidence, low sensitivity of measures and variable quality limit conclusions around contamination for procedures. A hierarchy of contamination from procedures is proposed for challenge/verification by future research which should consider standardised methodologies to facilitate research synthesis. CLINICAL SIGNIFICANCE: This manuscript addresses uncertainty around aerosol generating procedures (AGPs) in dentistry. Findings indicate a continuum of procedure-related aerosol generation rather than the common binary AGP or non-AGP perspective. The findings inform discussion around AGPs and direct future research to support knowledge and decision making around COVID-19 and dental procedures.


Asunto(s)
Aerosoles , COVID-19 , Odontología , Humanos , SARS-CoV-2
3.
Br Dent J ; 222(12): 944-948, 2017 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-28642531

RESUMEN

Introduction This paper is the third of four rapid reviews undertaken to explore the relationships between oral health and general medical conditions in order to support teams within Public Health England, health practitioners and policymakers.Aims This review aimed to explore the nature of the association between poor oral health and diabetes when found in the same individuals or populations, having reviewed the most contemporary evidence in the field.Methods The reviews were undertaken by four groups each comprising consultant clinicians from medicine and dentistry, trainees, public health and academics. The methodology involved a streamlined rapid review process and synthesis of the findings.Results The results identified a number of systematic reviews of low to high quality suggesting that diabetes is associated with periodontal disease, tooth loss, and oral cancer in particular, and that the management of oral diseases, most notably periodontal care, has a short-term beneficial influence on metabolic outcomes related to diabetes; however, there is no evidence that this is sustained over the long-term and reduces the prevalence of the long-term complications.Conclusion Current evidence, of mixed quality, suggests a number of associations between oral diseases and diabetes mellitus (diabetes). Further high quality research is required in this field.


Asunto(s)
Complicaciones de la Diabetes/etiología , Enfermedades de la Boca/etiología , Caries Dental/etiología , Humanos , Neoplasias de la Boca/etiología , Periodontitis/etiología , Factores de Riesgo , Pérdida de Diente/etiología
4.
Clin Otolaryngol ; 42(1): 104-114, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27185184

RESUMEN

BACKGROUND: Head and neck cancers [HNCs] are biologically heterogeneous tumours. The objectives of this study were to describe trends in incidence of HNCs amongst London residents by sex, age, anatomical site, deprivation and ethnicity. METHODS: Annual age-standardised incidence rates [ASRs] were calculated on HNC registration data, overall and for specific cancer sites, by sex and morphology (1985-2010) and area-based socio-economic deprivation score (2006-2010). Age-standardised incidence rate ratios [IRRs] for the main ethnic groups were calculated by cancer site, using White males and females as the reference groups (1998-2009). RESULTS: The ASR of HNC in males increased by 40% from 17.3 [95% CI: 15.8-18.6] to 24.2 [95% CI: 22.5-25.8] per 100 000 and in females by 87% from 7.0 [95% CI: 6.2-7.8] to 13.1 [95% CI: 11.9-14.2] per 100 000. Seventy-three per cent of cases spanned four cancer sites: larynx, thyroid, oral and oropharynx. Larynx was most common (23%), and had the highest male: female ratio (6 : 1); ASRs decreased significantly over time, most notably in males [P < 0.001]. Oral cavity was the second most common (21%), with a male: female ratio of 2 : 1, and increasing ASRs in both sexes [P < 0.001]. The majority of cases were male (64%) and from deprived areas (59%). Deprivation was associated with a significantly higher incidence for larynx (males), oropharynx (males and females) and oral cavity (females) [P < 0.05]. The age-specific rate for middle-aged adults (45-64 years) was high for oropharyngeal cancer. The incidence of thyroid cancers increased significantly in both sexes [P < 0.001], and this was the only site more common in females. One in five cases with known ethnicity was from a non-White group (20%). Compared with their White counterparts, Bangladeshi females had a higher incidence of oral, laryngeal and thyroid cancers; Chinese males and females had a higher incidence of nasopharyngeal cancer; and Pakistani and Indian females and Indian males also had higher incidence of oral cancer. CONCLUSIONS: HNCs are increasing in London males and females with significant variation by cancer site over time; oral and oropharyngeal cancers show the most significant rise, with implications for public health action and service provision.


