Quality of life measures in health care. III: Resource allocation.
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Ethical Theory↗
Biomedical subjects
D R Jones
Publications and source records attributed to D R Jones.
Autoantibodies in pet dogs owned by patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) occurs in human beings and in dogs. There is evidence to suggest that the disease is caused by a transmissible factor that may cross the species barrier. We investigated this possibility by looking for autoantibodies and serum protein abnormalities in serum samples from 15 pet dogs owned by patients with SLE and comparing results with those obtained with serum from 10 healthy dogs kept in a controlled environment and 9 dogs with autoimmune diseases. We used standard immunological assays modified for use with canine samples. Compared with the normal dogs, increased amounts of antibody to double-stranded DNA were found in serum from the SLE patients' dogs (median optical density [405 nm] = 0.117 vs 0.299; p = 0.0001), this latter amount being similar to that found in serum from the autoimmune group (0.201; p = 0.6). Abnormal serum protein electrophoresis patterns were found in samples from the autoimmune and SLE patients' dogs but not the normal dogs. These findings support the idea that exposure to common environmental factors or transmissible agents may have a role in causing SLE.
Animals↗
Comparison of POSSUM with APACHE II for prediction of outcome from a surgical high-dependency unit.
POSSUM and APACHE II scores from 117 consecutive admissions to a high-dependency unit after major surgery were correlated with 30-day morbidity and mortality rates. Thirteen patients (11 per cent) died and 59 (50 per cent) developed a postoperative complication. Receiver-operating characteristic curve analysis showed POSSUM to have good predictive value for mortality (area under curve 0.75) and morbidity (area under curve 0.82). APACHE II scores had a significantly inferior predictive value for mortality (area under curve 0.54) (P < 0.002). POSSUM was superior to APACHE II in prediction of mortality in patients admitted to a high-dependency unit after general surgery. Prediction of postoperative complications by POSSUM is accurate and may be useful for audit.
Adult↗
Growth cones and structural variation of synaptic end-bulbs in the cochlear nucleus of the adult cat brain.
To explore the potential for structural variation and new growth at the synapse, we studied the morphological patterns of the end-bulbs of cochlear nerve axons in adult cats by using rapid Golgi, reduced silver, and electron microscopic methods. Horseradish peroxidase labeling of these endings in the anterior division of the antroventral cochlear nucleus was produced by anterograde transport following injection into the cochlea. Three types of end-bulbs were distinguished, regardless of method: reticular, coalescent, and ringed forms, all synapsing on spherical bushy cells. The reticular variety corresponds to the classically described end-bulb and constitutes the majority in all regions of the tonotopic map. The ringed end-bulb, described here for the first time, forms an excitatory synaptic cuff around the base of a bushy cell's main dendrite; these endings were localized to the region receiving cochlear input in the 1-6 kHz range, which is used in vocalization. The coalescent ending forms a small fraction of the end-bulb population throughout the region studied. The findings raise the possibility of functional differences between these synaptic types. Growth cones and retraction clubs were present on most, if not all, of the end-bulbs in every adult cat studied. A systematic survey of the end-bulb patterns revealed a continuous gradient of variation, in which each synaptic type forms a distinct mode. These findings lead us to hypothesize that the end-bulbs are in a continual state of structural and functional flux. These endings should prove useful for studies on the modifiable properties of central synapses.
Animals↗
The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis.
We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.
Adult↗
Behavioral contagion in sibships.
A behavior is "contagious" if one person is more likely to exhibit it when a relevant other person has already done so. In this sense, behavioral contagion is commonly thought to contribute to many social problems, such as drug abuse and teenage promiscuity. In this paper we focus on behavioral contagion in sibships. Borrowing a model from the theory of contagious diseases, we show that contagion will cause prevalence to increase with sibship size. This model also allows us to estimate the magnitude of the contagious factor relative to non-contagious factors. Finally, we develop two statistical tests for the presence of contagion. Results are presented for participation in a skill-development program and four child-psychiatric conditions: neurosis, hyperactivity, somatization, and conduct disorder. Evidence is presented that program participation is probably contagious and conduct disorder possibly so. The other three child-psychiatric conditions are shown not to be contagious. Implications for research and practice are discussed.
Adolescent↗
The future of statistics and statisticians in European regulatory affairs.
Roles of statisticians in drug regulatory agencies include assessment of the adequacy of statistical aspects of the design of the programme of efficacy and safety studies, design of individual studies, data collection and quality assurance in each study, analysis of individual studies, interpretation of individual studies, and interpretation of results of the programme. These assessments should be made in collaboration with medical, pharmacological, and toxicological colleagues, and liaison with company statisticians before, during, and after submission of the application if the procedure is to be efficient. Recommendations for improving statistical quality of drug license applications and provision for their statistical review in Europe include: 1. Employment of more experienced, professional statistical assessors in both national and European Community (EC) regulatory authorities, with a wider group of supporting experts 2. Obligatory statistical coauthorship or validation of expert reports before submission of applications, and 3. Unified statistical guidelines for preparation of applications.
Drug and Narcotic Control↗
Oral contraceptive use and breast cancer risk: a meta-analysis of variations with age at diagnosis, parity and total duration of oral contraceptive use.
OBJECTIVE: To review published reports of risk of breast cancer with oral contraceptive use. DESIGN: Meta-analysis of study results, using regression techniques to explore the inter-study heterogeneity. SETTING: Twenty-seven epidemiological studies of breast cancer risk and oral contraceptive use published 1980-1989. MAIN OUTCOME MEASURES: Relative risk of breast cancer with oral contraceptive use; variations by age at diagnosis, parity, and total duration of use, and with study design characteristics. RESULTS: The overall relative risk estimate was 1.16 (95% CI 1.07-1.25) for the less than 45 years group, 1.21 (95% CI 0.99-1.47) for the nulliparous subgroup, and 1.27 (95% CI 1.12-1.44) for durations of use of more than 8 years. Source of subjects, their marital status, the type of study, data collection methods, matching for geographical area, the number of adjustment factors used in the study analysis, the country of study and the calendar period in which the study ended were all important explanatory factors for inter-study variation, but a substantial proportion of inter-study variation remained unexplained. CONCLUSIONS: These meta-analyses suggest that risk of breast cancer may be raised by around 20% in younger, nulliparous and long use duration subgroups of oral contraceptive users. Risk estimates appear to be influenced by several study design factors, which should be considered carefully in designing and reviewing future studies.
Age Factors↗
Can man's best friend provide clues to the aetiology of systemic lupus erythematosus?
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Animals↗
Baroreflex control of arterial blood pressure during involuntary diving in ducks (Anas platyrhynchos var.).
The dynamic role of arterial baroreceptors in control of mean arterial blood pressure (MAP), heart rate (HR), cardiac output (CO), hindlimb vascular (HLVR) and total peripheral (TPR) resistance responses to forced dives was investigated in acutely and chronically barodenervated ducks. To activate the baroreflex, the proximal end of one aortic nerve was stimulated electrically with bipolar electrodes that had been implanted under pentobarbital sodium anesthesia. Predive nerve stimulation caused CO to fall (by reducing HR; stroke volume remained constant), producing a decrease in MAP to half the prestimulation level. During diving (for 2.5-min periods) nerve stimulation did not affect HR and MAP after the first minute of submersion. Neither HLVR nor TPR contributed to the fall in MAP during aortic nerve stimulation before or during diving. The effects of nerve stimulation on HR and MAP were maintained to the end of dives in animals given 100% O2 to breathe before diving. In separate experiments, increasing arterial chemoreceptor input by perfusing one vascularly isolated carotid body with venous blood caused a reduction in the effects of aortic nerve stimulation on MAP. Arterial baroreceptors may thus act on HR to alter MAP early in the dive, but as the dive progresses the baroreflex is attenuated by an increase in peripheral chemoreceptor drive.
Animals↗
Metabolic responses to forced dives in Pekin duck measured by indirect calorimetry and 31P-MRS.
We tested the hypothesis that forced-dived ducks experience a reduction in metabolic rate during prolonged submergence. Unidirectionally ventilated conscious ducks were subjected to forced dives by temporarily stopping the airflow in the ventilation system and simultaneously filling a face mask with cold water. A typical cardiovascular response to submergence was observed: bradycardia and maintained arterial blood pressure. Phosphorylated metabolite concentrations in the pectoral muscle were measured noninvasively by phosphorus magnetic resonance spectroscopy (31P-MRS). ATP content was constant, and phosphocreatine was depleted via the creatine kinase reaction at a rate similar to the resting rate of ATP turnover, which was estimated to be 0.9 mumol.min-1 x g-1 in resting perfused pectoral muscle of pentobarbital-anesthetized ducks. Oxygen from myoglobin supplied at most 12% of the ATP required by the resting muscle during dives. Whole animal postdive excess oxygen consumption and blood lactic acid accumulation suggested that the shortfall in aerobic metabolism during forced dives was compensated by an increase in anaerobic metabolism.
