Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP-Hypertension-2

Objective: To perform a subgroup analysis on those patients in STOP-Hypertension-2 who had isolated systolic hypertension. Design and methods: The STOP-Hypertension-2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs (diuretics, beta-blockers) with that of newer ones [angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists]. In all, 6614 elderly patients with hypertension (mean age 76.0 years, range 70-84 years at baseline) were included in STOP-Hypertension-2. In the present subgroup analysis of STOP-Hypertension-2, isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg, in accordance with the Syst-Eur and Syst-China study criteria. In total, 2280 patients in STOP-Hypertension-2 met these criteria. In the study, patients were randomized to one of three treatment groups: “conventional” antihypertensive therapy with beta-blockers or diuretics (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or fixed-ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily); ACE inhibitors (enalapril 10 mg or lisinopril 10 mg daily); or calcium antagonists (felodipine 2.5 mg or isradipine 2.5 mg daily). Analysis was by intention to treat. Results: The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens: 35/13 mmHg in the conventional group (n = 717), 34/12 mmHg in the ACE inhibitor group (n = 724), and 35/13 mmHg in the calcium antagonist group (n = 708). Prevention of cardiovascular mortality, the primary endpoint of the study, did not differ between the three treatment groups. All stroke events, i.e. fatal and non-fatal stroke together, were significantly reduced by 25% in the newer-drugs group compared with the conventional group (95% CI 0.58-0.97; p = 0.027). This difference was attributable to reduction of non-fatal stroke while fatal stroke events did not differ between groups. New cases of atrial fibrillation were significantly increased by 43% (95% CI 1.02-1.99; p = 0.037) on “newer” drugs compared with “conventional” therapy, mainly attributable to the calcium antagonists. There were no significant differences between the three treatment groups with respect to the risks of myocardial infarction, sudden death or congestive heart failure. Conclusions: The analysis demonstrated that “newer” therapy (ACE inhibitors/calcium antagonists) was significantly better (25%) than “conventional” (diuretics/beta-blockers) in preventing all stroke in elderly patients with isolated systolic hypertension.     

Risk factors associated with snoring in women with special emphasis on body mass index: a population-based study

STUDY OBJECTIVES: Habitual snoring may be regarded as an indicator of sleep-disordered breathing, and the health consequences of sleep-disordered breathing are well-known. The aim of this study was to analyze the risk factors associated with habitual snoring in a large sample of women, with special emphasis on the determinants of snoring in women with different body mass index (BMI) levels.Design and setting: A cross-sectional, epidemiologic, population-based study was performed by using a postal questionnaire that was sent to a randomly selected sample of 6,817 women >/= 20 years of age in Uppsala, Sweden. RESULTS: The total prevalence of self-reported habitual snoring was 7.6%. There was a clear age dependence, with the highest prevalence of habitual snoring (14%) occurring between the ages of 50 and 59 years. Self-reported habitual snoring was related to BMI, neck circumference, and smoking >/= 10 cigarettes a day, after adjusting for possible confounders. When analyzing the influence of different risk factors in separate BMI groups, the results varied among the groups. The influence of alcohol dependence on snoring frequency was only significant in women with a BMI of < 20 kg/m(2), while physical inactivity was only associated with habitual snoring in women with a BMI of >/= 30 kg/m(2). CONCLUSIONS: The prevalence of self-reported habitual snoring in women was strongly dependent on age and BMI. The importance of other risk factors differed depending on BMI, with alcohol dependence being associated with self-reported snoring in lean women, whereas physical inactivity was a risk factor for self-reported snoring in women with a high BMI.     

Genomic loci susceptible to replication errors in cancer cells.

Microsatellite instability due to a deficiency in DNA mismatch repair is characteristic of a replication error (RER) phenotype. This widespread genomic instability is well documented in hereditary non-polyposis colon cancer (HNPCC) as well as subsets of sporadic carcinomas. Features of the RER phenotype such as the early appearance in tumour development and better prognosis of RER+ colorectal tumours render its examination important for cancer patients. Recently, we identified four loci that were shown to be highly susceptible to RER in cancer cells. Here, we used these loci to detect the RER phenotype in sporadic carcinomas of colon, breast, lung, endometrium and ovary. Replication errors revealed by these four markers followed the same tumour specificity as observed in HNPCC patients. In particular, 24% (6/25) of colorectal, 33% (4/12) of endometrial and 17% (2/12) of ovarian cancers displayed the RER phenotype characterized by an increased allelic mobility, whereas none of the breast (n = 22) and the lung (n = 27) carcinomas were found to be unstable. Assaying RERs sensitive loci provides us with a useful diagnostic tool for HNPCC-like sporadic tumours.     

