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Towards a wireless patient: chronic illness, scarce care and technological innovation in the United Kingdom.

'Modernization' is a key health policy objective in the UK. It extends across a range of public service delivery and organizational contexts, and also means there are radical changes in perspective on professional behaviour and practice. New information and communications technologies have been seen as one of the key mechanisms by which these changes can be engendered. In particular, massive investment in information technologies promises the rapid distribution and deployment of patient-centred information across internal organizational boundaries. While the National Health Service (NHS) sits on the edge of a pound sterling 6 billion investment in electronic patient records, other technologies find their status as innovative vehicles for professional behaviour change and service delivery in question. In this paper, we consider the ways that telemedicine and telehealthcare systems have been constructed first as a field of technological innovation, and more recently, as management solutions to problems around the distribution of health care. We use NHS responses to chronic illness as a medium for understanding these shifts. In particular, we draw attention to the shifting definitions of 'innovation' and to the ways that these shifts define a move away from notions of technological advance towards management control.

Chronic Disease↗

Use of semiquantitative food frequency questionnaires to estimate the distribution of usual intake.

The authors consider whether semiquantitative food frequency questionnaires can be used to survey a population to estimate the distribution of usual intake. They take as an assumption that, if they were possible to obtain, the mean of many food records or recalls would be an accurate representation of an individual's usual diet. They then assume that nutrient intake as measured by a questionnaire follows a linear regression model when regressed against the usual intake of that nutrient. If the coefficients in this regression relation were known, then the distribution of usual intake could be constructed from the responses to the questionnaire. Since one generally does not know the values of the coefficients, they need to be estimated from a calibration study in which respondents complete the questionnaire together with multiple food records or recalls. This can be done either through an internal subset of the data or through an independent external study. With an internal substudy, the authors find that food frequency questionnaires typically provide little information about the distribution of usual intake in addition to that obtained from the multiple records or recalls in the substudy. When the substudy is external, if it is small then having very large numbers of subjects completing food frequency questionnaires in the survey is no more efficient than having a few subjects completing food records or recalls. However, if the external substudy is large and accurately characterizes the relation between the questionnaire response and usual intake, food frequency questionnaires can provide a cost-efficient way of estimating the distribution of usual intake. These results do not apply to the different problem of correcting relative risks for the effects of measurement error.

Bias↗

Association of genetic variability within the Borrelia burgdorferi sensu lato with the ecology, epidemiology of Lyme borreliosis in Europe.

Lyme borreliosis (LB) represents the most common vector-borne zoonotic disease in the Northern Hemisphere. The infection is caused by the spirochetes of the Borrelia burgdorferi sensu lato (s.l.) complex which circulate between tick vectors and vertebrate reservoir hosts. The complex of Borrelia burgdorferi s.l. encompasses at least 12 species. Genetic variability within and between each species has a considerable impact on pathogenicity, clinical picture, diagnostic methods, transmission mechanisms and its ecology. The distribution of distinct genospecies varies with the different geographic area and over a time. In recent years, new molecular assays have been developed for direct detection and classification of different Borrelia strains. Profound studies of strain heterogeneity initiated a new approach to vaccine development and routine diagnosis of Lyme borreliosis in Europe. Although great progress has been made in characterization of the organism, the present knowledge of ecology and epidemiology of B. burgdorferi s.l. is still incomplete. Further information on the distribution of different Borrelia species and subspecies in their natural reservoir hosts and vectors is needed.

Animals↗

Distribution of serum lipoprotein(a) levels--a non-parametric analysis.

