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Biomedical subjects

A J Barton

Publications and source records attributed to A J Barton.

At least 19 recordsLinked to original sources

Pulmonary vascular resistance of children treated with nitrogen during early infancy.

BACKGROUND: We have empirically used supplemental nitrogen in newborns with a functional single ventricle and ductal-dependent systemic perfusion to prevent pulmonary vasodilation and deliver a greater proportion of flow to the systemic circulation. Thus, we reviewed patient outcome to determine whether adverse pulmonary vascular effects may be associated with this therapy. METHODS: From December 1991 to December 1995, the fraction of inspired oxygen was adjusted, with supplemental nitrogen if necessary, to maintain an oxygen saturation near 75% in 20 newborns awaiting heart transplantation. Medical records were reviewed to evaluate (1) the duration of nitrogen therapy, (2) pulmonary vascular histology, (3) postoperative pulmonary hemodynamics, and (4) survival. RESULTS: Thirteen patients underwent heart transplantation, 4 patients died without surgical intervention, and 3 patients underwent late aortic reconstruction. Supplemental nitrogen was used without exceeding a fraction of inspired oxygen of 0.21 for 38 +/- 6 days. One patient had evidence of changes of potentially irreversible pulmonary vascular disease. Pulmonary vascular resistance was not increased long-term in surviving patients. CONCLUSIONS: Supplemental nitrogen can be used to maintain a systemic oxygen saturation near 75% for an extended period in newborns with ductal-dependent systemic perfusion with no long-term adverse effect on pulmonary vascular resistance.

Administration, Inhalation↗

Improving patient outcomes through CQI: vascular access planning.

This article reports the use of the continuous quality improvement (CQI) process to improve patient outcomes. The FADE method (focus, analyze, develop, and execute) was used to focus on vascular access planning, analyze data concerning intravenous (i.v.) therapy, develop a vascular access planning algorithm, and execute implementation of the algorithm. An evaluation study revealed that patients whose vascular access planning was consistent with the algorithm reported fewer i.v.s, less difficulty starting i.v.s, and less stress; waited significantly less time until central venous line (CVL) placement (for those who received CVLs); and had significantly shorter lengths of stay.

Algorithms↗

Re-engineering intensive care: the role of informatics.

Managed care and quality improvement are two driving forces in the current health care environment. The pressure of capitation and the recent focus on outcomes of care have generated new incentives to restructure care delivery to control costs. Intensive care units, once revenue centers, are becoming cost centers. Re-engineering, or redesigning, the process of care entails examining premises for ability to provide services as well as considering how to do things more efficiently. The assumption is that all aspects of a process are legitimately subject to examination and restructuring. Information systems provide a powerful tool to support re-engineering. Nursing informatics, which pertains to nursing data, information, and knowledge has major implications for hospital information systems. This article explores possible changes in intensive care and the role of informatics in a changing health care environment.

Hospital Information Systems↗

Bacterial adhesion to orthopedic implant polymers.

The degradable polymers poly(orthoester) (POE), poly(L-lactic acid) (PLA), and the nondegradable polymers polysulfone (PSF), polyethylene (PE), and poly(ether ether ketone) (PEEK) were exposed to cultures of Staphylococcus epidermidis, Pseudomonas aeruginosa, or Escherichia coli. Bacteria washed and resuspended in phosphate buffered saline (PBS) adhered to polymers in amounts nearly twice those of bacteria that were left in their growth medium, tryptic soy broth (TSB). In TSB, there was variation in adhesion from species to species, but no significant variation from polymer to polymer within one species. In PBS there were significant differences in the amounts of bacteria adhering to the various polymers with the exception, of S. epidermidis, which had similar adhesion to all polymers. As a whole, P. aeruginosa was the most adherent while S. epidermidis was the least adherent. The estimated values of the free energy of adhesion (delta Fadh) correlated with the amount of adherent P. aeruginosa. When POE, PLA, and PSF were exposed to hyaluronic acid (HA) before exposure to the bacteria, there was 50% more adhesion of E. coli and P. aeruginosa on POE and PLA. With respect to bacterial adhesion, the biodegradable polymers (POE and PLA) in general were not significantly different from the nondegradable polymers.

