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PubMed2003

Enkephalinergic striatal projection neurons become less affected by quinolinic acid than substance P-containing striatal projection neurons as rats age.

While the excitotoxic vulnerability of striatal neurons is known to be greater in juvenile than adult animals, it is uncertain if striatal neuron types decline differentially in their vulnerability with age. To examine this issue, we unilaterally injected quinolinic acid (QA), an N-methyl-d-aspartate (NMDA) receptor agonist, into the striatum of juvenile and adult rats, and used in situ hybridization histochemistry with oligonucleotide probes for preproenkephalin and preprotachykinin mRNA to label surviving enkephalinergic (ENK) and substance P-containing (SP) neurons in adjacent sections through the injection center. The results confirmed that the region of severe damage is greater in young than adult animals, but revealed that at the very center of the QA injection, labeled neuron abundance was lower in adult than juvenile striatum. In juvenile rats, the vulnerability of the ENK neurons at all distances from the injection center was the same as that of the SP neurons. By contrast, in adult rats, the ENK neuron survival was greater than the SP neuron survival at all distances beyond the lesion center. The SP neuron survival outside the injection center in the adult rats was similar to that in juvenile rats, while the ENK neuron survival beyond the injection center was better in adult than juvenile rats. These data indicate that there is an age-dependent decrease in the vulnerability of ENK but not SP striatal projection neurons to QA-mediated injury in rats. The results also raise the possibility that, if an excitotoxic process is involved in HD pathogenesis, a differential age-related decline in the sensitivity of striatal projection neuron types to this process may contribute to the more uniform striatal neuron loss in juvenile-onset Huntington's disease (HD) and the more differential loss in adult-onset HD.

Aging↗
PubMed1999

Alabama coronary artery bypass grafting Cooperative Project: baseline data. Alabama CABG Cooperative Project Study Group.

BACKGROUND: The Alabama Cooperative CABG Project is a statewide process-oriented analysis of coronary artery bypass grafting (CABG). The purpose of this report is to present the first information generated by this analysis, which will serve as a baseline for subsequent quality improvement projects. METHODS: Medical records of Medicare beneficiaries from Alabama, a comparison state, and a national random sample who had isolated CABG between July 1, 1995, and June 30, 1996, were examined. Fifty-six demographic, procedural, and outcome variables were abstracted. Quality indicators identified by the Alabama Quality Assurance Foundation Study Group included: internal mammary artery use, prescription of aspirin at discharge, duration of postoperative intubation, use of intraaortic balloon pump, readmission to intensive care unit, hospital readmission within 30 days, return to the operating room for bleeding, and in-patient mortality. Benchmark performance rates for quality indicators reflecting care processes were calculated. RESULTS: Alabama, the comparison state, and the national sample consisted of 4,092, 2,290, and 1,119 patients, respectively. The processes of care and outcome, including risk-adjusted mortality, for CABG across the state of Alabama are generally similar to other states and nationwide samples. However, there was considerable variation at the local hospital level in Alabama for each quality indicator. CONCLUSIONS: The data provide a "snapshot" of practice patterns for CABG in Alabama. A specific quality indicator (duration of intubation) was identified as a focus for statewide improvement. Hospital-specific variations in quality indicators suggested opportunities for improvement in other indicators at a number of hospitals.

Aged↗
PubMed1998

Direct projections from the periaqueductal gray to pontine micturition center neurons projecting to the lumbosacral cord segments: an electron microscopic study in the rat.

Direct projections from the periaqueductal gray (PAG) to the pontine micturition center neurons directly projecting to the lumbosacral cord segments were observed electron microscopically in the rat by a double labeling method. Biotinylated dextran amine (BDA) was injected into the PAG and horseradish peroxidase (HRP) was injected into the lumbosacral cord segments. After injection of BDA into the ventrolateral part of the PAG, many BDA-labeled axons were seen light microscopically in Barrington's nucleus; a moderate number of them were found in the pontine tegmental region just ventral to Barrington's nucleus (D-region [Ding, Y-Q., Takada, M., Tokuno, H. and Mizuno, N., J. Comp. Neurol., 357 (1996) 318-330]). On the other hand, after injection of BDA into the dorsolateral part of the PAG, only a few BDA-labeled axons were seen in Barrington's nucleus or the D-region. BDA-labeled axon terminals were electron microscopically confirmed to be in synaptic contact with HRP-labeled dendrites and somata in Barrington's nucleus and the D-region. The results indicate that the ventrolateral part of the PAG is implicated in regulation of the micturition reflex.