The distribution of serum lipoprotein(a) [Lp(a)] concentration among Japanese male adults was evaluated using non-parametric methods. The following results were obtained. 1) Among healthy male adults undergoing a medical checkup, Lp(a) showed a highly skewed distribution towards the low level. The distribution could be regarded as a power normal distribution with the power order of 1/2. The median of Lp(a) level was 14.1 mg/dl (the 25th percentile was 6.2 mg/dl and the 75th percentile was 26.7 mg/dl). 2) The values of serum Lp(a) in subjects with vasospastic angina distributed at a higher level than for subjects with normal coronary arteries as diagnosed by coronary angiography. 3) The observed serum Lp(a) concentration moved to a higher range as the number of branches with significant stenosis on the coronary angiography increased. 4) Serum Lp(a) was one of the risk factors for ischemic heart disease. Its odds ratio when the cut-off value was set at 26.7 mg/dl or 30 mg/dl was 2.52 and 2.94, respectively. Information on the distribution of serum Lp(a) concentration is useful for estimating the coronary atherogenic factor.

Adult↗

Transit time dispersion in pulmonary and systemic circulation: effects of cardiac output and solute diffusivity.

We present an in vivo method for analyzing the distribution kinetics of physiological markers into their respective distribution volumes utilizing information provided by the relative dispersion of transit times. Arterial concentration-time curves of markers of the vascular space [indocyanine green (ICG)], extracellular fluid (inulin), and total body water (antipyrine) measured in awake dogs under control conditions and during phenylephrine or isoproterenol infusion were analyzed by a recirculatory model to estimate the relative dispersions of transit times across the systemic and pulmonary circulation. The transit time dispersion in the systemic circulation was used to calculate the whole body distribution clearance, and an interpretation is given in terms of a lumped organ model of blood-tissue exchange. As predicted by theory, this relative dispersion increased linearly with cardiac output, with a slope that was inversely related to solute diffusivity. The relative dispersion of the flow-limited indicator antipyrine exceeded that of ICG (as a measure of intravascular mixing) only slightly and was consistent with a diffusional equilibration time in the extravascular space of approximately 10 min, except during phenylephrine infusion, which led to an anomalously high relative dispersion. A change in cardiac output did not alter the heterogeneity of capillary transit times of ICG. The results support the view that the relative dispersions of transit times in the systemic and pulmonary circulation estimated from solute disposition data in vivo are useful measures of whole body distribution kinetics of indicators and endogenous substances. This is the first model that explains the effect of flow and capillary permeability on whole body distribution of solutes without assuming well-mixed compartments.

Adrenergic beta-Agonists↗

Comparison of an immunoperoxidase "sandwich" staining method and western blot detection of P-glycoprotein in human cell lines and sarcomas.

The applicability of a multilayer immunoperoxidase "sandwich" method (IpS) developed by Chan14 for the amplified detection of P-glycoprotein (Pgp) was investigated. The authors examined 15 formalin-fixed cell lines, as well as formalin-fixed, paraffin-embedded sections from single biopsies of 46 sarcomas. The cell lines included sensitive and multidrug resistant sublines (KB, A2780, MCF-7, HeLa) with various relative degrees of resistance to doxorubicin (Dox). The sarcoma biopsy specimens were selected on the basis of the results obtained in Western blot (WB) detection of Pgp (22 positive and 24 negative by WB) using C219 and C494 monoclonal antibodies to Pgp. The IpS method employed C219. The least resistant cell line in which Pgp could be detected by IpS was fivefold resistant to doxorubicin, whereas Pgp was detected by WB in cells greater than twofold resistant. Cell lines having greater than fivefold resistance to Dox were positive by both IpS and WB analyses. The less resistant cell lines contained more nonreactive cells whereas the highly resistant cell lines showed more homogeneous strong membrane reactions. Among the six cell lines determined to be Pgp negative by WB analysis, no false positive immunostaining by IpS existed. One of 22 WB positive and 7 of 24 WB-negative sarcoma biopsy specimens were positive by IpS methods. Reaction varied and was always focal (a minimum of 3-5 cells, ranging up to 3-4 high power fields) indicating pronounced heterogeneous distribution of Pgp. Thus, WB can detect low average (overall) levels of Pgp in tumor samples but such low concentrations of PgP at the single cell are not detectable by IpS methods. However, IpS can discern among many Pgp-negative cells small subpopulations of immunoreactive cells, which are not detected by WB analysis due to Pgp dilution by the membrane protein of numerous Pgp negative cells. IpS and WB used together as complementary methods can provide more complete information about Pgp distribution and content, particularly in the case of heterogeneous human tumors. The IpS method is more suitable for less drastically treated (not embedded) cell line specimens than for paraffin-embedded (routine) sections. Some modification of the present IpS protocol seems necessary to increase its sensitivity and reduce the disparity with WB results.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Absorption, distribution and elimination of alcohol: highway safety aspects.

