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Dr John has gone: assessing health professionals' contribution to remote rural community sustainability in the UK.

Due mainly to increasing difficulties in recruiting and retaining health professionals to work in remote and peripheral areas of Scotland, there is discussion of the need to implement new models of primary health care provision. However, innovative service models may imply a reduction in the number of health professionals who live and work in remote communities. Currently decisions about remodelling service provision are being taken by National Health Service stakeholders, apparently with little consideration of the wider social and economic impacts of change. This paper aims to argue that health professionals contribute to the fabric of rural life in a number of ways and that decisions about health service redesign need to take this into account. As well as fulfilling a wide health and social care role for patients, the authors seek to show that health professionals are important to the social sustainability of rural communities as, due to their unique position, they are often at the heart of networks within and between communities. The wider economic contribution of health services in remote communities is important, but often underplayed. The authors propose that theories of capital, principally the concept of social capital, could help in investigating the wider contribution of health professionals to their local communities. Ultimately, it is proposed that health services, as embodied in nurses, doctors and others, could be highly important to the ongoing livelihood and social infrastructure of fragile remote communities. Since this area is poorly understood, there is a need for prospective primary research and evaluation of service redesign initiatives.

Community Health Nursing↗

Responses of auditory cortical neurons to pairs of sounds: correlates of fusion and localization.

When two brief sounds arrive at a listener's ears nearly simultaneously from different directions, localization of the sounds is described by "the precedence effect." At inter-stimulus delays (ISDs) <5 ms, listeners typically report hearing not two sounds but a single fused sound. The reported location of the fused image depends on the ISD. At ISDs of 1-4 ms, listeners point near the leading source (localization dominance). As the ISD is decreased from 0.8 to 0 ms, the fused image shifts toward a location midway between the two sources (summing localization). When an inter-stimulus level difference (ISLD) is imposed, judgements shift toward the more intense source. Spatial hearing, including the precedence effect, is thought to depend on the auditory cortex. Therefore we tested the hypothesis that the activity of cortical neurons signals the perceived location of fused pairs of sounds. We recorded the unit responses of cortical neurons in areas A1 and A2 of anesthetized cats. Single broadband clicks were presented from various frontal locations. Paired clicks were presented with various ISDs and ISLDs from two loudspeakers located 50 degrees to the left and right of midline. Units typically responded to single clicks or paired clicks with a single burst of spikes. Artificial neural networks were trained to recognize the spike patterns elicited by single clicks from various locations. The trained networks were then used to identify the locations signaled by unit responses to paired clicks. At ISDs of 1-4 ms, unit responses typically signaled locations near that of the leading source in agreement with localization dominance. Nonetheless the responses generally exhibited a substantial undershoot; this finding, too, accorded with psychophysical measurements. As the ISD was decreased from ~0.4 to 0 ms, network estimates typically shifted from the leading location toward the midline in agreement with summing localization. Furthermore a superposed ISLD shifted network estimates toward the more intense source, reaching an asymptote at an ISLD of 15-20 dB. To allow quantitative comparison of our physiological findings to psychophysical results, we performed human psychophysical experiments and made acoustical measurements from the ears of cats and humans. After accounting for the difference in head size between cats and humans, the responses of cortical units usually agreed with the responses of human listeners, although a sizable minority of units defied psychophysical expectations.

Action Potentials↗

Fibronectin in the area opaca of the young chick embryo. Immunofluorescence and immuno-electron-microscopic study.

Distribution of fibronectin-like immunoreactivity was studied in the area opaca of the young chick embryo (stages 4-6 HH) by use of the immunofluorescence and protein A-coupled to colloidal gold techniques. Fibronectin, associated to the basement membrane, formed a fibrillar network, the pattern of which changed from the centre to the periphery of the area opaca. At the ultrastructural level, differences in fibronectin distribution were found between non-moving and moving cells. The epithelial-like cells presented fibronectin staining exclusively on their basal side. Actively migrating cells (edge and mesodermal cells) showed immunoreactive material localized around their entire surface and within the cytoplasm. The fibronectin distribution is discussed in relation to three important phenomena taking place during the early growth of the area opaca: anchorage and migration of the edge cells, modification of cell shape in relation to mechanical tension, and expansion of the area vasculosa.