Adenosine Triphosphate↗
Specificity of effect in psychiatric research.
In the last ten years the genes responsible for Huntington's disease and several other neurological disorders have been localized to specific chromosomes. Huntington's disease is now known to be caused by a gene on the short arm of chromosome 4. While these advances are welcome, they also pose a problem. All studies to date have been passive observational studies; none has been experimental. Arguably the most successful and significant attributions of cause in neurological history have been achieved by non experimental methods. This realization is somewhat disconcerting, considering that virtually all textbooks in epidemiology insist that true experiments (randomized trials) are the prime means of establishing cause. One cannot help but ask how these unauthorized successes were achieved. What are the principles of investigation that made them possible? In this paper we argue that the recent advances in neurological genetics, along with much else in human genetics, depend heavily on "specificity of effect." Just what this principle is and how it allows successful attribution of cause is explained. Various applications elsewhere in the medical and behavioural sciences and in psychiatry are discussed.
Chromosomes, Human, Pair 4↗
Blood flow distribution in submerged and surface-swimming ducks.
Observations that the response of the avian heart rate to submergence varies under different circumstances have led to speculation about variability of blood flow distribution during voluntary dives. We used a radiological imaging technique to examine the patterns of circulating blood flow in captive redhead ducks (Aythya americana) during rest, swimming, escape dives, forced dives and trapped escape dives and have shown that blood flow distribution in escape dives was the same as that in ducks swimming at the water surface. The response during trapped escape dives, however, was highly variable. Blood pressure was unchanged from the resting value during all activities. Predictions made about blood flow distribution during unrestrained dives on the basis of heart rate and other indirect data were confirmed in this study. However, the trapped escape dive responses indicated that heart rate alone is not always a reliable indicator of tissue blood flow in exercising ducks.
Animals↗
Anniversary congratulations.
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Aerospace Medicine↗
Meta-analysis of observational epidemiological studies: a review.
Meta-analyses (integration of findings by quantitative analyses of results of individual studies) are already widely used in the psychological and educational sciences and in the pooling of clinical trial results. Examples of the application of such techniques to the results of observational epidemiological studies are now proliferating. In this paper meta-analysis of the results of observational epidemiological studies is reviewed. Uncritical adoption of techniques used in pooled analyses of clinical trial results may be inappropriate. Some alternative approaches, including meta-regression techniques, are discussed, and illustrated with reference to examples of meta-analyses of studies of breast cancer risk following oral contraceptive use and of patterns of post-bereavement mortality. Although substantial difficulties beset the use of meta-analysis in epidemiology, many of these problems are also implicit in the execution of traditional, narrative reviews. Foremost among these difficulties are those associated with publication bias and with making due allowance for the quality of the studies being combined. Unlike traditional narrative reviews, meta-analyses require explicit statement of the criteria for the review and hence highlight these difficulties. Nonetheless, careful and critical application of appropriate meta-analytical techniques facilitates quantitative exploration of inhomogeneities in, and (where appropriate) synthesis of study results.
Epidemiologic Methods↗
Use of a direct enzyme-linked antiglobulin test for laboratory diagnosis of immune-mediated hemolytic anemia in dogs.
Detection of autoantibody, complement, or both bound to RBC is an essential requirement for unequivocal diagnosis of immune-mediated hemolytic anemia in dogs. An enzyme-linked antiglobulin test was adapted for laboratory diagnosis of this disease. The refinement and routine use of this assay have allowed further observation of the pathogenesis of the disease process. In particular, degree of hemolysis can be related to the degree of RBC sensitization associated with primary immune-mediated hemolytic anemia, and this correlation is highest for IgG autoantibody. Results indicate that autoantibody isotype might have an important role in the hemolytic process.
Anemia, Hemolytic, Autoimmune↗
Corporate Angel Network: everybody wins!
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Aircraft↗
Giant, benign, mucinous cystadenoma of the ovary: case study and literature review.
Benign, mucinous cystadenomas account for 15 per cent of all ovarian neoplasms. Of these, the giant variant occurs rarely. A morbidly obese, 52-year-old, white woman was seen for acute abdominal pain and diagnosed using computerized tomography as having a giant, benign, mucinous cystadenoma. At laparotomy, 21-kg cystic mass attached to the right ovary was removed. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. In such patients, special consideration must be given to hemodynamic and ventilatory monitoring and intraoperative fluid management. Recognition and subsequent surgical management of this and other large abdominal masses can be optimized by thoughtful, preoperative evaluation and careful planning of the operative approach.
Cystadenoma↗