Age-specific incidence, risk factors and outcome of acute abdominal aortic aneurysms in a defined population.

BACKGROUND: Contemporary population-based data on age-specific incidence and outcome from acute abdominal aortic aneurysm (AAA) events are needed to understand the impact of risk factor modification and demographic change, and to inform AAA screening policy. METHODS: In a prospective population-based study (Oxfordshire, UK, 2002-2014), event rates, incidence, early case fatality and long-term outcome from all acute AAA events were determined, both overall and in relation to the four main risk factors: smoking, hypertension, male sex and age. RESULTS: Over the 12-year interval, 103 incident acute AAA events occurred in the study population of 92,728 (men 72·8 per cent; 59·2 per cent 30-day case fatality rate). The incidence per 100,000 population per year was 55 in men aged 65-74 years, but increased to 112 at age 75-84 years and to 298 at age 85 years or above. Some 66·0 per cent of all events occurred in those aged 75 years or more. The incidence at 65-74 years was highest in male smokers (274 per 100,000 population per year); 27 (96 per cent) of 28 events in men aged less than 75 years occurred in ever-smokers. Mean(s.d.) age at event was lowest in current smokers (72·2(7·2) years), compared with that in ex-smokers (81·2(7·0) years) and never-smokers (83·3(7·9) years) (P < 0·001). Hypertension was the predominant risk factor in women (diagnosed in 93 per cent), with 20 (71 per cent) of all 28 events in women occurring in those aged 75 years or above with hypertension. The 30-day case fatality rate increased from 40 per cent at age below 75 years to 69 per cent at age 75 years or more (P = 0·008). CONCLUSION: Two-thirds of acute AAA events occurred at age 75 years or above, and more than 25 per cent of events were in women. Taken with the strong associations with smoking and hypertension, these findings could have implications for AAA screening.

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.

Dementia: the cost of care for behaviourally disturbed patients living in the community.

OBJECTIVE: To determine the cost of care of people with dementia and behavioural disturbances living in the community, which is currently unknown. DESIGN, SETTING & PATIENTS: This is a study of 12 randomly selected subjects attending a continuing care dementia day facility for people with behavioural disturbances. MEASURES: Hours of care received from different sources were recorded and costed. RESULTS: The total mean direct costs to the public services was pound400 per person per week. Caregiver's time costed at professional rates were pound1208 per person per week. CONCLUSIONS: Unpaid caregivers supported by publicly funded agencies provide a less expensive service compared to specialised institutional care.

Selective serotonin reuptake inhibitors and hyponatraemia: review and proposed mechanisms in the elderly.

The association between selective serotonin reuptake inhibitors (SSRIs) and hyponatraemia has been well documented, the elderly appearing to be at greatest risk. An analysis of data of hyponatraemia in the elderly using SSRIs from all published cases and from the Committee on Safety of Medicines found that the mean time to detection was about 3 weeks after commencing SSRIs. A wide range of time to detection (1-253 days) and non-specific symptoms suggest hyponatraemia is detected by chance rather than being specifically looked for. In the elderly there are physiological changes, a high prevalence of medical illnesses and concomitant drug use, which may precipitate hyponatraemia. Together with a risk of altered water regulation in psychiatric illness this may account for the particular susceptibility of the elderly to hyponatraemia whilst using SSRIs.

Placenta previa percreta with bladder involvement: new considerations and review of the literature.

Placenta previa percreta is a life-threatening condition. Antenatal diagnosis is important to establish and to optimize a plan of management. When bladder invasion occurs, other potential complications can result, including massive hemorrhage and the development of disseminated intravascular coagulation. Numerous modalities have been used successfully to treat these patients, but hysterectomy at delivery is the treatment most commonly used. A case of placenta previa percreta with suspected bladder invasion was diagnosed in a 35-year-old woman by routine office ultrasound examination at 19 weeks 6 days' gestation. She was managed conservatively until 36 weeks 3 days' gestation, at which time she underwent a modified classical Cesarean section after amniocentesis to confirm fetal lung maturity. The placenta was left in situ immediately postpartum. The patient underwent a prophylactic embolization of her hypogastric arteries and received methotrexate chemotherapy. Eight weeks later, she developed a low-grade coagulopathy and underwent a total abdominal hysterectomy. Conservative management intrapartum is thought to be appropriate, to avoid the risk of severe hemorrhage at the time of delivery. However, elective hysterectomy ought to be considered earlier (2-4 weeks postpartum) than the time suggested in the literature, to avoid the development of further complications, including coagulopathy.

Construction of a translational lacZ fusion system to study gene regulation in Neisseria gonorrhoeae.

A translational lacZ reporter system to study gene regulation in Neisseria gonorrhoeae (Ng) was developed. The pUC18-based vector pLES94 transforms Ng and recombines into the Ng chromosome at the site of the proAB genes. The vector contains a restriction site for cloning promoters that will result in a lacZ gene fusion. Initial cloning and characterization of promoters can be done in Escherichia coli. The vector contains both ApR and CmR genes, however the ApR gene is lost when the insert combines into the Ng chromosome. This system gives single copy expression of the fusion and does not result in the inactivation of the gene of interest.