Animals↗

PET studies in dementia.

Measurement of local cerebral glucose metabolism (lCMRGlc) by positron emission tomography (PET) and 18F-2-fluoro-2-deoxy-D-glucose (FDG) has become a standard technique during the past 20 years and is now available at many university hospitals in all highly developed countries. Many studies have documented a close relation between lCMRGlc and localized cognitive functions, such as language and visuoconstructive abilities. Alzheimer's disease (AD) is characterized by regional impairment of cerebral glucose metabolism in neocortical association areas (posterior cingulate, temporoparietal and frontal multimodal association cortex), whereas primary visual and sensorimotor cortex, basal ganglia, and cerebellum are relatively well preserved. In a multicenter study comprising 10 PET centers (Network for Efficiency and Standardisation of Dementia Diagnosis, NEST-DD) that employed an automated voxel-based analysis of FDG PET images, the distinction between controls and AD patients was 93% sensitive and 93% specific, and even in very mild dementia (at MMSE 24 or higher) sensitivity was still 84% at 93% specificity. Significantly abnormal metabolism in mild cognitive deficit (MCI) indicates a high risk to develop dementia within the next two years. Reduced neocortical glucose metabolism can probably be detected with FDG PET in AD on average one year before onset of subjective cognitive impairment. In addition to glucose metabolism, specific tracers for dopamine synthesis (18F-F-DOPA) and for (11C-MP4A) are of interest for differentiation among dementia subtypes. Cortical acetylcholine esterase activity (AChE) activity is significantly lower in patients with AD or with dementia with Lewy bodies (DLB) than in age-matched normal controls. In LBD there is also impairment of dopamine synthesis, similar to Parkinson disease.

Acetylcholine↗

Integrated technology for evaluation of brain function and neural plasticity.

