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1.
Ann R Coll Surg Engl ; 101(4): 231-234, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30773892

RESUMO

INTRODUCTION: Healthcare professionals increasingly recognise how human factors (HF) can contribute to medical error. An understanding of HF is also important during other high stakes activities such as summative assessments or examinations. National organisations hosting such events need to be aware of potential fatigue, boredom and stress that can occur in interviewers during these often repetitive activities. METHODS: A previously validated questionnaire based around the well known HF analysis and classification system (HFACS) was used to evaluate four factors (care and support, asking questions about the role as an interviewer, working within the rules and boundaries, and stress and pressure) at the 2018 UK general and vascular surgery trainee national selection process. RESULTS: A total of 92 questionnaires were completed and analysed (48% response rate). After recoding for negative phrased questions, no significant differences were found between years of experience in the selection process and mean scores obtained for all four factor items. Interviewers had a positive experience during national selection with mean factor scores ranging from 3.84 to 3.98 (out of a maximum satisfaction score of 5). CONCLUSIONS: Organisations need to plan carefully and recognise the human element to ensure that their interviewers are cared for during any high stakes assessment such as national selection. Our work suggests that a positive assessor experience will further help contribute to a reliable and fair recruitment process.


Assuntos
Cirurgia Geral , Seleção de Pessoal , Especialidades Cirúrgicas , Feminino , Humanos , Entrevistas como Assunto , Masculino , Seleção de Pessoal/métodos , Inquéritos e Questionários , Reino Unido , Procedimentos Cirúrgicos Vasculares
2.
BJS Open ; 1(3): 67-74, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29951608

RESUMO

BACKGROUND: The Intercollegiate Membership of the Royal College of Surgeons (MRCS) examination is undertaken by large numbers of trainees in the UK and internationally as a mandatory step within surgical training. Unlike some high-stakes medical examinations, the MRCS is yet to be validated. A quantitative study was undertaken to assess its predictive validity by investigating the relationship between MRCS (Parts A and B) and national selection interview scores for general and vascular surgery in the UK. METHODS: Pearson correlation coefficients were used to examine the linear relationship between each assessment, and linear regression analyses were employed to identify potential independent predictors of the national selection score. All UK medical graduates who attempted the interview in 2011-2015 were included. RESULTS: Some 84·4 per cent of the candidates (1231 of 1458) were matched with MRCS data. There was a significant positive correlation between the first attempt score at Part B of the MRCS examination and the national selection score (r = 0·38, P < 0·001). In multivariable analysis, 17 per cent of variance in the national selection first attempt score was explained by the Part B MRCS score and number of attempts (change in R 2 value of 0·10 and 0·07 respectively; P < 0·001). Candidates who required more than two attempts at Part B were predicted to score 8·1 per cent less than equally matched candidates who passed at their first attempt. CONCLUSION: This study supports validity of the MRCS examination, and indicates its predictive value regarding entry into specialist training.

3.
Tech Coloproctol ; 19(7): 411-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26081430

RESUMO

BACKGROUND: The use of biological materials for the repair of complex abdominal wall defects has increased over the years; however, the role of these materials in routine practice remains unclear. The aim of the study was to evaluate clinical outcomes following the use of Permacol™ porcine collagen surgical implant in complex abdominal wall repair. METHODS: This subset analysis of seven European sites from a multicentre retrospective study included patients undergoing open or laparoscopic surgery and treated with Permacol™ surgical implant. Inguinal, parastomal, diaphragmatic, perineal, and hiatal repairs were excluded. Only patients with at least 12 months of follow-up after surgery were included. RESULTS: A total of 109 patients (56 males and 53 females) were included. Patients had a median of two comorbidities (range 0-6). Thirty-three per cent of patients were treated for recurrent hernia. All but one case used an open approach. Sixty-six per cent were Center for Disease Control wound class II-IV at the time of surgery. Fascial closure was achieved in 69%. Median follow-up length was 720 days (range 368-2857). Recurrence rates at 1 and 2 years were 9.2 and 18.3 %, respectively, and were higher in cases without fascial closure. One-year recurrence was higher following use of an onlay technique (P = 0.025). In a multivariate analysis, among 16 comorbidities examined only fascial closure significantly impacted 1-year recurrence (P = 0.049). CONCLUSIONS: Data from this large retrospective multicentre European study strongly suggest the use of Permacol™ porcine collagen surgical implant to be safe and effective for complex abdominal wall repair. The recurrence rate was impacted by fascial closure.


