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Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.
The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.
Vancouver police raid needle exchange run by drug users.
The police claimed that drug trafficking was going on at the needle exchange run by the Vancouver Area Network of Drug Users, but they failed to provide any evidence to that effect. The police later apologized for their remarks and the exchange re-opened.
The effects of ultraviolet radiation on antibiotic-resistant bacteria in vitro.
Wound infections produced by antibiotic-resistant bacterial strains are particularly difficult to manage. This study examined the effectiveness of ultraviolet (UV) light treatment in killing antibiotic-resistant strains of Staphylococcus aureus and Enterococcus faecalis in vitro. Between 2 and 5 replications of each organism at 10(8) organisms/ml were prepared and plated on sheep blood agar medium and treated with UV light (254 nm, 15.54 mW/cm2 output). Irradiation times were 0, 2, 5, 8, 15, 30, 45, 60, 90 or 120 seconds. Bacterial cultures were then incubated at 35 degrees C for 24 hours. Kill rates were 99.9 percent for the methicillin-resistant strain of S. aureus (MRSA) at 5, 8, 15, 30, 45, 60 seconds and 100 percent at 90 and 120 seconds. Kill rates were 99.9 percent at 5, 8, 15, 30 seconds for vancomycin-resistant E. faecalis (VRE) and 100 percent at 45, 60, 90, 120 seconds. Similar results were found with UV light treatment of the antibiotic-susceptible strains of S. aureus and E. faecalis. A significant difference in kill rates at 30 seconds of UV exposure was detected between the antibiotic-resistant strain of S. aureus and the antibiotic-resistant strain of E. faecalis (Student's t test, p < 0.01). Significant differences were also detected in the kill rates at 30 second exposure times for the antibiotic-susceptible strains of S. aureus and E. faecalis. These findings suggest that the Enterococcal bacteria is more susceptible to the killing effects of UV. This data also suggests that UV light at 254 nm is bactericidal for antibiotic-resistant strains of S. aureus and E. faecalis at times as short as 5 seconds and that the enterococcal bacteria is more susceptible to the killing effects of UV. With recommended patient treatment times for infected wounds being significantly longer than 5 seconds, this data indicates that patient treatment times need to be re-examined.
Re: Practical use of rectal medications in palliative care.
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The binding of monomeric IgA to myeloid Fc alpha R: evidence for receptor re-cycling and determination of its affinity.
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Haemodialysis leucopenia: the role of membrane type and re-use.
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Selections from current literature. Re-thinking the management of atrial fibrillation: a new approach.
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A cohort study of unemployment as a cause of psychological disturbance in Australian youth.
Data from the Australian Longitudinal Survey, conducted by the Commonwealth Department of Employment, Education and Training, were analysed to estimate relative risk of psychological disturbance accompanying unemployment in young people aged 15-24 years. Two cohorts were surveyed annually over 4 years during the mid-to-late-1980s; one from the general 15-24 year-old population (N = 8995), and the other selected from Commonwealth Employment Service records (N = 2403). Such large respondent numbers allowed control of confounding by exclusion to isolate employment transition groups suitable for hypothesis testing and quantification of causal relationships. Psychological morbidity was measured using binary outcomes of the 12 item psychological component of the General Health Questionnaire. Excluded from the analysis were those who: suffered from pre-existing physical health problems; were dissatisfied in their job; were self-employed; underwent marriage breakdown during the inter-survey period; had become widowed during the inter-survey period. A Bayesian probabilistic approach was used to calculate probabilities of psychologically normal respondents becoming psychologically morbid, given prior transition from employment to unemployment. Mantel-Haenszel analysis was utilised to estimate relative risks in comparison to a control group of those remaining employed, after controlling for age and gender. An overall relative risk of becoming psychologically disturbed as a consequence of becoming unemployed was estimated to be 1.51 (95% CI: 1.15-1.99). The overall relative risk of recovery from psychological disturbance upon re-employment in those with psychological disturbance was estimated to be 1.63 (95% CI: 1.08-2.48). Residual psychological effects of past unemployment experience and the effects of long-term unemployment were investigated, but found to be non-significant in this study. There was some evidence of psychological adaptation to unemployment, but this was statistically insignificant. Unemployment was a significant cause of psychological disturbance in young people who were initially employed, not suffering physical ill-health, and psychologically normal; conversely, re-employment reversed the effect.
Extradural diamorphine in the control of pain following lumbar laminectomy.
Catheters were inserted into the extradural space under direct vision at the time of surgery for prolapsed intervertebral disc or lumbar canal stenosis. In the post-operative period, diamorphine (3 mg in 5 ml water) was injected through the catheter when patients requested analgesia. In only four of 49 patients was significant pain relief not achieved after extradural diamorphine injection. In four other patients it was not possible to use this method of analgesia throughout the two post-operative days as planned. As judged by the improved mobility and by grading on a linear analogue pain scale, the quality of analgesia achieved was better than after intramuscular papaveretum (10-20 mg) and extradural diamorphine was requested less frequently. There were no serious side-effects in the patients studied, although the technique was not used in patients over 55 years of age. Extradural diamorphine appeared to be less effective in two patients who had undergone re-explorations.
Evaluation of intestinal absorption after total gastrectomy with different methods of re-establishment of intestinal continuity.