The study of neural plasticity has expanded rapidly in the past decades and has shown the remarkable ability of the developing, adult, and aging brain to be shaped by environmental inputs in health and after a lesion. Robust experimental evidence supports the hypothesis that neuronal aggregates adjacent to a lesion in the sensorimotor brain areas can take over progressively the function previously played by the damaged neurons. It definitely is accepted that such a reorganization modifies sensibly the interhemispheric differences in somatotopic organization of the sensorimotor cortices. This reorganization largely subtends clinical recovery of motor performances and sensorimotor integration after a stroke. Brain functional imaging studies show that recovery from hemiplegic strokes is associated with a marked reorganization of the activation patterns of specific brain structures. To regain hand motor control, the recovery process tends over time to bring the bilateral motor network activation toward a more normal intensity/extent, while overrecruiting simultaneously new areas, perhaps to sustain this process. Considerable intersubject variability exists in activation/hyperactivation pattern changes over time. Some patients display late-appearing dorsolateral prefrontal cortex activation, suggesting the development of "executive" strategies to compensate for the lost function. The AH in stroke often undergoes a significant "remodeling" of sensory and motor hand somatotopy outside the "normal" areas, or enlargement of the hand representation. The UH also undergoes reorganization, although to a lesser degree. Although absolute values of the investigated parameters fluctuate across subjects, secondary to individual anatomic variability, variation is minimal with regards to interhemispheric differences, due to the fact that individual morphometric characters are mirrored in the two hemispheres. Excessive interhemispheric asymmetry of the sensorimotor hand areas seems to be the parameter with highest sensitivity in describing brain reorganization after a monohemispheric lesion, and mapping motor and somatosensory cortical areas through focal TMS, fMRI, PET, EEG, and MEG is useful in studying hand representation and interhemispheric asymmetries in normal and pathologic conditions. TMS and MEG allow the detection of sensorimotor areas reshaping, as a result of either neuronal reorganization or recovery of the previously damaged neural network. These techniques have the advantage of high temporal resolution but also have limitations. TMS provides only bidimensional scalp maps, whereas MEG, even if giving three-dimensional mapping of generator sources, does so by means of inverse procedures that rely on the choice of a mathematical model of the head and the sources. These techniques do not test movement execution and sensorimotor integration as used in everyday life. fMRI and PET may provide the ideal means to integrate the findings obtained with the other two techniques. This multitechnology combined approach is at present the best way to test the presence and amount of plasticity phenomena underlying partial or total recovery of several functions, sensorimotor above all. Dynamic patterns of recovery are emerging progressively from the relevant literature. Enhanced recruitment of the affected cortex, be it spared perilesional tissue, as in the case of cortical stroke, or intact but deafferented cortex, as in subcortical strokes, seems to be the rule, a mechanism especially important in early postinsult stages. The transfer over time of preferential activation toward contralesional cortices, as observed in some cases, seems, however, to reflect a less efficient type of plastic reorganization, with some aspects of maladaptive plasticity. Reinforcing the use of the affected side can cause activation to increase again in the affected side with a corresponding enhancement of clinical function. Activation of the UH MI may represent recruitment of direct (uncrossed) corticospinal tracts and relate more to mirror movements, but it more likely reflects activity redistribution within preexisting bilateral, large-scale motor networks. Finally, activation of areas not normally engaged in the dysfunctional tasks, such as the dorsolateral prefrontal cortex or the superior parietal cortex in motor paralysis, might reflect the implication of compensatory cognitive strategies. An integrated approach with technologies able to investigate functional brain imaging is of considerable value in providing information on the excitability, extension, localization, and functional hierarchy of cortical brain areas. Deepening knowledge of the mechanisms regulating the long-term recovery (even if partial), observed for most neurologic sequelae after neural damage, might prompt newer and more efficacious therapeutic and rehabilitative strategies for neurologic diseases.

Animals↗

Ultrastructural localization of coenzyme A phosphatase (CoA-Pase) activity to the GERL system in secretory ameloblasts of the rat incisor.

Enzymatic hydrolysis of the monoester phosphate group from coenzyme A (CoA) was studied in rat incisor ameloblasts by incubating specimens from glutaraldehyde-fixed teeth in a cytochemical medium prepared with acetyl-CoA as substrate and lead ions as capture agent for phosphate. Ameloblasts incubated for 1 hr at 37 degrees C and at pH 5.0 in this medium showed reaction product localized almost exclusively along the trans (mature) aspect of the Golgi apparatus within a network of small granules and interconnecting tubular channels that comprise the GERL system in this cell. Reaction product was otherwise seen in trace amounts only within some Golgi saccules, a few lysosomal dense bodies and, in rare instances, within an occasional focal area of the endoplasmic reticulum. No selective staining of the GERL system was seen in control ameloblasts incubated at either pH 7.2 or pH 9.0 with acetyl-CoA as substrate, or incubated at pH 5.0 with dephospho-CoA as substrate. Control experiments at pH 5.0 also revealed that reaction product selectively stained the GERL system in ameloblasts when other molecules resembling CoA were used as substrate (e.g., crotonyl-CoA, 3'-NADP+), but not when adenosine 3'-monophosphate (3'-AMP) was used as substrate. That is, ameloblasts incubated at pH 5.0 with 3'-AMP showed heavy deposits of reaction product at many sites throughout the cell, including most lysosomal dense bodies, the Golgi saccules, the GERL system, most secretory granules, the nucleus, and extensively throughout the endoplasmic reticulum. These findings suggest that the GERL system of ameloblasts contains a CoA-specific phosphatase activity that may function to convert CoA to dephospho-CoA at acid pH. Biochemical studies included with this investigation further indicate that CoA-Pase activity saturates at exceptionally low concentrations of substrate (KM = 30 microM CoA) compared to other acid-dependent phosphatases.