Assuntos
Parede Abdominal/cirurgia , Materiais Biocompatíveis/uso terapêutico , Colágeno/uso terapêutico , Hérnia Ventral/cirurgia , Herniorrafia/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente) , Fáscia/patologia , Feminino , Hérnia Ventral/classificação , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/etiologia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
4.
Environ Sci Process Impacts ; 17(2): 448-57, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25564248

RESUMO

A simplified and sensitive liquid chromatography mass spectrometry (LC-MS) method without requiring sample pre-concentration was successfully developed for detecting the occurrence of ultra-low (ng L(-1)) concentrations of benzotriazole (BTri), and its derivative 5-methyl benzotriazole (5-MeBT) in various Western Australian environmental water samples. The method detection limit was 2 ng L(-1), providing similar detection limits to other more process intensive methods where pre-concentration using solid phase extraction (SPE) was employed. The method was used to assess the occurrence of BTri and 5-MeBT in wastewater and surface water samples. Over a period of 12 months, BTri and 5-MeBT concentrations in secondary treated wastewater were measured, with the highest BTri and 5-MeBT concentrations observed during winter months at 78 ng L(-1) and 21 ng L(-1), respectively. The method was also used to assess the removal efficiency of BTri and 5-MeBT through an advanced water recycling plant (AWRP). While BTri was more persistent than 5-MeBT, both compounds were removed from the AWRP to <10 ng L(-1) (BTri) and <2 ng L(-1) (5-MeBT), with reverse osmosis (RO) providing the most effective treatment process for their removal.


Assuntos
Detergentes/análise , Monitoramento Ambiental , Água Doce/química , Triazóis/análise , Águas Residuárias/química , Poluentes Químicos da Água/análise , Austrália Ocidental
5.
Water Res ; 70: 184-95, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25528548

RESUMO

The fate of benzotriazole (BTri) and 5-methylbenzotriazole (5-MeBT) was investigated under anaerobic conditions at nano gram per litre concentrations in large-scale laboratory columns to mimic a managed aquifer recharge replenishment strategy in Western Australia. Investigations of BTri and 5-MeBT sorption behaviour demonstrated mobility of the compounds with retardation coefficients of 2.0 and 2.2, respectively. Degradation processes over a period of 220 days indicated first order biodegradation of the BTri and 5-MeBT under anaerobic aquifer conditions after a biological lag-time of approximately 30-60 days. Biodegradation half-lives of 29 ± 2 and 26 ± 1 days for BTri and 5-MeBT were respectively observed, with no threshold effect to biodegradation observed at the 200 ng L(-1). The detection of degradation products provided further evidence of BTri and 5-MeBT biodegradation. These results suggested that if BTri and 5-MeBT were present in recycled water recharged to the Leederville aquifer, biodegradation during aquifer passage is likely given sufficient aquifer residence times or travel distances between recycled water injection and groundwater extraction.


Assuntos
Água Subterrânea/química , Triazóis/química , Poluentes Químicos da Água/química , Anaerobiose , Sedimentos Geológicos/química
6.
Water Res ; 46(4): 1260-72, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-22244272

