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PubMed1993

Analysis of the immunohistochemical localization of collagen type III and V for the time-estimation of human skin wounds.

Collagen type III and V were visualized immunohistochemically in 79 surgically treated human skin wounds with a wound age between 8 h and 2.5 months. Network-like structures positively staining for collagen type III and associated with fibroblastic cells in the wound area were first detectable in a 2.5-day-old skin lesion and occurred regularly in wounds more than 5 days old. Collagen type V appeared first in the wound area after about 3 days, slightly later than collagen type III, and was detectable regularly in wounds with a survival time of 6 days or more. The immunohistochemical detection of collagen type III or type V thus indicates a wound age of at least 2-3 days. The lack of a positive reaction in a sufficient number of specimens indicates a wound age of less than 6 days. Even though both collagen types could also be detected in older wounds (wound age 2.5 months), further information for the time-estimation of older skin wounds cannot be given due to the observation that the time period during which reparative processes can be observed depends on the extent of the wound area.

Collagen↗

PubMed2005

A network approach for researching partnerships in health.

BACKGROUND: The last decade has witnessed a significant move towards new modes of governing that are based on coordination and collaboration. In particular, local level partnerships have been widely introduced around the world. There are few comprehensive approaches for researching the effects of these partnerships. The aim of this paper is to outline a network approach that combines structure and agency based explanations to research partnerships in health. Network research based on two Primary Care Partnerships (PCPs) in Victoria is used to demonstrate the utility of this approach. The paper examines multiple types of ties between people (structure), and the use and value of relationships to partners (agency), using interviews with the people involved in two PCPs--one in metropolitan Melbourne and one in a rural area. RESULTS: Network maps of ties based on work, strategic information and policy advice, show that there are many strong connections in both PCPs. Not surprisingly, PCP staff are central and highly connected. Of more interest are the ties that are dependent on these dedicated partnership staff, as they reveal which actors become weakly linked or disconnected without them. Network measures indicate that work ties are the most dispersed and strategic information ties are the most concentrated around fewer people. Divisions of general practice are weakly linked, while local government officials and Department of Human Services (DHS) regional staff appear to play important bridging roles. Finally, the relationships between partners have changed and improved, and most of those interviewed value their new or improved links with partners. CONCLUSION: Improving service coordination and health promotion planning requires engaging people and building strong relationships. Mapping ties is a useful means for assessing the strengths and weaknesses of partnerships, and network analysis indicates concentration and dispersion, the importance of particular individuals, and the points at which they will fragment. A narrative approach adds an assessment of whether the partnerships are being used and valued. The approach outlined here, which examines structure and agency as separate but related explanations, has much to offer in examining partnerships.

Journal Article↗

PubMed2003

Attenuation of neuropathic manifestations by local block of the activities of the ventrolateral orbito-frontal area in the rat.

Clinical and recent imaging reports demonstrate the involvement of various cerebral prefrontal areas in the processing of pain. This has received further confirmation from animal experimentation showing an alteration of the threshold of acute nociceptive reflexes by various manipulations in the orbito-frontal cortical areas. The present study investigates the possible involvement of this area in the modulation of neuropathic manifestations in awake rats. Several groups of rats were subjected to mononeuropathy following the spared nerve injury model, known to produce evident tactile and cold allodynia and heat hyperalgesia. The activity of the ventrolateral orbital areas was selectively blocked by using either chronic or acute injection of lidocaine, electrolytic lesion, or chemical lesion with kainic acid or 6-hydroxydopamine (6-OHDA). The effects of these manipulations were compared with those following lesion of the somatic sensorimotor cortical areas. Local injection of lidocaine resulted in a reversible depression of all neuropathic manifestations while electrolytic or chemical lesions elicited transient attenuation affecting mainly the heat hyperalgesia and to a lesser extent the cold allodynia. The magnitude of the observed effects with the different procedures used can be ranked as follows: 6-OHDA<lesion<electrolytic lesion<kainic acid lesion<lidocaine injection. The observed effects were transient despite the permanence of the lesions while lesion of the somatosensorimotor cortices produced sustained reduction of the neuropathic manifestations. Our results correlate well with the established connections of the ventrolateral orbital area with the thalamic nucleus subnucleus involved in the procession of thermal nociception. The transient effects reported following permanent lesions in the orbital areas may reflect its flexible role in pain modulation. This observation provides further evidence on the plasticity of the neural networks involved in the regulation of nociceptive behavior.

