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PubMed2001

An open, component-based information infrastructure to support integrated regional healthcare networks.

A fundamental requirement for achieving continuity of care is the seamless sharing of multi-clinical information. Several different technological approaches can be followed to enable the sharing of health record segments. In all cases interoperability between systems is a prerequisite and this requires presently a major technological challenge. Inter-operability can be achieved either through messages or through a more advanced approach based on a federation of autonomous systems. Message based integration is centered mainly on the exchange of HL7 and DICOM messages for achieving the functional integration of clinical information systems (CIS) at institutional or regional level. The federated approach is principally used for facilitating the virtual view of the Integrated Electronic Health Record (I-EHR), without having to replicate unnecessary information. Within the context of HYGEIAnet, which is the regional health telematics network of Crete, both approaches have been utilized for providing end users with seamless access to clinical information. Both are based on an open architecture, which provides the framework for the reuse of standardized common components and public interfaces. This work presents the experiences related to the implementation of "messaging" and "federating" in HYGEIAnet, which are used complementary to each other. A comparison of the two parallel approaches, together with their strengths and weaknesses is described, and evaluation is given from the technological as well as the end users' perspective. Emphasis is given on the technological challenges in developing open, component-based information infra-structure to support integrated service delivery.

Computer Communication Networks↗

PubMed2003

The Functional Brain Connectivity Workshop: report and commentary.

This report summarizes the presentations and discussions at a recent workshop entitled 'Functional Brain Connectivity', held in Düsseldorf, Germany. The aims of the workshop were to bring together researchers using different approaches to study connectivity in the brain, to enable them to share conceptual, mathematical and experimental ideas and to develop strategies for future work on functional integration. The main themes that emerged included: (1) the importance of anatomical knowledge in understanding functional interactions the brain; (2) the need to establish common definitions for terms used across disciplines; (3) the need to develop a satisfactory framework for inferring causality from functional imaging and electroencephalographic/magneto-encephalographic data; (4) the importance of analytic tools that capture the dynamics of neural interactions; and (5) the role of experimental paradigms that exploit the functional imaging of perturbations to cortical interactions.

Animals↗

PubMed1978

[Regulation processes in biological systems. II. Role of compartmentation and of organized multienzyme systems].

The picture, emerging from the experimental results on the physical association of multienzyme systems, is that the true physiological significance of the aggregated state can be understood only if it is correlated to the structural and functional integration of the cellular metabolic framework as a whole. The enzyme clusters exhibit two distinct functional properties. The first is the spatial translocation of intermediate substrates, the effect of which may be viewed as metabolic "channelling" or "vectorial catalysis" if the enzyme clusters are arrayed in some manner in the cell. The second is the coordinate regulation which represents an efficient and economical mean of controlling two or more functionally related enzymes. The common element to these two properties is the spatial character, which is potentially present in the function and the regulation of the intermediary metabolism. The biological systems, and metabolism in particular, exhibit both stability and variability; the latter sometimes assumes the character of periodicity. Whether the oscillations have a definite importance at the level of the intermediary metabolism itself, may well be questioned; the oscillatory faculties may rather serve as elements to be used in more complex functions of the biological systems. A thorough understanding of the role of clustered multienzyme systems and of the oscillatory phenomena in cellular metabolism demands a clearer physicochemical picture of the dynamic state of the living cell than we have at present. For this reason some of the generalizations derived from in vitro studies of single, isolated enzyme activities are not justified.

Adenosine Triphosphate↗

PubMed1982

[Molecular organization of the sarcoplasm of skeletal muscles in different functional states].

Changes in the molecular substrate of the frog gastrocnemius muscle sarcoplasm were studied at rest, under indirect suprathreshold stimulation and fatigue. The time course of changes in the sarcoplasm was evaluated from the intensity of recordable mitogenetic radiation of the muscle. At rest the muscle sarcoplasm was characterized by active maintenance of the functional integrity of nerve and muscle fibers, whereas under indirect stimulation and during fatigue this coordinating function was disturbed. Thus, the sarcoplasm is an important link in the regulation of coordinated changes in different structural elements of the muscle.

Animals↗

PubMed2000

Gap junctions and ion channels: relevance to erectile dysfunction.