RESUMO

Laboratory and field experiments were undertaken to assess the fate of N-nitrosodimethylamine (NDMA) in aerobic recycled water that was recharged into a deep anaerobic pyritic aquifer, as part of a managed aquifer recharge (MAR) strategy. Laboratory studies demonstrated a high mobility of NDMA in the Leederville aquifer system with a retardation coefficient of 1.1. Anaerobic degradation column and (14)C-NDMA microcosm studies showed that anaerobic conditions of the aquifer provided a suitable environment for the biodegradation of NDMA with first-order kinetics. At microgram per litre concentrations, inhibition of biodegradation was observed with degradation half-lives (260±20 days) up to an order of magnitude greater than at nanogram per litre concentrations (25-150 days), which are more typical of environmental concentrations. No threshold effects were observed at the lower ng L(-1) concentrations with NDMA concentrations reduced from 560 ng L(-1) to <6 ng L(-1) over a 42 day 14C-NDMA aerobic microcosm experiment. Aerobic (14)C-NDMA microcosm studies were also undertaken to assess potential aerobic degradation, likely to occur close to the recharge bore. These microcosm experiments showed a faster degradation rate than anaerobic microcosms, with a degradation half-life of 8±2 days, after a lag period of approximately 10 days. Results from a MAR field trial recharging the Leederville aquifer with aerobic recycled water showed that NDMA concentrations reduced from 2.5±1.0 ng L(-1) to 1.3±0.4 ng L(-1) between the recharge bore and a monitoring location 20 m down gradient (an estimated aquifer residence time of 10 days), consistent with data from the aerobic microcosm experiment. Further down gradient, in the anaerobic zone of the aquifer, NDMA degradation could not be assessed, as NDMA concentrations were too close to their analytical detection limit (<1 ng L(-1)).


Assuntos
Dimetilnitrosamina/análise , Água Subterrânea/química , Reciclagem , Poluentes Químicos da Água/análise , Anaerobiose , Biodegradação Ambiental , Brometos/análise , Isótopos de Carbono , Meia-Vida , Fatores de Tempo
7.
Water Res ; 45(8): 2550-60, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21396674

RESUMO

The fate of N-nitrosomorpholine (NMOR) was evaluated at microgram and nanogram per litre concentrations. Experiments were undertaken to simulate the passage of groundwater contaminants through a deep anaerobic pyritic aquifer system, as part of a managed aquifer recharge (MAR) strategy. Sorption studies demonstrated the high mobility of NMOR in the Leederville aquifer system, with retardation coefficients between 1.2 and 1.6. Degradation studies from a 351 day column experiment and a 506 day stop-flow column experiment showed an anaerobic biologically induced reductive degradation process which followed first order kinetics. A biological lag-time of less than 3 months and a transient accumulation of morpholine (MOR) were also noted during the degradation. Comparable half-life degradation rates of 40-45 days were observed over three orders of magnitude in concentration (200 ng L(-1) to 650 µg L(-1)). An inhibitory effect on microorganism responsible to the biodegradation of NMOR at 650 µg L(-1) or a threshold effect at 200 ng L(-1) was not observed during these experiments.


Assuntos
Água Doce/química , Nitrosaminas/metabolismo , Poluentes Químicos da Água/metabolismo , Purificação da Água/métodos , Abastecimento de Água , Anaerobiose , Biodegradação Ambiental , Água Doce/microbiologia , Nitrosaminas/análise , Poluentes Químicos da Água/análise
8.
Environ Sci Technol ; 38(24): 6846-54, 2004 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-15669348

RESUMO

A pilot-scale field trial was undertaken to evaluate the potential of in situ polymer mats (installed in series) as permeable reactive barriers within a treatment wall remediation system to induce sequential bioremediation of ammonium-contaminated groundwater. The treatment wall consisted of 10 m wide impermeable wings on either side of a 0.75 m wide permeable reactive zone flow-through box. Two polymer mats were positioned in the flow-through box. The upgradient polymer mat within the flow-through box was used to deliver oxygen to induce bacterial nitrification of the ammonium to nitrite/nitrate as the groundwater moved past. The downgradient polymer mat delivered ethanol to induce bacterial denitrification of the nitrite/nitrate to produce nitrogen gas. The field trial was carried out at a near-shore location. Initially the flow-through box was left open; however, this resulted in substantial groundwater mixing, which inhibited sequential remediation. Once the flow-through box was in-filled with gravel, groundwater mixing was reduced, achieving a greater than 90% reduction in total N. Estimated first-order half-lives for nitrification and denitrification rates were 1.2 and 0.4 d, respectively. Field nitrification half-lives were approximately an order of magnitude greater than rates determined in large-scale columns using soil and groundwater from the site, while denitrification half-lives were similar. The results of this pilot-scale field trial indicate that sequential bioremediation of ammonium-contaminated groundwater at field scale is feasible using in situ polymer mats as permeable reactive barriers, although hydraulic conditions can be complex in such barrier systems.