Asunto(s)
Carcinoma/epidemiología , Carcinoma/patología , Etnicidad/estadística & datos numéricos , Neoplasias de Cabeza y Cuello/epidemiología , Neoplasias de Cabeza y Cuello/patología , Población Blanca/estadística & datos numéricos , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Londres , Masculino , Persona de Mediana Edad , Distribución por Sexo , Factores Socioeconómicos , Adulto Joven
5.
Community Dent Health ; 33(1): 60-4, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27149776

RESUMEN

OBJECTIVES: First, to evaluate awareness of oral cancer amongst the young South-Asian community in London and identify any aspects of knowledge about oral cancer that are lacking; and, second, to determine whether demographic factors or health-related behaviours are associated with knowledge of oral cancer. RESEARCH DESIGN: Cross-sectional questionnaire survey. PARTICIPANTS: South Asians aged 18-44 years attending community centres or places of worship in London. MAIN OUTCOME MEASURES: Oral cancer awareness; health-related behaviours. RESULTS: Respondents (n = 201) were mainly male (61%), Indian (77%) and Hindu (35%). Over half (58%; n = 113) had one or more negative health-related behaviours and only 18% had attended a dentist in the previous two years. Chewing paan with betel nut (OR = 4.08, 95% CI = 1.58-10.59, p < 0.01), and time since last visit to a dentist (OR = 4.90, 95% CI = 2.13-11.28, p < 0.01) were independently associated with respondents level of knowledge of mouth cancer; the former positively and the latter negatively. CONCLUSIONS: The results suggest that young adults in the South Asian Community are exposed to a number of risk factors for oral cancer yet have poor knowledge of the implications of these health-related behaviours, and ways in which oral cancer can be detected earlier. The survey highlighted specific issues for action.


Asunto(s)
Pueblo Asiatico/psicología , Actitud Frente a la Salud , Conocimientos, Actitudes y Práctica en Salud , Grupos Minoritarios/psicología , Neoplasias de la Boca/psicología , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/psicología , Areca , Asia Sudoriental/etnología , Estudios Transversales , Atención Odontológica/estadística & datos numéricos , Escolaridad , Femenino , Conductas Relacionadas con la Salud , Hinduismo/psicología , Humanos , India/etnología , Londres , Masculino , Factores Sexuales , Uso de Tabaco/psicología , Adulto Joven
6.
Br Dent J ; 214(12): 633-42, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23787854

RESUMEN

OBJECTIVES: To estimate the frequency of trigeminal nerve injuries associated with local anaesthetic administration, as experienced by UK dentists. METHOD: A convenience sample of clinicians attending 12 study days over the UK was invited to complete an anonymised questionnaire exploring the nature of professional practice, dentists' practice demographics, experience of nerve injuries and related factors. Dental procedures related to reported trigeminal nerve injuries (TNIs) were divided into low risk, likely local anaesthetic (LA) related nerve injury, and high risk procedures, more likely to be direct nerve damage by the procedure (procedural related nerve injury). Data were analysed using Microsoft Excel and SPSS V17. RESULTS: Overall 79% of attendees completed a questionnaire (n = 415); clinicians held an average of 19 years' clinical experience. The numbers of clinicians surveyed included general dental practitioners (n = 290; 64%) and oral surgery (OS) specialists (n = 125; 36%). The estimated incidence of TNIs for the UK GDP workforce was 3,770 TNIs per year or 0.13 TNI per dentist per year. For specialists the incidence was increased to 0.39 TNI per specialist per year. Of all injuries only half were reported, mainly to indemnity organisations. LA-related injuries were most common for GDPs and third molar surgery for OS specialists. It is estimated that TNIs will occur in 1 in 3,289 high risk procedures such as third molar surgery and 1 in 14,330 for low risk procedures, such as restorative dentistry, most likely LA-related. From 25% to 29% of these dental procedures related TNIs were permanent. CONCLUSIONS: Nerve-related injuries in dentistry are not uncommon. Dental practitioners should be aware of the significant disability associated with iatrogenic nerve injuries and risk factors relating to LA-related trigeminal nerve injury. Clinicians should familiarise themselves with infiltration LA-techniques that may reduce these nerve injuries and with the Care Quality Commission regulations for reporting injuries to patients as a result of treatment.


Asunto(s)
Anestesia Dental/estadística & datos numéricos , Anestésicos Locales/efectos adversos , Odontólogos/estadística & datos numéricos , Enfermedad Iatrogénica/epidemiología , Traumatismos del Nervio Trigémino/epidemiología , Anestésicos Locales/administración & dosificación , Carticaína/administración & dosificación , Restauración Dental Permanente/estadística & datos numéricos , Odontología General/estadística & datos numéricos , Humanos , Incidencia , Lidocaína/administración & dosificación , Tercer Molar/cirugía , Bloqueo Nervioso/estadística & datos numéricos , Prevalencia , Estudios Prospectivos , Recuperación de la Función/fisiología , Factores de Riesgo , Cirugía Bucal/estadística & datos numéricos , Extracción Dental/estadística & datos numéricos , Reino Unido/epidemiología
7.
Br Dent J ; 213(7): 362-3, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23059677
8.
Br Dent J ; 213(6): 297-9, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22996481

RESUMEN

Oral cancer is increasingly common. The need for early detection and promoting prevention is greater than ever and relevant to all who are responsible for the care of patients. Recent addition of oral cancer detection to the list of continuing professional development (CPD) topics recommended by the General Dental Council (GDC) reflects this importance.


Asunto(s)
Atención Odontológica/métodos , Detección Precoz del Cáncer/métodos , Neoplasias de la Boca/diagnóstico , Competencia Clínica , Humanos , Neoplasias de la Boca/epidemiología , Neoplasias de la Boca/prevención & control , Derivación y Consulta , Factores de Riesgo , Reino Unido/epidemiología
9.
Chem Res Toxicol ; 13(10): 1011-9, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11080050

RESUMEN

Epidemiologic studies have shown causal relationships between air pollution particles and adverse health effects in susceptible subpopulations. Fly ash particles (containing water-soluble and insoluble metals) are a component of ambient air particulate pollution and may contribute to particulate-induced health effects. Some of the pathological effects after inhalation of the particles may be due to reactive oxygen species (ROS) produced by metal-catalyzed reactions. In this investigation, we analyzed emission source particulates oil fly ash (OFA) and coal fly ash (CFA) for metal content and solubility in relation to their ability to induce 2'-deoxyguanosine (dG) hydroxylation and DNA damage as measured by 8-oxo-dG formation by HPLC/UV-electrochemical detection (ECD). Water-soluble vanadium and nickel were present at the highest concentrations, and iron was present in trace amounts in OFA (5.1% V, 1.0% Ni, and 0.4% Fe by weight). In contrast, CFA comprised mostly of water-insoluble aluminosilicates and iron (9.2% Al, 12.2% Si, and 2.8% Fe by weight). As a first approach to gain insight into the mode of action of these particulates, we examined metal species-catalyzed kinetics of dG hydroxylation. Metal species at a concentration of 0.1 mM in the incubation mixture containing 0.1 mM dG under ambient air at room temperature catalyzed maximum 8-oxo-dG formation at 15 min with yields ranging from 0.05 to 0.17%, decreasing in the following order: vanadium(IV) > iron(II) > vanadium(V) > iron(III) > or = nickel(II). Insoluble Fe(III) oxide (Fe(2)O(3)) under similar conditions had no effect. Consistent with these results, OFA rich in vanadium and nickel concentrations showed a dose-dependent increase in the level of dG hydroxylation to 8-oxo-dG formation at particulate concentrations of 0.1-1 mg/mL (p < 0.05). In contrast, CFA with high concentrations of aluminosilicates and iron did not result in a significant increase in the level of 8-oxo-dG over that of the control, i.e., dG (p > 0.05). DMSO, a (*)OH scavenger, inhibited OFA-induced 8-oxo-dG formation, and metal ion chelators, deferoxamine (DFX), DTPA, and ferrozine blocked OFA-induced 8-oxo-dG formation. OFA and CFA induced 8-oxo-dG formation in a pattern similar to that observed for dG hydroxylation when calf thymus DNA was used as a substrate. Treatment of OFA particles with DFX before reacting with DNA or addition of a catalase in the incubation mixture significantly suppressed 8-oxo-dG formation (p < 0.05). These results suggest that metal availability, but not the concentration of metals present in CFA and OFA, is critical in mediating molecular oxygen-dependent dG hydroxylation and DNA base damage.


