Risk profiles and prognosis of treated and untreated hypertensive men and women in a population-based longitudinal study: the Reykjavik Study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe aim was to examine the risk profiles and prognosis of treated and untreated hypertensive subjects and examine to what degree confounding by indication was present in a population-based cohort study with up to 30-year follow-up. The study population consisted of 9328 men and 10 062 women, aged 33-87 years at the time of attendance from 1967 to 1996. The main outcome measures were myocardial infarction (MI), cardiovascular disease (CVD) mortality and all-cause mortality. Comparing the risk profiles between treated and untreated subjects entering the study showed significantly higher values for some risk factors for treated subjects. During the first 10 years, hypertensive men without treatment, compared with those treated, had a significantly lower risk of suffering MI, CVD and all-cause mortality, hazard ratio (HR) 0.72 (95% CI; 0.57, 0.90), 0.75 (95% CI; 0.59, 0.95) and 0.81 (95% CI; 0.61, 0.98), respectively. No significant differences in outcome were seen during the following 20 years. In identically defined groups of women, no significant differences in mortality were seen between groups. Subgroup analysis, at two stages of the study 5 years apart, revealed that some cardiovascular risk factors had a higher prevalence in hypertensive men who were treated at the later stage, compared with those who remained untreated (P=0.004). In conclusion, hypertensive treated men had a worse prognosis during the first 10 years of follow-up than untreated ones, which is most likely due to worse baseline risk profile. Hypertensive men that were treated at a later stage had a worse risk profile than those not treated at a later stage

CYP17 promoter polymorphism and breast cancer risk in males and females in relation to BRCA2 status

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldA T-C polymorphism in the promoter region of the CYP17 gene has been associated with male and female breast cancer risk as well as early-onset familial breast cancer. The potential role of this polymorphism was investigated in relation to breast cancer risk in Icelandic male and female carriers and noncarriers of a BRCA2 mutation. The study population consisted of 39 male and 523 female breast cancer cases and 309 male and 395 female controls. Of the cases, 15 males and 55 females carried a BRCA2 mutation. We did not find a significant association between male breast cancer risk and CYP17 genotypes. Among male breast cancer cases, the frequency of the CC genotype was higher among carriers of the 999del5 mutation (33.3%) than noncarriers (16.7%), although this difference also did not reach a statistical significance. No association was observed with breast cancer risk among females irrespective of menopausal status, stage of the disease or BRCA2 status. Our findings do not indicate a role for the CYP17 T-C polymorphism in female breast cancer, but a role in male carriers of a BRCA2 mutation could not be excluded because of the small sample size

Heterologous Expression and Maturation of an NADP-Dependent [NiFe]-Hydrogenase: A Key Enzyme in Biofuel Production

Hydrogen gas is a major biofuel and is metabolized by a wide range of microorganisms. Microbial hydrogen production is catalyzed by hydrogenase, an extremely complex, air-sensitive enzyme that utilizes a binuclear nickel-iron [NiFe] catalytic site. Production and engineering of recombinant [NiFe]-hydrogenases in a genetically-tractable organism, as with metalloprotein complexes in general, has met with limited success due to the elaborate maturation process that is required, primarily in the absence of oxygen, to assemble the catalytic center and functional enzyme. We report here the successful production in Escherichia coli of the recombinant form of a cytoplasmic, NADP-dependent hydrogenase from Pyrococcus furiosus, an anaerobic hyperthermophile. This was achieved using novel expression vectors for the co-expression of thirteen P. furiosus genes (four structural genes encoding the hydrogenase and nine encoding maturation proteins). Remarkably, the native E. coli maturation machinery will also generate a functional hydrogenase when provided with only the genes encoding the hydrogenase subunits and a single protease from P. furiosus. Another novel feature is that their expression was induced by anaerobic conditions, whereby E. coli was grown aerobically and production of recombinant hydrogenase was achieved by simply changing the gas feed from air to an inert gas (N2). The recombinant enzyme was purified and shown to be functionally similar to the native enzyme purified from P. furiosus. The methodology to generate this key hydrogen-producing enzyme has dramatic implications for the production of hydrogen and NADPH as vehicles for energy storage and transport, for engineering hydrogenase to optimize production and catalysis, as well as for the general production of complex, oxygen-sensitive metalloproteins

The chemistry and saturation states of subsurface fluids during the in situ mineralisation of CO2 and H2S at the CarbFix site in SW-Iceland

