Appropriateness Review: the law and the challenge.
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Biomedical subjects
Publications and source records attributed to B Edwards.
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Twenty-four-hour electrocardiographic tape-recording was used to investigate the incidence of arrhythmias in patients with suspected myocardial infarction who were receiving either propranolol, atenolol, or placebo. Recordings begun within 24 hours after admission to a coronary care unit showed that 76% of patients eventually found to have had a myocardial infarction had ventricular arrhythmias of a type generally regarded as serious, whereas of patients in whom myocardial infarction was not substantiated, only 24% had such arrhythmias. At one and six weeks after admission the incidence of arrhythmias ranged from 25% to 33% irrespective of diagnosis. Of patients monitored at both one and six weeks, however, only 5% had arrhythmias on each occasion. Patients treated with propranolol and atenolol showed a similar incidence of arrhythmias to those taking placebo. There was no difference in the incidence or type of arrhythmias recorded between patients who died and those who were still alive at six weeks.These results confirm that "serious" ventricular arrythmias occur in most patients during the acute phase of myocardial infarction and suggest that they do not constitute an independent risk factor. Beta-blockers showed little evidence of useful antiarrhythmic action in the dosage used, but increasing the dosage in suspected myocardial infarction is not practicable because of the risk of hypotension. The findings raise grave doubts about the value of studying arrhythmias to assess drugs intended to reduce mortality from myocardial infarction.
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A survey of members of the Infectious Diseases Society of America indicated that nocardial infections are not rare. Probably between 500 and 1,000 cases are recognized in the United States each year, of which 85% are serious pulmonary or systemic infections. Although nocardial infections are usually opportunistic infections in the compromised host, at least 15% of the infections in this series occurred in patients without a definable predisposing condition. Nocardial infections occurred in a random geographic distribution within this country, with affected males outnumbering females by 3:1. Most patients were between the ages of 21 and 50 years; however, the age range was broad. The number and variety of infections caused by Nocardia species other than Nocardia species other than Nocardia asteroides have been underestimated. Between 8.6% and 18.8% of pulmonary-systemic infections in this series were caused by species of Nocardia other than N. asteroides.
Screening tests for bacteriuria based on two different principles were evaluated in1582 schoolgirls aged 5-11 years, and in 26 girls aged 3-16 years attending hospitalwith symptomatic urinary tract infection. Tests for hypoglucosuria, performed by a semi-automated fluorometric method and with Uriglox strips on early-morning urine samples voided after overnight fasting, gave unacceptably high false-negative rates (16.7% and 20.8% respectively). Oxoid and Uricult dipslides were immersed in fresh midstreamspecimens of urine obtained at school and read overnight incubation at 37 degrees C. Both gave comparable results, with low false-positive rates and no false-negative responses. The higher cost of screening by dipslides was halved by using the "dipstream" technique, which also gave no false-negative results. Its false-positive rate of 13.5% could be reduced to 1.8% by disregarding colony counts of 10-8 non-faecal organisms and over per litre, which appear unimportant in schoolchildren. Bacteriuria was found in 2.3% of the schoolgirls; 39% of them had symptons, compared with 7.2% of the healthy girls, and 25% showed vesicoureteric reflux, which in 17% was associated with renalscarring. Since the natural history of covert bacteriuria and its relationship withreflux and scarring remain undetermined further research is required. The dipstreamtechnique offers a simple, reliable, and comparatively cheap screening method which could also be applied in general practice.
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With the advent of enzymatically induced chemiluminescence and improved instrumentation for luminometry, ultrasensitive detection of a wide variety of analytes is now possible using standard immunoassay and DNA probe formats. Model molecular orbital calculations and literature precedent suggest that the singlet efficiencies observed upon decomposition of dioxetanes appended with donor substituted aromatic moieties are dependent on substitution pattern. We have recently discovered, in a series of 3-(2'-spiroadamantane)-4-methoxy-4-acetoxynaphth-2'-yl-1,2-+ ++dioxetanes, that enzymatic generation of a non-conjugated, charge transfer excited state results in luminescence of markedly different properties than that observed from an isomeric, conjugated excited state. An example of the former type, 3-(2'-spiroadamantane)-4-methoxy-4-(7"-acetoxy)naphth-2'-yl- 1,2- dioxetane (1) emitting at 550 nm, not only provides an increase in phi CL, but exhibits a dramatic bathochromic shift of 80-110 nm from the 460 nm emission of the conjugated isomer 3-(2'-spiroadamantane)-4-methoxy-4-(6"-acetoxy)naphth-2'-yl- 1,2-dioxetane (2). These developments, along with the attendant glow-type luminescence kinetics displayed during the enzymatic decomposition of the new 'odd-pattern' dioxetane, allow the design of simple protocols capable of simultaneous or 'multichannel' detection of several analytes.
Enhanced chemiluminescent assays for hydrolase enzymes have been developed using proenhancer and pro-anti-enhancer substrates. Alkaline phosphatase is measured using disodium para-iodophenyl phosphate (proenhancer) which is converted to para-iodophenol and this in turn enhances the light emission from the horseradish peroxidase catalysed chemiluminescent oxidation of luminol by peroxide. An alternative strategy uses para-nitrophenyl phosphate which is converted by alkaline phosphatase to para-nitrophenol which inhibits the enhanced chemiluminescent reaction. The detection limit for the enzyme using the proenhancer and pro-anti-enhancer assays was 100 attomoles and 1 picomole, respectively. The proenhancer strategy was effective in assays for beta-D-galactosidase, beta-D-glucosidase and aryl sulfatase. A limited comparison of the proenhancer and a conventional colorimetric assay for an alkaline phosphatase label in an enzyme immunoassay for alpha-fetoprotein showed good agreement.
A sample of 31 schizophrenic patients free of anti-psychotic drugs was examined on admission to hospital. 14 (45%) exhibited depressed mood. The course of depressive symptoms and psychotic symptoms was followed weekly while the patients received increasing doses of haloperidol in a standardised regime. In 11 of the 14 patients there was a close correspondence between the course of depressive and psychotic symptoms, suggesting that in these cases, depression was an integral part of the schizophrenic illness. In the other three cases, clinical course of the various symptoms gave some support to the concepts of 'pharmacogenic' and 'post-psychotic depression', although it was not possible to choose between them.
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