The corporal myocyte is a critical determinant of erectile capacity whose functional integrity, in the vast majority of impotent patients, is sufficient to guarantee its relevance as a therapeutic target. As with numerous other smooth muscle cell types, ion channels are important modulators of corporal smooth muscle tone/contractility. As such, the transmembrane flow of ions (ie Ca(2+), K(+) and Cl(-)) plays an important role in modulating membrane potential and contractile status in individual human corporal smooth muscle cells, while intercellular ion flow ensures the functionality of myocyte cellular networks. The integral membrane proteins that selectively regulate many aspects of these critical transmembrane (eg K(+) and Ca(2+) channels) and intercellular (eg gap junctions) ionic movements have been identified. To date, the large conductance calcium-sensitive K(+) channel (ie K(Ca)), the metabolically regulated K+ channel (ie K(ATP)), and the L-type voltage-dependent Ca(2+) channel appear to be the most physiologically relevant nonjunctional ion channels. With respect to intercellular ionic/solute/second messenger movement, connexin43-derived gap junction channels are widely recognized as an obligatory component to normal integrative erectile biology. The presence of an intercellular pathway ensures that individual cellular alterations are carefully orchestrated in the rapid and syncytial fashion required for normal erectile function. This report reviews the known details concerning junctional and nonjunctional ion channels in human corporal tissue, and illustrates how one particular application of this knowledge, that is, preclinical studies utilizing low efficacy gene therapy (ie low transfection efficiency) with the K(Ca) channel has further confirmed the physiological relevance and therapeutic potential of gap junctions and ion channels to erectile physiology/dysfunction. International Journal of Impotence Research (2000) 12, Suppl 4, S15-S25.

Aging↗

PubMed1984

Cerebral monitoring of somatosensory evoked potentials during profoundly hypothermic circulatory arrest.

The factors that influence the functional integrity of the central nervous system during clinical procedures involving profoundly hypothermic circulatory arrest (PHCA) have not been objectively evaluated. Intraoperative monitoring of somatosensory evoked potentials (SEPs) was performed in nine infants undergoing PHCA during repair of congenital cardiac anomalies to investigate the short-term effects of this intervention on neurophysiologic function. Latency prolongation of the primary cortical (N18,P22) and cervical spinal cord (N13) responses, reflecting slowing of neural transmission with hypothermia, occurred as a power function of decreasing systemic temperature (p less than .01). The cortical evoked response disappeared during profound hypothermia (less than 18 degrees C), remaining absent throughout the period of circulatory arrest and for a variable period of time after reperfusion. Regression analysis indicated that the time required for the recovery of the cortical evoked response on reperfusion was a linear function of the time-temperature integral of the arrest period (p less than .001) and the pH at the onset of circulatory arrest (p less than .001). Neurologic complications occurred in three patients and included cortical blindness (n = 2) and a generalized seizure disorder (n = 1). Visual dysfunction was not reflected in the intraoperative SEP recordings, whereas prolonged delay of SEP recovery, indicative of global central nervous system injury, was observed in the patient who experienced seizures after the surgery. This preliminary experience with SEP monitoring during PHCA suggests a role for this modality in determining the short-term effects of this procedure on neurophysiologic function. The recovery characteristics of somatosensory neural transmission appear to be modulated by the duration of, and temperature and pH maintained during, the arrest period.

Body Temperature↗

PubMed1981

Brain dysfunction in mild to moderate hypoxia.

Hypoxia is commonly invoked to explain alterations in mental function, particularly in patients with cardiac pulmonary failure. The effects of acute graded hypoxia or higher integrative functions are well documented experimentally in man. Hypoxia in experimental animal models demonstrates that the pathophysiology is complex. In mild to moderate hypoxia, in contrast to severe hypoxia and to ischemia, the supply of energy for the brain is not impaired; cerebral levels of adenosine triphosphate (ATP) and adenylate energy charge are normal. In contrast, the turnover of several neurotransmitters is altered by mild hypoxia. For example, acetylcholine synthesis is reduced proportionally to the reduction in carbohydrate oxidation. This relationship holds in vitro and with several in vivo models of hypoxia. Pharmacologic and physiologic studies in man and experimental animals are consistent with acetylcholine having an important role in mediating the cerebral effects of mild hypoxia. These observations raise the possibility that treatments directed to cholinergic or other central neurotransmitter systems may benefit patients with cerebral syndromes secondary to chronic hypoxia.

Acetylcholine↗

PubMed2005

Volume regulatory function and sperm membrane dynamics as parameters for evaluating cryoprotective efficiency of a freezing extender.