In situ carbonation of basaltic rocks could provide a long-term carbon storage solution, which is essential for the success and public acceptance of carbon storage. To demonstrate the viability of this carbon storage solution, 175 tonnes (t) of pure CO2 and 73 tonnes (t) of a 75% CO2-24% H2S-1% H2-gas mixture were sequentially injected into basaltic rocks at the CarbFix site at Hellisheidi, SW-Iceland from January to August 2012. This paper reports the chemistry and saturation states with respect to potential secondary minerals of sub-surface fluids sampled prior to, during, and after the injections. All gases were dissolved in water during their injection into permeable basalts located at 500–800 m depth with temperatures ranging from 20 to 50 °C. A pH decrease and dissolved inorganic carbon (DIC) increase was observed in the first monitoring well, HN-04, about two weeks after each injection began. At storage reservoir target depth, this diverted monitoring well is located ∼125 m downstream from the injection well. A significant increase in H2S concentration, however, was not observed after the second injection. Sampled fluids from the HN-04 well show a rapid increase in Ca, Mg, and Fe concentration during the injections with a gradual decline in the following months. Calculations indicate that the sampled fluids are saturated with respect to siderite about four weeks after the injections began, and these fluids attained calcite saturation about three months after each injection. Pyrite is supersaturated prior to and during the mixed gas injection and in the following months. In July 2013, the HN-04 fluid sampling pump broke down due to calcite precipitation, verifying the carbonation of the injected CO2. Mass balance calculations, based on the recovery of non-reactive tracers co-injected into the subsurface together with the acid-gases, confirm that more than 95% of the CO2 injected into the subsurface was mineralised within a year, and essentially all of the injected H2S was mineralised within four months of its injection. These results demonstrate the viability of the in situ mineralisation of these gases in basaltic rocks as a long-term and safe storage solution for CO2 and H2S

Chronic kidney disease after liver, cardiac, lung, heart–lung, and hematopoietic stem cell transplant

Patient survival after cardiac, liver, and hematopoietic stem cell transplant (HSCT) is improving; however, this survival is limited by substantial pretransplant and treatment-related toxicities. A major cause of morbidity and mortality after transplant is chronic kidney disease (CKD). Although the majority of CKD after transplant is attributed to the use of calcineurin inhibitors, various other conditions such as thrombotic microangiopathy, nephrotic syndrome, and focal segmental glomerulosclerosis have been described. Though the immunosuppression used for each of the transplant types, cardiac, liver and HSCT is similar, the risk factors for developing CKD and the CKD severity described in patients after transplant vary. As the indications for transplant and the long-term survival improves for these children, so will the burden of CKD. Nephrologists should be involved early in the pretransplant workup of these patients. Transplant physicians and nephrologists will need to work together to identify those patients at risk of developing CKD early to prevent its development and progression to end-stage renal disease

Prognostic role of cardiovascular risk factors for men with cardiomegaly (the Reykjavik Study)

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe Reykjavik Study is a large population-based cohort study, starting in 1967. A total of 9,139 men, born in the years 1907 to 1934, have been followed for 4 to 24 years. Heart size was determined by chest roentgenogram in 2 planes and cardiomegaly, defined as a relative heart size exceeding 550 ml/m2, was detected in 517. Multivariate Cox regression analysis was used to estimate the independent contribution of variables measured at each participant's first visit to the risk of both all-cause and coronary artery disease (CAD) mortality. Cardiomegaly was detected in 3.7% of men aged 75 years. One half of these men had hypertension, one third had manifestations of CAD, and 37% had neither. Among men with cardiomegaly, the presence of CAD had marked deleterious effect on prognosis. Serum total cholesterol and systolic blood pressure were significant independent risk factors of CAD mortality with risk ratio of 1.008 per mg/dl serum cholesterol (95% confidence interval 1.00 to 1.01; p = 0.004) and 1.015/mm Hg (95% confidence interval 1.000 to 1.300; p = 0.043), respectively. Smoking > 25 cigarettes/day carried a 2.3-fold risk (95% confidence interval 1.3 to 4.4; p = 0.008) of all-cause mortality. The traditional risk factors for CAD, serum cholesterol, high blood pressure, and smoking maintain their detrimental effect on prognosis among patients with cardiomegaly. These findings have implications for secondary prevention, signifying that in the presence of cardiomegaly, complacency is not justified in controlling major risk factors for CAD

Prevalence of coronary heart disease in Icelandic men 1968-1986. The Reykjavik Study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe prevalence of coronary heart disease (CHD) was determined in a general population sample of 9141 Icelandic men aged 34-79 years, and the prevalence of four different forms of CHD was estimated separately: symptomatic infarction fulfilling WHO-MONICA criteria for definite myocardial infarction; myocardial infarction detected by ECG changes only (unrecognized, silent infarction); angina pectoris detected by the Rose questionnaire and associated with ECG manifestations of myocardial ischaemia, either at rest or during exercise, but no manifestations of myocardial infarction; angina pectoris without ECG changes indicative of myocardial ischaemia. The study was conducted in five stages allowing evaluation of trends from 1968-1986. Age was a major determinant of the prevalence of all forms of CHD. Thus, the prevalence of myocardial infarction (symptomatic or silent) rose from undetectable levels in the youngest age group (30-34 years) to around 12% (7% symptomatic and 5% silent) in the oldest group (75-79 years) and the prevalence of all forms of CHD rose from 4% in the youngest age group to 23% in the age group 70-74 years. Age-standardized comparison was carried out on the prevalence of the different forms of CHD at different stages of the study in 50-64-year-old men who were represented in all stages of the study. There was a gradual increase in the prevalence of myocardial infarction from 3% (symptomatic and silent combined, CI 1.9-4.8) in 1968 to 4.9% in 1986 (CI 3.9-6.1) (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS