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1.
Int J Surg Case Rep ; 72: 277-280, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32563085

RESUMO

BACKGROUND: Laparoscopy is a relatively new surgical approach in developing countries. Migrated foreign bodies into the body cavities could be very distressing to patients, relations and caregivers. There are paucity of migrated Steinmann pin and laparoscopic retrieval methods in literature. AIM: An innovative approach of laparoscopic retrieval of migrated sharp foreign body (Steinmann pin). METHODS: A two-port technique was used to retrieve the pin. These ports consisted of optical supra-umbilical port (10 mm) and left iliac fossa port of 10 mm. They were aligned in the direction of sharp end of the foreign body, to aid retrieval of the Steinmann pin. This procedure was performed on a 34-year-old man who presented with migration of Steinmann pin into abdominal cavity. He had open reduction of old unreduced left posterior hip dislocation. A Steinmann pin with a diameter of 4.5 mm and length of 140 mm was passed through the greater trochanter to the acetabular roof. The protruding end of the pin ought to have been bent. Three weeks post-surgery, the pin migrated. Physical examination revealed vague tenderness over supra pubic region. A hard pointed object was palpable in the right iliac fossa. Abdominal X-ray and ultrasound were suggestive but not definite for pin location. RESULTS: A sharp Steinman pin was retrieved from the abdominal cavity using laparoscopy. CONCLUSION: Migration of Steinmann pin is unusual. Laparoscopy is an innovative approach to foreign body retrieval. This could help reduce the morbidity that may be accompanied by other modalities such as open approach.

2.
Epidemiol Infect ; 147: e163, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-31063101

RESUMO

Influenza and respiratory syncytial virus (RSV) are common causes of respiratory tract infections and place a burden on health services each winter. Systems to describe the timing and intensity of such activity will improve the public health response and deployment of interventions to these pressures. Here we develop early warning and activity intensity thresholds for monitoring influenza and RSV using two novel data sources: general practitioner out-of-hours consultations (GP OOH) and telehealth calls (NHS 111). Moving Epidemic Method (MEM) thresholds were developed for winter 2017-2018. The NHS 111 cold/flu threshold was breached several weeks in advance of other systems. The NHS 111 RSV epidemic threshold was breached in week 41, in advance of RSV laboratory reporting. Combining the use of MEM thresholds with daily monitoring of NHS 111 and GP OOH syndromic surveillance systems provides the potential to alert to threshold breaches in real-time. An advantage of using thresholds across different health systems is the ability to capture a range of healthcare-seeking behaviour, which may reflect differences in disease severity. This study also provides a quantifiable measure of seasonal RSV activity, which contributes to our understanding of RSV activity in advance of the potential introduction of new RSV vaccines.


Assuntos
Influenza Humana/epidemiologia , Influenza Humana/patologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/patologia , Vigilância de Evento Sentinela , Inglaterra/epidemiologia , Humanos , Encaminhamento e Consulta , Telemedicina/métodos
3.
Epidemiol Infect ; 146(11): 1389-1396, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29972108

RESUMO

Understanding the burden of respiratory pathogens on health care is key to improving public health emergency response and interventions. In temperate regions, there is a large seasonal rise in influenza and other respiratory pathogens. We have examined the associations between individual pathogens and reported respiratory tract infections to estimate attributable burden. We used multiple linear regression to model the relationship between doctor consultation data and laboratory samples from week 3 2011 until week 37 2015. We fitted separate models for consultation data with in-hours and out-of-hours doctor services, stratified by different age bands. The best fitting all ages models (R2 > 80%) for consultation data resulted in the greatest burden being associated with influenza followed by respiratory syncytial virus (RSV). For models of adult age bands, there were significant associations between consultation data and invasive Streptococcus pneumoniae. There were also smaller numbers of consultations significantly associated with rhinovirus, parainfluenza, and human metapneumovirus. We estimate that a general practice with 10 000 patients would have seen an additional 18 respiratory tract infection consultations per winter week of which six had influenza and four had RSV. Our results are important for the planning of health care services to minimise the impact of winter pressures. •Respiratory pathogen incidence explains over 80% of seasonal variation in respiratory consultation data.•Influenza and RSV are associated with the biggest seasonal rises in respiratory consultation counts.•A third of consultation counts associated with respiratory pathogens were due to influenza.


