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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 181 records · Page 10Linked to original sources
PubMed2000

Hypercapnia can induce arousal from sleep in the absence of altered respiratory mechanoreception.

Possible mechanisms of arousal from respiratory stimuli include changes in PO(2), PCO(2), central respiratory drive, or respiratory mechanoreceptor activity. We sought to determine whether hypercapnia alone could induce arousal from sleep in four subjects with high (>/= C3) neurologically complete spinal cord injuries while on constant positive pressure mechanical ventilation (hence, respiratory mechanoreceptor activity remained constant). Subjects were chronically hypocapnic (mean baseline PET(CO(2)) = 21 mm Hg; range, 13-30 mm Hg). On the first night, the baseline rate of spontaneous awakenings was determined by polysomnography. On night two, FI(CO(2)) was increased rapidly in stable NREM sleep. Awakenings occurred in 19 of 19 trials within 5 min, with each subject waking and complaining of shortness of breath (mean time to arousal, 115 s; range, 26-264 s). It is unlikely that these were spontaneous, as the times to awakening during hypercapnia were much higher than during baseline conditions (p < 0.05). During rapidly induced hypercapnia, PET(CO(2)) overestimates the PCO(2) at the central chemoreceptors. To determine more precisely the PET(CO(2)) arousal threshold, PET(CO(2)) was increased slowly (approximately 2 mm Hg/min); arousal occurred at a mean PET(CO(2)) of 37 mm Hg (range, 23-45 mm Hg; mean change from baseline, 15.8 mm Hg, range, 10-20 mm Hg). Hence, both rapid and slow increases in PET(CO(2)) can induce arousal in humans in the absence of changes in respiratory mechanoreceptor activity.

Adult↗
PubMed2000

Reduced MLH1 expression in breast tumors after primary chemotherapy predicts disease-free survival.

PURPOSE: Loss of function or expression of the mismatch repair protein MLH1 and the tumor suppressor protein p53 have been implicated in acquired resistance to anticancer drugs. We have compared the expression of MLH1 and p53 in tumors from women with clinically node-positive breast cancer before and after primary (neoadjuvant) chemotherapy. Further, we have assessed the value of these markers as predictors of response to therapy by correlation with disease-free survival. PATIENTS AND METHODS: Immunohistochemistry scores of MLH1 and p53 expression were made on 36 tru-cut prechemotherapy biopsies and 29 paired postchemotherapy tumor samples. The significance of the change in scores and their correlation with disease-free survival were evaluated by the Wilcoxon signed rank sum test and Cox proportional hazards regression analysis, respectively. RESULTS: Primary chemotherapy results in a significant reduction in the percent of cells expressing MLH1 (P =.010). This change in MLH1 expression after chemotherapy is strongly associated with poor disease-free survival (P =.0025). Expression of p53 was not significantly altered by chemotherapy. Neither MLH1 nor p53 expression before chemotherapy predicted disease-free survival or tumor response to chemotherapy. Low MLH1 expression after chemotherapy was an independent predictor of poor disease-free survival on multivariate Cox analysis when considered with other clinicopathologic prognostic factors. CONCLUSION: Tumor cells that have reduced MLH1 expression seem to have a survival advantage during combined chemotherapy of locally advanced breast cancers, which supports the hypothesis that loss of MLH1 has a role in drug resistance. MLH1 expression after chemotherapy is an independent predictive factor for poor disease-free survival and may, therefore, define a group of patients with drug-resistant breast cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia.

The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.

Adult↗
PubMed2000

An investigation of three-dimensional scanning of human body surfaces and its use in the design and manufacture of prostheses.

The capture of highly accurate data describing the complex surfaces of the human body may prove extremely useful in many medical situations. The data provide a method of measuring and recording changes to the surface of a patient's soft tissue. The data may be applied to computer-controlled manufacturing techniques, such as rapid prototyping (RP). This enables accurate physical replicas of the patient topography to be produced. Such models may be used as an aid in the design and manufacture of prostheses. This paper describes an investigation aimed at identifying problems that may be encountered when scanning patients and describes the application of the resulting data in the design and manufacture of facial prostheses. The results of the experiment are presented together with a discussion of the accuracy and potential advantages afforded by this approach.

Biocompatible Materials↗
PubMed2000

Ecological risk assessment of endocrine disruptors.

