Antihypertensive efficacy of the angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril.

Drug therapy often fails to control hypertension. Azilsartan medoxomil (AZL-M) is a newly developed angiotensin II receptor blocker with high efficacy and good tolerability. This double-blind, controlled, randomised trial compared its antihypertensive efficacy and safety vs the angiotensin-converting enzyme inhibitor ramipril (RAM) in patients with clinic systolic blood pressure (SBP) 150-180 mm Hg. Patients were randomised (n=884) to 20 mg AZL-M or 2.5 mg RAM once daily for 2 weeks, then force-titrated to 40 or 80 mg AZL-M or 10 mg RAM for 22 weeks. The primary endpoint was change in trough, seated, clinic SBP. Mean patient age was 57±11 years, 52.4% were male, 99.5% were Caucasian. Mean baseline BP was 161.1±7.9/94.9±9.0 mm Hg. Clinic SBP decreased by 20.6±0.95 and 21.2±0.95 mm Hg with AZL-M 40 and 80 mg vs12.2±0.95 mm Hg with RAM (P<0.001 for both AZL-M doses). Adverse events leading to discontinuation were less frequent with AZL-M 40 and 80 mg (2.4% and 3.1%, respectively) than with RAM (4.8%). These data demonstrated that treatment of stage 1-2 hypertension with AZL-M was more effective than RAM and better tolerated.

Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women.

BACKGROUND AND AIMS: Serotonin (5-hydroxtryptamine, 5-HT) is an important factor in gut function, playing key roles in intestinal peristalsis and secretion, and in sensory signalling in the brain-gut axis. Removal from its sites of action is mediated by a specific protein called the serotonin reuptake transporter (SERT or 5-HTT). Polymorphisms in the promoter region of the SERT gene have effects on transcriptional activity, resulting in altered 5-HT reuptake efficiency. It has been speculated that such functional polymorphisms may underlie disturbance in gut function in individuals suffering with disorders such as irritable bowel syndrome (IBS). The aim of this study was to assess the potential association between SERT polymorphisms and the diarrhoea predominant IBS (dIBS) phenotype. SUBJECTS: A total of 194 North American Caucasian female dIBS patients and 448 female Caucasian controls were subjected to genotyping. METHODS: Leucocyte DNA of all subjects was analysed by polymerase chain reaction based technologies for nine SERT polymorphisms, including the insertion/deletion polymorphism in the promoter (SERT-P) and the variable tandem repeat in intron 2. Statistical analysis was performed to assess association of any SERT polymorphism allele with the dIBS phenotype. RESULTS: A strong genotypic association was observed between the SERT-P deletion/deletion genotype and the dIBS phenotype (p = 3.07x10(-5); n = 194). None of the other polymorphisms analysed was significantly associated with the presence of disease. CONCLUSIONS: Significant association was observed between dIBS and the SERT-P deletion/deletion genotype, suggesting that the serotonin transporter is a potential candidate gene for dIBS in women.

Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine.

We have identified a migraine locus on chromosome 19p13.3/2 using linkage and association analysis. We isolated 48 single-nucleotide polymorphisms within the locus, of which we genotyped 24 in a Caucasian population comprising 827 unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the insulin receptor gene showed significant association with migraine. This association was independently replicated in a case-control population collected separately. We used experiments with insulin receptor RNA and protein to investigate functionality for the migraine-associated single-nucleotide polymorphisms. We suggest possible functions for the insulin receptor in migraine pathogenesis.

Randomised controlled trials of staged teaching for basic life support: 2. Comparison of CPR performance and skill retention using either staged instruction or conventional training.

Teaching CPR in stages is a strategy designed to improve skill acquisition and retention. This method has been compared with conventional teaching in a randomised trial involving 495 volunteers. The first ('bronze') stage was simplified by omitting ventilation and giving compressions in sets of 50 with pauses to open the victim's airway; in the second ('silver') stage ventilation was introduced in a ratio of 50 compressions to five breaths, and in the third ('gold') stage, the volunteers were converted to conventional CPR. 51% of those taught by this method reattended for the second ('silver') stage compared with 25% who were taught conventional CPR and advised to return for a revision session. 38% of the staged group reattended for the third ('gold') compared with 8% for the conventional group. Modest improvement in skill acquisition has earlier been reported for the 'bronze' stage teaching, and this has been followed by better performance in some of the components tested after the subsequent stages. Comparisons after the 'gold' stage were limited by the small numbers who reattended for a third session of conventional training, but no special difficulties were noted in changing the ratio of compressions to ventilation that was necessary to convert the staged training volunteers to conventional CPR. The increased number of compressions that can be achieved by teaching 'bronze' stage CPR with no ventilation was retained, to a lesser degree, when the 'silver' ratio of 50 compressions to five breaths was compared with the conventional 15:2 ratio. Our observations suggest that during the first critical 8 min of a resuscitation attempt, 58% more compressions might be delivered by using the 50:5 ratio - an increase that is likely to result in a significant augmentation of blood flow with important clinical implications. More comparative information will become available when the results of unannounced home testing are analysed.

