Review article: NSAIDs, gastroprotection and cyclo-oxygenase-II-selective inhibitors.

In patients at high risk of NSAID-associated serious upper gastrointestinal complications, gastroprotection with misoprostol or a proton pump inhibitor should be considered. Only misoprostol, 800 micro g/day, has been shown to reduce serious upper gastrointestinal complications in a large clinical outcome trial. The benefit of Helicobacter pylori eradication in reducing NSAID-associated gastrointestinal toxicity is controversial, and routine testing for and eradication of H. pylori in NSAID users are not currently advised. The gastrointestinal safety of rofecoxib and celecoxib has been assessed in large clinical outcome trials which, on first analysis, show benefits over non-selective NSAIDs in the incidence of serious upper gastrointestinal complications. However, longer term gastrointestinal data from the celecoxib study (CLASS) and cardiovascular adverse event data from the rofecoxib study (VIGOR) have questioned the risk-benefit profile of these new drugs and, until they are better understood, it seems sensible not to use them routinely in large numbers of individuals. The gastrointestinal safety of meloxicam and etodolac has not been adequately assessed in such trials. Therefore, evidence for their use instead of non-selective NSAIDs, or instead of celecoxib or rofecoxib, is not robust.

Requirements for mini-exon inclusion in potato invertase mRNAs provides evidence for exon-scanning interactions in plants.

Invertases are responsible for the breakdown of sucrose to fructose and glucose. In all but one plant invertase gene, the second exon is only 9 nt in length and encodes three amino acids of a five-amino-acid sequence that is highly conserved in all invertases of plant origin. Sequences responsible for normal splicing (inclusion) of exon 2 have been investigated in vivo using the potato invertase, invGF gene. The upstream intron 1 is required for inclusion whereas the downstream intron 2 is not. Mutations within intron 1 have identified two sequence elements that are needed for inclusion: a putative branchpoint sequence and an adjacent U-rich region. Both are recognized plant intron splicing signals. The branchpoint sequence lies further upstream from the 3' splice site of intron 1 than is normally seen in plant introns. All dicotyledonous plant invertase genes contain this arrangement of sequence elements: a distal branchpoint sequence and adjacent, downstream U-rich region. Intron 1 sequences upstream of the branchpoint and sequences in exons 1, 2, or 3 do not determine inclusion, suggesting that intron or exon splicing enhancer elements seen in vertebrate mini-exon systems are absent. In addition, mutation of the 3' and 5' splice sites flanking the mini-exon cause skipping of the mini-exon, suggesting that both splice sites are required. The branchpoint/U-rich sequence is able to promote splicing of mini-exons of 6, 3, and 1 nt in length and of a chicken cTNT mini-exon of 6 nt. These sequence elements therefore act as a splicing enhancer and appear to function via interactions between factors bound at the branchpoint/U-rich region and at the 5' splice site of intron 2, activating removal of this intron followed by removal of intron 1. This first example of splicing of a plant mini-exon to be analyzed demonstrates that particular arrangement of standard plant intron splicing signals can drive constitutive splicing of a mini-exon.

Characterization of exon skipping mutants of the COP1 gene from Arabidopsis.

The removal of introns from pre-mRNA requires accurate recognition and selection of the intron splice sites. Mutations which alter splice site selection and which lead to skipping of specific exons are indicative of intron/exon recognition mechanisms involving an exon definition process. In this paper, three independent mutants to the COP1 gene in Arabidopsis which show exon skipping were identified and the mutations which alter the normal splicing pattern were characterized. The mutation in cop1-1 was a G-->A change 4 nt upstream from the 3' splice site of intron 5, while the mutation in cop1-2 was a G-->A at the first nucleotide of intron 6, abolishing the conserved G within the 5' splice site consensus. The effect of these mutations was skipping of exon 6. The mutation in cop1-8 was G-->A in the final nucleotide of intron 10 abolishing the conserved G within the 3' splice site consensus and leading to skipping of exon 11. The splicing patterns surrounding exons 6 and 11 of COP1 in these three mutant lines of Arabidopsis provide evidence for exon definition mechanisms operating in plant splicing.