Assuntos
Polímeros , Compostos de Amônio Quaternário/isolamento & purificação , Compostos de Amônio Quaternário/metabolismo , Poluentes do Solo/isolamento & purificação , Poluentes do Solo/metabolismo , Poluentes da Água/isolamento & purificação , Poluentes da Água/metabolismo , Biodegradação Ambiental , Microbiologia do Solo , Movimentos da Água
9.
Astrobiology ; 3(4): 823-50, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14987485

RESUMO

The oxidants produced by radiolysis and photolysis in the icy surface of Europa may be necessary to sustain carbon-based biochemistry in Europa's putative subsurface ocean. Because the subduction of oxidants to the ocean presents considerable thermodynamic challenges, we examine the formation of oxygen and related species in Europa's surface ice with the goal of characterizing the chemical state of the irradiated material. Relevant spectral observations of Europa and the laboratory data on the production of oxygen and related species are first summarized. Since the laboratory data are incomplete, we examine the rate equations for formation of oxygen and its chemical precursors by radiolysis and photolysis. Measurements and simple rate equations are suggested that can be used to characterize the production of oxidants in Europa's surface material and the chemical environment produced by radiolysis. Possible precursor molecules and the role of radical trapping are examined. The possibility of oxygen reactions on grain surfaces in Europa's regolith is discussed, and the earlier estimates of the supply of O(2) to the atmosphere are increased.


Assuntos
Júpiter , Oxidantes , Carbono , Dimerização , Radicais Livres , Hidrogênio , Gelo , Íons , Cinética , Luz , Modelos Químicos , Oxigênio/química , Peróxidos/química , Temperatura , Termodinâmica
10.
Environ Sci Technol ; 36(15): 3439-45, 2002 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-12188377

RESUMO

Large-scale column experiments were undertaken to evaluate the potential of in situ polymer mats (installed in series) to be used as permeable reactive barriers for delivery of oxidants and reductants to induce sequential bioremediation of ammonium-contaminated groundwater (approximately 120mg L(-1) NH4+-N), without bioaugmentation. The strategy was for the first group of polymer mats to deliver oxygen to induce bacterial nitrification of the ammonium to nitrite/ nitrate as the groundwater moved past and for the second group of polymer mats to deliver hydrogen or ethanol, to induce bacterial denitrification of the nitrite/nitrate to produce nitrogen gas. Once purging of the first polymer mat commenced, ammonium concentrations decreased downgradient from the polymer mats. Nitrification rates increased and stabilized over the 6-month experiment, with stable nitrification half-lives in the range 0.07-0.25 days. Nitrification most likely occurred in a biologically active zone at the polymer wall/aqueous interface. With hydrogen delivery via the polymer mats, a denitrification half-life (nitrate plus nitrite removal) of 3.5 days was induced. Denitrification rates were significantly enhanced when ethanol was delivered via a polymer mat, with denitrification half-lives in the range of 0.12-0.34 days. Nitrification/ denitrification rates were maintained for groundwater flow rates up to 300 m yr(-1), suggesting oxygen and ethanol delivery rates via the polymer mats were sufficient not to limit nitrification or denitrification. In soil columns, the polymer mat delivery system provided an effective and reliable technique for delivery of oxygen and hydrogen or ethanol for sequential nitrification/denitrification of ammonium-contaminated groundwater. Scale-up of this concept to a field pilot-scale is currently underway.


Assuntos
Nitrogênio/metabolismo , Polímeros , Compostos de Amônio Quaternário/química , Poluentes do Solo/análise , Poluição da Água/prevenção & controle , Biodegradação Ambiental , Etanol/análise , Meia-Vida , Oxirredução , Oxigênio/análise , Permeabilidade , Compostos de Amônio Quaternário/análise
11.
Surg Endosc ; 16(2): 358, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11967698