Assuntos
Medicina Geral/estatística & dados numéricos , Infecções Respiratórias/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Inglaterra/epidemiologia , Humanos , Incidência , Lactente , Influenza Humana/epidemiologia , Modelos Lineares , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estações do Ano , Fatores de Tempo , Adulto Jovem
4.
Epidemiol Infect ; 145(9): 1922-1932, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28413995

RESUMO

Seasonal respiratory illnesses present a major burden on primary care services. We assessed the burden of respiratory illness on a national telehealth system in England and investigated the potential for providing early warning of respiratory infection. We compared weekly laboratory reports for respiratory pathogens with telehealth calls (NHS 111) between week 40 in 2013 and week 29 in 2015. Multiple linear regression was used to identify which pathogens had a significant association with respiratory calls. Children aged <5 and 5-14 years, and adults over 65 years were modelled separately as were time lags of up to 4 weeks between calls and laboratory specimen dates. Associations with respiratory pathogens explained over 83% of the variation in cold/flu, cough and difficulty breathing calls. Based on the first two seasons available, the greatest burden was associated with respiratory syncytial virus (RSV) and influenza, with associations found in all age bands. The most sensitive signal for influenza was calls for 'cold/flu', whilst for RSV it was calls for cough. The best-fitting models showed calls increasing a week before laboratory specimen dates. Daily surveillance of these calls can provide early warning of seasonal rises in influenza and RSV, contributing to the national respiratory surveillance programme.


Assuntos
Infecções Respiratórias/epidemiologia , Telemedicina/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Inglaterra/epidemiologia , Humanos , Lactente , Recém-Nascido , Influenza Humana/epidemiologia , Influenza Humana/virologia , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Infecções Respiratórias/virologia , Estações do Ano , Adulto Jovem
5.
J Public Health (Oxf) ; 39(1): 184-192, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-26956114

RESUMO

Background: Public Health England (PHE) coordinates a suite of real-time national syndromic surveillance systems monitoring general practice, emergency department and remote health advice data. We describe the development and informal evaluation of a new syndromic surveillance system using NHS 111 remote health advice data. Methods: NHS 111 syndromic indicators were monitored daily at national and local level. Statistical models were applied to daily data to identify significant exceedances; statistical baselines were developed for each syndrome and area using a multi-level hierarchical mixed effects model. Results: Between November 2013 and October 2014, there were on average 19 095 NHS 111 calls each weekday and 43 084 each weekend day in the PHE dataset. There was a predominance of females using the service (57%); highest percentage of calls received was in the age group 1-4 years (14%). This system was used to monitor respiratory and gastrointestinal infections over the winter of 2013-14, the potential public health impact of severe flooding across parts of southern England and poor air quality episodes across England in April 2014. Conclusions: This new system complements and supplements the existing PHE syndromic surveillance systems and is now integrated into the routine daily processes that form this national syndromic surveillance service.


Assuntos
Vigilância da População/métodos , Saúde Pública , Estatística como Assunto/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Inglaterra/epidemiologia , Feminino , Medicina Geral , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Consulta Remota , Medicina Estatal , Adulto Jovem
7.
Epidemiol Infect ; 140(12): 2152-6, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22892324

RESUMO

Syndromic surveillance is vital for monitoring public health during mass gatherings. The London 2012 Olympic and Paralympic Games represents a major challenge to health protection services and community surveillance. In response to this challenge the Health Protection Agency has developed a new syndromic surveillance system that monitors daily general practitioner out-of-hours and unscheduled care attendances. This new national system will fill a gap identified in the existing general practice-based syndromic surveillance systems by providing surveillance capability of general practice activity during evenings/nights, over weekends and public holidays. The system will complement and supplement the existing tele-health phone line, general practitioner and emergency department syndromic surveillance systems. This new national system will contribute to improving public health reassurance, especially to meet the challenges of the London 2012 Olympic and Paralympic Games.


Assuntos
Plantão Médico/estatística & dados numéricos , Clínicos Gerais/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Vigilância em Saúde Pública/métodos , Esportes , Aniversários e Eventos Especiais , Agendamento de Consultas , Humanos , Londres , Visita a Consultório Médico/estatística & dados numéricos
8.
Epidemiol Infect ; 140(1): 100-5, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21473803

RESUMO

The Health Protection Agency/QSurveillance national surveillance system utilizes QSurveillance®, a recently developed general practitioner database covering over 23 million people in the UK. We describe the spread of the first wave of the influenza A(H1N1) pandemic 2009 using data on consultations for influenza-like illness (ILI), respiratory illness and prescribing for influenza from 3400 contributing general practices. Daily data, provided from 27 April 2009 to 28 January 2010, were used to give a timely overview for those managing the pandemic nationally and locally. The first wave particularly affected London and the West Midlands with a peak in ILI in week 30. Children aged between 1 and 15 years had consistently high consultation rates for ILI. Daily ILI rates were used for modelling national weekly case estimates. The system enabled the 'real-time' monitoring of the pandemic to a small geographical area, linking morbidity and prescribing for influenza and other respiratory illnesses.