Adrenergic Agents↗

PubMed2000

An AB recombinant and its parental HIV type 1 strains in the area of the former Soviet Union: low requirements for sequence identity in recombination. UNAIDS Virus Isolation Network.

In the former Soviet Union (SU) increasing numbers of HIV-1 infections among injecting drug users (IDU) have been reported, especially in the Ukraine. The main subtype transmitted among the IDUs seems to be subtype A, but limited numbers of subtype B cases have also been reported. In Kaliningrad, Russia, an AB recombinant strain was earlier shown to be responsible for the local outbreak. Here we describe the genetic relationship of HIV-1 strains circulating among IDUs in the former SU. For subtype A and the AB recombinant strains nearly full-length genomes were sequenced, and for one subtype B strain the entire envelope gene was cloned. The relationship between the AB recombinant strain and the subtype A and subtype B strains and the mosaic structure of the recombinant was studied by phylogenetic analysis. Ukrainian A and B strains were shown to be the probable parental viruses of the Kaliningrad AB recombinant strain. In the envelope gene the recombination breakpoint could also be precisely mapped to a region of similarity of only 14 base pairs. This suggests that only short stretches of absolute sequence identity may be needed for efficient RNA recombination between HIV-1 subtypes.

Base Sequence↗

PubMed1999

Neurocircuitries of the basal ganglia studied in organotypic cultures: focus on tyrosine hydroxylase, nitric oxide synthase and neuropeptide immunocytochemistry.

The nigrostriatal and mesolimbic systems of the rat were reconstructed using an organotypic culture model, whereby neonatal brain tissue was grown in vitro for approximately one month. The nigrostriatal system comprised of tissue from the substantia nigra, the dorsal striatum and the frontoparietal cortex, while the mesolimbic system included the ventral tegmental area, ventral striatum (including the fundus striati, accumbens nucleus, olfactory tubercle, lateral septum, ventral pallidum and piriform cortex) and cingulate cortex. These regions were also cultured alone or in pairs. The cultures were monitored in vitro, and after one month fixed in a formalin-picric acid solution, and processed for immunohistochemistry using antibodies raised against tyrosine hydroxylase, nitric oxide synthase, preprocholecystokinin, glutamate decarboxylase, neuropeptide Y, dopamine- and cyclic AMP-regulated phosphoprotein-32 and glial fibrillary acidic protein. The tissue survived in single, double or triple cultures, although differences were found depending upon the source and combination of cultured region. Neurons had localization and shape as in vivo. Local networks were especially prominent in the mesencephalon, where both tyrosine hydroxylase-positive axons spread from the "substantia nigra" to the rest of the tissue, and where nitric oxide synthase-positive networks also surrounded tyrosine hydroxylase-positive neurons. Glutamate decarboxylase-positive nerve terminals formed dense networks around tyrosine hydroxylase-positive neurons. In the striatum, nitric oxide synthase and dopamine- and cyclic AMP-regulated phosphoprotein-32 neurons were surrounded by tyrosine hydroxylase-positive nerve terminals. The nigral and ventral tegmental area dopamine neurons projected to striatal and cortical structures, but the projection from the ventral tegmental area to the cingulate cortex was more prominent. With regard to co-existence, preprochole-cystokinin-like immunoreactivities was found in many tyrosine hydroxylase-positive neurons and neuropeptide Y- and nitric oxide synthase-like immunoreactivity co-existed in striatal and cortical tissues. In general terms, the chemical neuroanatomy in the cultures was similar to that described earlier in vivo. Nitric oxide synthase staining was particularly intense. Taken together, the organotypic model captures many of the morphological and neurochemical features seen in vivo, providing a valuable model for studying neurocircuitries of the brain in detail, where 'normal' and 'pathological' conditions can be simulated.