RESUMO

The use of laparoscopy in the assessment and treatment of blunt abdominal trauma has been reported for both adults and children. With increasing surgical experience and improvements in equipment, an expanding range of therapeutic interventions is available. The management of a 7-year-old boy who sustained blunt abdominal trauma during a fall from a bicycle is described. He was hemodynamically stable, but his abdomen remained tender, with guarding in the right upper quadrant. Serial ultrasound scans showed a thick-walled gallbladder and increasing intraabdominal fluid. Laparoscopy was used both as a diagnostic tool, and then as a therapeutic method. Diagnostic laparoscopy showed a ruptured gallbladder treated by laparoscopic cholecystectomy. A 3-cm grade 1 liver laceration also was identified, which required no intervention. Free bile was aspirated and the peritoneal cavity thoroughly lavaged. The child made a rapid postoperative recovery. The ultimate aim in the management of blunt trauma is to avoid unnecessary laparotomy while preventing undue delay in the detection of significant intraabdominal pathology. Computed tomography scanning, ultrasound scanning, and diagnostic peritoneal lavage all have strengths for detecting different injury types, but they also have a low specificity in determining the need for laparotomy. The advantages and limitations of laparoscopy in hemodynamically stable children who have sustained injuries from blunt trauma are discussed. The authors recommend laparoscopy in experienced hands as an additional tool for the optimal management of selected trauma cases.


Assuntos
Traumatismos Abdominais/cirurgia , Laparoscopia/métodos , Ferimentos não Penetrantes/cirurgia , Acidentes por Quedas , Ciclismo , Criança , Colecistectomia Laparoscópica , Vesícula Biliar/lesões , Vesícula Biliar/cirurgia , Humanos , Masculino
12.
Eur J Biochem ; 268(8): 2338-43, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11298752

RESUMO

The conversion of cholesterol to pregnenolone by cytochrome P450scc is the rate-determining step in placental progesterone synthesis. The limiting component for placental cytochrome P450scc activity is the concentration of adrenodoxin reductase in the mitochondria, where it permits cytochrome P450scc to work at only 16% of maximum velocity. Adrenodoxin reductase serves to reduce adrenodoxin as part of the electron transfer from NADPH to cytochrome P450scc. We therefore measured the proportion of adrenodoxin in the reduced form in intact mitochondria from the human placenta during active pregnenolone synthesis, using EPR. We found that the adrenodoxin pool was only 30% reduced, indicating that the adrenodoxin reductase concentration was insufficient to maintain the adrenodoxin in the fully reduced state. As both oxidized and reduced adrenodoxin can bind to cytochrome P450scc we tested the ability of oxidized adrenodoxin to act as a competitive inhibitor of pregnenolone synthesis. This was done in a fully reconstituted system comprising 0.3% Tween 20 and purified proteins, and in a partially reconstituted system comprising submitochondrial particles, purified adrenodoxin and adrenodoxin reductase. We found that oxidized adrenodoxin is an effective competitive inhibitor of placental cytochrome P450scc with a Ki value half that of the Km for reduced adrenodoxin. We conclude that the limiting concentration of adrenodoxin reductase present in placental mitochondria has a two-fold effect on cytochrome P450scc activity. It limits the amount of reduced adrenodoxin that is available to donate electrons to cytochrome P450scc and the oxidized adrenodoxin that remains, competitively inhibits the cytochrome.


Assuntos
Adrenodoxina/metabolismo , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Mitocôndrias/metabolismo , Oxigênio/metabolismo , Placenta/metabolismo , Ligação Competitiva , Catálise , Detergentes/farmacologia , Relação Dose-Resposta a Droga , Fenômenos Eletromagnéticos , Espectroscopia de Ressonância de Spin Eletrônica , Transporte de Elétrons , Ferredoxina-NADP Redutase/metabolismo , Humanos , Cinética , Polissorbatos/farmacologia , Pregnenolona/biossíntese , Fatores de Tempo
13.
J R Coll Surg Edinb ; 46(1): 20-8, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11242739

RESUMO

The development and refinement of pelvic pouch surgery now allows the excision of a diseased colon while maintaining transanal faecal continence. The success of restorative proctocolectomy is largely dependent on careful patient selection combined with meticulous surgical technique. The authors discuss the main indications for restorative proctocolectomy and describe the surgical procedure.