Outcomes associated with supportive periodontal therapy in smokers and nonsmokers.

PURPOSE: This study evaluated the effects of smoking status on retrospective clinical and radiographic measures of periodontal disease and compared these to prospective changes in digital radiographic bone height. METHODS: Clinical data on moderate (4 to 6 mm) and severe (> 6 mm) periodontal pocket depths, and bleeding on probing, were obtained from 95 subjects on suggested three-month supportive periodontal therapy (SPT) for AAP Class III/IV periodontitis. Standardized radiographic data were obtained concerning posterior interproximal alveolar bone height from 36 of the 95 subjects using computer-assisted digital technology at baseline and one year later. The subjects were divided into groups by smoking status: current, former, and never. Data were evaluated using a general linear statistical model. RESULTS: Evaluation of clinical data showed that current smokers exhibited a significantly higher percentage of moderate (18%) and severe (1%) periodontal pockets than nonsmokers (10% and 0%, respectively; p < 0.002). Baseline radiographic interproximal bone height loss also was greater in current smokers (5.75 +/- 1.07 v. 4.64 +/- 1.16 mm). Bone loss over one year occurred in 5% of the sites, but was not significantly different among groups. CONCLUSION: Clinical periodontal pockets and bone loss accumulated more rapidly in smokers, even though they submitted to regular supportive periodontal therapy. Although this population was clinically compliant over a one year period, digital radiography showed a high incidence of detectable bone loss. The impact of smoking, however, may require longer than one year to show longitudinal changes. It is recommended that a periodic radiographic analysis on bone height be considered during SPT, and longer term studies be conducted in order to accurately identify the outcome of smoking status on this variable.

Action sequence for layperson cardiopulmonary resuscitation.

Although some minor modifications were forged, the general consensus was to maintain most of the current guidelines for phone first/phone fast, no-assisted-ventilation CPR, the A-B-C (vs C-A-B) sequence of CPR, and the recovery position. The decisions to leave these guidelines as they are were based on a lack of evidence to justify the proposed changes, coupled with a reluctance to make revisions that would require major changes in worldwide educational practices without such evidence.Nonetheless, some major changes were made. The time-honored procedure ol pulse check by lay rescuers was eliminated altogether and replaced with an assessment for other signs of circulation. Likewise, it was recommended that even the professional rescuer now check for these other signs of circulation. Although professional rescuers may simultaneously check for a pulse, they should do so only for a short period of time (within 10 seconds). There was also enthusiasm for deleting the ventilation aspect of EMS dispatcher-assisted CPR instructions that are provided to rescuers at the scene who are inexperienced in CPR. lt was made clear, though, that the data are applicable only to adult patients who are receiving CPR and that the data are appropriate most for EMS systems with rapid response times.

Spectroscopic characterisation and identification of ecdysteroids using high-performance liquid chromatography combined with on-line UV--diode array, FT-infrared and 1H-nuclear magnetic resonance spectroscopy and time of flight mass spectrometry.

A prototype multiply hyphenated reversed-phase HPLC system has been applied to the analysis of a mixture of pure ecdysteroids and an ecdysteroid-containing plant extract. Characterisation was achieved via a combination of diode array UV, 1H NMR, FT-IR spectroscopy and time of flight (TOF) mass spectrometry. This combination of spectrometers allowed the collection of UV, 1H NMR, IR and mass spectra for a mixture of pure standards enabling almost complete structural characterisation to be performed. The technique was then applied to a partially purified plant extract in which 20-hydroxyecdysone and polypodine B were identified despite incomplete chromatographic resolution and the presence of co-chromatographing interferents. The experimental difficulties in the use of such a systems for these analytes are described.