Acid Phosphatase↗

Enhanced synchrony in epileptiform activity? Local versus distant phase synchronization in generalized seizures.

Synchronization is a fundamental characteristic of complex systems and a basic mechanism of self-organization. A traditional, accepted perspective on epileptiform activity holds that hypersynchrony covering large brain regions is a hallmark of generalized seizures. However, a few recent reports have described substantial fluctuations in synchrony before and during ictal events, thus raising questions as to the widespread synchronization notion. In this study, we used magnetoencephalographic recordings from epileptic patients with generalized seizures and normal control subjects to address the extent of the phase synchronization (phase locking) in local (neighboring) and distant cortical areas and to explore the ongoing temporal dynamics for particular ranges of frequencies at which synchrony occurs, during interictal and ictal activity. Synchronization patterns were found to differ somewhat depending on the epileptic syndrome, with primary generalized absence seizures displaying more long-range synchrony in all frequency bands studied (3-55 Hz) than generalized tonic motor seizures of secondary (symptomatic) generalized epilepsy or frontal lobe epilepsy. However, all seizures were characterized by enhanced local synchrony compared with distant synchrony. There were fluctuations in the synchrony between specific cortical areas that varied from seizure to seizure in the same patient, but in most of the seizures studied, regardless of semiology, there was a constant pattern in the dynamics of synchronization, indicating that seizures proceed by a recruitment of neighboring neuronal networks. Together, these data indicate that the concept of widespread "hypersynchronous" activity during generalized seizures may be misleading and valid only for very specific neuronal ensembles and circumstances.

Adolescent↗

[Functional recuperation following lesions of the primary somatosensory fields. Study of compensatory mechanisms].

During a long time, lesions of the primary somatosensory area (S I) were considered as generating severe and definitive neurological sequelae. However, recent reports described a recovery following stroke and resective surgeries (for epilepsy or tumor). On the basis of these observations, of experimentations in animals, and of studies of the (re)organization of eloquent areas in man using new methods of functional mapping, brain plasticity phenomena underlying the recovery were analyzed. They seems to implicate the recruitment of local areas (sensory redundancies within S I), regional areas (primary motor area, secondary somatosensory area, posterior parietal cortex, insula), controlateral eloquent regions, and even learning of new compensatory strategies. Such data could allow us to extend surgical indications of resection of lesions located within S I. An improvement of our knowledge of these functional reshaping phenomena (unmasking of latent networks and/or participation of eloquent homologous and/or sprouting) and then their prediction remains mandatory, with the goal to optimize the surgical preplanning in functional regions, taking account of the individual dynamic spatiotemporal cortical organization. This better knowledge seems to be obtained by studying the correlations between pre- and post-operative functional neuroimaging (fMRI, MEG) data, and the intraoperative functional mapping results.

Animals↗

Hospital cost drivers: an evaluation of 1998-2001 state-level data.

OBJECTIVE: To evaluate the determinants of increased hospital inpatient expenditure growth since 1998. DATA SOURCES AND METHODS: Multivariate regression analyses were estimated for 1998-2001 utilizing state-level information from nationally representative population sources, US government agencies, and aggregate expenditures estimated from a nationally representative large health insurance plan (LHIP). RESULTS: During 1998-2001, LHIP inpatient expenditures per member increased by an average of 5.9% annually, twice the 2.9% annual rate of inflation. Overall level of economic activity, price-level variation, hospital technology, hospital market, and healthcare labor force are the most important drivers of recent trends in inpatient expenditures. Inpatient costs were responsive to hospital market characteristics. Each 1% increase in for-profit and medical system (chain ownership) hospital percentage was associated with approximately a 2% increase in inpatient expenditures. Each 1% increase in network (shared purchasing or other arrangement, but not ownership) hospital percentage was associated with a 1% decrease in inpatient expenditures. Each 1% increase in the gap between registered nurse demand and supply led to a 0.5% to 1% increase in hospital inpatient expenditures per capita. CONCLUSIONS: Many characteristics contribute to inpatient expenditure growth, such as local area wages and incomes per capita, and physician market characteristics, but are not directly influenced by hospital market policies. Hospital technology and market structure are the 2 factors that are most directly amenable to healthcare policy intervention. Hospital occupancy and case-mix severity also have substantial effects on inpatient expenditure growth. With the nurse supply shortage projected to increase by 40% between 2000 and 2005, upward pressures on inpatient costs will remain.

