RESUMEN
BACKGROUND: To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients. METHODS: Three thousand seven hundred fifty men with prostate cancer and 3956 cancer-free controls were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA, C61G), four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), and one allele in NBS1 (657del5). RESULTS: The NBS1 mutation was detected in 53 of 3750 unselected cases compared with 23 of 3956 (0.6%) controls (odds ratio (OR)=2.5; P=0.0003). A CHEK2 mutation was seen in 383 (10.2%) unselected cases and in 228 (5.8%) controls (OR=1.9; P<0.0001). Mutation of BRCA1 (three mutations combined) was not associated with the risk of prostate cancer (OR=0.9; P=0.8). In a subgroup analysis, the 4153delA mutation was associated with early-onset (age ≤ 60 years) prostate cancer (OR=20.3, P=0.004). The mean follow-up was 54 months. Mortality was significantly worse for carriers of a NBS1 mutation than for non-carriers (HR=1.85; P=0.008). The 5-year survival for men with an NBS1 mutation was 49%, compared with 72% for mutation-negative cases. CONCLUSION: A mutation in NBS1 predisposes to aggressive prostate cancer. These data are relevant to the prospect of adapting personalised medicine to prostate cancer prevention and treatment.
Asunto(s)
Proteínas de Ciclo Celular/genética , Proteínas Nucleares/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Proteína BRCA1/genética , Biomarcadores de Tumor/genética , Quinasa de Punto de Control 2 , Genes BRCA1 , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
Ochratoxin A (OTA) was analyzed in human serum and kidney samples, collected in Poland in the Pomeranian region from March to September 2005. OTA was determined using reversed phase liquid chromatography with fluorescence detection. The collected samples were from patients after nephrectomy (9 from men and 11 from women) and control serum samples from people without kidney diseases (3 and 3, respectively). The mean concentration OTA in serum of the healthy group was 0.37 ng/ml in both men and women. In patients subjected to nephrectomy it reached 1.06 ng/ml in men and 0.94 ng/ml in women, the mean content of ochratoxin A in kidneys was 0.23 ng/g and 0.20 ng/g, respectively. The highest concentration of OTA in serum among the patients subjected to nephrectomy was 3.77 ng/ml in men and 2.27 ng/ml in women while in kidneys 0.45 ng/g and 0.39 ng/g, respectively.
RESUMEN
Laparoscopic instrumentation is constantly being refined in an attempt to achieve the proficiency, flexibility, and tactile feedback that would be available if the human hand were small enough to be used in laparoscopic surgery. The EndoHand (DAUM GmbH, Schwerin, Germany) is a novel laparoscopic three-fingered hand developed as an advancement over standard laparoscopic tools. Grasping and manipulation ability, dexterity, and tactile feedback were compared with those of current laparoscopic instrumentation. Experiments included measurement of achievable angles of approach to a fixed point behind a 2-cm-tall obstruction, completion time and error rates during a pelvic trainer dexterity task, and tactile feedback using a device invented to simulate tissue resistance. Subjectively, the EndoHand was able to pick up a range of objects similar to those graspable by a Babcock clamp. More complex types of manipulation were possible with the EndoHand because of its wrist joint. The range of approach angles to the fixed point was 35 degrees to 90 degrees with the EndoHand and 70 degrees to 90 degrees with the straight instruments. The dexterity of the EndoHand was significantly less than that of the other two instruments, as measured by time (P = 0.0002) and errors (P = 0.02). Standard instruments were also more accurate in the tactile feedback trials (P = 0.02). The EndoHand is a prototype of a unique new generation of laparoscopic instruments. Although it falls short in both dexterity and tactile feedback, significant promise is shown in its ability to perform sophisticated manipulation of objects and its flexibility to work at a larger range of angles to the target tissue. The EndoHand may be most useful on the nondominant hand of the surgeon to assist with positioning and holding tissue in a specific orientation. Clinical trials will determine its eventual role in laparoscopic surgery.