Distribution of gonococcal lipopolysaccharide biosynthesis genes among strains of Neisseria gonorrhoeae and other neisserial species.

A plasmid, pTME6, containing Neisseria gonorrhoeae lipopolysaccharide biosynthesis genes was used as a probe to analyze DNA from strains of N. gonorrhoeae, N. meningitidis and various commensal Neisseria by Southern blotting. Chromosomal DNA from 26 gonococcal strains probed with 32P-labeled pTME6 produced five different hybridization patterns. No correlation between hybridization pattern and auxotype, serotype, serum sensitivity or SDS-urea-PAGE migration of LPS was observed. DNA from strains of N. meningitidis, N. lactamica and N. cinerea, but not other commensal Neisseria species, hybridized strongly to pTME6.

Organized packaging of kinetoplast DNA networks.

The kinetoplast DNA (kDNA) of Trypanosoma equiperdum is organized as a complex structure of catenated circular DNA molecules. The major component of the kDNA network is the one kilobase minicircle that is present at about 10,000 copies per network. We have developed two assays to examine the structure of kDNA networks compacted in vitro with spermidine. Our results suggest that minicircles are arranged into a regular structure with an exposed domain which is DNAase I- and restriction-sensitive and a protected domain which is resistant to restriction endonucleases and DNAase I. This regularly packaged structure is dependent upon spermidine compaction and the circularity of the kDNA, but does not require supercoiled minicircles or catenated networks.

Cloning genes for proline biosynthesis from Neisseria gonorrhoeae: identification by interspecific complementation of Escherichia coli mutants.

DNA from Neisseria gonorrhoeae KH45 was partially digested with Sau3A and inserted into the BamHI site of the cloning vector pLES2 . After introduction into Escherichia coli JM83 by transformation, two different size classes of plasmids were isolated that could complement the proAB deletion of JM83 . These plasmids ( pLES4 and pLES7 ) were characterized by restriction endonuclease digestion. Southern hybridization demonstrated that the inserts had sequence homology. Various deletions of these plasmids were constructed that had lost the ability to complement the proA lesion of chi 463, the proB lesion of chi 340, or both (plasmids pLES9 , pLES8 , and pLES10 , respectively). These deleted plasmids were introduced into a proline-requiring strain of N. gonorrhoeae, F62, with plasmids pLES4 , pLES7 , and pLES8 possessing the ability to correct the proline requirement of F62. Further analysis indicated that the hybrid plasmids were stably maintained as plasmids in N. gonorrhoeae.

Construction and characterization of a new shuttle vector, pLES2, capable of functioning in Escherichia coli and Neisseria gonorrhoeae.

In vitro recombination techniques were used to construct a bifunctional shuttle vector capable of functioning in Neisseria gonorrhoeae and Escherichia coli. This 6-kb plasmid contains a selectable phenotype, beta-lactamase production, which functions in both organisms. It also contains the lac region from pUC9 that allows for the direct selection of hybrid plasmids in the appropriate E. coli hosts by disruption of beta-galactosidase alpha complementation. The lac region contains several unique restriction sites useful for cloning: EcoRI, SmaI, BamHI and SalI.

Rhizobium japonicum mutants defective in symbiotic nitrogen fixation.

Rhizobium japonicum strains 3I1b110 and 61A76 were mutagenized to obtain 25 independently derived mutants that produced soybean nodules defective in nitrogen fixation, as assayed by acetylene reduction. The proteins of both the bacterial and the plant portions of the nodules were analyzed by two-dimensional polyacrylamide gel electrophoresis. All of the mutants had lower-than-normal levels of the nitrogenase components, and all but four contained a prominent bacteroid protein not observed in wild-type bacteroids. Experiments with bacteria grown ex planta suggested that this protein was derepressed by the absence of ammonia. Nitrogenase component II of one mutant was altered in isoelectric point. The soluble plant fraction of the nodules of seven mutants had very low levels of heme, yet the nodules of five of these seven mutants contained the polypeptide of leghemoglobin. Thus, the synthesis of the globin may not be coupled to the content of available heme in soybean nodules. The nodules of the other two of these seven mutants lacked not only leghemoglobin but most of the other normal plant and bacteroid proteins. Ultrastructural examination of nodules formed by these two mutants indicated normal ramification of infection threads but suggested a problem in subsequent survival of the bacteria and their release from the infection threads.

Use of two-dimensional polyacrylamide gel electrophoresis to identify and classify Rhizobium strains.

Fifty-seven strains of various Rhizobium species were analyzed by two-dimensional gel electrophoresis. Since the protein pattern on such gels is a reflection of the genetic background of the tested strains, similarities in pattern allowed us to estimate the relatedness between these strains. All group II rhizobia (slow growing) were closely related and were very distinct from group I rhizobia (fast growing). Rhizobium meliloti strains formed a distinct group. The collection of R. leguminosarum and R. trifolii strains together formed another distinct group. Although there were some similarities within the R. phaseoli, sesbania rhizobia, and lotus rhizobia, the members within these seemed much more diverse than the members of the above groups. The technique also is useful to determine whether two unknown strains are identical.