Cost of Illness↗

A regional analysis of alpha-spectrin in the isolated Mauthner neuron and in isolated axons of the goldfish and rabbit.

Isolated dendrites, somata, and desheathed axons of the goldfish Mauthner neuron (M-cell), in addition to other isolated myelin sheath-free axons of the goldfish spinal cord and of rabbit lumbar ventral roots, were shown by immunochemical and immunofluorescence techniques to contain alpha-spectrin (fodrin). alpha-Spectrin appeared to be organized as a randomly distributed reticular network, localized to the surface of isolated neuronal cellular structures. In addition, alpha-spectrin was also distributed nonrandomly at specialized cellular sites. These sites included synaptic junctions and morphologically differentiated nodes of Ranvier (i.e., rabbit axons, but not goldfish axons). At the latter sites, it is possible to demonstrate that alpha-spectrin is co-localized with F-actin, as indicated by a striking correspondence of fluorescent images due to double labeling, using the indirect immunofluorescence technique with alpha-spectrin antiserum, and direct binding of F-actin by rhodamine-conjugated palloidin. However, the spectrin-actin network at synaptic junctions appears to be distributed over the entire area of junctional contact and is not just restricted to postsynaptic densities. The possibility of a duality of roles of spectrin in membrane-related motile and anchorage functions is discussed.

Animals↗

Local adjustment of blood and lymph circulation in the hormonal regulation of reproduction in female pigs--facts, conclusions and suggestions for future research.

Arteries, veins, capillaries and lymphatic vessels situated in the mesovarium and mesosalpinx of domestic animal species (pig, cow, sheep) form the periovarian vascular complex. Particular components of the periovarian vascular complex interact functionally and morphologically creating a specific environment for numerous physiological processes. The complex plays an essential role in the system of the retrograde transfer of the ovarian hormones. This phenomenon is especially well documented in pigs. The efficiency of the retrograde transfer of estradiol and progesterone from blood and lymph leaving the gonad to blood of the ovarian artery (expressed as percentage of their concentration in the ovarian venous blood) as well as the rate of the retrograde transfer of these hormones to the ovary (measured in nanograms or picograms per minute) is presented and discussed in this paper. No simple relationship was found between hormone concentration in ovarian venous effluent and the efficiency or the rate of their retrograde transfer during the estrous cycle. It appears that two processes contribute to the highly efficient retrograde transfer of ovarian hormones into the ovary in the periovarian vascular complex: 1/ direct hormone permeation from the ovarian vein into the adjacent branches of the ovarian artery through the counter-current mechanism; 2/ indirect permeation of ovarian hormones consisting of two stages. The first stage includes the permeation of hormones from lymph leaving the ovary via the subovarian lymphatic vascular network as well as lymph and venous blood, leaving the mesosalpinx and going to capillaries and tiny venous vessels in the entire mesovarium. These tiny mesovarium vessels connect and then branch out again to form the veno-venous network on the surface of branches of the ovarian artery. The second stage includes the permeation of hormones from the veno-venous blood into the branches of the ovarian artery. The authors present a hypothesis that the retrograde transfer of ovarian hormones may participate in the feedback regulation of ovarian function. The relationship between the retrograde transfer of ovarian hormones in the area of periovarian vascular complex and local elevation of steroid hormone concentrations in blood supplying the oviduct and uterus is presented. The paper also includes suggestions for future research.