Key aspects of the pharmacokinetics of alcohol are highly relevant to highway safety. Of particular pertinence are the partition of alcohol between various body tissues and fluids and the resulting alcohol concentration ratios for blood: breath and other body fluids, as well as the irregularity and short-term fluctuations of the blood and breath alcohol curves. Most alcohol pharmacokinetics parameters are subject to wide intersubject variability, as exemplified by peak blood alcohol concentrations reached on ingestion of identical weight-adjusted doses, time to peak after end of drinking and the rate of alcohol elimination from the blood. This great biological intersubject variability, when combined with sex-, age- and time-related differences, makes the blood alcohol information in widely distributed alcohol consumption nomograms and tables based on mean data inappropriate as a guide for the drinking behavior of individuals. Although there is good statistical correlation between the alcohol concentration of different body tissues and fluids in the fully postabsorptive state, wide individual variations from the population mean alcohol partition values exist. It is often impossible to determine whether the postabsorptive state has been reached at any given time. Those factors make it impossible or infeasible to convert the alcohol concentration of breath or urine to the simultaneous blood alcohol concentration with forensically acceptable certainty, especially under per se or absolute alcohol concentration laws. Inclusion of breath alcohol concentrations in drinking-driving statutes, as definitions or per se offense elements, makes unnecessary the conversion of breath alcohol analysis results into equivalent blood alcohol concentrations. Urine alcohol concentrations are inadequately correlated with blood alcohol concentrations or with driver impairment, and analysis of bladder urine is, therefore, inappropriate in traffic law enforcement. Significantly large sex-related differences in pharmacokinetic parameters have been demonstrated (e.g., in peak blood alcohol concentrations for weight-adjusted doses). The effects of age and time of day have been less extensively studies and are less clear. Breath and blood alcohol time curves are subject to short-term fluctuations from the trend line and other irregularities, and often do not follow the typical Widmark pattern. From the existing information on pharmacokinetics of alcohol and the characteristics and variability of blood and breath alcohol versus time curves, the following conclusions can be reached.(ABSTRACT TRUNCATED AT 400 WORDS)

Accident Prevention↗

The development of cranial nerve and visceral afferents to the nucleus of the solitary tract in the rat.

We have used carbocyanine dye tracing techniques to examine the distribution of afferents from the facial, trigeminal and vagal nerves to the nucleus of the solitary tract (NST) in the developing rat (E13 to P13). Crystals of DiI (1, 1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) were placed (unilaterally) into the facial or trigeminal ganglia, or into the cervical vagus nerve, and the sections examined with a laser scanning confocal microscope. Inputs from some peripheral structures (tongue, aortic arch, right atrium and lung) to the NST were also analyzed to provide information on the distribution of organ-specific afferents. No afferents were labeled following DiI placement in the above sites at E13. At E14, a few axons from the geniculate ganglion of the facial nerve were present in the NST anlage, but these were restricted to the area adjacent to the solitary tract. These axons began to invade the medial NST at E15. By E17, facial afferent axons had become widespread throughout rostral NST and from E19 the distribution of DiI labeling displayed a morphologically mature pattern. DiI-labeled afferent axons from the trigeminal nerve first emerged into the NST anlage at E14, initially coursing medially to penetrate the ventricular zone. Between E15 and E17, axonal density increased markedly but after E17 became progressively confined to the lateral NST. Axons from the vagus nerve first appeared in the caudal NST as early as E14 and coursed directly into the proliferative zone of the alar plate at all rostrocaudal levels by E15. From E19 through postnatal life, the distribution of vagal afferent axons was essentially stable with particularly dense label in the caudal NST. Cranial nerve afferents to the NST appear to be distributed to appropriate sites from the beginning of ingrowth, with the exception of trigeminal afferents, where some small initial exuberance was found. The terminal fields derived from selected peripheral organs such as lung, right atrium, aortic arch and tongue were also predominantly distributed to appropriate subnuclei from the beginning of ingrowth into the NST, although organ-specific afferent fields appeared to develop dense arbors somewhat later than did individual cranial nerves. Electron microscopy was used to examine regional synapse development in the rat NST. There was some delay between the ingrowth of afferents to the NST (E15) and the first appearance of synaptic thickenings. The earliest synapses were simple (usually) symmetrical membrane thickenings (from E17) and vesicles did not appear until E19. High synaptic density within the C subnucleus appeared during early postnatal life. Synaptic glomeruli, which are a characteristic feature of afferent input to the adult NST, had not developed by birth, indicating that the pre- and perinatal function of the NST must be mediated through simpler, single, axodendritic inputs to NST neurons.