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Axilla surgery severely affects quality of life: results of a 5-year prospective study in breast cancer patients.
No long-term prospective study has investigated arm morbidity and patient quality of life. It is unclear to what extent breast cancer patients suffer from arm problems, how long such problems affect their lives, and whether quality of life improves as arm problems abate. This prospective cohort study aims to provide data on the clinical factors associated with arm dysfunction, to estimate its prevalence and to relate arm morbidity to quality of life. The Munich Cancer Registry records clinical details of all cancer patients in and around Munich. Quality of life information was provided directly by breast cancer patients (n = 990) over 5 years. Arm morbidity, including movement limitations, swelling and lymph drainage, and quality of life (EORTC QLQ-C30) were assessed. Up to 5 years after diagnosis, 38% of patients were still experiencing arm problems (swelling and limited movement). Consistently over the 5 years, quality of life was significantly (p < 0.001) lower for patients with arm difficulties. For those whose arm problems dissipated, quality of life significantly improved (p < 0.01). A logistic regression analysis showed that extent of axilla surgery (p < 0.003), comorbidity (CVD and diabetes) (p < 0.003), employment (p < 0.01), younger age (p < 0.02), and operating clinic (p < 0.05) significantly contributed to arm problems. Axilla surgery should be re-evaluated since arm morbidity has such a profound effect on patient quality of life.
Early and late results of re-operation for coronary artery disease: a 13-year experience.
A second coronary artery bypass grafting procedure was performed for recurrent angina in 119 patients between 1970 and mid-1983. Angiographic findings were assessed and computerized using the Brandt myocardial scoring system. The myocardial score was similar prior to the first and second operations. Graft failure was the most common indication for re-operation, either alone (48%) or in combination with progression of coronary artery disease (29%) or incomplete revascularization (10%). Progression of coronary artery disease alone was an indication in 9% and previous incomplete revascularization alone in 4%. The completeness of revascularization at the end of operation was analysed using a new index, the myocardial score/graft coverage rate. This showed that revascularization was less complete at the second operation than at the first (P less than 0.0001). The hospital mortality at re-operation was 2.5% and the peri-operative myocardial infarction rate was 9.2%. The follow-up period was 54 months (range 10-160 months). Actuarial survival was 94% at 5 years and 74% at 10 years. The average onset of recurrent angina was earlier after the second operation than after the first (P = 0.001). Using a cumulative actuarial curve, survival at 8 years was 85%, a further 6% of patients had undergone a third or fourth operation, and a further 25% were in NYHA Classes III or IV. Therefore 54% achieved a good or excellent result. It was concluded that re-operation is a worthwhile procedure.
Sustained "slow-fast" and "fast-slow" AV nodal re-entrant tachycardia in a patient with recurrent supraventricular tachycardia.
A case is presented of a 21-year-old woman with recurrent paroxysmal supraventricular tachycardia. Electrophysiologic study demonstrated the presence of both antegrade and retrograde dual AV nodal conduction pathways and both conventional slow-fast and atypical fast-slow forms of the AV nodal re-entrant tachycardia could be induced. Both tachycardias were successfully suppressed with a combination of digoxin and verapamil.
Re: A critical assessment of high-earning orthodontists in the General Dental Services of England and Wales (1990-91)--Turbill, Richmond and Wright.
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Comparison of intermittent and continuous palliative chemotherapy for advanced colorectal cancer: a multicentre randomised trial.
BACKGROUND: Policies of UK clinicians regarding the duration of chemotherapy for patients with advanced colorectal cancer are not consistent. We aimed to compare effectiveness of continuous and intermittent chemotherapy in such patients. METHODS: Patients who responded or had stable disease after receiving 12 weeks of the regimens described by de Gramont and Lokich, or raltitrexed chemotherapy, were randomised to either intermittent (a break in chemotherapy, re-starting on the same drug on progression), or continuous chemotherapy until progression. FINDINGS: 354 patients (178 intermittent, 176 continuous) were enrolled from 42 UK centres. At randomisation, 41% of participants had part or complete response; 59% were stable. Only 66 (37%) patients allocated to intermittent treatment restarted as planned, after a median of 130 days. Median time on treatment after restarting was 84 days. Patients in the continuous group remained on treatment for a median of a further 92 days. Similar proportions of patients in both groups received second-line therapy. Patients on intermittent chemotherapy had significantly fewer toxic effects and serious adverse events than those in the continuous group. There was no clear evidence of a difference in overall survival (hazard ratio 0.87 favouring intermittent, 95% CI 0.69-1.09, p=0.23). INTERPRETATION: Our findings provided no clear evidence of a benefit in continuing therapy indefinitely until disease progression. They showed that it is safe to stop chemotherapy after 12 weeks and re-start the same treatment on progression in patients with chemosensitive advanced colorectal cancer.
Re: kinematic and kinetic evaluation of the ankle joint before and after tendo Achilles lengthening in patients with spastic diplegia -- J Pediatr Orthop 2005;25:479-483.
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To the editor: Re: A-Rahman, Pedler S, Bray R, The effect of anesthetic gases on the growth of Pseudomonas aeruginosa, Haemophilus influenzae, and Staphylococcus aureus, Pediatr Pulmonol 2002;34:226-227.
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