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1.
BMC Med Educ ; 21(1): 504, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34560852

RESUMO

BACKGROUND: An ageing population leads up to increasing multi-morbidity and polypharmacy. This demands a comprehensive and interprofessional approach in meeting patients' complex needs. This study describes graduate students' experiences of working practice based in interprofessional teams with complex patients' care needs in nursing homes. METHOD: Students from advanced geriatric nursing, clinical nutrition, dentistry, medicine and pharmacy at the University of Oslo in Norway were assigned to groups to examine and develop a care plan for a nursing home patient during a course. Focus groups were used, 21 graduate students participating in four groups. Data were collected during spring 2018, were inductively analysed according to a thematic analysis method (Systematic Text Condensation). An analytical framework of co-ordination practices was applied to get an in-depth understanding of the data. RESULTS: Three themes were identified: 1) Complex patients as learning opportunities- an eye-opener for future interprofessional collaboration 2) A cobweb of relations, and 3) Structural facilitators for new collective knowledge. Graduate university students experienced interprofessional education (IPE) on complex patients in nursing homes as a comprehensive learning arena. Overall, different co-ordination practices for work organization among the students were identified. CONCLUSIONS: IPE in nursing homes facilitated the students' scope from a fragmented approach of the patients towards a relational and collaborative practice that can improve patient care and strengthen understanding of IPE. The study also demonstrated the need for preparatory teamwork training to gain maximum benefit from the experience. Something that can be organized by the education institutions in the form of a stepwise learning module and as an online pre-training course in interprofessional teamwork. Further, focusing on the need for well thought through processes of the activity by the institutions and the timing the practice component in students' curricula. This could ensure that IPE is experienced more efficient by the students.


Assuntos
Educação em Enfermagem , Educação Interprofissional , Idoso , Atitude do Pessoal de Saúde , Grupos Focais , Humanos , Relações Interprofissionais , Casas de Saúde
2.
Occup Med (Lond) ; 67(8): 644-647, 2017 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-29016957

RESUMO

BACKGROUND: General practitioners (GPs) report sickness absence certification as challenging. They express need for support with functional assessment beyond guidelines and reforms. Case-specific collegial one-to-one guidance for other clinical topics has proved popular with GPs and may be an acceptable and effective way to improve GPs skills and competence in sickness absence certification. AIMS: To present a new model of case-specific colleague guidance focusing on the management of long-term sickness absence and to describe its feasibility in terms of application and reception among GPs, and also GPs' self-reports of effects on their practice. METHODS: Randomly selected GPs received case-specific collegial guidance over a 12-month period, in two Norwegian trials, delivered by former GPs employed by the social security administration. We measured reception and perceived effects by GPs' self-report and registered participation and withdrawal rates. RESULTS: The participation rate (n = 165) was 94%, and no GPs withdrew during training. Among the 116 GPs responding to the survey (70%), 112 (97%; 95% CI 92-99) stated they would recommend it to their colleagues. Considerable benefit from the guidance was reported by 68 (59%; 95% CI 50-68). The GPs self-reported other effects on their sickness absence certification, specifically an increased use of part-time sickness absence (Fit-Note equivalent). CONCLUSIONS: This model of case-specific colleague guidance to aid GPs' management of long-term sickness absence is feasible and was popular. This type of guidance was perceived by GPs to be somewhat beneficial and to alter their sickness absence certification behaviour, though the true impact requires further testing in controlled trials.


Assuntos
Clínicos Gerais/estatística & dados numéricos , Licença Médica , Avaliação da Capacidade de Trabalho , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Política Organizacional , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos , Inquéritos e Questionários
3.
J Anim Sci ; 95(11): 4708-4717, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29293724