Animals↗

PubMed1995

Selective transport of blood-borne interleukin-1 alpha into the posterior division of the septum of the mouse brain.

Film autoradiography was used to demonstrate the transport and sites of accumulation of blood-borne radioiodinated interleukin-1 alpha (II-1 alpha) and other cytokines into the brain after intravenous administration. [125 I]Il-1 alpha, [125I]Il-1 beta, [125I]interleukin-1 receptor antagonist (II-1ra), and [125I]tumor necrosis factor-alpha (TNF alpha) labeled the choroid plexus and the capillary network 30 min after injection into the blood, suggesting that these areas may serve as sites of blood-to-brain transport. [125I]Il-1alpha, but not [125I]Il-1beta, [125I]Il-1ra, [125I]TNF alpha, or [125I]interleukin-2 (Il-2), was also found localized to the caudal region of the septal nuclei. Only unlabeled II-1 alpha was able to inhibit this accumulation. These findings provide further evidence for the passage of select cytokines across the blood-brain barrier (BBB) and are the first to identify a target site within the central nervous system (CNS) for a transported cytokine.

Animals↗

PubMed1998

Recognition memory in rats--II. Neuroanatomical substrates.

A discussion of the neuroanatomical systems thought to be of importance for the mediation of recognition memory in the rat warrants consideration of different, but not necessarily exclusive concepts. An important concept is the hypothesis that a dichotomy in the neural systems mediating spatial and non-spatial (item) memory exists in the rat. We have adopted a model of recognition memory suggesting that information about previously encountered items is stored in a dynamic pattern of neural activity and not in a localized representation. These patterns are features of distributed neuronal networks and different networks may process different forms of recognition memory. Two parallel-distributed neuronal networks are proposed in the rat. Network 1 is essential for the processing of non-spatial/item recognition memory processes and incorporates the cortical association areas such as TE1, TE2 and TE3, the rhinal cortices, the mediodorsal thalamic nucleus and prefrontal cortical areas. Network 2 comprises the hippocampus, mamillary bodies, anterior thalamic nuclei and medial prefrontal areas, especially the prelimbic cortex, and is suggested to be pivotal for the processing of spatial recognition memory.

Animals↗

PubMed1998

Influence of speech-coding strategy on cortical activity in cochlear implant users: a positron emission tomographic study.

The effects of a speech-coding strategy of cochlear implant (CI) on cortical activity were evaluated using positron emission tomography. The CIs used in the present study were those of a 22-channel system using the Multipeak speech-coding strategy (MPEAK) and the spectral peak strategy (SPEAK). On comparing the 2 groups, it was found that the speech-tracking performance was significantly higher in the SPEAK group than in the MPEAK group. Regional cerebral blood flow (rCBF) was measured during the silent resting, noise stimulus and speech stimulus periods. The increase in rCBF was localized mainly in the primary auditory area during the noise stimulus period. The increase in rCBF in the auditory association area during the speech stimulus period was stronger in the SPEAK group than in the MPEAK group. This finding suggests that the SPEAK strategy activates more speech processing neuronal networks in the auditory association area than the MPEAK strategy.

Acoustic Stimulation↗

PubMed2003

Plasticity of cortical projections after stroke.