Processing of the lipocalin alpha(1)-microglobulin by hemoglobin induces heme-binding and heme-degradation properties

Alpha(1)-microglobulin is a 26-kd protein, widespread in plasma and tissues and well-conserved among vertebrates. Alpha(1)-microglobulin belongs to the lipocalins, a protein superfamily with highly conserved 3-dimensional structures, forming an internal ligand binding pocket. The protein, isolated from urine, has a heterogeneous yellow-brown chromophore bound covalently to amino acid side groups around the entrance of the lipocalin pocket. Alpha(1)-microglobulin is found in blood both in free form and complex-bound to immunoglobulin A (IgA) via a half-cystine residue at position 34. It is shown here that an alpha(1)-microglobulin species, which we name t-alpha(1)-microglobulin (t = truncated), with a free Cys34 thiol group, lacking its C-terminal tetrapeptide, LIPR, and with a more polar environment around the entrance of the lipocalin pocket, is released from IgA-alpha(1)-microglobulin as well as from free alpha(1)-microglobulin when exposed to the cytosolic side of erythrocyte membranes or to purified oxyhemoglobin. The processed t-alpha(1)-microglobulin binds heme and the alpha(1)-microglobulin-heme complex shows a time-dependent spectral rearrangement, suggestive of degradation of heme concomitantly with formation of a heterogeneous chromophore associated with the protein. The processed t-alpha(1)-microglobulin is found in normal and pathologic human urine, indicating that the cleavage process occurs in vivo. The results suggest that alpha(1)-microglobulin is involved in extracellular heme catabolism.     

Calculating Workplace WBGT from Meteorological Data: A Tool for Climate Change Assessment

The WBGT heat stress index has been well tested under a variety of climatic conditions and quantitative links have been established between WBGT and the work-rest cycles needed to prevent heat stress effects at the workplace. While there are more specific methods based on individual physiological measurements to determine heat strain in an individual worker, the WBGT index is used in international and national standards to specify workplace heat stress risks. In order to assess time trends of occupational heat exposure at population level, weather station records or climate modelling are the most widely available data sources. The prescribed method to measure WBGT requires special equipment which is not used at weather stations. We compared published methods to calculate outdoor and indoor WBGT from standard climate data, such as air temperature, dew point temperature, wind speed and solar radiation. Specific criteria for recommending a method were developed and original measurements were used to evaluate the different methods. We recommend the method of Liljegren et al. (2008) for calculating outdoor WBGT and the method by Bernard et al. (1999) for indoor WBGT when estimating climate change impacts on occupational heat stress at a population level.     

Effect of chronic daily oral administration of 17βoestradiol and norethisterone on the isoforms of serum gonadotrophins in post-menopausal women

OBJECTIVE Chronic treatment with 17βoestradlol (E₂Implants has been found to counteract the formation of more acidic isoforms of the gonadotrophins in post-menopausal women. Oral medication with an oestrogen in combination with a progestagen is a common hormone replacement therapy (HRT) in post-menopausal women. The present study investigated the effect of such a therapy on the concentration and charge of the gonadotrophin isoforms in serum. DESIGN Serum samples were obtained from 20 post-menopausal women, mean age 60 years (range 50–72 years), treated with continuous dally oral medication of 2 mg E₂ combined with 1 mg norethisterone acetate (NETA). FSH, LH and E₂ in the serum was measured with fluoroimmunoassays. The median charge and charge heterogeneity of the FSH and LH isoforms were determined for each serum by electrophoresis in 0·1% agarose suspension. Sera from 20 post-menopausal women without a history of HRT served as controls. The results were compared with those from previous studies on post-menopausal women treated with E₂ Implants and on women with normal menstrual cycles. RESULTS The E₂ level in the oral-E₂+ NETA treated women was 198-610 pmol/l, within the range expected during the mid-luteal phase of the normal menstrual cycle and similar to that of the group of women with an E₂ Implant. The mean LH level was similar to that of the luteal phase of the cycle and significantly lower than that of the controls (P < 0·001), the E₂ Implant group (P < 0·001) and at the follicular phase of the cycle (P < 0·01). The mean FSH level was slmllar to that of the folllcular phase and the E₂ implant group but lower than that of the controls (P < 0·001) and higher than at the luteal phase of the cycle (P < 0·01). The mean values for median charge of both FSH and LH were less acidic than those of the controls (P < 0·001) but more acidic than those for the E₂ Implant group (P < 0·01; P < 0·001) and for different phases of the menstrual cycle (P < 0·05; P < 0·001). The mean degree of charge heterogeneity of FSH was larger (P < 0·01), while that of LH was smaller (P < 0·01), than for the controls. The mean concentrations of SHBG in the oral E₂+ NETA group, the E₂ implant group and the controls were similar. CONCLUSION Chronic oral therapy with 2mg 17β oestradiol combined with 1 mg norethisterone in post-menopausal women efficiently decreased the serum gonadotrophin levels but only partly counteracted the formation of the more acidic isoforms of FSH and LH after menopause. The differences in the charge for both FSH and LH between the E₂ Implant and the oral E₂+ NETA treated groups may be due to the differences in route of administration of E₁ or to the effect of norethisterone or both.     

Cadmium exposure from smoking cigarettes: variations with time and country where purchased

Cadmium has been determined in 26 brands of cigarettes purchased in eight different countries throughout the world and in 16 different samples of cigarettes produced in Sweden between 1918 and 1968. In addition the amount of cadmium released from smoking one cigarette to the particulate phase collected from a smoking simulation machine, corresponding to the amount actually inhaled by a smoker, has been determined. The cadmium concentration in different brands of cigarettes ranged from 0.19 to 3.0 micrograms Cd/g dry wt, with a general tendency toward lower values in cigarettes from developing countries. No systematic change in the cadmium concentration of cigarettes with time could be revealed. The amount of cadmium inhaled from smoking one cigarette containing about 1.7 microgram Cd was estimated to be 0.14 to 0.19 microgram, corresponding to about 10% of the total cadmium content in the cigarette.