RESUMO

The primary objective of this survey was to investigate the relationship between qualitative maternal behavioral scores (nest building activities, sow communication, and sow carefulness), piglet mortality, and the number of weaned piglets on commercial farms with loose-housed lactating (Norsvin Landrace × Yorkshire) sows. Second, the impact of these scores on productivity compared with the physical condition of sows (movement disorders, body condition, and shoulder lesions) was assessed. Data on maternal care behaviors and physical condition were collected on 895 sows from 45 commercial farms. Farmers scored sows on their physical condition (movement disorders [MD], BCS, and shoulder lesions [SL]) and qualitative maternal care behaviors (nest building activities [NEST] prior to farrowing and sow communication [COM] and sow carefulness [CARE] after farrowing, while sows were standing and moving and just before lying down). There was a low positive correlation between NEST and COM ( = 0.10, = 0.026) and between NEST and CARE ( = 0.15, = 0.010) but a high positive correlation between COM and CARE ( = 0.57, < 0.001). Higher COM and CARE were associated with lower piglet mortality ( ˂ 0.001 and = 0.013, respectively), and a greater number of weaned piglets was associated with higher scores for NEST ( = 0.009), COM ( < 0.001), and CARE ( = 0.009). Maternal care behavior had a greater impact on piglet mortality and the number of weaned piglets than sow physical condition (MD, BCS, and SL). We tested 7 different models (combinations of behavioral scores) and compared their relative predictive accuracies using Akaike information criteria. The model including COM and CARE had the best predictive accuracy for piglet mortality/weaned piglets. There was between-sow variation in maternal care behaviors (COM and CARE), and both were unaffected by litter size. Because these behaviors were also easy to score for the farmers, combining COM and CARE has the greatest potential to be tested in nucleus herds for calculation of genetic variation and heritability and should be taken into account in future breeding programs for sows.


Assuntos
Comportamento Materno , Suínos/fisiologia , Animais , Animais Recém-Nascidos , Feminino , Abrigo para Animais , Lactação , Tamanho da Ninhada de Vivíparos , Fenótipo , Gravidez , Desmame
4.
Pharmacogenetics ; 5(4): 199-206, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8528266

RESUMO

The enzyme NAD(P)H:quinone oxidoreductase (NQO1) catalyses bioreduction and bioactivation reactions. A mutation in the NQO1 gene had previously been demonstrated in a cancer cell line with reduced NQO1 activity. In this study, several regions of the NQO1 locus were examined for constitutional variation at the DNA level. The previously described mutation in exon 6 was detected by the single-strand conformation polymorphism technique. This was confirmed by sequencing to result from a C-->T substitution. Genotype analysis in the Centre d'Etude Polymorphisme Humain (CEPH) reference panel revealed two alleles with frequencies of 0.87 and 0.13 and demonstrated Mendelian transmission. Genotype distributions were consistent with Hardy-Weinberg equilibrium. Linkage analysis mapped the gene locus to chromosome 16q. NQO1 was felt to be a candidate gene for the susceptibility to lung cancer, given its potential role in protection against carcinogenic compounds. The frequency of NQO1 variants was examined in 150 lung cancer cases and in two reference populations. The allele distribution in CEPH parent controls was significantly different from cases (chi 2 = 5.52, p = 0.019), but no difference was noted between cases and a healthy local reference population. When the local reference distribution was stratified on smoking status, a significant difference was observed (chi 2 = 3.88, p = 0.048).(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Cromossomos Humanos Par 16 , Neoplasias Pulmonares/genética , NAD(P)H Desidrogenase (Quinona)/genética , Mutação Puntual , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples , Fumar/genética , Alelos , Sequência de Bases , Estudos de Casos e Controles , Mapeamento Cromossômico , Primers do DNA , Éxons , Ligação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Pulmonares/epidemiologia , Dados de Sequência Molecular , NAD(P)H Desidrogenase (Quinona)/metabolismo , Reação em Cadeia da Polimerase , Fumar/epidemiologia
5.
Cancer Epidemiol Biomarkers Prev ; 3(6): 511-4, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8000303

RESUMO

CYP1A1 is a gene of the cytochrome P-450 family that has been proposed to be a biomarker of cancer risk. We introduce a polymerase chain reaction-based assay to measure allelic variability in exon 7 of the CYP1A1 gene. This genetic variant is associated with an amino acid change at residue 462 in the aryl hydrocarbon hydroxylase protein product. Previously, measurement of CYP1A1 genotypes at this variant site required two assays, one to detect each allele. By using three primers in a single polymerase chain reaction rather than two primers in each of two polymerase chain reactions, the proposed assay may facilitate population-based study protocols. We estimate the frequency of this polymorphism in a Caucasian population to be 0.03, with an observed heterozygosity of 0.06. We have also confirmed the Mendelian segregation of this polymorphism in four multigeneration Centre d'Etude du Polymorphisme Humain families and have placed this locus in a multilocus linkage map on chromosome 15q. The distribution of this polymorphism was the same in breast cancer cases as in two sets of healthy controls.


Assuntos
Alelos , Neoplasias da Mama/enzimologia , Sistema Enzimático do Citocromo P-450/genética , Amplificação de Genes , Reação em Cadeia da Polimerase , Adulto , Hidrocarboneto de Aril Hidroxilases/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 15 , Éxons/genética , Frequência do Gene , Ligação Genética/genética , Variação Genética/genética , Humanos , Polimorfismo Genético/genética , Vigilância da População , Fatores de Risco , População Branca/genética
6.
Semin Oncol ; 24(4 Suppl 12): S12-81-S12-88, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9331128

RESUMO

We previously reported a 62% response rate and 54% 1-year survival rate for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered by 24-hour infusion in combination with fixed-dose carboplatin to treat patients with advanced non-small cell lung cancer (NSCLC). Myelosuppression proved dose limiting, but was substantially reduced by the routine use of granulocyte colony-stimulating factor during the second and subsequent cycles. Activity for paclitaxel 135 mg/m2 and 200 mg/m2 by 1-hour infusion every 3 weeks in patients with NSCLC, with minimal myelosuppression and the suggestion of a dose-response relationship, has been reported. In November 1994, we initiated a phase II trial in patients with advanced, measurable, chemotherapy-naive NSCLC using paclitaxel 175 mg/m2 given in 1 hour, and carboplatin dosed to a fixed target area under the concentration-time curve of 7.5 every 3 weeks. In the absence of grade 4 myelosuppression, paclitaxel was escalated on an intrapatient basis by 35 mg/m2 per cycle to a maximum dose of 280 mg/m2 by cycle 4. Granulocyte colony-stimulating factor was not routinely used. Of the 57 patients accrued, 44 (81%) are Eastern Cooperative Oncology Group performance status 1. The median patient age is 64 years. To date, 54 patients are fully evaluable for toxicity. In the first 20 evaluable patients accrued (cohort A), myelosuppression was tolerable, but cumulative peripheral sensory neuropathy proved dose limiting: grade > or = 1 in 15 (75%) patients and grade 3 in six (30%), generally occurring at paclitaxel doses > or = 215 mg/m2 and obligating at least three patients to be removed from study despite absence of disease progression. The protocol was consequently revised. The starting dose of paclitaxel was reduced to 135 mg/m2 with intrapatient dose escalations of 40 mg/m2 per cycle, to a maximum paclitaxel dose of 215 mg/m2, recapitulating the original dosing schema used in Fox Chase Cancer Center study 93-024. For the 35 patients enrolled in the second cohort (cohort B), treatment has been better tolerated. Of 21 evaluable patients, 13 (62%) have experienced peripheral sensory neuropathy, grade 3 in only one (5%) patient. Myelosuppression also has been less pronounced, with 44% grade 4 granulocytopenia and 38% grade > or =3 thrombocytopenia in cohort B compared with 70% and 50%, respectively, in cohort A. Of the first 22 patients accrued to cohort A, 12 (55%) had major objective responses. Median event-free survival is 24 weeks and median survival is 47 weeks. Of the 35 evaluable patients in cohort B, nine (26%) have had major objective responses. Median event-free survival is 22 weeks. It is too early to report median survival. Paclitaxel given by 1-hour infusion in combination with carboplatin at a fixed target area under the concentration-time curve of 7.5, although active in advanced NSCLC, is associated with problems that compromise its efficacy. Higher dose levels yield intolerable toxicity, evidenced by the incidence of neurotoxicity (rather than myelosuppression) that was dose and protocol limiting at paclitaxel doses exceeding 215 mg/m2. Lower doses, while more tolerable, appear to be associated with lower response rates.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Área Sob a Curva , Carboplatina/administração & dosagem , Carboplatina/farmacocinética , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/farmacocinética , Análise de Sobrevida
7.
Cancer Chemother Pharmacol ; 29(4): 305-8, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1537077