Assuntos
Proctocolectomia Restauradora/métodos , Humanos , Seleção de Pacientes , Complicações Pós-Operatórias , Cuidados Pré-Operatórios , Técnicas de Sutura , Suturas
14.
Acc Chem Res ; 33(10): 665-71, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11041830

RESUMO

This Account describes the near-UV and visible luminescences emitted from crystalline, polycrystalline, and amorphous ices as a result of excitation by UV light. Vibrationally resolved, short-lived luminescence around 340 nm arises from excited O(2) formed by the reaction of two O atoms. Long-lived luminescence around 420 nm is tentatively assigned to a spin-forbidden (4)sigma(-) --> X(2)Pi transition of OH. This Account gives a history of the research into this little-known phenomenon, places it in the context of other spectroscopic studies of gaseous and solid water, and proposes future directions for the work.


Assuntos
Gelo , Raios Ultravioleta , Medições Luminescentes
15.
Ann Surg ; 228(2): 167-72, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9712560

RESUMO

OBJECTIVE: To determine the optimal management of symptomatic non-parasitic liver cysts. SUMMARY BACKGROUND DATA: Management options for symptomatic nonparasitic liver cysts lack substantiation through comparative studies with respect to safety and long-term effectiveness. METHODS: A retrospective review of the surgical management of patients with hepatic cysts between October 1988 and August 1997 was undertaken to determine morbidity rates and to assess long-term recurrence. RESULTS: Thirty-eight patients (35 women, 3 men) underwent 48 operations for symptomatic hepatic cysts of mean diameter 12 cm, with a mean follow-up of 41 months. Twenty-three patients had simple cysts, and 15 patients had polycystic liver disease (PCLD). The symptomatic recurrence rates after laparoscopic or open deroofing for simple cysts were 8% and 29%, and for PCLD 71% and 20%, respectively. There were no symptomatic recurrences after 14 hepatic resections. There were no perisurgical deaths; however, morbidity rates were significant after laparoscopic deroofing, open deroofing, and hepatic resection (25%, 36%, and 50%, respectively). CONCLUSIONS: Selection of patients with truly symptomatic hepatic cysts is crucial before considering interventional techniques. For simple cysts, radical laparoscopic deroofing is usually curative; open deroofing should be reserved for cysts inaccessible by laparoscopy. The latter technique is well tolerated; however, long-term symptom control is unpredictable in patients with PCLD. Hepatic resection for PCLD provides satisfactory long-term symptom control but has an appreciable morbidity rate. Although laparoscopic and open deroofing procedures are less reliable in the long term for solitary cysts, they might be useful steps before embarking on this major procedure.


Assuntos
Cistos/diagnóstico , Cistos/cirurgia , Hepatopatias/diagnóstico , Hepatopatias/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
16.
Proc Natl Acad Sci U S A ; 93(17): 9049-54, 1996 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-8799152

RESUMO

We have investigated the influence of genetic instability [replication error (RER) phenotype] on APC (adenomatous polyposis coli), a gene thought to initiate colorectal tumorigenesis. The prevalence of APC mutations was similar in RER and non-RER tumors, indicating that both tumor types share this step in neoplastic transformation. However, in a total of 101 sequenced mutations, we noted a substantial excess of APC frameshift mutations in the RER cases (70% in RER tumors versus 47% in non-RER tumors, P < 0.04). These frameshifts were characteristic of mutations arising in cells deficient in DNA mismatch repair, with a predilection for mononucleotide repeats in the RER tumors (P < 0.0002), particularly (A)n tracts (P < 0.00007). These findings suggest that the genetic instability that is reflected by the RER phenotype precedes, and is responsible for, APC mutation in RER large bowel tumors and have important implications for understanding the very earliest stages of neoplasia in patients with tumors deficient in mismatch repair.


Assuntos
Polipose Adenomatosa do Colo/genética , Proteínas do Citoesqueleto/genética , Reparo do DNA , Mutação da Fase de Leitura , Mutagênese , Polipose Adenomatosa do Colo/etiologia , Proteína da Polipose Adenomatosa do Colo , Sequência de Bases , Transformação Celular Neoplásica , Replicação do DNA , DNA Satélite , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular
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