Animals↗
PubMed1999

Direct projections from the medial preoptic area to spinally-projecting neurons in Barrington's nucleus: an electron microscope study in the rat.

Direct projections from the medial preoptic area (MPO) to the pontine micturition center neurons directly projecting to the lumbosacral spinal cord were revealed electron microscopically in the rat by a double labeling method. Biotinylated dextran amine (BDA) was injected into the MPO and horseradish peroxidase (HRP) was injected into the lumbosacral cord segments. At light microscopic level, BDA-labeled presumptive axon terminals completely overlapped with HRP-labeled neurons in Barrington's nucleus. Electron microscopic observation showed that some BDA-labeled axon terminals made synaptic contacts with dendrites of HRP-labeled neurons in Barrington's nucleus. The present results indicated that the MPO may be involved in the modulation of the pontine micturition reflex in the rat.

Animals↗
PubMed2000

Beta-endorphin-, adrenocorticotrophic hormone- and neuropeptide y-containing projection fibers from the arcuate hypothalamic nucleus make synaptic contacts on to nucleus preopticus medianus neurons projecting to the paraventricular hypothalamic nucleus in the rat.

The nucleus preopticus medianus is known to be situated in a key site in pathways regulating the paraventricular hypothalamic nucleus. To investigate the innervation pattern to nucleus preopticus medianus neurons by afferent fibers containing beta-endorphin, adrenocorticotrophic hormone and neuropeptide Y, a retrograde tracing method was combined with immunohistochemistry for these peptides in the rat. In the first experiment with injection of a retrograde tracer in the nucleus preopticus medianus, retrogradely labeled neurons were found in many regions throughout the brain. Among these, the arcuate hypothalamic nucleus contained a number of retrogradely labeled neurons showing immunoreactivity to the neuropeptides examined. About 20%, 20% and 40% of retrogradely labeled arcuate hypothalamic nucleus neurons showed beta-endorphin, adrenocorticotrophic hormone and neuropeptide Y immunoreactivity, respectively. About 18% and 57% of retrogradely labeled neurons in the nucleus tractus solitarius and ventrolateral medulla, respectively, were immunoreactive to neuropeptide Y. There were many more neuropeptide Y-immunoreactive projections to the nucleus preopticus medianus from the arcuate hypothalamic nucleus than those from the medulla. None of the retrogradely labeled neurons in the medulla showed immunoreactivity to beta-endorphin or adrenocorticotrophic hormone. In the second experiment with injection of a retrograde tracer in the paraventricular hypothalamic nucleus, electron microscopic observation revealed that retrogradely labeled neurons in the nucleus preopticus medianus were in synaptic contact with beta-endorphin-, adrenocorticotrophic hormone- and neuropeptide Y-immunoreactive axon terminals. The present finding indicates that nucleus preopticus medianus neurons projecting to the paraventricular hypothalamic nucleus are innervated by beta-endorphin-, adrenocorticotrophic hormone- and neuropeptide Y-containing arcuate hypothalamic nucleus neurons in addition to being innervated by neuropeptide Y-containing catecholaminergic medullary neurons which have been reported in our previous study.

Adrenocorticotropic Hormone↗
PubMed1999

Identification of an efferent projection from the paraventricular nucleus of the hypothalamus terminating close to spinally projecting rostral ventrolateral medullary neurons.

The paraventricular nucleus of the hypothalamus is increasingly being viewed as an important site for cardiovascular integration because of its connections to regions in the brain and spinal cord which are known to be important in cardiovascular control. Like the vasomotor neurons of the rostral ventrolateral medulla, descending axons from paraventricular neurons can be identified that form synapses on sympathetic preganglionic neurons in the thoracic spinal cord. The purpose of this study was to determine whether paraventricular axons project to the rostral ventrolateral medulla and whether they are closely apposed to reticulospinal neurons in this region. Descending paraventricular axons were labelled with biotin dextran amine, while rostral ventrolateral medullary neurons were retrogradely labelled from the spinal cord with wheatgerm agglutinin conjugated to horseradish peroxidase. This revealed, within the rostral ventrolateral medulla, paraventricular axon and terminal varicosities closely apposed to and apparently contiguous with retrogradely labelled spinally projecting neurons. Thus our study at the light microscopical level has shown the potential for the paraventricular nucleus to directly influence rostral ventrolateral reticulospinal neurons. We suggest these connections, if confirmed by electron microscopy, could be one means by which activation of paraventricular neurons elicits alterations in blood pressure.