RESUMO

Phosphonacetyl-L-aspartate (PALA), in inhibitor of aspartate transcarbamylase that depletes uridine nucleotide pools, selectively potentiates the antitumor activity of 5-fluorouracil (5-FU) in preclinical models. Due to the promising results we obtained using PALA/5-FU in colorectal cancer, we performed a phase II trial in patients presenting with advanced pancreatic cancer. PALA was given intravenously at 250 mg/m2 on day 1, followed 24 h later by 2,600 mg/m2 5-FU given by 24-h infusion. Treatments were repeated weekly. A total of 41 patients who had not previously undergone chemotherapy were entered in the trial; of these, 35 were evaluable for response. Toxicity was generally mild to moderate; neurotoxicity (13/35) and diarrhea (8/35) predominated. Among the 35 patients, 1 achieved a complete response and 4, a partial remission, for an overall response rate of 14%. The median survival was 5.1 months. Pretreatment with PALA alone was not sufficient to enhance the activity of 5-FU in pancreatic cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácido Aspártico/administração & dosagem , Ácido Aspártico/efeitos adversos , Ácido Aspártico/análogos & derivados , Avaliação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Infusões Intravenosas , Masculino , Neoplasias Pancreáticas/mortalidade , Ácido Fosfonoacéticos/administração & dosagem , Ácido Fosfonoacéticos/efeitos adversos , Ácido Fosfonoacéticos/análogos & derivados , Análise de Sobrevida
8.
Clin Lung Cancer ; 3(2): 125-32; discussion 133, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14659027

RESUMO

The paclitaxel/carboplatin combination has demonstrated promising activity in metastatic non-small-cell lung cancer (NSCLC); therefore, we mounted an exploratory study of these agents with thoracic radiation (TRT) in locally advanced NSCLC. Eligibility stipulated a Karnofsky performance status >or= 70%, weight loss or= 2 esophagitis has corresponded to length (> 16 cm) of esophagus in the radiation treatment field (Fisher's exact test, P = 0.006). The partial response rate to induction therapy was 40% and to the combined modality therapy was 60%. The median survival for all 49 patients is 15.3 months, with a median disease-free survival (DFS) of 7.8 months. In the subset of 22 patients treated on the phase I portion of the study, the median survival and DFS were 18.5 months and 13.5 months, respectively. Induction therapy with paclitaxel and carboplatin followed by concurrent chemoradiotherapy with the same agents is an active and well-tolerated treatment approach in locally advanced NSCLC. To date, paclitaxel 175 mg/m2 plus carboplatin AUC 5 administered at 3-week intervals for 2 cycles is safe in combination with TRT.

9.
Soc Sci Med ; 46(4-5): 581-90, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9460837

RESUMO

The use of minor tranquilizers (hypnotics and anxiolytics) during the last month before a questionnaire was answered was studied in a postal survey of a nation-wide representative sample of Norwegian physicians (n = 1467), aged 25 to 69 years. The response rate was 73%. A total of 12.2% of the physicians had used minor tranquilizers in the past month, one third of these on a daily or weekly basis. There was no gender difference. High age, high mental distress, and working outside the hospital was identified as risk factors for drug use. Compared to a representative sample of subjects from the general population with the same age and education level, (The Nord-Trøndelag Health Survey), more male physicians than males in the comparison sample had used minor tranquilizers in the past month, also when controlled for subjective well-being. However, the physicians had used the drugs more sporadic. When self-prescription of minor tranquilizers was studied in a different sample of 1024 Norwegian physicians, it was found that 72.6% of the physicians had self-prescribed the drugs. There was no gender difference in self-prescribing.


Assuntos
Ansiolíticos/uso terapêutico , Médicos/estatística & dados numéricos , Automedicação/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Idoso , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Reprodutibilidade dos Testes , Fatores de Risco
10.
Soc Sci Med ; 52(2): 249-58, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11144781

RESUMO

Practice of breast self-examination (BSE) and cervical cancer testing (Pap smear tests) was studied in a nation-wide Norwegian representative sample of 284 female physicians aged 24-67. BSE was performed at least once a month in 30.6% of the cases, and 54.6% had a Pap smear test once every third year at least. BSE was never practised among 19.2% of the physicians, the main reasons being that they forgot it, or that they stated that they were in a low risk group or had no symptoms of disease. 16.2% had never had routine Pap smears, and these physicians claimed that they were in a low risk group or had no symptoms of disease, that they had a problem in finding a physician to attend, or that they forgot to take the test. A subgroup of 135 physicians aged 35-49 years was compared with 738 women with higher university education included from a nation-wide representative sample of the general population of Norway. A significantly higher percentage of physicians practised BSE monthly or more often compared with other university educated women. However, a significantly lower percentage of the physicians had Pap smear tests every third year or more frequently. The positive association between being a physician and practising BSE, and the negative association between being a physician and having Pap smear tests, remained after controlling for potential confounders in multivariate analyses.