The European Centre for Ecotoxicology and Toxicology of Chemicals proposes a tiered approach for the ecological risk assessment of endocrine disruptors, integrating exposure and hazard (effects) characterization. Exposure assessment for endocrine disruptors should direct specific tests for wildlife species, placing hazard data into a risk assessment context. Supplementing the suite of mammalian screens now under Organization for Economic Cooperation and Development (OECD) validation, high priority should be given to developing a fish screening assay for detecting endocrine activity in oviparous species. Taking into account both exposure characterization and alerts from endocrine screening, higher tier tests are also a priority for defining adverse effects. We propose that in vivo mammalian and fish assays provide a comprehensive screening battery for diverse hormonal functions (including androgen, estrogen, and thyroid hormone), whereas Amphibia should be considered at higher tiers if there are exposure concerns. Higher tier endocrine-disruptor testing should include fish development and fish reproduction tests, whereas a full life-cycle test could be subsequently used to refine aquatic risk assessments when necessary. For avian risk assessment, the new OECD Japanese quail reproduction test guideline provides a valuable basis for developing a test to detecting endocrine-mediated reproductive effects; this species could be used, where necessary, for an avian life-cycle test. For aquatic and terrestrial invertebrates, data from existing developmental and reproductive tests remain of high value for ecological risk assessment. High priority should be given to research into comparative endocrine physiology of invertebrates to support data extrapolation to this diverse fauna.

Amphibians↗
PubMed2000

Effects of different forms of school contact on children's attitudes toward disabled and non-disabled peers.

BACKGROUND: There have been fluctuations in research interest into the inclusion of children with disabilities in mainstream schools over the last twenty years. It is still not clear what methods, practices and types of contact are most likely to promote positive attitudes in children toward disabled peers and disability generally. AIMS: To consider two theoretical models of inter-group contact, both claiming to identify precursors for generalised attitude change, in relation to the attitudes of non-disabled children toward disabled peers as a function of different classroom contact. SAMPLE: Participants were 256 non-disabled school children aged 5-11 years (128 girls and 128 boys). METHODS: Measures of sociometric preference and the evaluation of psychological and physical attributes were used to ascertain children's perceptions of known and unknown peers with disabilities. RESULTS: A relationship was found between the type of contact the children had with disabled peers, and their perceptions of psychological and physical attributes (stereotypes) of groups of unknown disabled and non-disabled peers. CONCLUSIONS: Results show generalisation of stereotypic attitude/judgments from one type of disability to another as a consequence of the two types of contact situation. Findings have important implications for integrating disabled children into mainstream.

Attitude↗
PubMed2000

Function and composition of pulmonary surfactant and surfactant-derived fatty acid profiles are altered in young adults with cystic fibrosis.

STUDY OBJECTIVES: To determine whether chronic lung inflammation in young adult patients with cystic fibrosis (CF) alters the composition and function of surfactant and surfactant components in bronchoalveolar secretions. DESIGN: A prospective, descriptive study. SETTING: An adult CF center in a tertiary health-care center. PARTICIPANTS: Thirteen normal volunteer (NV) subjects recruited via local advertising and 15 CF patients recruited from the CF center. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We performed BAL and measured surfactant-associated protein A (SP-A) via enzyme-linked immunosorbent assay in BAL fluid (BALF), and quantitated total phospholipid, phospholipid subclass, and fatty acid subclass content of extracted BALF. We also determined the protein and phospholipid content, SP-A content, and functional characteristics of surfactant isolated from BALF via high-speed centrifugation. The phospholipid-to-protein ratio (milligram/milligram) of surfactant isolated by centrifugation (mean +/- SEM) was 1.01 +/- 0.07 for NV subjects and 2.62 +/- 0.42 for CF patients (p = 0.0001). Minimal surface tension was < 1 dyne.s.cm(-5) in all samples from NV subjects, but 21.9 +/- 0.73 dyne.s.cm(-5) for surfactant from CF patients. Immunoblotting of isolated surfactant revealed a marked decrease in SP-A for CF patients, compared to NV subjects. However, mean concentrations of SP-A in BALF that had not been subjected to high-speed centrifugation to isolate surfactant were not significantly different for CF patients (4.7 +/- 0.8 microgram/mL) vs NV subjects (4.6 +/- 0.2 microgram/mL). Additionally, phospholipid-to-protein ratios (0.32 +/- 0.04 for NV subjects vs 0.10 +/- 0.02 for CF patients; p < 0.0001) in extracted uncentrifuged BALF, and SP-A-to-protein ratios (microgram/milligram) in BALF were significantly depressed (74 +/- 8 for NV subjects vs 16 +/- 3 for CF patients; p < 0.0001). The phospholipid and fatty acid subclass profiles of extracted CF BALF vs NV BALF revealed a decreased mean phosphatidylcholine-to-sphingomyelin ratio (20.7 +/- 10.0 vs 55.2 +/- 8.7; p = 0.002), increased oleic acid content (12.1 +/- 2.3 nmol/mL vs 3.2 +/- 0.9 nmol/mL; p < 0.01), and increased arachidonic acid content (2.2 +/- 0.5 nmol/mL vs 0.6 +/- 0.3 nmol/mL; p < 0.05) for CF patients. CONCLUSIONS: Altered phospholipid-to-protein ratios and phospholipid subclasses, altered surfactant-derived fatty acid profiles, high minimal surface tension, and decreased association of SP-A with lipid components of isolated surfactant indicate that surfactant components are considerably altered and dysfunctional in lower respiratory tract secretions of CF patients. Surfactant composition and function are altered in CF, and the pattern of phospholipid and surfactant-derived fatty acid subclass alterations in CF are characteristic of ongoing lung injury and may depress surfactant function.