Ischemic stroke produces cell death and disability, and a process of repair and partial recovery. Plasticity within cortical connections after stroke leads to partial recovery of function after the initial injury. Physiologically, cortical connections after stroke become hyperexcitable and more susceptible to the induction of LTP Stroke produces changes in the distribution and laterality of sensory, motor, and language representations within the brain that correlate with functional recovery. Anatomically, ischemic lesions induce axonal sprouting within local, intracortical projections and long distance, interhemispheric projections. This postischemic axonal sprouting establishes substantially new patterns of cortical connections with de-afferented or partially damaged brain areas. Axonal sprouting after ischemic lesions is induced by a transient pattern of synchronous, low-frequency neuronal activity in a network of cortical areas connected to the infarct. This pattern of neuronal activity that induces axonal sprouting in the adult after ischemic lesions resembles that seen in the developing brain during axonal elongation and synaptogenesis. Thus, stroke induces a process of remapping and reconnection within the adult brain through changes in neuronal activity that may involve a reactivation of developmental programs in areas connected to the infarct.

Animals↗

PubMed1989

Current comment. (xxii) Traveller-Gypsies and general practitioners in East London: the role of the Traveller health visitor.

Traveller-Gypsy communities in the United Kingdom (UK) have higher morbidity and mortality levels than the national average and their members have only limited access to primary and preventative health care services in most areas. Results of a questionnaire survey of general practitioners (GPs) in East London support previous evidence that the appointment of specially trained health visitors could help improve levels of understanding between GPs and Traveller families and so help Travellers make more effective use of conventional local primary care networks. The relevance of this specific example for other minority populations is evident.

Ethnicity↗

PubMed2000

Measuring the "managedness" and covered benefits of health plans.

STUDY AIMS: (1) To develop indexes measuring the degree of managedness and the covered benefits of health insurance plans, (2) to describe the variation in these indexes among plans in one health insurance market, (3) to assess the validity of the health plan indexes, and (4) to examine the association between patient characteristics and the health plan indexes. Measures of the "managedness" and covered benefits of health plans are requisite for studying the effects of managed care on clinical practice and health system performance, and they may improve people's understanding of our complex health care system. DATA SOURCES/STUDY SETTING: As part of our larger Physician Referral Study, we collected health insurance information for 189 insurance product lines and 755 products in the Seattle, Washington metropolitan area, which we linked with the study's data for 2,277 patients recruited in local primary care offices. STUDY DESIGN: Managed care and benefit variables were constructed through content analysis of health plan information. Principal component analysis of the variables produced a managedness index, an in-network benefits index, and an out-of-network benefits index. Bivariable analyses examined associations between patient characteristics and the three indexes. PRINCIPAL FINDINGS: From the managed care variables, we constructed three provider-oriented indexes for the financial, utilization management, and network domains of health plans. From these, we constructed a single managedness index, which correlated as expected with the individual measures, with the domain indexes, with plan type (FFS, PPO, POS, HMO), with independent assessments of local experts, and with patients' attitudes about their health insurance. For benefits, we constructed an in-network benefits index and an out-of-network benefits index, which were correlated with the managedness index. The personal characteristics of study patients were associated with the managed care and benefit indexes. Study patients in more managed plans reported somewhat better health than patients in less managed plans. CONCLUSIONS: Indexes of the managedness and benefits of health plans can be constructed from publicly available information. The managedness and benefit indexes are associated with the personal characteristics and health status of study patients. Potential uses of the managed care and benefits indexes are discussed.

Abstracting and Indexing↗

PubMed1988

[The structuro-functional modulus of the microcirculatory network of the cerebral cortex in rats].

Complex investigation carried out in rats with the aid of polarographic microelectrodes revealed a mosaic distribution of blood supply within a small volume of nerve tissue in resting. The activation of cortical neurons was accompanied by local functional hyperemia and increased level of oxygen available. The hyperemia spread over a 200-300 mu area corresponding to the sides of neuronal columns. The data obtained have shown that the system of the cortex blood circulation and oxygen transport to neural tissues is based on a special microcirculatory module responsible for circulatory-metabolic supply of separate groups of neurons and composed as vertically oriented columns.