Animals↗

Simulation of the distribution of parental strains' genomes in RC strains of mice.

Recombinant Congenic strains (RC strains) were developed to facilitate mapping of genes influencing complex traits controlled by multiple genes. They were produced by inbreeding of the progeny derived from a second backcross from a common 'donor' inbred strain to a common 'background' inbred strain. Each RC strain contains a random subset of approximately 12.5% of genes from the donor strain and 87.5% of genes from the background strain. In this way the genetic control of a complex disease may be dissected into its individual components. We simulated the production of the RC strains to study to what extent they have to be characterized in order to obtain sufficient information about the distribution of the parental strains' genomes in these strains and to acquire insight into parameters influencing their effectiveness in mapping quantitative trait loci (QTLs). The donor strain genome in the RC strains is fragmented into many segments. Genetic characterization of these strains with one polymorphic marker per 3.3 centiMorgans (cM) is needed to detect 95% of the donor strain genome. The probability of a donor strain segment being located entirely in between two markers of background strain origin that are 3 cM apart (and hence escaping detection) is 0.003. Although the donor strain genome in the RC strains is split into many segments, the largest part still occurs in relatively long stretches that are mostly concentrated in fewer than 13 autosomes, the median being 9 autosomes. Thus, in mapping QTLs, the use of RC strains facilitates the detection of linkage.

Animals↗

Mean corpuscular volume-dependent deviations in red blood cell distribution width between Sysmex NE-8000 and SF-3000.

Values for red blood cell distribution width yield information concerning size heterogeneity of red blood cell populations. Comparative studies between various haematology analysers are obligatory to quantify apparatus-dependent deviations with respect to accuracy and subsequent consequences with respect to clinical interpretation of results. In this study a comparative assessment is performed between a Sysmex SF-3000 and NE-8000 Haematology Analyser. Fifty-four specimens with abnormal red blood cell volumes and a hundred specimens from apparently healthy subjects were assayed. Systematic deviations in values concerning red blood cell distribution width are demonstrated to show a tendency to decrease towards higher mean corpuscular volume values.

Anemia↗

The distribution of micro-organic contaminants in river bed-sediment cores.

There is little information available on the distributions of micro-organic contaminants in river bed-sediments below a depth of 5 cm. The aim of this study is to determine the concentrations and distributions of contaminants in river bed-sediments up to 1 m depth and to make an assessment of the results. The approach taken was to collect five cores from each of two lowland rivers in southern England, the first a rural river and the second a dominantly urban catchment. The cores were analysed for micro-organic compounds and sediment/sediment porewater characteristics. Compounds detected were polyaromatic hydrocarbons (naphthalene, fluoranthene and pyrene), pesticides (carbaryl, linuron, fenpropimorph, the synthetic pyrethroids, and prometryn), and non-ionic surfactant residue (nonylphenol). A particularly important finding was that some micro-organic contaminants penetrated to depths of 1 m, and in one of the rivers they were detected in undisturbed Eocene substrata. The more hydrophobic contaminants showed a clear depth distribution with higher concentrations towards the top of the cores. The less hydrophobic contaminants demonstrated no systematic trend suggesting they had become soluble in porewaters and subsequently travelled within the cores. Partition between the porewater and sediment appeared to be controlling the distribution of the compounds with depth.

