Topological time-series analysis of a string experiment and its synchronized model.
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Journal Article↗
Biomedical subjects
R Brown
Publications and source records attributed to R Brown.
Symbol sequence statistics in noisy chaotic signal reconstruction.
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Journal Article↗
Idiotypic oligonucleotide probes to detect myeloma cells by mRNA in situ hybridization.
An mRNA in situ hybridization (ISH) method which used non-radioactive idiotypic oligonucleotide probes has been used to detect malignant cells in the bone marrow and peripheral blood of patients with multiple myeloma. For each of two patients with multiple myeloma a pair of biotinylated antisense oligonucleotide probes (18-22mer) was prepared from non-germline sequences of the rear-ranged immunoglobulin heavy chain (IgH) gene. These oligonucleotide sequences were not homologous with any previously published sequence. The probes from each patient were specific as shown by a failure to hybridize to any cells from six other myeloma patients and four normal individuals. Specific staining of IgH gene mRNA occurred only when the myeloma cells and the sequence of the probe used were from the same patient. Using simultaneous fluorescent immunocytochemistry it was shown that more than 95% of the ISH-positive cells expressed the malignant light chain in their cytoplasm. ISH positive cells were found in 1-4% of the peripheral blood mononuclear fraction of these two patients. These studies show that idiotypic oligonucleotide IgH gene probes can be used to identify individual cells belonging to the malignant clone and offer the possibility of developing innovative tumour-specific therapeutic procedures using antisense technology for patients with myeloma.
Base Sequence↗
Digital blood flow response to body warming, cooling, and rewarming in patients with Raynaud's phenomenon.
Although the diagnosis of Raynaud's phenomenon (RP) is usually made easily from a careful history, the assessment of RP severity is difficult, for the vasopastic attacks are not easily induced under experimental conditions. In this study, the laser Doppler flowmetry (LDF) technique was used to quantify digital blood flow, which was standardized by body cooling and warming in patients with RP. Twenty-one healthy subjects and 56 RP patients were studied: 7 had primary RP, 22 had suspected secondary Raynaud's syndrome (susp RS), and 27 had systemic sclerosis (SSc)-associated secondary Raynaud's syndrome (SSc RS). The inherent variability in the acral cutaneous circulation was minimized by whole-body warming and cooling. Digital blood flow values at environmental temperatures of 40 degrees C, 12 degrees C, and after rewarming, to 40 degrees C were recorded, as was the time taken for blood flow to reach 25%, 50%, and 75% of the full effects of whole-body cooling and rewarming. Patients with primary RP and susp RS had normal blood flow values at ambient temperatures of 40 degrees C, 12 degrees C, and after rewarming to 40 degrees C when compared with controls, but they had significantly faster vasoconstrictor responses to whole-body cooling, suggesting a heightened sympathetic activity. Additionally, they had slower vasodilator responses with longer 25%max response time to whole-body rewarming. Patients with SSc RS had significantly lower blood flow values at 40 degrees C after initial warming and following subsequent rewarming, and despite a normal vasoconstrictor response to cooling, it took longer for them to vasodilate during rewarming, suggesting that poor digital blood flow in these patients may be more related to digital vasculature abnormalities and not an increase in sympathetic activity. In conclusion, our assessment technique can be used to quantify digital blood flow in patients with RP and may be potentially useful in the investigation of the etiologic role of the sympathetic nervous system in RP.
Adult↗
Health education intervention strategies: recommendations for future research.
While the ultimate goal of health education interventions is to positively influence health status, more proximal indicators of success are changes in intermediate outcomes, or impact. Because health education interventions work through intermediate outcomes, the linkage to health status is often assumed to be at a conceptual or theoretical level. The term health education intervention strategy is a heuristic device used to conceptualize and organize a large variety of activities. There is a wide range of studies and reports in the literature that either test specific intervention strategies or report on larger health education efforts combining several strategies. This article organizes the discussion to focus on individual-, community-, and policy-level interventions. Mass communications are also considered, and the authors comment on program planning issues that cut across specific interventions at the individual, community, and policy levels. Eleven recommendations are offered for future health education intervention research.
Community Health Services↗
The avian lung: is there an aerodynamic expiratory valve?
The unidirectional gas-flow pattern through the avian lung is thought to result from 'aerodynamic valves'; support for this hypothesis lies mainly in the failure to find any evidence for anatomical valves. During expiration, air flows from the caudal air sacs through the major exchange area of the lung, the paleopulmonic parabronchi, instead of bypassing the lungs via the intrapulmonary bronchus. We tested whether the effectiveness of this expiratory flow control mechanism depends on aerodynamic factors, especially convective inertial forces that depend on gas density and flow velocity. In pump-ventilated, anaesthetized geese, a bolus of tracer gas was introduced into both the right and left caudal thoracic air sacs during an end-inspiratory pause. During the first expiration, the rise of tracer levels within the caudal trachea was measured. Valve efficacy was positively correlated with the rate of expiratory gas flow, V·ao (range 8­200 ml s-1). At flows assumed to occur during exercise in geese (V·ao>100 ml s-1), the expiratory valve efficacy was approximately 95 %; it was less effective at lower flows. Surprisingly, the density (rho) of the background gas (rho of He/O2=0.43 g l-1, Ar/O2=1.72 g l-1 or SF6/O2=5.50 g l-1) had no effect on expiratory valving. We suggest two possible mechanisms that might explain this unusual combination of flow dependence without density dependence. (1) If airway geometry changes occurred between experiments with different gases, flow in the vicinity of the expiratory valve may have varied independently from flow measured at the airway opening. (2) Alternatively, valving may depend on dynamic compression of the intrapulmonary bronchus, which could depend mainly on viscous resistance and thus on flow velocity but not gas density.
Journal Article↗
Use of monoclonal antibodies in immunoelectron microscopy.
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Animals↗
Cholesterol-related health behaviors in rural elderly persons.
1. Hypercholesterolemia in the elderly is a major risk factor for cardiovascular disease. 2. Elderly subjects were found to be concerned about their cholesterol, but awareness of beneficial cholesterol reduction strategies and desirable cholesterol levels were low. 3. Major concerns for the rural elder are accessibility to cholesterol screening, explanation of the results of screening, and education about dietary interventions. 4. Nurses developing health promotion programs for rural elders need to incorporate methods which promote accessibility to screening and follow-up, understandable written information, and family support.
Aged↗
Effect of increased intra-abdominal pressure on hepatic extraction and clearance of fentanyl in neonatal lambs.
Fentanyl, an opioid metabolized by hepatic mixed function oxidases, is commonly administered as the primary anesthetic for neonates undergoing surgery. Pharmacokinetic studies have suggested that abdominal surgery in neonates decreases fentanyl clearance, contending that this results from increases in intra-abdominal pressure (IAP) decreasing hepatic blood flow. To examine the effects of IAP on hepatic blood flow and fentanyl clearance, we infused fentanyl to eight neonatal lambs, measured regional blood flows by using the radionuclide-labeled microsphere technique and determined hepatic fentanyl extraction and clearance and hepatic oxygen extraction and consumption at three levels of IAP: 0, 12 and 18 mm Hg. Increased IAP did not affect portal or hepatic blood flow or ductus venosus shunt. Fentanyl extraction was 16.5 +/- 3.0% (mean +/- S.E.) at 0 mm Hg of IAP. Increased IAP decreased hepatic extraction of fentanyl, thereby decreasing fentanyl clearance. Increased IAP did not affect hepatic oxygen extraction or consumption. In two additional animals in which serial measurements of hepatic blood flow were obtained, increased IAP (15 mm Hg) transiently decreased hepatic blood flow with recovery to control values at 2 hr. The authors conclude that fentanyl is poorly extracted by neonatal livers, in contrast to its large extraction ratio in adults. The decrease in fentanyl clearance with increased IAP is consistent with pharmacokinetic studies demonstrating decreased clearance in neonates undergoing abdominal surgery. However, the present study suggests that the mechanism of decreased clearance is decreased hepatic function (decreased fentanyl extraction) rather than decreased hepatic blood flow.
Abdomen↗
The application of an anthropometric database of elderly and disabled people.
We report on the development of an anthropometric database of elderly and disabled people for use by designers. The problems encountered by the designer in developing products for the elderly and disabled are highlighted. Reference is made to previous work carried out using computer modelling to simulate the human product interface, and the problems in specifying the anthropometric data are discussed. From a review of existing anthropometric databases we have noted the lack of data on the elderly and disabled. Not only is there insufficient dynamic anthropometric data available, but there are no standards for the measurement techniques to produce this data. We report briefly on parallel work by the group which is looking at anthropometric measurement techniques, and the computer modelling of the human product interface for elderly and disabled people. The lack of dynamic anthropometric data that is appropriate for use by designers and rehabilitation engineers is the major area to be addressed by the database. We investigate the use of existing medical data available as a possible solution to the problem. The database will also seek to address the problem through its methodology of interpretation and presentation.
Aged↗
Techniques in anthropometry applied to disabled and elderly populations.
We discuss the requirements of anthropometric and biomechanical data for specific application to the design of assistive devices and other products for elderly and disabled populations, including body size, shape, range of motion and strength data. We analyse available information and the practical and statistical problems involved in the collection of data from such populations. We comment on the different human interface design issues posed by various types of device and compare a task-specific approach to ergonomic analysis with the use of a generic biomechanical database. The specific requirements of a useful biomechanical data collection system intended to fulfil this need, and the conditions under which a practical system would have to operate are discussed. We review a range of available measurement techniques, including manual, mechanical, optical and electronic systems and discuss their relative fitness for the task in question. We propose an approach to the collection of multi-variable biomechanical data from the analysis of various tasks and discuss the use of computer models and other means of interpreting such data to make it available to product designers and engineers.
Aged↗
Depression in Parkinson's disease: a psychosocial viewpoint.
We started this chapter by examining a simple psychological model that depression was a straightforward reaction to the severity of the physical impairment of Parkinson's disease, and that the relationship between the two factors was essentially linear. Because of the progressive nature of the disease, it followed that any such relationship would also be reflected in factors such as stage of illness and duration. As seen, however, the data have consistently failed to support such a simple reactive model. Examining the equivalent literature on other physical disorders revealed a remarkably similar picture suggesting that the model is largely inadequate in general, as well as in relation to Parkinson's disease. This inadequacy, however, should not be taken as evidence that psychological factors are unimportant. Rather, it suggests only that we need a more comprehensive model linking chronic disabling illness and depression. One revision suggested by the evidence was to consider nonlinear relationships, for example, between depression and stage of illness. Adopting a broader perspective, one may suppose that the risk of depression may change over the course of disease progression. For example, at the very beginning, diagnosis and the process of coming to terms with the fact of having a progressive and disabling illness may be sufficient to cause depression. Later in the course of the illness, progressive deterioration and increasing dependency may once again provoke depression. At any stage, a rapid deterioration (from whatever level) or the development or worsening of treatment complications may cause fresh concerns and require a fresh period of adjustment. Although the depression may be similar in each of these cases, the mediating psychological factor is different. In between these times, the individual may adapt to the illness and its consequences and show less vulnerability to depression. A further modification of the model is to consider the influence of multiple factors. While any one factor may individually predict depression only weakly, in combination, they may explain the observed pattern of depression more accurately. Although little evidence is available, there is the suggestion that a combination of physical and psychological factors may provide a clearer picture of depression severity. The final, major modification suggested is to view the broad consequences of the physical disease, rather than the severity of the symptoms themselves.(ABSTRACT TRUNCATED AT 400 WORDS)
Activities of Daily Living↗
Rectal thiopental sodium for sedation of pediatric patients undergoing MR and other imaging studies.
PURPOSE: To determine the efficacy and safety of rectal thiopental sodium as a sedation agent for pediatric imaging. METHODS: Four hundred sixty-two infants and children were sedated with rectal thiopental sodium for MR, CT, or nuclear imaging in 1992 and 1993. Patients received screening histories and physical examinations before sedation, and parents gave informed consent. Sedated patients were monitored by pulse oximetry and direct observation. Twenty-four-hour telephone follow-up to assess delayed side effects was performed successfully in 325 patients. RESULTS: Examinations were successfully completed in 96% of patients. The average time from drug administration to sedation was 12.2 minutes. The average time from sedation to discharge from radiology was 71.1 minutes. Eleven percent of patients had desaturation below the pulse oximetric baseline easily treated with oxygen and head positioning. Twenty-four-hour telephone follow-up in 325 patients revealed a 34% incidence of minor rectal irritation and diarrhea, sleepiness, nausea and vomiting, or ataxia. CONCLUSIONS: Rectal thiopental sodium is a safe and effective drug for pediatric sedation.
Administration, Rectal↗
Organization, management, and client effects on staff burnout.
Employee burnout is perceived to be a serious problem in human service organizations serving persons with severe mental illness. There has been considerable investigation of burnout and many of its possible causes, but little investigation of the role of client severity in relationship to burnout. Furthermore, theoretical models linking environmental context, organization structure, and management processes to burnout have seldom been proposed or examined. Building on our previous work, we employ a theoretical framework that conceptualizes environmental context, organization structure, management processes, client severity and staff characteristics as influencing work satisfaction and burnout. We examine this in a survey of 311 staff in 42 community mental health service organizations. Controlling for individual staff characteristics, results suggest that organization structure, culture, and management process are important to work environment and in turn to satisfaction and subsequently to burnout. Contrary to the literature, client severity was not associated with burnout nor to work dissatisfaction.
Burnout, Professional↗
Topoisomerase I and II activity in human breast, cervix, lung and colon cancer.
The identification of human DNA topoisomerases as cellular targets for active anti-cancer drugs has stimulated further interest in topoisomerase function in tumour biology. Topoisomerase I and II catalytic activity is detectable in many normal and malignant tissues. However, little is known about the expression of topoisomerases in most human solid tumours. The present study evaluated topoisomerase I and II activity in biopsy samples from 86 patients with breast, lung, cervix or colon cancers. Significant intra- and inter-tumour variation in topoisomerase expression was observed. Topoisomerase I activity was relatively high in cervix and colon tumours in comparison to lung and breast cancers. Topoisomerase II activity was high in cervix, colon and lung cancers relative to breast cancer. Topoisomerase I and II activity co-segregated in individual colon tumour samples, but no correlation was observed in cervix, lung or breast tumours. The large heterogeneity in both topoisomerase I and II activity within a tumour type suggests a mechanism for variable response to topoisomerase-directed therapy. The differences in activity between tumour groups suggest that the potential efficacy of inhibitors of topoisomerase I in colon and cervical tumours may be greater than in lung and breast tumours. Future in vivo evaluation is required to establish the clinical relevance of the observed heterogeneity in topoisomerase activity.
Breast Neoplasms↗
Cell cycle arrests and radiosensitivity of human tumor cell lines: dependence on wild-type p53 for radiosensitivity.
Loss of p53 function has been shown to cause increased resistance to ionizing radiation in normal murine cells; however, the role of p53 in radioresistance of human tumor cells is less clear. Since wild-type p53 function is required for radiation-induced G1 arrest, we measured G1 arrest in 12 human tumor cell lines that have a wide range of radiosensitivities (surviving fraction at 2 Gy, 0.11-0.8). We observed a significant correlation between the level of ionizing radiation-induced G1 arrest and radiosensitivity. Cell lines having G1 arrest are more radiosensitive. There is no correlation between maximal G2 arrest and radiosensitivity. Expression of a dominant-negative mutant of p53 (codon 143, Val to Ala) in transfectants of the radiosensitive human ovarian cell line A2780 abrogates the radiation-induced G1 arrest. Such mutant p53 transfectants are more resistant to ionizing radiation than the parental line and vector-alone transfectants, as measured by clonogenic assays. These results support the concept that wild-type p53 function is required for sensitivity of tumor cells to DNA-damaging agents, such as ionizing radiation, and that the loss of p53 function in certain human tumor cells can lead to resistance to ionizing radiation.
G1 Phase↗
Arrest of preterm labour and prolongation of gestation with glyceryl trinitrate, a nitric oxide donor.
13 women admitted consecutively in preterm labour were recruited to an observational study of the effect of glyceryl trinitrate (GTN) patches on uterine contractions and prolongation of pregnancy. All twenty episodes of preterm labour (at 23-33 weeks' gestation) responded. 1 patient delivered because of cervical incompetence despite cessation of uterine contractions. The mean prolongation of pregnancy was 34 days. 8 babies have been born so far, and are progressing well. GTN patches appear to be a safe, well-tolerated, and non-invasive method of suppressing uterine contractions in preterm labour.
Administration, Cutaneous↗