Assuntos
Sistemas de Gerenciamento de Base de Dados , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/epidemiologia , Pandemias/estatística & dados numéricos , Vigilância da População/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Bases de Dados Factuais , Medicina Geral/estatística & dados numéricos , Humanos , Lactente , Influenza Humana/virologia , Pessoa de Meia-Idade , Reino Unido/epidemiologia
10.
Epidemiol Infect ; 136(3): 360-9, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17445314

RESUMO

The UK has had a pneumococcal polysaccharide vaccination (PPV) programme for groups at higher risk of invasive disease since 1992. This paper presents data from a sample of primary-care practices (Q-RESEARCH) of PPV uptake in patients according to their risk status. Of 2.9 million registered patients in 2005, 2.1% were vaccinated with PPV in the preceding 12 months and 6.5% in the preceding 5 years. Twenty-nine per cent of the registered population fell into one or more risk groups. The proportion of each risk group vaccinated in the previous 5 years ranged from 69% (cochlear implants), 53.4% (splenic dysfunction), 36.5% (chronic heart disease), 34.7% (diabetes), 22.9% (immunosuppressed), 28.7% (chronic renal disease), 15.9% (sickle cell disease) to 12.6% (chronic respiratory disease). Uptake was lower in areas where the non-white proportion of population was >10%. In conclusion, there remain large gaps in the uptake of PPV in several high-risk populations in the United Kingdom. Effective strategies need to be developed to address these deficiencies.


Assuntos
Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/imunologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/etiologia , Prevalência , Medição de Risco , Vacinação , País de Gales/epidemiologia
11.
Anim Reprod Sci ; 102(1-2): 98-110, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17088028

RESUMO

In seasonal dairy production systems a high level of reproductive performance is required to maintain a 365-day calving interval. Compared with many countries New Zealand dairy cattle are fertile, with an average calving interval of 368 days and first service conception rates of around 55%. However, fertility has been demonstrated to have declined over the past 15-years. An extended interval from calving to first luteal activity (CLA) has previously been identified as a major cause of infertility in New Zealand dairy cows. This paper investigates the phenotypic relationship between CLA and reproductive performance in a population of second cross FriesianxJersey dairy cattle. The data consists of 1780 lactations, from 801 individuals that were managed in a seasonal, pasture-based dairy production system. Overall, reproductive performance in the herd was high, with first service conception rates of over 60% and more than 80% of the herd pregnant within 42-days of the start of the breeding period. Animals were divided into six groups of at least 270 animals per group based on CLA (50 days). First service conception rates and the interval from the start of mating to conception were not statistically different between the CLA groups (p>0.05), despite the number of oestrous cycles prior to first mating being inversely proportional to CLA. However, only 47% of animals with a CLA of >70 days (n=88) were pregnant within 21-day of the start of mating, compared with 65% of animals with CLA of <70 days. Animals that had not ovulated by 1-week prior to the start of mating also had reduced reproductive performance (45% versus 67% pregnant within 21-days of the start of mating, p<0.001). The poor reproductive performance of animals with CLA>70 days is likely to be due to a lower proportion of animals having ovulated by the start of mating (0.28 versus 0.95, p<0.001). Contrary to previous findings in non-seasonal production systems the length of CLA was not related to fertility, except when CLA was greater than 70 days.


