Need for analysis drives data warehouse appeal.
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Biomedical subjects
Publications and source records attributed to J Evans.
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The Scope of Professional Practice liberates nurses, midwives and health visitors from previous role constraints, while keeping the focus on the patient. Some of the adjustments to the scope of practice require the individual practitioner to obtain explicit verbal or written consent.
Mutations in the murine Pax (paired-box)-3 gene results in a number of developmental abnormalities including a deficiency in sensory neurons. To determine the role that Pax-3 plays in neuronal cell development, we have studied the expression of Pax-3 in the ND7 neuronal cell line. Upon serum starvation, Pax-3 mRNA expression fell rapidly. Within 2 h of the removal of serum a 2-3-fold decrease in Pax-3 expression was observed and by 6 h Pax-3 mRNA expression was undetectable. Interestingly this decrease in Pax-3 expression could be reversed by the addition of serum growth factors. This rise in Pax-3 expression upon growth factor addition, was followed by an increase in cell proliferation and a reduction in neurite outgrowth, suggesting that Pax-3 may play a role in mediating cellular responses to these factors in neuronal cells.
BACKGROUND: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment. PURPOSE: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy were compared. METHODS: In the trial, patients were initially assigned to receive either tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. RESULTS: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P < .0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P < .0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued tamoxifen treatment. Survival was 96% for those who discontinued tamoxifen compared with 94% for those who continued tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with tamoxifen therapy. CONCLUSIONS AND IMPLICATIONS: The benefit from 5 years of tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing tamoxifen therapy for more than 5 years.
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The neural basis of normal and scrambled face processing was investigated by recording evoked potentials from 21 electrodes at standard EEG sites, with respect to a nose reference. Temporal negativities were found that result from two overlapping phenomena: they arise from the polarity reversal on temporal electrodes of the vertex P2, a positive wave peaking about 170-200 ms after the onset of a face stimulus, and also from an overlapping 'processing negativity' of long duration associated with the processing difficulty of the scrambled face stimulus. The comparisons of scalp potential and current density mappings support the proposal that some neuronal networks are active both for faces and scrambled faces and are compatible with the involvement of the superior temporal sulcus, the inferotemporal cortex and the parahippocampal and fusiform gyri, whereas the processing negativity would only involve the deepest generators of this network. Furthermore, the encoding of both faces and scrambled faces seems to take place predominantly in the right hemisphere.
Colour duplex scanning is reported to be an accurate non-invasive tool for the diagnosis of lower-extremity arterial disease. The authors at the South Coast Vascular Laboratory have conducted a prospective audit to determine the efficacy of colour duplex scanning in a vascular surgical practice. The aims of this prospective trial were to compare the accuracy of colour duplex scanning with intra-arterial digital subtraction angiography (DSA) in the localization and classification of aortoiliac and femoropopliteal artery disease. Ninety-one lower limbs in 50 patients were evaluated independently by colour duplex scanning and DSA. The lower-limb vasculature was divided into eight segments: infrarenal aorta, common iliac artery, external iliac artery, common femoral artery, proximal, middle and lower thirds of the combined length of the superficial femoral and above-knee popliteal artery, and lastly the below-knee popliteal artery. A total of 558 arterial segments were examined. The Kappa value of duplex scanning compared with 'gold standard' DSA was 0.57. For detecting haemodynamically significant arterial lesions of > 50% reduction in diameter, duplex scanning had a sensitivity of 75%, specificity of 90%, positive predictive value of 77% and negative predictive value of 89% compared with DSA. The level of accuracy obtained does not support the use of duplex as a sole method of investigation for lower-extremity arterial disease in the authors' case. However, the high negative predictive value of colour duplex may be useful in excluding haemodynamically significant disease. This study emphasizes the importance of prospective auditing to determine individual accuracy with duplex examination for arterial disease, and enables clinical decision making to be based on tests with a known accuracy.