Androstenedione↗

Most anchoring fibrils in human skin originate and terminate in the lamina densa.

Anchoring fibrils (AF) at the dermo-epidermal junction are well characterized as ultrastructural entities. They are composed mainly of collagen VII and play a key role in dermo-epidermal adhesion. Previous studies have suggested that AF originate in the lamina densa (LD), extend perpendicularly into the dermis, and insert into amorphous elements, called "anchoring plaques," in the dermal connective tissue. To elucidate the precise structural organization of the AF network in human skin, we analyzed quantitatively the distribution of different domains of collagen VII in the epidermal basement membrane zone, using various techniques of immunoelectron microscopy with a range of domain-specific antibodies that we prepared. Some electron-dense amorphous structures (ie, anchoring plaques) that were positive with aminoterminal end of collagen VII could be recognized only by pre-embedding en bloc labeling, and not by postembedding section labeling of immunoelectron microscopy. Quantitative analysis of surface labeling with postembedding immunoelectron microscopy demonstrated that most (> 90%) gold particles labeling the epitopes in the aminoterminal (NC-1 domain) of collagen VII were precisely localized to the LD, whereas no specific labeling was observed in the dermis. Most (> 90%) of the gold particles labeling the carboxyterminal end of collagen VII localized at a 160- to 360-nm distance from the LD, and most (> 90%) of the labeling epitopes in the central triple-helical collagenous domain were distributed between the LD and up to 360 nm from it; no specific labelings were observed beyond this area. These results suggest that most (> 90%), if not all, of the AF in human skin do not extend perpendicularly into the dermis, but instead originate and terminate in the LD, forming individual semicircular loops that constitute a network of AF.

Adolescent↗

Rangewide phylogeography of a bird-dispersed Eurasian shrub: contrasting Mediterranean and temperate glacial refugia.

We studied the phylogeography of alder buckthorn (Frangula alnus), a bird-dispersed shrub or small tree distributed over most of Europe and West Asia and present in three of the four main refugia of West Palaearctic temperate woody plants: the Iberian Peninsula, the Balkans and Anatolia. A total of 78 populations from 21 countries were analysed for chloroplast DNA variation using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and 21 different haplotypes were distinguished. We found a very strong overall population differentiation (GST = 0.81) and phylogeographical structure, and a sharp contrast between the haplotype-rich refugia and the almost completely uniform area of postglacial colonization. The haplotype network comprises three lineages made up of haplotypes from the Iberian Peninsula, Anatolia with the Caucasus, and temperate Europe. The Iberian and the Anatolian branches represent parts of a major lineage that spans over the whole northern Mediterranean Basin and some neighbouring areas and probably dates back to the Tertiary. Many haplotypes of this lineage are distributed locally and most populations are fixed for a single haplotype; these populations have apparently been very stable since their establishment, experiencing negligible gene flow and few mutations. The temperate European lineage consists of one very widespread and abundant plus six locally distributed haplotypes. Four of them are located in Southeast Europe, the putative refugium of all extant temperate European populations. Contrary to populations from Iberia and Anatolia, F. alnus populations from the southeastern European refugium have most genetic variation within populations. Bird-mediated seed dispersal has apparently allowed not only a very rapid postglacial expansion of F. alnus but also subsequent regular seed exchanges between populations of the largely continuous species range in temperate Europe. In contrast, the disjunct F. alnus populations persisting in Mediterranean mountain ranges seem to have experienced little gene flow and have therefore accumulated a high degree of differentiation, even at short distances. Populations from the southern parts of the glacial refugia have contributed little to the postglacial recolonization of Europe, but their long-term historical continuity has allowed them to maintain a unique store of genetic variation.

DNA, Chloroplast↗

Routes of transmission and consequences of small ruminant lentiviruses (SRLVs) infection and eradication schemes.