Assuntos
Bovinos/fisiologia , Corpo Lúteo/fisiologia , Indústria de Laticínios , Fertilidade/fisiologia , Estações do Ano , Envelhecimento , Animais , Peso Corporal , Feminino , Inseminação Artificial/veterinária , Leite , Ovulação/fisiologia , Parto , Fenótipo , Gravidez
13.
Eur J Clin Microbiol Infect Dis ; 23(7): 535-8, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15221614

RESUMO

This study was conducted to examine the relationship between age, material deprivation, and hospital admissions for selected gynaecologic infections in an English health region. Data from hospital episode statistics relating to hospital admissions for pelvic inflammatory disease (PID), infections of the uterus, and infections of the cervix, vagina, and vulva were obtained. Townsend deprivation scores (based on 1991 census data) were allocated by linking postcodes of cases to enumeration districts (EDs) and then assigning the EDs to appropriate quintiles of material deprivation. Both single variable and multivariable (Poisson regression) analyses were performed. For women with PID, the risk of hospitalisation increased with increasing deprivation (P<0.0001), and women in the most deprived quintile were at increased risk (relative risk [RR] 1.31; 95% confidence interval [95%CI] 1.24-1.39) for hospitalisation. Multivariable analysis identified an elevated risk of hospital admission in women aged 25-44 years for PID (RR 2.03; 95%CI 0.84-4.87) and infections of the cervix, vagina, and vulva (RR 1.47; 95%CI 1.16-1.87), and the incidence of both conditions increased significantly with age. In summary, the results obtained suggest that women from the most deprived areas are at greatest risk of hospitalisation for gynaecologic infections, particularly PID. Preventive measures together with earlier diagnostic, treatment, and referral procedures are required to reduce morbidity.


Assuntos
Doenças dos Genitais Femininos/terapia , Hospitalização/estatística & dados numéricos , Doença Inflamatória Pélvica/epidemiologia , Pobreza , Adolescente , Adulto , Distribuição por Idade , Idoso , Análise de Variância , Atitude Frente a Saúde , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/terapia , Criança , Pré-Escolar , Intervalos de Confiança , Feminino , Doenças dos Genitais Femininos/diagnóstico , Doenças dos Genitais Femininos/epidemiologia , Pesquisas sobre Atenção à Saúde , Humanos , Incidência , Pessoa de Meia-Idade , Análise Multivariada , Doença Inflamatória Pélvica/diagnóstico , Estudos Retrospectivos , Medição de Risco , Reino Unido/epidemiologia
14.
J Public Health (Oxf) ; 26(1): 88-94, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15044582

RESUMO

BACKGROUND: The Royal College of General Practitioners Weekly Returns Service (WRS) is a network of sentinel general practices providing weekly data on illnesses diagnosed in general practice across England and Wales. The WRS contributes to the surveillance of infectious disease, most notably influenza. We use Geographical Information Systems (GIS) techniques to establish whether the practice populations of the current WRS are representative of the general population. METHODS: This study compares the practice population with the general population using the Department of the Environment, Transport and Regions (DETR) Indices of Deprivation 2000 scores for English wards. RESULTS: Comparisons at the national level reveal that the WRS population is less deprived than the general population. At a supra-regional level the WRS practice population shows the same North-South differences as the national population, but the proportions of patients in the more deprived and least deprived wards are more exaggerated in the WRS population. A supplementary analysis reveals that the WRS has no patients in the most deprived wards of London. CONCLUSION: The differences have implications for the future recruitment of practices to the WRS. Previous studies have demonstrated the effect of socio-economic deprivation on GP consultation rates. To ensure that the consultation rates reported by the WRS will better reflect consulting patterns in the general population the WRS will need to recruit practices with patients in the most deprived areas of the South and less deprived areas in the North of England. This study demonstrates the value of GIS in the establishment of surveillance systems.


Assuntos
Doenças Transmissíveis/epidemiologia , Bases de Dados Factuais , Medicina de Família e Comunidade/estatística & dados numéricos , Sistemas de Informação Geográfica , Informática em Saúde Pública , Vigilância de Evento Sentinela , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Atenção Primária à Saúde/estatística & dados numéricos , Fatores Socioeconômicos , Medicina Estatal , País de Gales/epidemiologia
15.
Commun Dis Public Health ; 6(3): 231-7, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14708274

RESUMO

Influenza is recognised as a major cause of excess hospital admissions during winter months. This study sets out to quantify admissions related to influenza during the last twelve winters and to examine the importance of age. Total admission data for respiratory disorders in adults for England during the years 1989 to 2001 have been used. Weekly admission data were examined in five-year age bands. Influenza epidemics were identified from clinical incidence data in the community. Baseline admission levels were determined by averaging weekly incidence data from weeks in which there was no clinical evidence of influenza activity. Excess admissions were estimated from the difference between observed and baseline admissions after adjusting the baseline in each group and year for the secular trend. Estimates for all adults were consolidated from the five-year age bands. Bed occupancy was estimated by applying data on average bed stay to excess admissions in age- and year-specific groups. We estimated 2.7% of all respiratory admissions were related to influenza. Excess admissions were strongly age related. Of the 16,227 annual average excess, 52% occurred in persons over 75 years. The excess admissions account for an average 145,544 bed days annually, two thirds (69%) in persons over 75 years. Annual excess bed occupancy was highest in 1999/2000 (39,512) though 30,000 excess admissions per year is not unusual. Hospital admissions due to influenza remain a major problem for health service delivery particularly in elderly populations. Though robust programmes of vaccination are needed, vaccination by itself will not eliminate the impact of influenza on hospital admissions in winter.