England↗

Distribution of Campylobacter pylori in the human stomach obtained at postmortem.

The distribution of Campylobacter pylori, its prevalence, and its relationship to gastritis and urease activity have been studied in 54 postmortem stomachs. Infection was confirmed by finding C. pylori in a Gram-stained smear of gastric mucus harvested from the entire stomach. Eight tissue specimens were obtained from predetermined sites from each stomach and examined for histologic gastritis and urease activity. Thirty-seven per cent of stomachs were infected, and of these 80% had widespread histologic gastritis. The detection of urease activity provided information on the distribution of the organism and had a high correlation with histologic gastritis. The organism is capable of infecting any area of the stomach. Infection is common and is more prevalent in Polynesian subjects (60%) than in Caucasians (19%).

Adolescent↗

Database challenges and solutions in neuroscientific applications.

In the scientific community, the quality and progress of various endeavors depend in part on the ability of researchers to share and exchange large quantities of heterogeneous data with one another efficiently. This requires controlled sharing and exchange of information among autonomous, distributed, and heterogeneous databases. In this paper, we focus on a neuroscience application, Neuroanatomical Rat Brain Viewer (NeuART Viewer) to demonstrate alternative database concepts that allow neuroscientists to manage and exchange data. Requirements for the NeuART application, in combination with an underlying network-aware database, are described at a conceptual level. Emphasis is placed on functionality from the user's perspective and on requirements that the database must fulfill. The most important functionality required by neuroscientists is the ability to construct brain models using information from different repositories. To accomplish such a task, users need to browse remote and local sources and summaries of data and capture relevant information to be used in building and extending the brain models. Other functionalities are also required, including posing queries related to brain models, augmenting and customizing brain models, and sharing brain models in a collaborative environment. An extensible object-oriented data model is presented to capture the many data types expected in this application. After presenting conceptual level design issues, we describe several known database solutions that support these requirements and discuss requirements that demand further research. Data integration for heterogeneous databases is discussed in terms of reducing or eliminating semantic heterogeneity when translations are made from one system to another. Performance enhancement mechanisms such as materialized views and spatial indexing for three-dimensional objects are explained and evaluated in the context of browsing, incorporating, and sharing. Policies for providing the system with fault tolerance and avoiding possible intellectual property abuses are presented. Finally, two existing systems are evaluated and compared using the identified requirements.

Animals↗

Pulmonary parenchymal disease: evaluation with high-resolution CT.

Usefulness of high-resolution computed tomography (HRCT) in locating pulmonary parenchymal disease in relation to the pulmonary lobule was evaluated in 71 patients, including 30 with normal pulmonary parenchyma and 41 with various pulmonary diseases. Both 10-mm-thick sections and 1.5- or 3.0-mm-thick HRCT scans were obtained. Distribution of pulmonary parenchymal disease was classified as centrilobular, panlobular, perilobular, bronchovascular, or nonlobular. Intralobular classification of disease distribution was more feasible in less severely diseased regions. HRCT revealed thickened intralobular bronchovascular bundles in patients with bronchiolitis obliterans, mycoplasma pneumonia, and pulmonary tuberculosis and thickening of both bronchovascular bundles and perilobular structures in patients with sarcoidosis, lymphangitis carcinomatosa, and malignant lymphoma. Centrilobular areas of increased attenuation were seen in patients with bronchopneumonia and pulmonary cryptococcosis. Centrilobular emphysema and bronchiolectasis were recognized only on HRCT images. The improved clarity and sharpness of parenchymal abnormalities on HRCT images, even in severely involved areas, provide additional information about disease distribution.

Female↗

IgG subclasses to food proteins in atopic and normal individuals.