Small ruminant lentiviruses (SRLV = maedi-visna in sheep and caprine arthritis encephalitis in goats) are distributed throughout most countries of the world, particularly Europe. Laboratories from 16 European countries established collaborations within the framework of a COST (CO-operation in the field of Scientific and Technical Research) action sponsored by the European Union in order to (i) better organize their research programmes on SRLVs and (ii) to coordinate efforts to combat these two diseases. After five years, a consensus conference--the first one in the veterinary medicine field--concluded the work of this network of laboratories by reviewing the present position and discussing three important questions in the field of SRLVs: routes of transmission, consequences of infection and potential role of eradication programmes at either a European or local level, according to the situation in each country or region. This paper brings together existing information regarding these questions and identifies areas for future research.

Animals↗

Paxillin localizes to the lymphocyte microtubule organizing center and associates with the microtubule cytoskeleton.

Paxillin is a focal adhesion-associated protein that functions as a multi-domain adapter protein, binding several structural and signaling molecules. alpha-Tubulin was identified as an interacting protein in a two-hybrid screen using the paxillin C-terminal LIM domain as a bait. In vitro binding assays with glutathione S-transferase-paxillin demonstrated an interaction of alpha-tubulin with the C terminus of paxillin. Another member of the tubulin family, gamma-tubulin, bound to both the N and the C terminus of paxillin. The interaction between paxillin and both alpha- and gamma-tubulin in vivo was confirmed by co-immunoprecipitation from human T lymphoblasts. Immunofluorescence studies revealed that, in adherent T cells, paxillin localized to sites of cell-matrix interaction as well as to a large perinuclear region. Confocal microscopy revealed that this region corresponds to the lymphocyte microtubule organizing center, where paxillin colocalizes with alpha- and gamma-tubulin. The localization of paxillin to this area was observed in cells in suspension as well as during adhesion to integrin ligands. These data constitute the first characterization of the interaction of paxillin with the microtubule cytoskeleton, and suggest that paxillin, in addition to its well established role at focal adhesions, could also be associated with the lymphocyte microtubule network.

Cell Adhesion Molecules↗

Subepithelial vascular patterns in bronchial dysplasias using a high magnification bronchovideoscope.

BACKGROUND: We have developed a method of high magnification bronchovideoscopy that enables improved observation of subepithelial vascular patterns of the bronchial mucosa. A study was undertaken to investigate the value of high magnification bronchovideoscopy in the detailed examination of dysplasia in the bronchial mucosa of patients with abnormal mucosal fluorescence. METHODS: Thirty one patients with sputum cytology specimens suspicious or positive for malignancy were entered into the study. Conventional white light examination was first performed under local anaesthesia and fluorescence bronchoscopy was also carried out using a light induced fluorescence endoscopy (LIFE) lung system. A high magnification bronchovideoscope (XBF 200HM2) was then used to examine the microvascular network in the bronchial mucosa at sites of normal and abnormal fluorescence and the images obtained were compared with pathological diagnoses from bronchial biopsy specimens. Vascular area ratios were calculated using image analysing apparatus. RESULTS: Vascular networks with regular patterns were observed at 20 of 22 abnormal fluorescence sites in biopsy specimens from patients with bronchitis. However, vascular networks with increased vessel growth and complex networks of tortuous vessels of various sizes were observed in 15 of 21 abnormal fluorescence sites in dysplasia specimens. There was a significant difference between bronchitis and dysplasia specimens (OR=25, 95% CI 5.5 to 113, p<0.0001). Mean vascular area ratios from 16 normal bronchial epithelium specimens with normal fluorescence, and 22 bronchitis and 21 dysplasia specimens with abnormal fluorescence were 0.054 (95% CI 0.039 to 0.07), 0.095 (95% CI 0.072 to 0.118), and 0.173 (95% CI 0.143 to 0.203), respectively. The results indicate a statistically significant increase in vascular area in the three groups (p<0.0001). CONCLUSION: Areas of increased vessel growth and complex networks of tortuous vessels in the bronchial mucosa detected using a high magnification bronchovideoscope at sites of abnormal fluorescence may enable discrimination between bronchitis and dysplasia.