Assuntos
Hospitalização/estatística & dados numéricos , Influenza Humana/epidemiologia , Doenças Respiratórias/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Inglaterra/epidemiologia , Hospitalização/tendências , Humanos , Pessoa de Meia-Idade , Estações do Ano
16.
Commun Dis Public Health ; 4(3): 178-82, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11732356

RESUMO

This study assessed whether NHS Direct could be a useful source of surveillance data for communicable diseases, using influenza as a pilot condition. Data on the weekly total number of calls and the number from people reporting influenza-like symptoms to three pilot NHS Direct sites were collected between November 1999 and March 2000. NHS Direct data were compared with routinely available influenza surveillance data. The NHS Direct call rate peaked at 331 per 100,000 population in week 52 of 1999. The percentage of calls for 'influenza-like illness' (one site) peaked at 15% during week 51. Information about weekly call numbers to NHS Direct could be produced in a timely way. It was not clear whether the observed peak in calls reflected a true increase in influenza or whether it was the result of an increase in calls over the Christmas/Millennium holiday period due to more difficulty in accessing other services. The ability to assess the proportion of calls made directly by, or on behalf of, each age group will be of vital importance in interpreting seasonal respiratory disease.


Assuntos
Planejamento em Saúde/métodos , Linhas Diretas , Influenza Humana/epidemiologia , Vigilância da População/métodos , Medicina Estatal , Surtos de Doenças , Indicadores Básicos de Saúde , Linhas Diretas/estatística & dados numéricos , Humanos , Projetos Piloto , Estações do Ano , Fatores de Tempo , Reino Unido/epidemiologia
17.
J Invertebr Pathol ; 75(4): 251-8, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10843831

RESUMO

The pathogenicity of Vespula vulgaris wasp workers and larvae to a range of fungi was determined. All fungi were isolated in New Zealand and included isolates from Vespula, known generalist insect pathogens, and isolates generally nonpathogenic to insects. Workers and larvae were highly susceptible to pathogenic isolates at high spore concentrations (>1.75 x 10(5) cfu/individual). Eight isolates, two of Metarhizium anisopliae, five of Beauveria bassiana, and one of Aspergillus flavus were pathogenic while a single isolate of M. flavouiride var. novazealandicum, Cladosporium sp., and Paecilomyces sp. were not. The transfer of spores between workers, and between workers and larvae, was also investigated using several different application methods. Transfer of spores occurred between treated and untreated individuals, and for some of the application methods sufficient spores were transferred to cause mortality of the nontreated individuals. These findings are related to the potential of fungi for the control of wasps.


Assuntos
Fungos/fisiologia , Himenópteros/microbiologia , Himenópteros/fisiologia , Controle Biológico de Vetores , Animais , Bioensaio , Larva/microbiologia , Longevidade , Esporos Fúngicos/fisiologia
18.
Cancer Res ; 60(2): 431-8, 2000 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-10667598

RESUMO

The DNA repair-deficient genetic disorders xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) can both result from mutations in the XPD gene, the sites of the mutations differing between the two disorders. The hallmarks of XP are multiple pigmentation changes in the skin and a greatly elevated frequency of skin cancers, characteristics that are not seen in TTD. XP-D and most TTD patients have reduced levels of DNA repair, but some recent reports have suggested that the repair deficiencies in TTD cells are milder than in XP-D cells. We reported recently that inhibition of intracellular adhesion molecule-1 (ICAM-1) expression by UVB irradiation was similar in normal and TTD cells but increased in XP-D cells, suggesting a correlation between ICAM-1 inhibition and cancer proneness. In the first part of the current work, we have extended these studies and found several other examples, including XP-G and Cockayne syndrome cells, in which increased ICAM-1 inhibition correlated with cancer proneness. However, we also discovered that a subset of TTD cells, in which arg112 in the NH2-terminal region of the XPD protein is mutated to histidine, had an ICAM-1 response similar to that of XP-D cells. In the second part of the work, we have shown that TTD cells with this specific NH2-terminal mutation are more sensitive to UV irradiation than other TTDs, most of which are mutated in the COOH-terminal region, and are indistinguishable from XP-D cells in cell killing, incision breaks, and repair of cyclobutane pyrimidine dimers. Because the clinical phenotypes of these patients do not obviously differ from those of TTDs with mutations at other sites, we conclude that the lack of skin abnormalities in TTD is independent of the defective cellular responses to UV. It is likely to result from a transcriptional defect, which prevents the skin abnormalities from being expressed.