Animals↗
PubMed1999

Excitatory projections from the anterior hypothalamus to periaqueductal gray neurons that project to the medulla: a functional anatomical study.

The present study was designed to investigate the organization of excitatory projections from regions of the anterior hypothalamus that are known to co-ordinate autonomic and sensory functions to medullo-output neurons in the periaqueductal gray. The induction of Fos protein was used to identify neurons in the periaqueductal gray that were activated synaptically by chemical stimulation at sites in the anterior hypothalamus from which either increases or decreases in arterial blood pressure were evoked (pressor sites and depressor sites, respectively). This was combined with retrograde tracing using fluorescent latex microspheres from sites in the medulla. When compared to control animals, neuronal activation at pressor sites in the anterior hypothalamus evoked Fos-like immunoreactivity in significantly more neurons in all but one sub-division of the periaqueductal gray (P at least < 0.05). The majority of Fos-positive neurons following a pressor response were located in the caudal half of the periaqueductal gray where significantly more neurons contained Fos-like immunoreactivity in lateral than in any other sub-division (P < 0.01). In all but two of 14 subdivisions of the periaqueductal gray, the numbers of neurons that expressed Fos-like immunoreactivity following stimulation at depressor sites in the anterior hypothalamus were not significantly different from controls. When neuronal activation at pressor or depressor sites in the anterior hypothalamus was combined with retrograde tracing from the rostral ventrolateral medulla, nucleus raphe magnus and/or nucleus raphe obscurus the majority of double-labelled neurons were located in the caudal half of the periaqueductal gray. Comparisons between the numbers of double-labelled neurons that resulted from different combinations of hypothalamic and medullary injection sites revealed that neuronal activation at pressor sites in the anterior hypothalamus combined with retrograde tracing from the rostral ventrolateral medulla resulted in the greatest numbers of double-labelled neurons. The identification of double-labelled neurons indicates that medullo-output neurons in the periaqueductal gray receive excitatory inputs predominantly from pressor compared to depressor sites in the anterior hypothalamus. These results are discussed in relation to the roles of the different longitudinal columns of the periaqueductal gray, and the organisation of their projections to the medulla, in the co-ordination of autonomic and sensory functions.

Animals↗
PubMed2006

Determinants of nutrition improvement in a large-scale urban project: a follow-up study of children participating in the Senegal Community Nutrition Project.

OBJECTIVE: To study individual determinants of differential benefit from the Senegal Community Nutrition Project (CNP) by monitoring improvement in children's weight-for-age index (WA) or underweight status (WA < -2 Z-scores) during participation. DESIGN: A follow-up study using the CNP child monitoring data. Linear general models compared variations in WA according to 14 factors describing the beneficiaries and CNP services. SETTING: Poor neighbourhoods of Diourbel, a large city in Senegal, West Africa. Over a 6-month period, the CNP provided underweight or nutritionally at-risk 6-35-month-old children with monthly growth monitoring and promotion and weekly food supplementation, provided that mothers attended weekly nutrition education sessions. SUBJECTS: All the children who participated in the first two years of the project (n=4084). RESULTS: Mean WA varied from -2.13 (standard deviation (SD) 0.82) to -1.58 (SD 0.81) Z-scores between recruitment and the end of the follow-up. The lower the child's initial WA, the greater was their increase in WA but the lower was the probability of recovery from underweight. Only 61% of underweight children recovered. Six months of CNP services may not be sufficient for catch-up growth of severely underweight children. The number of food supplement rations received was not a direct indicator of the probability of recovery. After adjustment for services received and initial WA, probability of recovery was lower in girls, in younger children, in twins and when mothers belonged to a specific ethnic group. CONCLUSIONS: Determinants of benefit from CNP differed from the risk factors for underweight. Identification of participants with a lower probability of recovery can help improve outcome. Moreover, an explanation for the lack of recovery could be that many underweight children are stunted but not necessarily wasted.

Adult↗
PubMed2004

The organization of the corticonuclear and olivocerebellar climbing fiber projections to the rat cerebellar vermis: the congruence of projection zones and the zebrin pattern.

The zonal organization of the corticonuclear and the olivocerebellar climbing fiber projections to the vermis of the cerebellum of the rat was compared to the pattern of zebrin-positive and zebrin-negative bands in material double-stained for zebrin II and for different anterograde tracers injected in subnuclei of the inferior olive, or retrograde tracers injected in the cerebellar and vestibular target nuclei of the Purkinje cells of the vermis. Projection zones A(1), A(X), X, B, C(X) in the vermis and A(2) (accessory A zone) and C(2) in the hemisphere were defined by their efferent corticonuclear and their afferent climbing fiber connections, and were found to share the same topographical framework with the zebrin pattern.

Animals↗
PubMed1999

Do superior colliculus projection zones in the inferior pulvinar project to MT in primates?

In order to determine the relationship of superior colliculus inputs to thalamic neurons projecting to the middle temporal visual area (MT), injections of wheat germ agglutinin conjugated with horseradish peroxidase were placed in the superior colliculus of three owl monkeys, with injections of Fast Blue in the MT. The locations of labelled terminals and neurons in the posterior thalamus were related to four architectonically distinct nuclei of the inferior pulvinar (Stepniewska & Kaas, Vis. Neurosci. 14, pp.1043-1060, 1997). Fast Blue injections in the MT labelled neurons largely in the medial nucleus of the inferior pulvinar. A few labelled neurons were found in the adjoining central medial nucleus of the inferior pulvinar, as well as in the lateral pulvinar and the dorsal lateral geniculate nucleus. Superior colliculus inputs were most dense in the posterior and medial nuclei of the inferior pulvinar. There were sparser inputs to the central lateral nucleus of the inferior pulvinar, locations in the lateral and medial pulvinar, and the dorsal lateral geniculate nucleus. The results indicate that the medial nucleus of the inferior pulvinar, the major projection zone to the MT, does not receive a significant input from the superior colliculus.

Animals↗
PubMed2003

European Emergency Data Project (EED Project): EMS data-based health surveillance system.

Emergency Medical Services (EMS) constitute a unique component of health care at the interface between primary and hospital care. EMS data within the pre-hospital setting represents an unparalleled source of epidemiological and health care information that have so far been neglected for public health monitoring. The European Emergency Data Project (EED Project) thus intends to identify common indicators for European EMS systems and to evaluate their suitability for integration into a comprehensive public health monitoring strategy. The article provides a brief overview on objectives and methodology in the form of a progress report.

Benchmarking↗
PubMed1999

The Berkeley Drosophila Genome Project gene disruption project: Single P-element insertions mutating 25% of vital Drosophila genes.

A fundamental goal of genetics and functional genomics is to identify and mutate every gene in model organisms such as Drosophila melanogaster. The Berkeley Drosophila Genome Project (BDGP) gene disruption project generates single P-element insertion strains that each mutate unique genomic open reading frames. Such strains strongly facilitate further genetic and molecular studies of the disrupted loci, but it has remained unclear if P elements can be used to mutate all Drosophila genes. We now report that the primary collection has grown to contain 1045 strains that disrupt more than 25% of the estimated 3600 Drosophila genes that are essential for adult viability. Of these P insertions, 67% have been verified by genetic tests to cause the associated recessive mutant phenotypes, and the validity of most of the remaining lines is predicted on statistical grounds. Sequences flanking >920 insertions have been determined to exactly position them in the genome and to identify 376 potentially affected transcripts from collections of EST sequences. Strains in the BDGP collection are available from the Bloomington Stock Center and have already assisted the research community in characterizing >250 Drosophila genes. The likely identity of 131 additional genes in the collection is reported here. Our results show that Drosophila genes have a wide range of sensitivity to inactivation by P elements, and provide a rationale for greatly expanding the BDGP primary collection based entirely on insertion site sequencing. We predict that this approach can bring >85% of all Drosophila open reading frames under experimental control.