Aged↗

An update on thermosensitive neurons in the brain: from cellular biology to thermal and non-thermal homeostatic functions.

TS neurons in the brain, particularly in the POA, play a central role in thermoregulation, based on the good correlations between the activity of TS neurons and the thermoregulatory responses. Such relationships have been observed during (1) thermal (hypothalamic and peripheral) and (2) pharmacological (amines, neuropeptides, cytokines, and exogenous drugs) stimulations, (3) during modulation of neural inputs from extraPOA brain regions, and (4) during actual thermoregulatory responses. In vitro studies utilizing tissue slice preparations and dissociated cellular preparations have revealed some mechanisms of thermal transduction of central TS neurons, which are apparently endowed with the unique characteristics of thermosensitivity. The high degree of convergence of thermal signals from local and remote sites on TS neurons suggests that locally TS neurons in one site of CNS are connected to TS neurons in the other sites, thus forming neural networks of TS neurons within the brain and the spinal cord. The findings that 40-70% of POA TS neurons respond to divergent types of non-thermal homeostatic signals and have abundant mutual connections with divergent areas of brain (limbic system and association cortices) indicate that TS neurons may be involved in the coordination of thermal and non-thermal homeostatic functions controlled in the hypothalamus.

Animals↗

Patterns of inter- and intralaminar GABAergic connections distinguish striate (V1) and extrastriate (V2, V4) visual cortices and their functionally specialized subdivisions in the rhesus monkey.

Local GABAergic connections are undoubtedly important for the operation of cerebral cortex, including the tuning of receptive field properties of visual cortical neurons. In order to begin to correlate specific configurations of GABAergic networks with particular receptive field properties, we examined the arrangement of GABAergic neurons projecting to foci in compartments of known functional specialization in striate (area V1) and extrastriate (areas V2, V4) cortices of rhesus monkeys. GABAergic cells were detected autoradiographically following microinjections into supragranular, granular, or infragranular layers of 5, 10, or 50 nl of 3H-nipecotic acid, which selectively exploits the GABA reuptake mechanism. These injections produced complex inter- and intralaminar distributions of retrograde perikaryal labeling that was selective for GABA-immunopositive neurons and glia. The pattern of retrograde labeling depended on both the laminar and cytoarchitectonic location of injection sites. In all cases, a high density of labeled neurons was present in the immediate vicinity of injection sites, with the density of labeled neurons decreasing for the most part uniformly with horizontal distance. Injections in supragranular layers produced relatively widespread labeling (up to 1.5-1.7 mm from the center of injections) in upper layers, whereas in granular and infragranular layers, labeling was confined to a radius of 0.25-0.5 mm. Conversely, injections in infragranular layers produced labeling that was widest (up to 1 mm) in lower layers, but more laterally restricted in supragranular layers. Injections in granular layers, on the other hand, produced an even distribution of labeling, 0.6-1.0 mm in diameter, throughout all layers. Comparably placed injections in V1, V2, and V4 resulted in patterns of labeling that were distinguished by features including stepwise increases in the lateral extent of labeling from striate to extrastriate areas, and the circular versus markedly elongated intralaminar distribution of labeled neurons in V1 and V4 versus V2. Further, for superficial injections, labeling was present in all layers in V1 and V2, but did not extent below the top layer V in area V4. These findings offer clear examples of organizational differences in the intrinsic inhibitory connections of visual cortices. The results also demonstrate that the number of GABAergic neurons projecting to any spot in cortex decreases systematically with horizontal distance from the spot, and that radiolabeled cells do not coalesce to form slabs, columns, or clusters. This relatively even distribution of retrogradely labeled cells in the tangential plane is consistent with recent computer simulations (Worgotter and Koch, 1991) that suggest that inhibitory neurons broadly tuned as a population can produce the specific response properties of cortical neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