Asunto(s)
Carbono/toxicidad , Carbón Mineral/toxicidad , Daño del ADN/efectos de los fármacos , Desoxiguanosina/química , Residuos Industriales/análisis , Metales/toxicidad , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Carbono/análisis , Catálisis , Bovinos , Quelantes/química , Cromatografía Líquida de Alta Presión , Carbón Mineral/análisis , Ceniza del Carbón , Desoxiguanosina/análogos & derivados , Dimetilsulfóxido , Hidroxilación , Indicadores y Reactivos , Metales/análisis , Oxidación-Reducción , Material Particulado , Espectrofotometría Ultravioleta
11.
Int J Paediatr Dent ; 10(1): 19-26, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11310122

RESUMEN

OBJECTIVES: To determine dental caries prevalence in a group of HIV positive children and their reported dental health behaviour. DESIGN: Standardized epidemiological dental examination and structured interview. SETTING: Paediatric HIV outpatient department in a South London hospital. STUDY POPULATION: HIV-positive children attending the above outpatient clinic over a 6-month period (30 subjects) and parents (20 informants). METHODS: Epidemiological examination of children was undertaken by one trained and calibrated examiner to determine caries prevalence using dmft/DMFT. Parents were interviewed to obtain information on their children's dental health behaviour: toothbrushing, diet, fluoride; oral medication and dental attendance were explored. RESULTS: Sixty-three per cent (n = 19) of children had dental caries experience, much of it untreated. Mean dmft/DMFT was 4.4. Sixty per cent (n = 18) of all children presented with active or untreated caries and the care index for those at/under age 5 years was low (10%). Unfavourable dental health behaviour included: consumption of nonmilk extrinsic sugars at night, use of sugar-based medications, low fluoride intake, late commencement of toothbrushing and poor dental attendance. Dental health was not considered a priority for many of these children. Parents did not necessarily disclose their child's HIV status on dental attendance. CONCLUSION: Caries prevalence was high, much of the disease untreated, and unfavourable dental health behaviour, including the use of sugar-based medicines was common. HIV infected children should be considered a high caries risk and receive appropriate dental care, in terms of both treatment and preventive services, following confirmation of seropositivity.


Asunto(s)
Atención Dental para Enfermos Crónicos , Caries Dental/complicaciones , Infecciones por VIH/complicaciones , Conductas Relacionadas con la Salud , Niño , Preescolar , Índice CPO , Atención Odontológica/estadística & datos numéricos , Caries Dental/epidemiología , Caries Dental/psicología , Dieta Cariógena , Sacarosa en la Dieta/administración & dosificación , Femenino , Fluoruros/efectos adversos , Humanos , Lactante , Entrevistas como Asunto , Londres/epidemiología , Masculino , Grupo de Atención al Paciente , Vehículos Farmacéuticos , Prevalencia , Encuestas y Cuestionarios , Cepillado Dental
13.
Laryngoscope ; 105(6): 606-9, 1995 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7769943

RESUMEN

The charts of 258 patients undergoing tonsillectomy with or without adenoidectomy between June 1991 and June 1993 were reviewed. One hundred sixty-nine of these patients received ketorolac tromethamine during the perioperative period as a nonnarcotic alternative for postoperative pain management. The incidence of postoperative hemorrhage among patients who received ketorolac tromethamine was 10.1%, compared to 2.2% in those patients who received narcotic analgesia only. The average time to adequate oral intake and discharge was evaluated. Ketorolac appeared to moderately decrease the time to adequate oral intake. The use of ketorolac did not significantly alter the time to discharge. The increased incidence of postoperative hemorrhage in patients receiving ketorolac should be considered before this medication is used in the perioperative period. The risk/benefit ratio of ketorolac use as a postoperative analgesic may be better demonstrated in a prospective study.


Asunto(s)
Adenoidectomía , Analgésicos/efectos adversos , Analgésicos/uso terapéutico , Hemorragia/epidemiología , Complicaciones Posoperatorias/epidemiología , Tolmetina/análogos & derivados , Tonsilectomía , Trometamina/efectos adversos , Trometamina/uso terapéutico , Adolescente , Adulto , Niño , Preescolar , Combinación de Medicamentos , Femenino , Humanos , Incidencia , Lactante , Ketorolaco Trometamina , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/prevención & control , Estudios Retrospectivos , Factores de Tiempo , Tolmetina/efectos adversos , Tolmetina/uso terapéutico
14.
Teratog Carcinog Mutagen ; 14(4): 183-92, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-7992230