Assuntos
Neoplasias da Mama/diagnóstico , Autoexame de Mama/estatística & dados numéricos , Teste de Papanicolaou , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Médicas/psicologia , Médicas/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/estatística & dados numéricos , Adulto , Testes Diagnósticos de Rotina/estatística & dados numéricos , Feminino , Humanos , Medicina/estatística & dados numéricos , Pessoa de Meia-Idade , Noruega , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Especialização , Inquéritos e Questionários
14.
Scand J Public Health ; 29(1): 71-5, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11355720

RESUMO

BACKGROUND: Physicians seem to have problems in accepting their own illness, and they tend to avoid taking sick leave. This study reports the diseases that physicians bring to work, and discusses selected factors associated with the behaviour of working when ill. METHODS: Of a random sample of 1,476 Norwegian physicians, 70% answered a mailed, anonymous questionnaire as a part of The Norwegian Medical Association's health survey. RESULTS: During one year, 80% of the physicians had worked during an illness for which they would have sick-listed their patients. More than half of the physicians in the study had worked whilst having an infectious disease. Factors independently associated with the behaviour of working when ill include being in the age group 30-39 years, working as a clinician outside hospital, having received medical treatment during the last three years, and having low job satisfaction. CONCLUSION: A large number of physicians work whilst having infections and other diseases. This behaviour might be harmful to the physicians themselves as well as to their patients and staff members.


Assuntos
Médicos/psicologia , Licença Médica/estatística & dados numéricos , Adulto , Idoso , Distribuição de Qui-Quadrado , Doenças Transmissíveis/epidemiologia , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Satisfação no Emprego , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Noruega , Inquéritos e Questionários
15.
Tidsskr Nor Laegeforen ; 119(30): 4555-60, 1999 Dec 10.
Artigo em Norueguês | MEDLINE | ID: mdl-10827503

RESUMO

The municipality of Sandnes became a separate medical district in 1866. The district physicians' reports give us an insight into health and living conditions in this district in the last half of the 19th century. This paper is based on a study of all statistical data and physicians' comments concerning the Sandnes district for the 1866-1900 period. The incidence of various diseases is estimated. Mental illness seems to have been more frequent in Sandness than in the rest of the county. In the physicians' reports, this was explained by the dominance of religious Puritanism in the district. The incidence of other disease, such as typhoid fever, tuberculosis and scarlet fever, did not differ essentially between Sandnes and the county as a whole. The living conditions in the district were rather good during the whole period, though the physicians' reports provide interesting insight in changes from one year to another.


Assuntos
Surtos de Doenças/história , Epidemiologia/história , Nível de Saúde , Fatores Socioeconômicos , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/história , Epidemiologia/tendências , História do Século XIX , Humanos , Higiene , Incidência , Transtornos Mentais/epidemiologia , Transtornos Mentais/história , Noruega/epidemiologia
16.
J Intern Med ; 255(4): 494-502, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15049884

RESUMO

OBJECTIVE: We examined the prevalence and factors associated with use of cholesterol-lowering statins in the population. METHODS: Demographic, medical, anthropometric and lifestyle data was obtained from 6233 men and 7521 women born in 1924/25, 1940/41, 1955 and 1960 that participated in the Oslo Health Study 2000-2001. A nonfasting blood sample was collected. RESULTS: Of subjects with a heart attack, angina, stroke or diabetes 45% of men and 35% of women were taking a statin (P < 0.001). Of subjects with cardiovascular disease (CVD) or diabetes taking statins 61% of men and 40% of women achieved total serum cholesterol levels < or =5 mmol L(-1). The odds ratio for taking a statin was increased amongst subjects who also took antihypertensive drug(s) or acetylsalicylic acid, subjects with a family history of coronary heart disease (CHD) and women who had visited the general practitioner within the last year. Amongst presumed healthy subjects use of statins increased from about 1% in women aged 40-45 years, to 7% at age 60 and to 12% at age 75 whilst the corresponding figures for men were 3%, 8% and 9%, respectively. About 22% of men but <2% of women aged 60 who were not taking statins had a 10-year Framingham CHD risk score >20%. Determinants of statin use were similar to those amongst subjects with CVD or diabetes. CONCLUSION: People with CVD or diabetes remain undertreated with statins, women more so than men. Use of other preventive drugs, the family history and recent contact with the general practitioner were the most important determinants of statin use in primary and secondary prevention. Amongst healthy subjects aged 60 or 75 years women received statins disproportionately to their low CHD risk compared with men.