OBJECTIVES: To compare collagen, elastin and smooth muscle contents of varicose and control long saphenous veins. DESIGN: Collagen, elastin and muscle were estimated stereologically using random sampling and histological staining. MATERIALS: Varicose vein samples were collected from nine patients (mean age 52 years, range 34-64 years) undergoing vein stripping, sample sites being saphenofemoral junction and knee. Control samples were taken from five patients (mean age 58 years, range 38-76 years) presenting for femoral-popliteal bypass at equivalent levels. METHODS: Veins were fixed, sectioned transversely, and stained with Picric Acid Sirius Red. Analysis of samples was performed using point and intersection counting on vertically projected images. RESULTS: Using two way analysis of variance tests, varicose saphenous veins had significantly larger wall areas (p < 0.01) and higher amounts of collagen (p < 0.01). Collagen content and wall area were significantly larger proximally compared to distally in both control and varicose veins (p < 0.05) with a higher content of smooth muscle and elastin in varicose veins proximally compared to distally (p < 0.05). There was no difference in wall thickness or elastin content between the two groups. CONCLUSIONS: This suggests that varicose veins are a dynamic response to venous hypertension and are not thin walled structures as previously thought.
BACKGROUND & AIMS: In the gastrointestinal tract, prostaglandins are implicated as important mediators of normal physiological processes. Prostaglandin G/H synthase (PGHS) is the first enzyme leading to the formation of prostaglandins. Two forms exist: the constitutive PGHS-1 and the inducible PGHS-2 isoforms. The purpose of this study was to examine the expression of PGHS-1 and -2 in gastrointestinal tissues. METHODS: PGHS-1 and -2 expression and activity were examined in rat, dog, monkey, and human gastrointestinal tracts by immunoblot and biochemical assays. RESULTS: PGHS-1 but not PGHS-2 protein was identified in all gastrointestinal tissues. PGHS-1 protein varied throughout the gastrointestinal tracts; interspecies differences were also noted. Immunohistochemical studies showed PGHS-1 staining of rat endothelial cells in all gastrointestinal regions; PGHS-2-specific staining was noted in a subset of macrophages in 3 of 22 rats examined. Elevated activity was shown in tissues expressing greater concentrations of PGHS-1 protein. Indomethacin, a nonsteroidal anti-inflammatory drug that inhibits both isoforms, inhibited prostaglandin synthesis, whereas NS-398, a selective PGHS-2 inhibitor, showed little or no inhibition of prostaglandin synthesis in gastrointestinal tissues. CONCLUSIONS: These results indicate that prostaglandins produced in normal gastrointestinal tissue and required for normal physiological functioning are derived from the PGHS-1 isoform.
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In the United States, there was an increase in the number of reported cases of Lyme disease in 1994 compared with previous years. The majority of cases occurred in the Northeast and Midwest, which are areas with established foci of Borrelia burgdorferi. Advances in the understanding of the epidemiology and ecology of ixodes ticks, the established vector for transmission of Lyme disease, provided strategies for reducing tick populations and the risk of acquiring disease. Dissemination of B. burgdorferi from the site of a tick bite likely occurs, in part, via attachment to host plasmin and subsequent degradation of glycoproteins. Analysis of T cell immune responses in mice contributed to our understanding of differences in disease susceptibility. Vaccination of patients with previous Lyme disease has been found to be safe, and clinical trials of vaccine efficacy are currently under way.
Prolonged exposure to weightlessness is known to produce a variety of cardiovascular changes, some of which may influence the astronaut's performance during a mission. In order to find a reliable indicator of cardiovascular adaptation to weightlessness, we analyzed data from nine male subjects after a 24-hour period of normal activity and after a period of simulated weightlessness produced by two hours in a launch position followed by 20 hours of 6 degrees head-down tilt plus pharmacologically induced diuresis (furosemide). Heart rate, arterial pressure, thoracic fluid index, and radial flow were analyzed. Autoregressive spectral estimation and decomposition were used to obtain the spectral components of each variable from the subjects in the supine position during pre- and post-simulated weightlessness. We found a significant decrease in heart rate power and an increase in thoracic fluid index power in the high frequency region (0.2-0.45 Hz) and significant increases in radial flow and arterial pressure powers in the low frequency region (<0.2 Hz) in response to simulated weightlessness. However, due to the variability among subjects, any single variable appeared limited as a dependable index of cardiovascular adaptation to weightlessness. The backward elimination algorithm was then used to select the best discriminatory features from these spectral components. Fisher's linear discriminant and Bayes' quadratic discriminant were used to combine the selected features to obtain an optimal index of adaptation to simulated weightlessness. Results showed that both techniques provided improved discriminant performance over any single variable and thus have the potential for use as an index to track adaptation and prescribe countermeasures to the effects of weightlessness.