Animals↗

PubMed2006

Enhancing palliative care delivery in a regional community in Australia.

Although access to palliative care is a fundamental right for people in Australia and is endorsed by government policy, there is often limited access to specialist palliative care services in regional, rural and remote areas. This article appraises the evidence pertaining to palliative care service delivery to inform a sustainable model of palliative care that meets the needs of a regional population on the mid-north coast of New South Wales. Expert consultation and an eclectic literature review were undertaken to develop a model of palliative care service delivery appropriate to the needs of the target population and resources of the local community. On the basis of this review, a local palliative care system that is based on a population-based approach to service planning and delivery, with formalized integrated network agreements and role delineation between specialist and generalist providers, has the greatest potential to meet the palliative care needs of this regional coastal community.

Aged↗

PubMed2005

New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical electrostimulations.

Despite a better understanding of the organization of the cortical network underlying the semantic system, very few data are currently available regarding its anatomo-functional connectivity. Here, we report on a series of 17 patients operated on under local anaesthesia for a cerebral low-grade glioma located within the dominant hemisphere. Prior to and during resection, intraoperative electrical stimulation was used to map sensorimotor and language structures so that permanent neurological deficits could be avoided. In a number of cases, cortical and subcortical stimulation caused semantic paraphasias. Using postoperative MRI, we correlated these functional findings with the anatomical locations of the sites where semantic errors were elicited by stimulation, especially at the subcortical level, with the aim of studying the connectivity underlying the semantic system. In temporal gliomas, cortical sites involved in semantic processing were found around the posterior part of the superior temporal sulcus, with subcortical pathways reproducibly located under the depth of this sulcus. In insular gliomas, although stimulation elicited no semantic disturbances at the cortical level, such semantic paraphasias were generated at the level of the anterior floor of the external capsule. In frontal tumours, cortical regions implicated in semantics were detected in the lateral orbitofrontal region and dorsolateral prefrontal cortex, with subcortical fibres located under the inferior frontal sulcus. All these eloquent structures were systematically preserved, thereby avoiding permanent postoperative deficits. Our results provide arguments in favour of the existence of a main ventral subcortical pathway underlying the semantic system, within the dominant hemisphere, joining the two essential cortical epicentres of this network: the posterior and superior temporal areas, and the orbitofrontal and dorsolateral prefontal regions. Such a ventral stream might anatomically partly correspond to the inferior fronto-occipital fasciculus.

Adolescent↗

PubMed2001

Breast cancer audit: adapting national audit frameworks for local review of clinical practice.

OBJECTIVE: To assess the value of using a nationally devised data set for breast cancer audit at a local level for reviewing clinical practice. DESIGN: Audit proforma based on the Scottish Cancer Therapy Network (SCTN) minimum data set and database completed prospectively from January 1999. SETTING: Hairmyres Hospital, a district general hospital within Lanarkshire Acute Services NHS Trust. SUBJECTS: The inclusion criteria were those developed by SCTN for the core minimum data set for breast cancer (SCTN 1999). RESULTS: The results indicate that the SCTN minimum data set can be usefully employed to collect prospective data on breast cancer. The data set is sensitive enough to identify any problem areas, which can be reviewed at greater detail when required. This datset is a robust mechanism for collecting meaningful and comparable data both at a local and national level. CONCLUSIONS: The use of SCTN's minimum data set has been successful for local review of practice. This has led to the identification of "out-liers" from the normal range of process indicators and further internal examination of these at a local level by individual clinicians is under way. This exercise has also proved fruitful in identification of other fields, which can be added to the data set to refine the data collected. The database provided by SCTN is easily manipulated allowing for refinement where required. Breast cancer audit carried out in this way is a useful way of reflecting on clinical practice throughout the multidisciplinary team.

Breast Neoplasms↗

PubMed1987

Immunohistochemical evidence for a spinothalamic pathway co-containing cholecystokinin- and galanin-like immunoreactivities in the rat.