In the past years a series of functional assays has been developed to determine the structural, morphological and functional integrity of the plasma membrane and sperm acrosomal membrane. Cell volume regulation is an important physiological function crucial for the success of cryopreservation. In this study, the effects induced by freezing-thawing were judged by evaluating the functional characteristics of frozen-thawed semen samples submitted to secondary stress such as osmotic challenge or incubation under capacitating conditions, following cryopreservation. Prior to freezing, dog semen samples were diluted in the presence or absence of Equex STM Paste, which contains sodium dodecyl sulphate (SDS) as the active ingredient. Cell volume regulation and capacitation and calcium ionophore-induced membrane dynamics were assessed in freshly diluted and frozen-thawed semen samples by electronic volume measurement and flow cytometry. Cryopreservation led to a disturbance of the volume regulatory function and to a rapid decrease in the proportion of acrosome-reacted live spermaotozoa. Extender containing Equex STM Paste had a protective effect on isotonic cell volume, on regulatory function under hypertonic conditions, and on the proportion of live acrosome-reacted cells. The evaluation of the functional state of sperm submitted to secondary stress after freezing-thawing leads to a more subtle characterization of sperm function and helps improve the cryoprotective efficiency of the extender.

Acrosome↗

PubMed2006

Evaluation of planning and implementation for an innovative health centre.

The South Calgary Health Centre, a new venture for the Calgary Health Region, was mandated to be an accessible, integrated, community-based health services facility. A comprehensive evaluation provided details on planning and implementation. Functional integration was a large focus of the planning and was operationalized as central admitting, shared charts, shared space and co-location of clinical services with no history of integration. Challenges are discussed and recommendations for future health centres developed.

Alberta↗

PubMed1997

Photoprocesses.

The development of supramolecular chemistry has allowed the construction of structurally organized and functionally integrated chemical systems capable of elaborating the energy and information input of photons to perform complex functions. Model systems capable of mimicking the two fundamental steps of photosynthesis, namely light harvesting and photoinduced charge separation, have recently been developed.

Carbohydrate Conformation↗

PubMed2000

A transgenic perspective on plant functional genomics.

Transgenic crops are very much in the news due to the increasing public debate on their acceptance. In the scientific community though, transgenic plants are proving to be powerful tools to study various aspects of plant sciences. The emerging scientific revolution sparked by genomics based technologies is producing enormous amounts of DNA sequence information that, together with plant transformation methodology, is opening up new experimental opportunities for functional genomics analysis. An overview is provided here on the use of transgenic technology for the functional analysis of plant genes in model plants and a link made to their utilization in transgenic crops. In transgenic plants, insertional mutagenesis using heterologous maize transposons or Agrobacterium mediated T-DNA insertions, have been valuable tools for the identification and isolation of genes that display a mutant phenotype. To discover functions of genes that do not display phenotypes when mutated, insertion sequences have been engineered to monitor or change the expression pattern of adjacent genes. These gene detector insertions can detect adjacent promoters, enhancers or gene exons and precisely reflect the expression pattern of the tagged gene. Activation tag insertions can mis-express the adjacent gene and confer dominant phenotypes that help bridge the phenotype gap. Employment of various forms of gene silencing technology broadens the scope of recovering knockout phenotypes for genes with redundant function. All these transgenic strategies describing gene-phenotype relationships can be addressed by high throughput reverse genetics methods that will help provide functions to the genes discovered by genome sequencing. The gene functions discovered by insertional mutagenesis and silencing strategies along with expression pattern analysis will provide an integrated functional genomics perspective and offer unique applications in transgenic crops.

Crops, Agricultural↗

PubMed1989

Actions of extracellular matrix on Sertoli cell morphology and function.

Sertoli cells were isolated and cultured in the absence or presence of extracellular matrix (ECM) to determine whether ECM may influence Sertoli cell function on a molecular level. As previously described, a morphological analysis of the cells indicated that ECM allows the expression of a columnar histotype and the formation of junctional complexes. The combined actions of ECM and hormones were found to have a profound effect in promoting the expression of a polarized Sertoli cell morphology. In our investigation of the effects of ECM on Sertoli cells, we used transferrin and androgen-binding protein (ABP) production as biochemical markers of Sertoli cell function. The presence of ECM was found to cause a 25% increase in the basal level of transferrin production; however, ECM had no effect on the basal level of ABP production by Sertoli cells. Regulatory agents such as follicle-stimulating hormone (FSH) and a combination of FSH, insulin, retinol, and testosterone stimulated the production of both transferrin and ABP. The ability of hormones to stimulate these Sertoli cell functions was not influenced by the presence of ECM. Similar results were obtained with 2-microns- or 50-microns-thick ECM and with a seminiferous tubule biomatrix preparation. ECM was found to increase the maintenance of long-term Sertoli cell cultures; however, the decline in Sertoli cell functional integrity, which occurs during cell culture, was not affected by the presence of ECM. An additional functional parameter examined was the radiolabeled proteins secreted by Sertoli cells. ECM did not promote the production or affect the electrophoretic profile of Sertoli cell-secreted proteins under basal or hormonally stimulated conditions. Combined results indicated that although ECM allowed the expression of a normal Sertoli cell histotype, ECM had no major effects on the Sertoli cell functions analyzed nor on the hormonal regulation of these functions. The inability of ECM to affect Sertoli cell function on a molecular level is discussed with regard to environmental as opposed to regulatory cellular interactions. Our observations imply that dramatic effects of ECM on cell morphology do not necessarily correlate to subsequent effects on cellular function.