Assuntos
Sobrevivência Celular/efeitos da radiação , DNA Helicases , Reparo do DNA/genética , Proteínas de Ligação a DNA , Doenças do Cabelo/genética , Cabelo/anormalidades , Molécula 1 de Adesão Intercelular/genética , Proteínas/genética , Neoplasias Cutâneas/genética , Fatores de Transcrição , Xeroderma Pigmentoso/genética , Linhagem Celular , Síndrome de Cockayne/genética , Relação Dose-Resposta à Radiação , Fibroblastos/efeitos da radiação , Humanos , Fenótipo , Schizosaccharomyces/genética , Neoplasias Cutâneas/complicações , Raios Ultravioleta , Xeroderma Pigmentoso/complicações , Proteína Grupo D do Xeroderma Pigmentoso
19.
Proc Natl Acad Sci U S A ; 94(16): 8658-63, 1997 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-9238033

RESUMO

The xeroderma pigmentosum group D (XPD) protein has a dual function, both in nucleotide excision repair of DNA damage and in basal transcription. Mutations in the XPD gene can result in three distinct clinical phenotypes, XP, trichothiodystrophy (TTD), and XP with Cockayne syndrome. To determine if the clinical phenotypes of XP and TTD can be attributed to the sites of the mutations, we have identified the mutations in a large group of TTD and XP-D patients. Most sites of mutations differed between XP and TTD, but there are three sites at which the same mutation is found in XP and TTD patients. Since the corresponding patients were all compound heterozygotes with different mutations in the two alleles, the alleles were tested separately in a yeast complementation assay. The mutations which are found in both XP and TTD patients behaved as null alleles, suggesting that the disease phenotype was determined by the other allele. If we eliminate the null mutations, the remaining mutagenic pattern is consistent with the site of the mutation determining the phenotype.


Assuntos
DNA Helicases , Proteínas de Ligação a DNA , Doenças do Cabelo/genética , Mutação , Proteínas/genética , Fatores de Transcrição , Xeroderma Pigmentoso/genética , Linhagem Celular , Reparo do DNA/genética , Reparo do DNA/efeitos da radiação , Fibroblastos/efeitos da radiação , Humanos , Raios Ultravioleta , Proteína Grupo D do Xeroderma Pigmentoso
20.
Free Radic Biol Med ; 22(1-2): 343-7, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-8958160

RESUMO

Ataxia-telangiectasia (A-T) is a human autosomal recessive disease characterised by immunodeficiency, extreme sensitivity to ionising radiation and progressive cerebellar ataxia. The defective gene has recently been cloned and is a member of the phosphatidylinositol 3-kinase family. We have investigated the possibility that the neurodegeneration in A-T might be induced by an endogenously formed mutagen causing radiation-like damage. Nitric oxide is known to be formed in the cerebellum and we present evidence that A-T fibroblasts are hypersensitive to killing by the nitric oxide donor S-nitrosoglutathione (GSNO), as are fibroblasts from a radiosensitive individual without ataxia. Killing was determined as loss of colony forming ability. GSNO induces dose-dependent DNA strand breakage, but to no greater extent in A-T fibroblasts. Breakdown of GSNO to nitrite and nitrate appears to occur to the same extent in both normal and A-T fibroblasts. Cell killing by GSNO appears to be associated in both types of cell with formation of nitrite, rather than nitrate, as the ultimate oxidation product of nitric oxide.


Assuntos
Ataxia Telangiectasia/induzido quimicamente , Hipersensibilidade a Drogas/etiologia , Glutationa/análogos & derivados , Óxido Nítrico/biossíntese , Compostos Nitrosos/toxicidade , Ataxia Telangiectasia/patologia , Morte Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Fibroblastos/efeitos dos fármacos , Glutationa/toxicidade , Humanos , Valores de Referência , S-Nitrosoglutationa
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