RESUMO
The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.
Assuntos
Citocromo P-450 CYP3A/genética , DNA Ligases/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Neoplasias Ovarianas/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , DNA Ligase Dependente de ATP , Feminino , Genótipo , Heterozigoto , Homozigoto , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Ovarianas/patologia , Fatores de RiscoRESUMO
During surgical procedures with extracorporeal circulation the method of hemoconcentration by means of blood ultrafiltration was employed to control hemodilution in 84 patients. Disposable plate or hollow fiber dialyzers and a specially designed hemoconcentrator were used. The amount of ultrafiltrate received from one patient varied between 750 and 6250 cc, with a mean of 2588 +/- 221 cc, which was almost similar to the amount of cardioplegic solution given to the patients. Hemoconcentration by means of ultrafiltration is a relatively simple, safe and effective method of hemodilution control during extracorporeal circulation. In contrast to the centrifuging method (plasmapheresis) it preserves plasma proteins. The method is indicated for patients undergoing surgical procedures with heart-lung bypass and uncontrolled profound hemodilution, especially for patients with renal insufficiency. Hemoconcentration helps to reduce blood loss and bank blood usage. The employment of this method is not accompanied by any significant disturbances in humoral homeostasis. Hemoconcentration requires a larger volume of electrolyte solutions (sodium bicarbonate, potassium chloride) during heart-lung bypass. The method can be recommended for routine use in clinics operating on the open heart.
Assuntos
Sangue , Procedimentos Cirúrgicos Cardíacos , Circulação Extracorpórea/métodos , Ultrafiltração , Ponte Cardiopulmonar , Hemodiluição , HumanosRESUMO
Total substitution of lung gas exchange function can be achieved by oxygenating all blood in a heart-lung machine and requires thoracotomy. In accordance with calculations based on physical principles, if extracorporeal oxygenation is combined with barometric pressure raised to 3 atm, half of the cardiac output will suffice to maintain normal blood oxygenation. Excessive amounts of oxygen dissolved in blood passed through an oxygenator will suffice for the total oxygenation of the rest of the blood. This assumption was investigated in 15 experiments on dogs and one human patient in a hyperbaric chamber. The bubble oxygenator and pneumatic membrane pumps were used. The results suggest that this method of total substitution of lung gas exchange function is feasible. This technique does not require thoracotomy and can be carried out on a patient in any position on the operating table. This method can be used during bronchoscopy treatment, lung lavage, and trachea surgery.