Bacterial Adhesion↗

Measurement of bacterial growth rates on polymers.

A video microscope system and a mathematical model were developed to observe and model the early stage of bacterial growth on polymer surfaces. Glass slides were coated with polyorthoester, poly(L-lactic acid), and polysulfone, and inserted into a laminar flow cell to expose them to bacterial cultures of Staphylococcus epidermidis, Pseudomonas aeruginosa, or Escherichia coli. The free energy of adhesion (delta Fadh) was determined from contact-angle measurements. The microscopic observations along with the mathematical model allowed measurement of the rates of adhesion, release, and growth. The growth rate of P. aeruginosa on the various surfaces correlated to the delta Fadh. The growth rates of all species on all of the surfaces were slower than the growth rates of the bacteria in suspension. The mathematical model is valid for early growth before the bacteria form a complete monolayer, and is useful in predicting and modeling early growth of bacteria on implanted biomaterials.

Bacterial Adhesion↗

Alteration in brain presenilin 1 mRNA expression in early onset familial Alzheimer's disease.

The expression of the presenilin 1 (PS-1) gene has been investigated by in situ hybridization in early onset familial Alzheimer's disease (FAD), late onset Alzheimer's disease (AD) and normal control brain. Mutations in this gene are responsible for chromosome 14-linked FAD. We have found that presenilin 1 mRNA is present throughout the human brain with a distribution consistent with both a glial and neuronal localization. The in situ hybridization pattern was similar for the controls, the early onset FAD cases and the late onset AD cases. However, one of the two forms of the mRNA for PS-1, the long form (which contains a sequence encoding a four amino acid (VRSQ) insert at its 5' end) was significantly reduced in early onset FAD brain compared with late onset AD. We suggest that this long transcript may alter the normal pathway for processing of amyloid precursor protein, the protein which appears to be central in the pathogenesis of AD.

Adult↗

Presenilin-1 is processed into two major cleavage products in neuronal cell lines.

Presenilin-1 (PS-1) has been identified as the protein encoded by the chromosome 14 locus that, when mutated, leads to familial Alzheimer's disease (FAD). Using PS-1 transfected SHSY5Y neuroblastoma cells, we have demonstrated by immunodetection, using polyclonal antibodies, that PS-1 is processed to give two fragments: an N-terminal 28 kDa fragment, and a C-terminal 18 kDa fragment. In a number of non-transfected cell types, most PS-1 is detected as the cleaved products. The molecular weights of the PS-1 cleavage products suggest that the cleavage point will most probably be within a region of the hydrophilic loop domain coded for by either exon 8 or 9 of the PS-1 gene. The clustering of FAD mutations within exon 8 strongly suggests that it encodes a key functional domain. It seems likely that the cleavage of PS-1 is crucial to some aspect of its functionality. An understanding of this process will give insights into the pathology of AD, and may offer new opportunities for therapeutic intervention.

Amino Acid Sequence↗

The effects of Alzheimer's disease, other dementias, and premortem course on beta-amyloid precursor protein messenger RNA in frontal cortex.

There are conflicting data regarding alterations in beta-amyloid precursor protein (APP) mRNAs in Alzheimer's disease (AD). This may be due partly to variables such as agonal state and choice of control group. We have used in situ hybridization histochemistry to study expression of APP mRNAs, with and without the domain encoding the Kunitz protease inhibitor, in a way that overcomes some of the limitations of the current data. Tissue from frontal cortex was collected at rapid autopsy from patients with AD or other cognitive impairments whose terminal phase was prospectively assessed. There were three main findings. Firstly, the amount of APP mRNAs correlated strongly with glutamate decarboxylase activity and was reduced in association with terminal pyrexia. These correlations suggest that agonal state affects APP mRNA and, therefore, that differences in premortem course may contribute to the varying changes in APP transcript abundance reported in AD. Secondly, a reduction of both forms of APP mRNA, normalized to polyadenylated mRNA, was found in AD compared with normal controls and with non-AD dementias. This supports findings that the APP-related pathology of AD is not due to overexpression of APP mRNA or an altered proportion of Kunitz protease inhibitor-containing isoforms. Thirdly, the amount of APP mRNA correlated inversely with that of heat-shock protein (hsx70) mRNA. This relationship was unexpected given current theories that APP expression occurs as part of a stress response, and suggests that other factors predominate in determining neocortical APP mRNA content in neurodegenerative disorders.