Androgen-Binding Protein↗

PubMed2001

Exact multilocal renormalization group and applications to disordered problems.

We develop a method, the exact multilocal renormalization group (EMRG) which applies to a broad set of theories. It is based on the systematic multilocal expansion of the Polchinski-Wilson exact renormalization group (ERG) equation together with a scheme to compute correlation functions. Integrating out explicitly the nonlocal interactions, we reduce the ERG equation obeyed by the full interaction functional to a flow equation for a function, its local part. This is done perturbatively around fixed points, but exactly to any given order in the local part. It is thus controlled, at variance with projection methods, e.g., derivative expansions or local potential approximations. Our EMRG method is well-suited to problems such as the pinning of disordered elastic systems, previously described via functional renormalization group (FRG) approach based on a hard cutoff scheme. Since it involves arbitrary cutoff functions, we explicitly verify universality to O(epsilon=4-D), both of the T=0 FRG equation and of correlations. Extension to finite temperature T yields the finite size (L) susceptibility fluctuations characterizing mesoscopic behavior (Deltachi)2 approximately L(straight theta)/T, where straight theta is the energy exponent. Finally, we obtain the universal scaling function to O(epsilon(1/3)) which describes the ground state of a domain wall in a random field confined by a field gradient, compare with exact results and variational method. Explicit two loop exact RG equations are derived and the application to the FRG problem is sketched.

Journal Article↗

PubMed1978

Etiology of primary osteoporosis: an hypothesis.

By convention, osteoporosis has been described in two categories: 1) primary (involutional or postmenopausal), and 2) secondary, in association with a wide variety of pathologic disorders. Primary osteoporosis is the ultimate consequence of progressive bone loss, which starts in the middle of the fourth decade. Given the apt name of "adult bone loss," it is considered to be a universal phenomenon in that it afflicts all people of all races and both sexes. However, careful analysis of past studies generates evidence that not every person of advanced age loses bone. The etiology of "adult bone loss," and thus of primary osteoporosis, is conceded to be unknown or at least controversial. Nevertheless, the complex dependencies of bone metabolism on the functional integrity of major organ systems imply a multifactorial etiology. The age-related progressive declines in functional reserves of major organ systems may indicate that primary osteoporosis evolves secondarily to a protracted suboptimal metabolic support of bone remodeling. Further confirmation of this hypothesis may have important implications for the prophylactic management of primary osteoporosis.

Bone and Bones↗

PubMedDate not supplied

Selective vulnerability of hippocampus and disturbances of memory storage after mild unilateral ischemia of gerbil brain.

The effect of selective injury of hippocampal neurons on the consolidation of memory traces was studied in gerbils (meriones unguiculatus) after production of mild cerebral ischemia. The right carotid artery was permanently ligated, and animals without gross neurological deficits ("symptom-negative" gerbils) were selected. Eight days and eight weeks after vascular ligation, cell counts of hippocampal neurons were carried out and correlated with regional blood flow and the acquisition of operant behaviour. Eight days after carotid artery occlusion, learning behaviour was significantly impaired although the number of hippocampal neurons had not changed and blood flow had even increased above normal. After eight weeks, learning behaviour and blood flow were normal but now a significant loss of pyramidal neurons was present in the CA1 and CA2 sectors of the hippocampus. Our observations demonstrate that it is possible to detect subtle functional disturbances by appropriate behavioural investigation before manifestation of selective injury of the hippocampus. Recovery of integrative function, despite persistent cellular damage, provides further evidence for central nervous plasticity.

Animals↗

PubMed1995

Airway mucus and epithelial function in a canine model of single lung autotransplantation.