RESUMEN

Previous studies demonstrated that cigarette smoking is associated with high elevations in levels of both cytochrome P450 1A1 (CYP1A1) and DNA adducts in human placenta. To date, the identity of the smoking related DNA adducts is not known. The DNA adducts identified in placenta of smokers could result from chemicals present in cigarette smoke, substances formed by CYP 1A1 metabolic activation of endogenous compounds, noncigarette related exposures or a combination of these processes. Exposure to contaminated rice oil containing large doses of polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) also resulted in massive elevation of CYP 1A1 in human placenta but formation of DNA adducts directly from this exposure has not previously been reported. The purpose for comparing the two populations was to test the hypothesis that if CYP 1A1 induction results in the metabolic activation of endogenous compounds, then DNA adducts should also be present in PCB/PCDF exposed tissues exhibiting high CYP 1A1 activity and some of the adducts detected in the placental DNA from smokers may be identified as those derived from the metabolic activation of endogenous compounds. To test this hypothesis, we measured DNA adducts using 32P-postlabeling to analyze placental DNA from women exposed to PCB/PCDF and from cigarette smokers where levels of CYP 1A1 were similarly elevated. There was no evidence of DNA adducts among specimens obtained from PCB/PCDF exposed individuals. These data suggest that CYP 1A1 induction alone (in the absence of cigarette smoking) does not induce the formation of DNA adducts detectable by this approach, and that smoking related adducts are not a consequence of CYP 1A1 induction mediated activation of endogenous compounds or xenobiotics other than cigarette smoke.


Asunto(s)
Sistema Enzimático del Citocromo P-450/biosíntesis , ADN/metabolismo , Isoenzimas/biosíntesis , Placenta/metabolismo , Bifenilos Policlorados/toxicidad , Fumar/metabolismo , Hidrocarburo de Aril Hidroxilasas/biosíntesis , Benzofuranos/metabolismo , Benzofuranos/toxicidad , Dibenzofuranos Policlorados , Exposición a Riesgos Ambientales , Inducción Enzimática/efectos de los fármacos , Femenino , Humanos , Bifenilos Policlorados/metabolismo , Embarazo
15.
Artículo en Inglés | MEDLINE | ID: mdl-8268777

RESUMEN

To determine the feasibility of using human sperm cells for DNA 32P-postlabeling analyses, and to evaluate the baseline level and the possible presence of smoking-related DNA adducts in these cells, sperm DNA was isolated from specimens obtained from 12 heavy smokers, 12 light smokers, and 12 nonsmokers. Background levels of radioactivity were minimized by using magnet transfer of 32P-labeled mononucleotides to new polyethyleneimine cellulose plates. Compared with placental tissues, few adducts were observed. Diffuse radioactivity observed in some of the autoradiograms was minimally above background but the level of radioactivity expressed as putative adducts/nucleotide was not related to smoking status. It was not clear, in some cases, whether this radioactivity was associated with chemically bound adducts or was from nonspecifically bound chemicals, radiolabeled enzymes, or other proteins. One major discrete DNA adduct of unknown chemical structure was detected in three of the 36 samples analyzed (one nonsmoker and two smokers). Based on the level of radioactivity associated with various dilutions of a benzo(a)pyrene-derived adduct, our limit of sensitivity was at least 1.2 adducts/10(9) nucleotides. Our study emphasizes the need to more clearly define the significance of background radioactivity associated with DNA adduct maps where the measured adduct levels approximate detection limits defined by visual observance of adduct spots. This point is particularly relevant given that the 32P-postlabeling procedures rely, in part, on visual verification of the presence of DNA adducts.


Asunto(s)
ADN/análisis , Fumar/genética , Espermatozoides/química , Adulto , Estudios de Factibilidad , Humanos , Masculino , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
16.
Carcinogenesis ; 14(4): 637-43, 1993 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8472327