Adult↗
PubMed2000

Randomized trials of dichlorphenamide in the periodic paralyses. Working Group on Periodic Paralysis.

Although the carbonic anhydrase inhibitors have been used in the treatment of the primary periodic paralyses (PPs), their efficacy has not been demonstrated in double-blind, placebo-controlled trials. Therefore, we tested the efficacy of dichlorphenamide (DCP; Daranide), a potent carbonic anhydrase inhibitor, in the treatment of episodic weakness in the primary PPs. We performed two multicenter, randomized, double-blind, placebo-controlled crossover trials, one involving 42 subjects with hypokalemic periodic paralysis (HypoPP) and the other involving 31 subjects with potassium-sensitive periodic paralysis (PSPP). In each trial, two 8-week treatment periods were separated by an active washout period of at least 9 weeks. The primary outcome variable in the HypoPP trial was the occurrence of an intolerable increase in attack severity or frequency (end point). The primary outcome variable in the PSPP trial was the number of attacks per week. In the HypoPP trial, there were 13 subjects who exhibited a preference (in terms of the end point) for either DCP or placebo, and 11 of these preferred DCP. In the PSPP trial, DCP significantly reduced attack rates relative to placebo. DCP also significantly reduced attack rates relative to placebo in the HypoPP subjects. We conclude that DCP is effective in the prevention of episodic weakness in both HypoPP and PSPP.

Adolescent↗
PubMed2000

Lipid profiles of obese children and adolescents before and after significant weight loss: differences according to sex.

BACKGROUND: Childhood obesity has been associated with elevated serum levels of total cholesterol, triglycerides, and low-density lipoproteins (LDLs). We observed the lipid profiles of obese female subjects versus obese male subjects before and after significant weight loss. METHODS: We studied 29 girls and 21 boys enrolled in a multidisciplinary weight reduction program. RESULTS: Measures were taken at enrollment and at 10 weeks. Significant improvements were observed for changes in percentage of ideal body weight and total cholesterol and triglyceride levels. In addition, LDL decreased significantly in girls but not in boys. CONCLUSIONS: A combination of diet, behavior modification, and exercise, is an effective instrument for lowering total cholesterol and triglyceride levels in obese children. In addition, girls tend to be more susceptible to a decrease in LDL level, which might result in an increased cardiovascular protective effect.

Adolescent↗
PubMed2000

Optimal design of connectivity in neural network training.

Many authors consider neural network (NN) supervised training as an optimization process during which the weights are iteratively adjusted in order to minimise an error (cost) function, which represents the difference between the obtained and the aimed output. The error function surface is usually nonconvex, can be highly convoluted, with many plateaux and long narrow troughs, and can encounter many saddle and local minima (LM) points. Because backpropagation (BP), which is widely used method for supervised learning, uses local methods for optimization, it can get stuck in LM. This can make learning very difficult and sometimes its convergence to optimal solution--not possible. In this paper we propose a stochastic method for global optimization (GO), which make use of a uniformly distributed LP tau sequence of points. The developed technique is tested with common benchmark problems and used for neural network supervised learning. The conducted tests show that the proposed method can be successfully used for an optimal supervised training of small size NN.

Neural Networks, Computer↗
PubMed2000

The application of computer aided product development techniques in medical modelling topic: rehabilitation and prostheses.