Aged↗

Area of residence and the risk of institutionalization.

Many of the sociodemographic, health status, and social support characteristics that predict the use of health services by elders vary by area of residence. Yet, little is known about how these factors affect the risk of institutionalization in rural, small city, and urban areas. The purpose of this research was to: (a) determine the rate of institutionalization over a two-year period for impaired community-dwelling elders in rural, small city, and urban areas; (b) test for residence differences in sociodemographic, health status, and social support characteristics likely to influence the risk of institutionalization; and (c) examine their effect on the probability of being institutionalized in each area of residence. Although rural elders are less likely to be placed in a nursing home than their small city or urban counterparts, race and level of impairment affect the risk of institutionalization more in rural than in urban areas.

Aged↗

Decomposing area of residence differences in multiple regression studies: the relative contributions of independent variables and model coefficients.

When rural/urban differences are found in health status or health care use, it is often desirable to identify those factors (such as age, social structure, income, etc.) that influence such differences. To this end, researchers often test rural/urban differences in age, social structure, income, etc., for statistical significance. Also, researchers commonly perform multivariate analyses (such as multiple regressions) to examine rural-urban differences in the influence of various independent variables on the dependent variable of interest. Frequently, researchers discover: (1) statistically significant rural/urban differences in the independent variables (such as age, social structure, income, etc.) and (2) statistically significant rural/urban differences in the effects of these independent variables (i.e., statistically significant rural/urban differences in regression coefficients). The analysis typically stops here, without addressing the relative contributions of (1) and (2) to the rural/urban differences in the dependent variable. This paper argues that the relative contributions of (1) and (2) have important implications for the way policy-makers address rural health problems. This paper presents a method for assessing the relative contributions of differences in the independent variables and differences in regression coefficients to observed differences in the dependent variable, and illustrates the application of the method by analyzing rural/urban differences in the risk of institutionalization.

Data Collection↗

Data needs for decision support of chief nurse executives.

The dynamic changes in healthcare require accurate data on which chief nurse executives can base their decisions. Once these data are available, they must be organized efficiently to assist with decision making. The author presents the results from a national Delphi study, in which data elements for the decision support of chief nurse executives were delineated.

Data Collection↗

Air-water interface displaces adsorbed bacteria.

Video microscopy was employed to observed the spatial distribution of Staphylococcus epidermidis and Pseudomonas aeruginosa adherent to glass and polymer substrates. During rinsing procedures the bacteria remained in their original positions when the surfaces were rinsed with saline for 3 min followed by ethanol for 3 min before exposure to air. When the surfaces were rinsed with saline only, the air-liquid interface disrupted the spatial distribution of the bacteria, removing and redepositing the bacteria in clumps. A moving air-liquid interface of a gas bubble on substrate also displaced bacteria. Such artefacts produced by air-water interfaces should be avoided during bacterial adhesion experiments.

Adsorption↗

Heat shock protein (hsx70) mRNA expression in human brain: effects of neurodegenerative disease and agonal state.

Heat shock proteins (hsps) are involved in the response by cells to stress including hyperthermia, hypoxia and injury. Previous work has demonstrated expression of messenger RNA (mRNA) encoding 70 kDa hsps (hsp70) in animal brain in response to stimuli such as these. We have used in situ hybridization histochemistry to assess the distribution and quantity of a specific hsp70 (called hsx70) mRNA in frontal cortex and cerebellum from normal and demented patients whose pre-mortem course had been documented. In cortex, hsx70 mRNA was concentrated over pia mater and glia but was also present over neurons; in cerebellum, hsx70 mRNA was prominent over granule cells but absent from Purkinje cells. Detection of hsx70 mRNA did not correlate with pre-mortem factors such as pyrexia or coma. Increased hsx70 mRNA was found in frontal cortex white matter in Alzheimer's disease and in a mixed group of other neurodegenerative disorders. No changes occurred in cerebellum. The data provide further evidence for altered hsp gene expression in dementia, and support the existence of a stress response occurring in brains affected by such diseases.

Aged↗

Pre- and postmortem influences on brain RNA.