Using nurse case management to promote self-efficacy in individuals with rheumatoid arthritis.

Rheumatoid arthritis is a chronic disabling illness commanding a large portion of healthcare resources. The literature indicates that the holistic management of chronic illness has demonstrated a favorable impact on the course of the disease and its outcome. In response to these reports, a nurse case manager delivery system was implemented within a tertiary care teaching hospital to coordinate an interdisciplinary treatment plan for patients with rheumatoid arthritis. The system supported the belief that although intervention is important, self-efficacy skills have an impact on patients' coping skills. Patient care incorporates inpatient and ambulatory care services, and patients are discharged after completing scheduled visits through ambulatory care services. This article describes how patients can manage their own disease if they are provided with the necessary tools. Patients can learn to trust and use their own judgment which can lead to self-efficacy. Another study is currently under way to further evaluate this method of care delivery.

Survival in early onset dementia: effects of urbanization and socio-economic deprivation.

We estimated survival of patients with early onset Alzheimer's disease (AD) or vascular dementia (VaD) presenting to psychiatric hospitals in Scotland (1974-1988) and related this to age, gender and socio-economic variables. Hospital records of 1794 early onset dementia patients were reviewed. We identified 451 patients with early onset AD and 384 with VaD. Survival to death was calculated from symptom onset and presentation. Small geographical areas (postcode sectors) were classified by urban/rural category and deprivation score. Five-year survival from presentation of early onset AD was 32% for men and 43% for women compared to 22% for men and 36% for women with VaD. We conclude that increased age at presentation was associated with shorter survival in early onset AD and VaD. Socio-economic deprivation was associated with longer survival in VaD. The effects of urban/rural score were accounted for by the major effects of socio-economic deprivation.

Epidemiology of presenile Alzheimer's disease in Scotland (1974-88) I. non-random geographical variation.

BACKGROUND: Factors that determine geographical differences in incidence rates of 'probable' presenile Alzheimer's disease (AD PSD) may help to clarify the possible role of the environment in its aetiology. METHOD: We have ascertained the treated incidence of AD PSD in Scotland by scrutiny of hospital cassenotes and searched for cases outside hospital settings. Small area geographical analysis compared the observed distribution of cases (each allocated to one of Scotland's 898 postcode sectors) with the estimated random distribution of cases. RESULTS: There was non-random geographical distribution of AD PSD but not of the comparison conditions (vascular dementia (VaD), motor neurone disease, prostatic or ovarian cancers). Substantial differences between Scottish regions were probably not attributable to methodological artefact, as other techniques of case finding showed the same regional differences. CONCLUSIONS: The observed differences in incidence of AD PSD between Scotland's regions are real and some localities have a higher incidence, mostly in central Scotland.

Epidemiology of Alzheimer's presenile dementia in Scotland, 1974-88.

OBJECTIVE: To describe the epidemiology of presenile Alzheimer's disease in Scotland from 1974 to 1988. DESIGN: Retrospective review of hospital records of patients aged less than 73 years admitted to psychiatric hospital with various diagnoses of dementia. Diagnoses were classified by National Institute for Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association Criteria and the Hachinski score. Completeness of the study sample was evaluated by scrutiny of neurology outpatient and general hospital records. SETTING: All general psychiatric hospitals in Scotland. SUBJECTS: All patients with onset of dementia aged 40-64. MAIN OUTCOME MEASURES: Probable and broad Alzheimer's disease, sex of patient, age at onset. RESULTS: 5874 psychiatric hospital records, 129 neurology outpatient records, and 89 records from non-psychiatric hospitals were examined. 317 patients met criteria for probable Alzheimer's disease, 569 met criteria for broad Alzheimer's disease, and 267 met those for multi-infarct dementia. Minimal incidences per 100,000 population aged 40-64 years were 22.6 (95% confidence interval, 20.2 to 25.2) and 40.5 (38.9 to 42.3) per 100,000 for probable and broad Alzheimer's disease. In the 1981 census year the annual incidence of probable Alzheimer's disease was 1.6 (1.0 to 2.6). Women were at greater risk with incidence rates for probable Alzheimer's disease of 28.2 (24.5 to 32.4) per 100,000 compared with 16.5 (13.8 to 19.8) per 100,000 for men. The incidence per 100,000 for multi-infarct dementia was greater in men (25.1, 23.3 to 27.1) than women (13.4, 12.1 to 14.8). CONCLUSION: Female sex seems to be positively associated with development of Alzheimer's disease before age 65 years.