IgG subclass antibodies to ovalbumin (OVA), gliadin (GLI) and beta-lactoglobulin (beta-lac) were determined in 18 atopic subjects and 18 age- and sex-matched controls. IgG antibodies to OVA and GLI were found predominantly as IgG4 subclass, with the IgG antibodies to beta-lac distributed evenly between IgG2, IgG3 and IgG4 in both groups. The proportion of anti-OVA IgG antibodies in the IgG3 subclass was significantly higher in the atopic group (22%) than in the nonatopic group (8%: p < 0.001). The proportion of anti-GLI IgG3 antibodies was also higher in the atopic group (43%) than the nonatopic group (24%: p < 0.001). OVA subclass antibodies in the atopic and nonatopic subjects were mainly IgG4, and GLI subclass antibodies were mainly IgG3 and IgG4. This study provides information on the distribution of IgG subclasses to food proteins, and in particular those related to protein GLI. The importance of IgG3 subclasses in atopic disease is highlighted; this phenomenon, to our knowledge, has not previously been reported.

Adult↗

The distribution of estrogen receptor-beta mRNA in forebrain regions of the estrogen receptor-alpha knockout mouse.

Neurons in the hypothalamus of estrogen receptor alpha-knockout (ER alphaKO) mice have been shown to concentrate radiolabeled estrogen and estrogen treatment regulates the expression of progesterone receptor mRNA. The purpose of the present study was to utilize in situ hybridization histochemistry to determine the anatomical distribution of ER beta mRNA in ER alphaKO mouse forebrain. The results of these studies revealed an extensive distribution of ER beta mRNA in the hypothalamic regions including medial preoptic area, suprachiasmatic nucleus, paraventricular nucleus, dorsomedial nucleus, medial tuberal nucleus, and the premammillary nuclei. Additional labeled perikarya were also detected in the glomerular layer of the olfactory bulb; tenia tecta; anterior septum; bed nucleus of the stria terminalis; medial, basolateral and cortical nuclei of the amygdala; cerebral and entorhinal cortex; the septohippocampal nucleus; Ammon's horn of the hippocampus and the dorsal raphe. The results of these in situ hybridization histochemical studies have provided novel information about the distribution of ER beta mRNA in the ER alphaKO mouse forebrain. In addition, these morphological data provides evidence that estrogen may exert its actions in the ER alphaKO mouse brain via ER beta and thereby maintain organizational and activational effects.

Animals↗

[Significance of self-help groups for psychosocial rehabilitation in cancer].

Experiences of cancer patients' self-help groups can provide impulses for the programming of rehabilitation measures. Exemplary is the information work (information procurement and distribution) of these groups. Problems emanating from disturbed interpersonal relationships and the stigma of the disease are dealt with implicitly rather than explicitly, with only certain patients, however, benefitting selectively from this kind of coping, depending on the stage of the disease and on their social context. The groups succeed in substituting missing or disturbed interpersonal relationships, they sometimes however find it difficult to ward off those aspects of isolation that have arisen with the onset of the disease. These difficulties weigh on other parts of the informal network, especially on the families.

Adaptation, Psychological↗

A model of the magnetic fields created by single motor unit compound action potentials in skeletal muscle.

We have developed a computationally simple model for calculating the magnetic-field strength at a point due to a single motor unit compound action potential (SMUCAP). The motor unit is defined only in terms of its anatomical features, and the SMUCAP is approximated using the tripole model. The distributed current density J is calculated within the volume defined by the motor unit. The law of Biot and Savart can then be cast in a form necessitating that J be integrated only over the region containing current sources or conductivity boundaries. The magnetic-field strength is defined as the summation of the contributions to the field made by every muscle fiber in the motor unit. Applying this model to SMUCAP measurements obtained using a high-resolution SUper Conducting Quantum Interference Device (SQUID) magnetometer may yield information regarding the distribution of action currents (AC's) and the anatomical properties of single motor units within a muscle bundle.

Action Potentials↗