Phase I and II enzyme polymorphisms as risk factors for Barrett's esophagus and esophageal adenocarcinoma: a systematic review and meta-analysis.

Although several studies have examined the association between phase I/II enzyme polymorphisms and esophageal adenocarcinoma (EAC) and/or Barrett's esophagus (BE), their overall findings remain unclear. We performed a systematic review and meta-analysis to determine whether phase I/II polymorphisms are independent risk factors for either BE or EAC. We employed keyword searches in multiple databases to identify studies published before October 1, 2007. Single-nucleotide polymorphisms (SNPs) examined in > or =3 studies were meta-analyzed to obtain a pooled estimate of effect. Meta-analysis suggested the minor allele for GSTP1 Val(105) conveys modest excess risk (odds ratio [OR](BE)= 1.50, 95% confidence interval [CI] 1.16-1.95; OR(EAC)= 1.20, 95% CI 0.94-1.54). No excess risk was observed with GSTM1 null (OR(BE)= 0.77, 95% CI: 0.56-1.08; OR(EAC)= 1.08, 95% CI: 0.79-1.48), GSTT1 null (OR(BE)= 1.35, 95% CI: 0.91-2.01; OR(EAC)= 0.84, 95% CI: 0.48-1.49), or CYP1A Val(462) (OR(EAC)= 0.89, 95% CI: 0.40-1.97). Insufficient data existed to meta-analyze remaining SNPs. Our review identified GSTP1(Ile105Val) as a possible risk factor for BE and EAC in Caucasian males. No excess risk was observed for other phase I/II polymorphisms with sufficient data to meta-analyze. Additional studies are needed to determine if GSTP1 conveys excess risk in females or non-Caucasians and to evaluate other phase I/II polymorphisms.

Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study).

BACKGROUND: Acute coronary, cerebrovascular, and peripheral vascular events have common underlying arterial pathology, risk factors, and preventive treatments, but they are rarely studied concurrently. In the Oxford Vascular Study, we determined the comparative epidemiology of different acute vascular syndromes, their current burdens, and the potential effect of the ageing population on future rates. METHODS: We prospectively assessed all individuals presenting with an acute vascular event of any type in any arterial territory irrespective of age in a population of 91 106 in Oxfordshire, UK, in 2002-05. FINDINGS: 2024 acute vascular events occurred in 1657 individuals: 918 (45%) cerebrovascular (618 stroke, 300 transient ischaemic attacks [TIA]); 856 (42%) coronary vascular (159 ST-elevation myocardial infarction, 316 non-ST-elevation myocardial infarction, 218 unstable angina, 163 sudden cardiac death); 188 (9%) peripheral vascular (43 aortic, 53 embolic visceral or limb ischaemia, 92 critical limb ischaemia); and 62 unclassifiable deaths. Relative incidence of cerebrovascular events compared with coronary events was 1.19 (95% CI 1.06-1.33) overall; 1.40 (1.23-1.59) for non-fatal events; and 1.21 (1.04-1.41) if TIA and unstable angina were further excluded. Event and incidence rates rose steeply with age in all arterial territories, with 735 (80%) cerebrovascular, 623 (73%) coronary, and 147 (78%) peripheral vascular events in 12 886 (14%) individuals aged 65 years or older; and 503 (54%), 402 (47%), and 105 (56%), respectively, in the 5919 (6%) aged 75 years or older. Although case-fatality rates increased with age, 736 (47%) of 1561 non-fatal events occurred at age 75 years or older. INTERPRETATION: The high rates of acute vascular events outside the coronary arterial territory and the steep rise in event rates with age in all territories have implications for prevention strategies, clinical trial design, and the targeting of funds for service provision and research.

Direct assessment of completeness of ascertainment in a stroke incidence study.

BACKGROUND AND PURPOSE: Validity of comparisons of stroke incidence between studies or time periods depends on the completeness of ascertainment. Ascertainment cannot be reliably assessed indirectly by statistical methods, such as capture-recapture. We report the first use of direct methods to determine the completeness of different ascertainment strategies in a population-based stroke incidence study (Oxford Vascular Study). METHODS: We assessed completeness of 2 different ascertainment strategies: the core methods common to most previous incidence studies and core plus supplementary methods used in some studies (including access to carotid and brain imaging referrals and assessment of patients referred as "transient ischemic attack" or "recurrent stroke"). We assessed completeness of ascertainment in 2 ways. First, we searched anonymized primary care electronic patient records of the whole study population (n=90,542). Second, we interviewed and followed-up a high-risk subset of our study population: all patients who had an acute coronary or peripheral vascular event or a related elective investigation or intervention. RESULTS: 126 strokes were ascertained by the core plus supplementary methods, of which only 108 were identified by the core methods alone. Only 2 additional incident strokes were identified by access to primary care electronic patient records of the whole study population. Assessment and follow-up of 1103 high-risk individuals (5.5% of our total study population aged older than 60 years) identified 16 incident strokes. However, all 16 had already been ascertained by the core plus supplementary methods. CONCLUSIONS: The core methods of ascertainment used in some stroke incidence studies lead to significant underascertainment. However, direct assessment of ascertainment suggests that the supplementary methods used in recent studies can lead to near-complete ascertainment.

Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study).

BACKGROUND: The incidence of stroke is predicted to rise because of the rapidly ageing population. However, over the past two decades, findings of randomised trials have identified several interventions that are effective in prevention of stroke. Reliable data on time-trends in stroke incidence, major risk factors, and use of preventive treatments in an ageing population are required to ascertain whether implementation of preventive strategies can offset the predicted rise in stroke incidence. We aimed to obtain these data. METHODS: We ascertained changes in incidence of transient ischaemic attack and stroke, risk factors, and premorbid use of preventive treatments from 1981-84 (Oxford Community Stroke Project; OCSP) to 2002-04 (Oxford Vascular Study; OXVASC). FINDINGS: Of 476 patients with transient ischaemic attacks or strokes in OXVASC, 262 strokes and 93 transient ischaemic attacks were incident events. Despite more complete case-ascertainment than in OCSP, age-adjusted and sex-adjusted incidence of first-ever stroke fell by 29% (relative incidence 0.71, 95% CI 0.61-0.83, p=0.0002). Incidence declined by more than 50% for primary intracerebral haemorrhage (0.47, 0.27-0.83, p=0.01) but was unchanged for subarachnoid haemorrhage (0.83, 0.44-1.57, p=0.57). Thus, although 28% more incident strokes (366 vs 286) were expected in OXVASC due to demographic change alone (33% increase in those aged 75 or older), the observed number fell (262 vs 286). Major reductions were recorded in mortality rates for incident stroke (0.63, 0.44-0.90, p=0.02) and in incidence of disabling or fatal stroke (0.60, 0.50-0.73, p<0.0001), but no change was seen in case-fatality due to incident stroke (17.2% vs 17.8%; age and sex adjusted relative risk 0.85, 95% CI 0.57-1.28, p=0.45). Comparison of premorbid risk factors revealed substantial reductions in the proportion of smokers, mean total cholesterol, and mean systolic and diastolic blood pressures and major increases in premorbid treatment with antiplatelet, lipid-lowering, and blood pressure lowering drugs (all p<0.0001). INTERPRETATION: The age-specific incidence of major stroke in Oxfordshire has fallen by 40% over the past 20 years in association with increased use of preventive treatments and major reductions in premorbid risk factors.

Multiple-quantum magic-angle spinning and dynamic-angle spinning NMR spectroscopy of quadrupolar nuclei.

Several aspects of the Multiple-Quantum Magic-Angle Spinning (MQMAS) technique (L. Frydman and J.S. Harwood, J. Am. Chem. Soc., 117 (1995) 5367) are compared with Dynamic-Angle Spinning (DAS). Examples of MQMAS spectra are shown for I = 3/2 nuclei with CQ up to 3.6 MHz, and for 27Al (I = 5/2) with CQ up to 10 MHz. The MQMAS linewidth is largely independent of the magnitude of the homonuclear dipolar interaction, while the spinning sideband manifold is similar to that observed in DAS experiments. MQMAS is technically simple and routinely useful for studying nuclei with short spin-lattice relaxation times, but care must be taken in its use for quantitative studies as the excitation of the triple-quantum coherence is not uniform. In this regard, MQMAS is most useful for samples with small quadrupolar coupling constants. In the specific case of 17O, DAS would give spectra with excellent resolution in comparison to MQMAS. The different advantages of DAS and MQMAS make them useful complementary techniques in many cases. Two additional methods are also presented for extracting the chemical shift anisotropy (CSA) directly for quadrupolar nuclei using the multiple-quantum scheme.

Cooperative organization of inorganic-surfactant and biomimetic assemblies.

A model that makes use of the cooperative organization of inorganic and organic molecular species into three dimensionally structured arrays is generalized for the synthesis of nanocomposite materials. In this model, the properties and structure of a system are determined by dynamic interplay among ion-pair inorganic and organic species, so that different phases can be readily obtained through small variations of controllable synthesis parameters, including mixture composition and temperature. Nucleation, growth, and phase transitions may be directed by the charge density, coordination, and steric requirements of the inorganic and organic species at the interface and not necessarily by a preformed structure. A specific example is presented in which organic molecules in the presence of multiply charged silicate oligomers self-assemble into silicatropic liquid crystals. The organization of these silicate-surfactant mesophases is investigated with and without interfacial silicate condensation to separate the effects of self-assembly from the kinetics of silicate polymerization.