Accuracy and completeness of Scottish mental hospital in-patient data.

In Scotland the Information and Statistics Division of the Scottish Office Home and Health Department maintains a computerised record of patients who have been admitted to, discharged from or have died in Scottish mental hospitals. This data source is of particular value to those involved in planning health care provision and to epidemiologists. The present study assesses the quality of these data in relation to patients with verified presenile dementia who have been discharged from the Royal Edinburgh Hospital between 1974 and 1988. Seventeen per cent of presenile patients were not identified and 23% of patients were wrongly classified. More than 93% of patients with presenile Alzheimer's disease were identified, though often under a variety of other diagnostic codes. These findings highlight limitations of the data supplied and suggest that the usefulness of this enviable and unique data source could be enhanced if the medical profession took greater care in clearly stating an International Classification of Diseases diagnosis in a patient's hospital record.

Strength and bite, Part 2: Testing isometric strength using a MORA set to a functional criterion.

The effect on isometric strength of biting on three intraoral devices and habitual occlusion was analyzed. Only subjects who showed a relative weakness to the Isometric Deltoid Press (IDP) when biting as opposed to maintaining the mandible in an unsupported rest position were included in the study. Both in the original 35 subjects and the 23 subjects returning on the second day, performance wearing the appliance set by a functional criterion of peak strength (locking) to the IDP was significantly greater than wearing a placebo appliance and a bite raising appliance that deflected the mandible 1 mm to the left. Strength biting on the appliance set by a functional criterion was significantly greater than all these conditions. Strength biting in habitual trials that were matched with the deflection condition was found to be significantly greater than that biting in the placebo condition. It was concluded that a relationship does exist between bite and isometric strength. Previous speculation about the role of placebo effect was not substantiated by the data gathered in this experiment.

Survival in presenile Alzheimer's and multi-infarct dementias.

Duration of survival in patients who had died of presenile Alzheimer's disease (AD) or presenile multi-infarct dementia (MID) in 13 mental hospitals in Scotland are described and contrasted. The duration of survival was significantly longer from symptom onset to death in AD (mean 7.4 years) than in MID (mean 5.8 years). Most of this difference was accounted for by a longer duration between symptom onset and presentation to hospital care in AD (mean 3.2 years) than in MID (mean 2.4 years). Age at onset and gender did not influence survival duration in AD or MID.

A tracking system for conducting epidemiological case-control studies.

The automated-respondent tracking system (ARTS) is an event-driven management system developed to monitor data collection during large epidemiological case-control studies. ARTS facilitates the conduct and management of these studies by eliminating the problems and limitations of manually monitoring subjects. This system, developed on an IBM 3032, consists of a series of programs linked by a general update program. Data captured on each subject for every study phase are used to generate lists of subjects requiring further action by the study staff. Additionally, ARTS produces reports reflecting a study's progress. Improved study management and reduced clerical load justify the system's costs. Concepts and programming principles applied to ARTS can be generalized to other epidemiological study designs.

Multiple primary cancers: relative risk in New Mexico's triethnic population.

A review of the population-based New Mexico Tumor Registry data identified 446 patients with nonsimultaneous multiple primary cancers, excluding non-melanoma skin cancers and carcinomas in situ of the uterine cervix. Expected numbers of cases were established by observing the person-years of exposure to the risk of developing a second or subsequent primary cancer and then applying the appropriate locally determined age-, sex-, ethnic-, and site-specific cancer incidence rates. The relative risk (observed/expected) of developing a second primary cancer was elevated for "Anglo" and Spanish American cancer patients in comparison with the risk of developing a first primary cancer in persons who have never had one. Only six cases of nonsimultaneous multiple primary cancer were observed (6.39 expected) in the region's American Indian population. There were differences in site-site associations among the three ethnic groups, but in many categories there were too few cases for analysis.