When considering reconstructive surgery it is often difficult to ascertain the exact nature of affected internal anatomy. Although advances in Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) have enabled the generation of 3D reconstructions of internal anatomy, they are often only available as fixed 2D images. These may obscure important details or prove ambiguous depending upon the angle of view. Another problem is maintaining accuracy of reconstruction that may involve osteotomy, tissue grafts or implants. In such circumstances the ability to plan and rehearse complex procedures can prove invaluable, greatly improving surgical results whilst helping to eliminate potential errors and reducing theatre time. In this context 3D scan data can be treated as the equivalent of Computer Aided Design (CAD) data and can be applied to the production of accurate physical models. The approach undertaken by the DERC is based on close collaboration with surgical departments and enables the rapid and economic production of medical models based on CT/MRI data. This paper illustrates the transfer of product design technologies into a clinical context. Specifically, the use of 3D surface scanning and rapid prototyping technologies as an aid to post operative reconstruction is described. An evaluation of the application of product development tools within a clinical context is presented. The paper concludes with an assessment of likely future application in this area.

Computer-Aided Design↗
PubMed2000

Describing a model of nursing as a focus for psychiatric nursing care.

This thesis would not be complete in it's review of Psychiatric nursing and Psychiatric nurse education, without reference to one of the fundamental changes that is occurring in nursing. One of the major changes that had occurred in recent years has been in the focus of nursing management nurses are placing much more emphasis on nursing diagnosis and nursing theories and are detaching from the more traditional medical model when planning nursing care. This movement towards a greater autonomy in planning their nursing care is assisting nurses in becoming a professional and independent group. Nurses are establishing a body of knowledge and skills which may be called "nursing science". Through the use of nursing models for planning patient and health care, nurses are offering a better service to the individual and the community. These changes in the focus of care commenced in the 1950's within the United States with the introduction of nursing models and theories. The Philosophies and concepts of these theories have outlined various methods and ways that the nurse could better plan and organize their professional work, including patient assessment and care. As early as 1953 the term "nursing diagnosis" was introduced by Fray to describe a step in the organization of a nursing care plan. (1) The various nursing models and theories seemed to have coincided with the movement through the 1950's and 1960's within America towards more generic based integrated curricula.

Curriculum↗
PubMed1999

The bone marrow plasma cell labeling index by flow cytometry.

The bone marrow plasma cell labeling index is the most important prognostic indicator for patients with multiple myeloma. Traditionally, this test has been performed as a two color immunofluorescent microscope technique which is time consuming and requires a degree of subjectivity in its interpretation. We have assessed various adaptations of this method to flow cytometry. A bromodeoxyuridine method has been compared with a propidium iodide DNA method to detect cells in S phase and CD38-FITC has been compared with CD38-FITC + CD138-FITC and CD38-biotin + streptavidin FITC to identify plasma cells. The mean channel fluorescent intensity of the plasma cell peaks for each of these markers was 12. 7, 17.4 and 35.3 respectively demonstrating the superiority of CD38-biotin + streptavidin FITC. Analysis after propidium iodide staining provided a good correlation with the slide technique (r = 0. 71; P < 0.0001) but the bromodeoxyuridine method did not correlate with the slide method (r = 0.09; P = NS). The labeling index values obtained from either of the flow methods were greater than the microscopic method. Thus a labeling index of >4% will replace the traditional >1% threshold for identifying patients with a significantly increased labeling index. The advantages of the new method are that it takes less time to perform, is more objective and provides additional data on ploidy and cell cycle status.

ADP-ribosyl Cyclase↗
PubMed1999

Clinical relevance of the molecular mechanisms of resistance to anti-cancer drugs.

Resistance to anti-cancer drugs (drug resistance) can be defined in the laboratory by the amount of anti-cancer drug that is required to produce a given level of cell death (drug response). Clinical drug resistance can be defined either as a lack of reduction of the size of a tumour following chemotherapy or as the occurrence of clinical relapse after an initial 'positive' response to anti-tumour treatment. Many studies of tumour samples do not directly measure drug resistance in the laboratory (because it is difficult to perform functional assays on tumour tissue); instead, key proteins or genes that are involved in particular mechanisms of drug resistance have been proposed as 'markers' of drug resistance. In this review, we have focused on the problems that can arise when attempts are made to relate the relevance of laboratory-identified molecular mechanisms of drug resistance to anti-cancer drug resistance that occurs in patients.

Journal Article↗