RESUMEN

An acknowledged weakness of current testing programmes for genotoxic hazard has been the potential insensitivity of the established mouse bone marrow micronucleus test and rat liver unscheduled DNA synthesis (UDS) assays to direct-acting or short-lived mutagens, which may be consumed at the site of initial contact. In such cases, in vivo test systems sampling tissues such as the skin or the stomach would provide valuable data. To test these principles a stomach UDS assay was evaluated using the potent locally active mutagen 1-chloromethylpyrene (1-CMP). Contrary to expectations, no UDS response was observed 16 h following 1-CMP dosage by oral gavage. To confirm the integrity of the 1-CMP used for the stomach UDS assay, a sample of the stored chemical was re-evaluated in vitro and shown to be still strongly positive in the Ames assay and to have alkylating activity at least 15 min after incubation at stomach acid pH. No UDS response was observed when test dose levels were reduced or when earlier sampling times were used. Other genotoxic endpoints were examined in stomach. 32P-Postlabelling analysis revealed high levels of adduct formation in gastric DNA. An assay utilizing electrophoresis of DNA (the comet assay) showed the occurrence of DNA damage following dosing with 1-CMP in vivo. These positive results confirmed that 1-CMP should be regarded as a potential in vivo genotoxin. The failure to detect a UDS response to 1-CMP in stomach was investigated; a strong UDS response was observed in an in vitro hepatocyte UDS assay of 1-CMP indicating that the rat was capable of repairing 1-CMP-derived DNA adducts. Pretreatment of rats with hydroxyurea depressed the level of incorporation of thymidine into DNA both in negative and positive [methyl-N-nitrosoguanidine (MNNG)] controls. The results of these studies indicated that the protease digestion method employed did not selectively or efficiently sample those cells with any UDS response to 1-CMP or MNNG, and the activity seen for the latter was most likely due to the presence of S phase cells within the digests. As a result of the finding that UDS responses were not demonstrated for the potent direct-acting mutagens 1-CMP and MNNG, the protease digestion/scintillation method for stomach UDS does not appear to have general value in a screening programme for locally active genotoxic agents.


Asunto(s)
ADN/biosíntesis , Pirenos/toxicidad , Estómago/efectos de los fármacos , Administración Oral , Animales , Médula Ósea/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , ADN/efectos de los fármacos , ADN/metabolismo , Hidroxiurea/toxicidad , Masculino , Ratones , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Pirenos/administración & dosificación , Pirenos/metabolismo , Ratas , Ratas Endogámicas F344
17.
Gastrointest Endosc ; 38(6): 651-6, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1473667

RESUMEN

We performed a prospective, randomized, double-blind study to evaluate the efficacy of the currently recommended low doses of midazolam for conscious sedation compared with diazepam for colonoscopy. Each agent was administered in a fixed ratio dose in combination with meperidine, and titrated incrementally to allow for adequate sedation prior to initiating and during the procedure. The currently recommended starting dose of midazolam (0.03 mg/kg) proved to be very appropriate for pre-medication. In contrast, the currently recommended starting dose of diazepam (0.10 mg/kg) proved excessive in 21% of patients (especially in those aged > 65). The low initial and incremental doses of midazolam compared favorably with diazepam in all efficacy parameters studied and exceeded diazepam in post-procedure amnesia scores (p = 0.01). Moreover, the sedative effects of midazolam at these lower doses were not lost despite long duration procedures (> 40 min). We conclude that midazolam, given in small incremental doses, in combination with meperidine, produces effective conscious sedation for colonoscopy and exceeds diazepam in its amnestic effect.


Asunto(s)
Colonoscopía , Sedación Consciente , Diazepam/administración & dosificación , Midazolam/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Diazepam/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Meperidina/administración & dosificación , Midazolam/efectos adversos , Persona de Mediana Edad , Estudios Prospectivos
18.
Carcinogenesis ; 12(9): 1685-91, 1991 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1893529

RESUMEN

Two versions of the 32P-postlabeling assay (nuclease P1 and butanol extraction) enhance the detection limit of polycyclic aromatic hydrocarbon (PAH)-modified DNA. Previously published studies suggest that DNA adducts derived from N-substituted aryl compounds are poorly recovered in the nuclease P1 version. In this study, both versions were employed to ascertain whether the apparent differences in sensitivity could be used to select diagnostically for nitroaromatic-DNA adducts derived by treating calf thymus DNA with organic extracts isolated from four diesel and one gasoline vehicle emission particles. We enhanced the formation of nitrated-PAH-derived adducts through xanthine oxidase (XO)-catalyzed nitroreduction of nitrated-PAHs, constituents previously detected in the diesel emissions. Chromatographic mobilities of the XO-derived DNA adducts were compared to adducts detected in calf thymus DNA resulting from rat liver S9-mediated metabolism. All four diesel organic extracts treated with XO resulted in the formation of one major DNA adduct, chromatographically distinct from the multiple DNA adducts detected in the rat liver S9-treated incubations. This adduct was detectable with the butanol extraction but not the nuclease P1 version of the 32P-postlabeling assay and was chromatographically similar to DNA adducts formed following XO nitroreduction of 1-nitropyrene or ascorbic acid treatment of 1-nitro-8-nitroso-pyrene and 1-nitro-6-nitrosopyrene. In contrast, when S9 activation was used, multiple DNA adducts were detected along a diagonal zone of radioactivity and were radioactively labeled with equivalent efficiency irrespective of the assay version employed. The in vitro calf thymus DNA model described in this study enhances the diagnostic potential of the 32P-postlabeling assay through the selective formation of nuclease P1-sensitive N-substituted aryl-derived DNA adducts.