We describe here a rapid polymerase chain reaction (PCR)-based method for the identification of HLA-DRB1*0401-*0412 alleles. The method is based on the generation of specific DNA heteroduplex patterns between PCR products derived from selective group-specific amplification of the various DRB1*04 alleles and PCR products derived from two synthetic DNA heteroduplex generator (DHG) molecules following non-denaturing polyacrylamide minigel electrophoresis. One DHG was designed to detect DRB1*0401, *0405, *0407, *0408, and *0409 alleles, whilst the other was designed to detect DRB1*0402, *0403, *0404, *0406, *0410, *0411, and *0412 alleles. Characteristic heteroduplex patterns were obtained for all DRB1*04 alleles tested both in homozygous and heterozygous situations. Both DHG and PCR-SSP (sequence-specific primer) typing were performed on 41 DRB1*04 positive DNAs from Singaporean Chinese blood donors and complete concordance in results was obtained. HLA-DRB1*0403, *0405, and *0406 were found to account for 95% of the DRB1*04 alleles in the population studied. The DHG technique described is technically simple and rapid since it essentially involves only two PCR amplifications per individual subtyping. The technique is particularly useful for resolving DRB1*04 combinations which are indistinguishable by PCR-SSO (sequence-specific oligonucleotide) or PCR-SSP subtyping.
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This study investigated differences in impulsivity between patients admitted to hospital for the first time after an act of deliberate self-harm (DSH), and those admitted after repetition of DSH. A total of 185 subjects, who were admitted to general hospital wards and referred for psychiatric assessment after DSH, completed self-report questionnaires including the impulsiveness (I-V-E) questionnaire. The presence of factors known to be predictive of repetition was recorded, including any history of DSH. Subjects with a history of DSH had significantly higher scores for impulsiveness than those who were presenting for the first time. Those presenting for the first time had higher scores than expected when compared with normative data after correcting for age and sex. Impulsiveness appears to be an important personality trait in DSH, in particular repeated DSH, and merits further investigation.
OBJECTIVE: To investigate the immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccines in children with sickle cell disease. DESIGN: Open study. SETTING: Haemoglobinopathy clinic. SUBJECTS: Children with homozygous haemoglobin SS disease (HbSS), sickle haemoglobin C disease (HbSC), and sickle-beta thalassaemia disease (HbS-beta Thal). INTERVENTIONS: Children over the age of 2 years received a single dose of Hib-tetanus toxoid conjugate vaccine (PRP-T). MAIN OUTCOME MEASURES: Antibody response to Hib polysaccharide (PRP) approximately one month after vaccination. RESULTS: 77 children over the age of 2 years were studied,, 55 with HbSS, 16 with HbSC, and six with HbS-beta Thal. Before vaccination, 44% had anti-PRP IgG titres less than the level associated with long term protection (1.0 microgram/ml). After a single dose of PRP-T all children mounted an antibody titre > 1 microgram/ml. Geometric mean anti-PRP IgG titre achieved postvaccination (45.2 micrograms/ml 95% confidence interval (CI) 31.6 to 64.8) was comparable to that of a healthy population. Children with HbSC, however, had a significantly higher antibody titre postvaccination (91.1 micrograms/ml; 95% CI 32.7 to 254.4) than the children with HbSS (36.7 micrograms/ml; 95% CI 25.1 to 52.9). CONCLUSIONS: Children with a diagnosis of sickle cell disease who are over the age of 2 years make a vigorous antibody response to a single dose of PRP-T vaccine and hence we suggest unimmunised individuals in this group should receive a single dose of a Hib conjugate vaccine.