Using indirect immunofluorescence technique combined with retrograde tracing as well as surgical lesions, a system of spinothalamic neurons containing both galanin- and cholecystokinin-like immunoreactivity has been defined. The cell bodies are located in the lumbar segments L1-L5 with a preferential localization dorsal to the central canal at rostral levels and lateral to the canal at caudal levels. The cells project via the ventral part of the lateral funiculus to the most ventral and posterior parts of thalamus. Here a distinct, varicose terminal network was seen extending caudally from an area lateral to the medial lemniscus, running medially over the medial lemniscus, traversing the parafascicular nucleus and running dorsal to the fasciculus retroflexus into the periventricular gray matter. Transection of various parts of the spinal cord as well as retrograde tracing experiments indicate that the spinothalamic galanin cholecystokinin system represents a crossed pathway. The present results demonstrate that a spinothalamic system can be characterized by its content of galanin- and cholecystokinin-like peptides, two putative messenger molecules. It is only a minor component of the total spinothalamic projection.

Animals↗

PubMed2006

Propagation of spike and wave activity to the medial prefrontal cortex and dorsal raphe nucleus of WAG/Rij rats.

Although there is pharmacological evidence for the involvement of the serotonergic system in the expression of spike and wave discharges (SWDs) in experimental absence epilepsy, no direct investigation of this paroxysm in the dorsal raphe nucleus (DRN), one of the main serotonergic nuclei, has been carried out. We have now recorded the EEG simultaneously with local field potentials and unit activity in DRN from WAG/Rij rats, one of the best established models of absence epilepsy during spontaneous SWDs. We have also compared this activity to that in the thalamocortical networks, where SWDs are generated, and in the medial prefrontal cortex (mPFC), as this brain area is reciprocally connected to the DRN. We have found that SWDs propagate to the DRN with a short delay, and that the firing rate of its neurons changes during this type of paroxysm. These results provide the first direct evidence for clear alterations in the firing properties of mPFC and DRN neurons during spontaneous SWDs.

Action Potentials↗

PubMed2005

Role for dopamine neurons of the rostral linear nucleus and periaqueductal gray in the rewarding and sensitizing properties of heroin.

There is a mesencephalic dopaminergic network outside the ventral tegmental area (VTA), including structures such as the rostral linear nucleus (RLi) and periaqueductal gray (PAG). These nuclei project to neural areas implicated in reinforcing effects of drugs, indicating that they could participate in opiate reward. The objectives were to study the morphological characteristics of the dopamine network of the RLi/PAG region, and to discern its role on rewarding and sensitizing effects of heroin in rats, following dopamine depletion or local injection of dopaminergic antagonists. The findings indicated that this network is composed of small cells in the RLi/ventral PAG, large multipolar dopamine PAG neurons, and periaqueductal PAG neurons. Following repeated heroin, large PAG neurons and small RLi/ventral PAG cells (not periaqueductal neurons) were activated, since tyrosine-hydroxylase was adaptively induced, without changes in protein kinase Aalpha. After dopamine depletion, small RLi/ventral PAG neurons and large cells of the PAG (not periaqueductal ones) were selectively affected by the neurotoxin. Dopamine neurons of the nearby VTA and dorsal raphe were not affected, as revealed by cell counting. After lesion, 'anxiety-like' responses and basal locomotion were not altered. However, conditioned place preference to heroin was found to be abolished, as well as heroin-induced motor sensitization. Following infusions of dopaminergic antagonists into RLi/PAG, D(2) (not D(1)) receptor blocking dose-dependently abolished heroin-induced reward. The present study provides evidence that dopamine neurons of the RLi/PAG region (excluding PAG periaqueductal cells) show adaptive biochemical changes after heroin, and mediate the rewarding and sensitizing effects of this drug. D(2) dopamine receptors within the RLi/PAG region participate in these effects.

Analysis of Variance↗