Asunto(s)
Contaminantes Atmosféricos/toxicidad , ADN/efectos de los fármacos , Gasolina , Nitratos/química , Compuestos Policíclicos/toxicidad , Animales , Biotransformación , Cromatografía Liquida , ADN/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Oxidación-Reducción , Radioisótopos de Fósforo , Compuestos Policíclicos/metabolismo , Compuestos Policíclicos/farmacocinética , Ratas , Xantina Oxidasa/metabolismo
19.
Mutat Res ; 243(4): 281-9, 1990 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-2325693

RESUMEN

1-Chloromethylpyrene (1-CMP) has been evaluated as a model mutagen and toxin related to the ultimate electrophiles derived from benzo[a]pyrene and 1-nitropyrene. It was mutagenic to Salmonella (greater than 100 pg/plate) and exceptionally reactive to DNA when assessed by the 32P-postlabelling technique. 1-CMP was inactive in a mouse bone micronucleus assay when administered by gavage, probably due to hydrolysis, whose kinetics have been studied (t1/2 approximately 23 min at 37 degrees C). However, as expected, it was a potent skin toxin as determined by its activity as a mitogen to mouse skin and its contact allergenicity, as determined using the local lymph node proliferative assay. It is concluded that 1-CMP will probably be a potent human skin carcinogen and contact allergen.


Asunto(s)
Mutágenos , Pirenos/toxicidad , Piel/efectos de los fármacos , Animales , Carcinógenos , ADN/efectos de los fármacos , Femenino , Hidrólisis , Ganglios Linfáticos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos CBA , Pruebas de Micronúcleos , Radioisótopos de Fósforo , Salmonella/efectos de los fármacos , Glándulas Sebáceas/efectos de los fármacos
20.
Carcinogenesis ; 11(2): 205-11, 1990 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-2105856

RESUMEN

Identification of DNA adducts in peripheral lymphocytes could serve as a means of monitoring human exposure to potential genotoxic agents. In this study, DNA from peripheral lymphocytes of smokers and nonsmokers was examined for adducts by the P1 nuclease 32P-postlabeling technique. Thin layer chromatography (TLC) maps from both groups revealed multiple DNA adducts which ranged from no adducts for one individual to six adducts for a different individual. The total DNA adduct concentrations were approximately one adduct in 10(8)-10(10) normal nucleotides. Comparison of the adduct TLC profiles revealed individual variation in both pattern and level of DNA adducts. The type and amount of adduct was not influenced by smoking history and remained unchanged in four out of six subjects who were resampled after a 1 month interval. The capacity of lymphocytes to form BaP-derived DNA adducts after a 72 h incubation with 10(-6) M [3H]BaP was measured by both high-performance liquid chromatography (HPLC) and 32P-postlabeling analysis. The in vitro adduct values detected by [3H]nucleoside concentrations on HPLC ranged from 1 to 7 fmol adduct per micrograms DNA (3.3-23.3 adducts per 10(7) nucleotides). The [3H]nucleoside values were consistent with values obtained by 32P-postlabeling of the same sample (correlation coefficient of 0.88). No relationship was apparent between the capacity of lymphocytes to form a [3H]BaP-derived adduct in vitro and the concentration of any adduct, or total adducts present in untreated lymphocytes. These results suggest that multiple DNA adducts are present in lymphocytes from nonsmokers as well as smokers, although the profile and extent of these adducts can vary among individuals. The relationship of the lymphocyte DNA adducts detected in this study to human cancer susceptibility remains to be determined.


Asunto(s)
Aductos de ADN , ADN/metabolismo , Linfocitos/análisis , Fumar/metabolismo , 7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido/análisis , Adolescente , Adulto , Benzo(a)pireno/metabolismo , Cromatografía en Capa Delgada , ADN/análisis , Femenino , Humanos , Masculino , Radioisótopos de Fósforo
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