Assuntos
Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Anti-Hipertensivos/uso terapêutico , Aspirina/uso terapêutico , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/epidemiologia , Doença das Coronárias/prevenção & controle , Saúde da Família , Medicina de Família e Comunidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde
17.
Am J Pathol ; 142(4): 1131-9, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7682763

RESUMO

p53 alterations were studied in a group of 22 primary squamous cell carcinomas (SCC) of the head and neck and in 10 cell lines derived from SCC. Positive immunohistochemical detection of p53 was accomplished in 10 of 22 primary tumors and in 7 of 10 SCC cell lines. Loss of heterozygosity of chromosome 17p, were the p53 gene is localized, was seen in five of seven SCC lines studied. DNA sequencing of the p53 gene of these five cell lines that had lost one allele showed p53 mutations in the remaining allele. In addition, from six primary SCC that exhibited loss of heterozygosity of chromosome 17p, three showed missense mutations of the p53 gene. The mutations of primary tumors and SCC cell lines were scattered in the midregion of the gene, affecting codons 151, 155, 174, 194, 220, 248, and 273. Five of these mutations modified guanine residues, a phenomenon that has been associated with the effect of carcinogens contained in tobacco smoke. Collectively these data show that approximately 50% of primary tumors and cell lines derived from SCC of the head and neck showed abnormalities of the p53 gene. In addition, it is of interest to note that the most invasive cell lines, as determined in an in vivo assay using xenotransplantation of tumor cells into denuded rat tracheal grafts, exhibited the most intense staining. Similarly, of five very advanced primary tumors, four showed intense p53 immunostain. These observations support the evidence that alterations in this tumor suppressor gene could be related to late events in tumor progression.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma/genética , Regulação Neoplásica da Expressão Gênica , Genes p53 , Carcinoma/patologia , Carcinoma de Células Escamosas/patologia , Códon , Humanos , Imuno-Histoquímica/métodos , Mutação , Reação em Cadeia da Polimerase , Coloração e Rotulagem , Células Tumorais Cultivadas
18.
Proc Natl Acad Sci U S A ; 92(6): 2384-7, 1995 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-7892276

RESUMO

Aflatoxin B1 (AFB1) has been postulated to be a hepatocarcinogen in humans, possibly by causing p53 mutations at codon 249. AFB1 is metabolized via the phase I and II detoxification pathways; hence, genetic variation at those loci may predict susceptibility to the effects of AFB1. To test this hypothesis, genetic variation in two AFB1 detoxification genes, epoxide hydrolase (EPHX) and glutathione S-transferase M1 (GSTM1), was contrasted with the presence of serum AFB1-albumin adducts, the presence of hepatocellular carcinoma (HCC), and with p53 codon 249 mutations. Mutant alleles at both loci were significantly overrepresented in individuals with serum AFB1-albumin adducts in a cross-sectional study. Mutant alleles of EPHX were significantly overrepresented in persons with HCC, also in a case-control study. The relationship of EPHX to HCC varied by hepatitis B surface antigen status and indicated that a synergistic effect may exist. p53 codon 249 mutations were observed only among HCC patients with one or both high-risk genotypes. These results indicate that individuals with mutant genotypes at EPHX and GSTM1 may be at greater risk of developing AFB1 adducts, p53 mutations, and HCC when exposed to AFB1. Hepatitis B carriers with the high-risk genotypes may be an even greater risk than carriers with low-risk genotypes. These findings support the existence of genetic susceptibility in humans to the environmental carcinogen AFB1 and indicate that there is a synergistic increase in risk of HCC with the combination of hepatitis B virus infection and susceptible genotype.


Assuntos
Aflatoxina B1/metabolismo , Carcinoma Hepatocelular/genética , Epóxido Hidrolases/genética , Genes p53 , Variação Genética , Glutationa Transferase/genética , Neoplasias Hepáticas/genética , Aflatoxina B1/análise , Aflatoxina B1/sangue , Carcinoma Hepatocelular/epidemiologia , Estudos de Casos e Controles , China , Códon , DNA/análise , Predisposição Genética para Doença , Genótipo , Antígenos de Superfície da Hepatite B/sangue , Humanos , Inativação Metabólica/genética , Neoplasias Hepáticas/epidemiologia , Mutação Puntual , Reação em Cadeia da Polimerase , Valores de Referência , Fatores de Risco , Albumina Sérica/análise
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