Many potentially valuable techniques for the understanding of human neurobiological and neuropathological processes require the use of RNA obtained from postmortem tissue. As with earlier neurochemical studies, there are two particular problems posed by such tissue in comparison with tissue from experimental animals. These are the postmortem interval and the condition of the patient prior to death, referred to as the agonal state. We review the nature and extent of the effects of postmortem interval and agonal state on RNA in brain tissue, with particular reference to the study of neuropsychiatric disorders. Perhaps surprisingly, postmortem interval has at most a modest effect on RNA. Abundant intact and biologically active RNA is present in tissue frozen 36 h or more after death. Postmortem interval does not account for the marked variability observed among human brains in all RNA parameters. Despite the overall stability of RNA after death, some evidence suggests that individual RNAs may undergo postmortem decay. Less attention has been paid to the effects of agonal state. The existing data indicate that events in the premortem period such as hypoxia and coma can affect the amount of some messenger RNAs. The nature of agonal state influences depends on the messenger RNA in question, though the basis for this selective vulnerability is unknown. No agonal state effect on overall RNA level or activity has been found. The data show that postmortem brain tissue can be used for RNA research. However, considerable attention must be paid to controlling for the influences of pre- and postmortem factors, especially when quantitative analyses are performed.

Animals↗

Alzheimer's disease: specific increases in a G protein subunit (Gs alpha) mRNA in hippocampal and cortical neurons.

The GTP binding protein, Gs, activates adenyl cyclase in direct response to stimulation of several neurotransmitter receptors. In situ hybridization histochemistry (ISHH) with a 35S-labelled oligonucleotide has been used to detect the mRNA encoding the alpha subunit of Gs (Gs alpha) in human hippocampus, temporal and visual cortices and cerebellum, and its level has been compared between Alzheimer's disease (AD) and control brains. A marked regional increase was found in the hippocampus of AD cases. Analysis of levels of Gs alpha mRNA in individual constituent pyramidal cells confirmed this increase (3 to 4-fold in densitometric units) in hippocampal fields CA1, CA3 and CA4, as well as in temporal cortex. Levels of Gs alpha mRNA were also determined relative to total poly(A)+ mRNA in the same cell populations in each case. Gene-specific elevation of Gs alpha mRNA was thereby confirmed in hippocampal fields, and also in temporal cortex. No changes were seen in visual cortex. The increase in Gs alpha mRNA may represent a response by AD neurons in affected areas to receptor alterations, or to an abnormality in receptor-G protein coupling. Alternatively, altered G protein gene expression might be a pathogenic event underlying changes in linked receptor populations.

Aged↗

Increased muscarinic receptor messenger RNA in Alzheimer's disease temporal cortex demonstrated by in situ hybridization histochemistry.

A 35S-labelled synthetic oligonucleotide directed against part of the mRNA coding for the M1 subtype muscarinic receptor was used for in situ hybridization histochemistry in sections of human temporal cortex. M1 receptor mRNA was found in cell populations throughout the grey matter, especially in pyramidal cells. Quantitative densitometric analysis of autoradiograms was used to compare levels of this mRNA between Alzheimer's disease and controls. A significant (2.7-fold) increase in hybridization signal was found in Alzheimer's disease cases, both in absolute terms and relative to total polyadenylated mRNA as determined by hybridization with an oligodeoxythymidine probe. Elevated levels of muscarinic receptor mRNA may reflect up-regulation of transcription of this gene in response to the cholinergic deficits occurring in the disease.

Alzheimer Disease↗

Terminal coma affects messenger RNA detection in post mortem human temporal cortex.

In situ hybridization histochemistry has been used to study the amount of M1 muscarinic receptor mRNA in temporal cortex from subjects with Alzheimer's disease and other neurodegenerative disorders, where the duration of terminal coma was known. Total polyadenylated mRNA and glutamate decarboxylase activity were also measured. Both muscarinic receptor mRNA and enzyme activity showed a significant decline with increasing duration of terminal coma, but were not related to diagnosis. Polyadenylated mRNA signal did not show an association with coma. These data indicate the need to consider the nature of the terminal illness in post mortem studies of mRNA as well as for neurochemical research.

Alzheimer Disease↗