Alleles↗
PubMed1995

A European project assessing the appropriateness of hospital utilization: background, objectives and preliminary results. The Project Steering Group and the Coordinating Center.

This paper presents the background, objectives and preliminary results of a coordinated European Project involving researchers in seven countries aimed at harmonizing methods to assess inappropriate use of hospital care and qualifying its determinants. After briefly reviewing the philosophy of the European Union "Concerted Action" program in the context of current attempts at reforming the way health care is financed and delivered in several member states, the paper presents results obtained so far. Besides a method workshop where the approaches and methodologies used were compared, during the first year the following tasks have been undertaken: (a) identification and appraisal of a few dozen empirical studies conducted in various countries; (b) qualitative comparison of the instruments used to assess appropriateness; (c) initial development of a common list of reasons for inappropriate hospital use of potential relevance in European health care systems. While the project has already undoubtedly indicated the great potential of European collaboration in health services research, the large number of unpublished studies traced indicates--among other things--the need to create channels through which results of this type of research can be disseminated.

Algorithms↗
PubMed1980

The SENIC Project. Study on the efficacy of nosocomial infection control (SENIC Project). Summary of study design.

With the emergence of nosocomial infections as a serious problem among US hospitals, the Center for Disease Control undertook in 1974 a nationwide study to evaluate approaches to infection control. The three-phased project, now known as the Study on the Efficacy of Nosocomial Infection Control, or SENIC Project, was designed with three primary objectives: 1) to determine whether (and, if so, to what degree) the implementation of infection surveillance and control programs (ISCPs) has lowered the rate ofnosocomi al infection, 2) to describe the current status of ISCPs and infection rates, and 3) to demonstrate the relationships among characteristics of hospitals and patients, components of ISCPs, and changes in the infection rate. With data collection completed in a nationally representative sample of hospitals, analysis is underway to identify approaches to infection control that are most effective for the least cost to hospitals and to point out additional specific questions to be answered by future research.

Centers for Disease Control and Prevention, U.S.↗
PubMed1988

Projected increases in the number of dementia cases for 29 developed countries: application of a new method for making projections.

A method is described for making projections of increases in dementia cases over a given base year. The method is based on a statistical model relating dementia prevalence to age that is derived from the results of all published prevalence studies. This method was applied to United Nations population projections for 29 developed countries to arrive at expected increases in number of dementia cases in each country for the period 1980 to 2025.

Aged↗
PubMed2004

The UNAIDS Estimation and Projection Package: a software package to estimate and project national HIV epidemics.

This paper describes the Estimation and Projection Package (EPP) for estimating and projecting HIV prevalence levels in countries with generalised epidemics. The paper gives an overall summary of the software and interface. It describes the process of defining and modelling a national epidemic in terms of locally relevant sub-epidemics and the four epidemiological parameters used to fit a curve to produce the prevalence trends in the epidemic. It also provides an example of using the EPP in a country with a generalised epidemic. The paper discusses the strengths and weaknesses of the software and its envisaged future developments.

Adolescent↗
PubMed2006

Improving projections at the country level: the UNAIDS Estimation and Projection Package 2005.

BACKGROUND: UNAIDS has developed the Estimation and Projection Package (EPP) as a tool for national programmes to use for making national estimates and short term projections of HIV prevalence. EPP provides direct input to Spectrum, which produces incidence, deaths, and AIDS impacts. METHODS: The latest version, EPP 2005, includes substantial methodological improvements over the previous version. These include: (1) parallel, but unique, interfaces for generalised and concentrated epidemics; (2) use of maximum likelihood fitting procedures; (3) a new procedure, known as level fits, adjusting for expansion of national surveillance systems into lower prevalence sites; (4) provisions for handling turnover in at-risk populations, including the reassignment of HIV positive former members to lower risk populations; and (5) user-defined calibration to HIV prevalence levels from general population or other epidemiological surveys. RESULTS: Following regional training in mid 2005, this new version has been applied by many national programmes to make their end of 2005 estimates of HIV infections. UNAIDS has combined these national estimates to form the 2005 global HIV and AIDS estimates. CONCLUSION: EPP 2005 is a substantial improvement over previous versions, forming a solid base for the next round of modifications. Proposed modifications for that next version are presented for the reader's information.

Disease Outbreaks↗