Impaired mucociliary function following lung transplantation has been reported in several human and animal studies. This could be a result of altered ciliary function or mucus properties or both. We assessed airway epithelial function by means of transepithelial potential difference (PD) measurements and physical analysis of mucus. Six mongrel dogs underwent single lung autologous transplantation. Measurements were performed preoperatively and 1, 2, 4, and 10 months postoperatively. At 1 and 2 months postoperatively, there was a significant fall in PD for the transplanted, left mainstem bronchus only (-13.5 +/- 1.7 mV at 1 month and -14.6 +/- 1.7 mV at 2 months postoperatively vs -18.6 +/- 2.3 mV preoperatively, baseline; p < 0.001 for both). The PD values in the small airways, right mainstem bronchus, and the trachea remained unchanged. At 2 months postoperation, the mucus collection rate on the left side was increased (p = 0.03), while the mucus viscoelasticity was decreased (p = 0.04). By 4 months postoperation, all epithelial parameters had returned to baseline, and there was no difference in radioaerosol clearance between the two lungs. The PD decrease and alterations in secretion rate and viscoelasticity reflect disturbed epithelial functional integrity at the site of anastomosis still present at 2 months postoperation. Recovery of bronchial epithelial function and clearance in canine studies of lung autotransplantation after healing of the anastomosis area suggest that persistent impairment of lung clearance observed in some long-term human lung transplantation survivors may be due to other mechanisms such as impaired healing or epithelial function or both, during immunosuppressive therapy. Mucociliary function in the anastomosis area is compromised until complete healing ensues; we speculate that chest physiotherapy may aid in overcoming this obstacle.

Animals↗

PubMed1993

The immune system: your defensive partner and offensive foe.

Immune function and inflammation are normal physiologic processes essential to health and well-being. However, overactivity of any inflammatory or immune responses can result in tissue-damaging reactions that threaten the functional integrity of tissues and organs. This article reviews the normal defense responses of inflammation and immune function as well as selected conditions resulting from offensive or hyperactive inflammatory and immune responses. The selected conditions include those seen more often in the acute and critical-care setting, such as tissue-damaging inflammation, drug allergy, autoimmunity, and transplant rejection.

Anaphylaxis↗

PubMed2002

Peptides and Ageing.

A technology has been developed for manufacturing of biologically active complex peptide preparations from extracts of different tissues. In particular, the pineal preparation (Epithalamin) augments the in vitro outgrowth of explants from the pineal gland but not from other tissues, the latter being stimulated by peptide preparations from respective tissues. Epithalamin increases melatonin production by the pineal gland of rats, improves immunological parameters in rats and mice, produces anticarcinogenic effects in different experimental models, stimulates antioxidant defenses, and restores the reproductive function in old rats. These effects are combined in the ability of Epithalamin to increase the lifespan in rats, mice, and fruit flies. Many of these effects are reproduced in clinical trials, which have demonstrated the geroprotector activity of Epithalamin in humans. Among the effects of the thymic preparation Thymalin, those related to its ability to stimulate immunity are the most prominent. This ability is associated with anticarcinogenic and geroprotector activities. Clinical trials of the peptide preparations obtained from other organs including the prostate, the cerebral cortex, and the eye retina, have demonstrated beneficial effects reflected by the improvement of the conditions of respective organs. Based on the data about the amino acid compositions of the peptide preparations, novel principles of the design of biologically active short peptides possessing tissue-specific activities has been developed. Dipeptides specific for the thymus and tetrapeptides specific for the heart, liver, brain cortex, and pineal glands stimulate the in vitro outgrowth of explants of respective organs. Interestingly, for eye retina and the pineal gland, a common tetrapeptide Ala-Glu-Asp-Gly (Epitalon) has been designed, probably reflecting the common embryonal origin of these two organs. Epitalon reproduces the effects of Epithalamin including those related to its geroprotector activity. In particular, Epitalon increases the lifespan of mice and fruit flies and restores the circadian rhythms of melatonin and cortisol production in old rhesus monkeys. At the same time, Epitalon prolongs the functional integrity of the eye retina in Campbell rats with hereditary Retinitis Pigmentosa and improves the visual functions in patients with pigmental retinal degeneration. Changes in gene expression were observed to be produced by the short peptide preparations. Therefore, the effects of Epitalon are suggested to be mediated by transcriptional machinery common for the pineal gland and the retina and, probably, for regulation of melatonin production in fruit flies. Based on three decades of studies of the peptide preparations, the peptide theory of ageing has been put forward. According this theory, ageing is an evolutionary determined biological process of changes in gene expression resulting in impaired synthesis of regulatory and tissue-specific peptides in organs and tissues, which provokes their structural and functional changes and the development of diseases. Correspondingly, correction of such disorders by means of stimulation of peptide production in the organism or through their delivery can promote the normalisation of disturbed body functions.

Aging↗