The in situ detectability of the neuroanatomical tracer Phaseolus vulgaris-leucoagglutinin (PHA-L)

We determined the in situ detectability of the neuroanatomical tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). The tracer was bilaterally injected in the nucleus accumbens of the ventral striatum of young adult rats. After post-injection survival periods ranging from 4.5 to 16 weeks, sections of the brain were subjected to immunocytochemical detection of the transported PHA-L. We examined the labelled neurons in the injection sites, the labelled local and efferent fibres, and the labelled terminal structures in the ventral pallidum. Up to 4.5 weeks after the injection, the PHA-L-labelled neurons in the injection site were completely stained and displayed dendrites with numerous spines. There was also good visualization of local axonal plexuses and of the efferent fibres and their varicosities along the trajectories to and in the termination areas. Six and a half weeks after the injection, the fibres coursing from the injection site to the termination area were difficult to visualize. By contrast, the injection site contained labelled cell bodies, dendrites with few spines, weakly stained fibres, and punctate labelling. In the termination areas there was a clear, punctate terminal labelling in addition to weak fibre labelling. Between 8 and 10 weeks after the injection, labelled neurons in the injection site could be visualized as well as a cloud of punctate staining in the termination area, but labelled fibres and dentritic spines were not observed. Eleven weeks after the injection, label was no longer demonstrable in terminals. After survival periods of 13 weeks and longer, the only labelled structures were weakly PHA-L-immunoreactive perikarya at the injection site, surrounded by punctate labelling.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anatomically distinct output channels of the caudate nucleus and orofacial dyskinesia: critical role of the subcommissural part of the globus pallidus in oral dyskinesia

The findings in this feline study indicate that the enkephalin-positive subcommissural part of the globus pallidus, which is known to contain GABA and cholinergic cells projecting to the cortex, is innervated by the anterodorsal region of the caudate nucleus, but not by the core. Like stimulation of a particular subclass of dopamine receptors in the anterodorsal region of the caudate nucleus, inhibition of the GABA receptors in the noted part of the globus pallidus resulted in orofacial dyskinesia, viz. tic-like contractions of the facial, eye and ear muscles, and tongue protrusions. This phenomenon was elicited by intrapallidal injections of the GABA antagonist picrotoxin in a dose-dependent manner and could be attenuated by the GABA agonist muscimol. Previous studies have already shown that neither stimulation of the dopamine receptors in the core of the caudate nucleus nor any manipulation with the first- and second-order output-stations of the latter brain region, viz. (a) those regions of the substantia nigra, pars reticulata which receive afferents from the caudate nucleus, and (b) those regions of the intermediate layers of the superior colliculus which receive afferents from the latter nigral region, ever resulted in orofacial dyskinesia. These findings support the hypothesis that the anatomically distinct input-output channels of the caudate nucleus are differentially involved in orofacial dyskinesia. The clinical impact of these findings is discussed in view of the L-3,4-dihydroxyphenylalanine-induced tardive dyskinesia in man. In addition, the relevance of the anatomical data is discussed in view of the co-occurrence of Parkinson's Disease and Dementia of Alzheimer-type in certain patients.     

Immunohistochemical Characterization of the Shell and Core Territories of the Nucleus Accumbens in the Rat

The nucleus accumbens in the rat has been parcelled into shell and core subdivisions. Despite accumulating evidence for such a division of the nucleus accumbens, these territories have not been delineated throughout the rostrocaudal extent of the nucleus. In the present study, an attempt has been made to delineate the shell and core using the distribution of calcium-binding protein immunoreactivity, substance P immunoreactivity and acetylcholinesterase activity in transverse and horizontal sections through the nucleus accumbens. It was found that the pattern of calcium-binding protein immunoreactivity provides the most unequivocal criterion to divide the nucleus accumbens into a ventral and medial, peripheral shell displaying low to moderate immunostaining, and a more laterally and dorsally located, strongly stained inner core. In most parts of the nucleus, borders seen in the calcium-binding protein immunoreactivity pattern can also be recognized in the distributions of substance P immunoreactivity and acetylcholinesterase activity. It is concluded that the shell occupies most of the rostral part of the nucleus accurnbens, whereas rostrally the core is represented only in the most lateral part. Differences in staining intensities for all three markers indicate that both the shell and core have a heterogeneous structure. Patterns of connectivity appear to support the division of the nucleus accumbens as indicated by calcium-binding protein immunoreactivity in the present study.     

Increased cost sharing and changes in noncompliance with specialty referrals in The Netherlands

Introduction

The compulsory deductible, a form of patient cost-sharing in the Netherlands, has more than doubled during the past years. There are indications that as a result, refraining from medical care has increased. We studied the relation between patient cost-sharing and refraining from medical care by evaluating noncompliance with referrals to medical specialists over several years.

Relationships of the Dendritic Arborizations of Ventral Striatomesencephalic Projection Neurons With Boundaries of Striatal Compartments. An In Vitro Intracellular Labelling Study in the Rat

We studied the relationships of the dendrites of ventral striatomesencephalic projection neurons with the compartmental structure of the ventral striatum, as revealed by enkephalin immunohistochemistry. Lightly fixed slices were employed in which Lucifer yellow was intracellulary injected into neurons that were retrogradely labelled following Fast Blue injections in the ventral tegmental area. Double immunohistochemical staining was carried out using antisera to Lucifer yellow and Leu-enkephalin. Most of the 226 injected cells were located in the core region of the nucleus accumbens. All these neurons were of the small- to medium-sized spiny type. The dendritic arborizations of over 90% of the cells remained within the compartment in which the parent cell bodies resided. The dendrites of most of these neurons abutted the border of the compartment, whereas a smaller number of neurons had dendrites that were distant from any compartmental boundary. The dendrites of fewer than 10% of the neurons crossed the borders of compartments. Only a few cells were injected in the shell region of the nucleus accumbens. None of these neurons extended its dendrites into the core region of the nucleus or into the territory of the clusters of small cells which characterize the shell. The present results demonstrate that the dendrites of the great majority of ventral striatomesencephalic neurons comply with the boundaries of ventral striatal enkephalin compartments. Together with the results of previous studies showing that such compartments are selectively innervated by thalamic and cortical afferents, and have outputs to different areas in the ventral mesencephalon, the present data suggest the existence of discrete channels through the ventral striatum.     

Public trust in Dutch health care

This article describes the development of a valid and reliable instrument to measure different dimensions of public trust in health care in the Netherlands. This instrument is needed because the concept was not well developed, or operationalized in earlier research. The new instrument will be used in a research project to monitor trust and to predict behaviour of people such as consulting "alternative practitioners". The idea for the research was suggested by economic research into public trust. In the study, a phased design was used to overcome the operationalization problem. In the first phase, a qualitative study was conducted; and, in the second, a quantitative study. In the first phase, more than 100 people were interviewed to gain insight into the issues they associated with trust. Eight categories of issues that were derived from the interviews were assumed to be possible dimensions of trust. On the basis of these eight categories and the interviews, a questionnaire was developed that was used in the second phase. In this phase, the questionnaire was sent to 1500 members of a consumer panel; the response was 70 percent. The analysis reveals that six of the eight possible dimensions appear in factor analysis. These dimensions are trust in: the patient-focus of health care providers; macro policies level will have no consequences for patients; expertise of health care providers; quality of care; information supply and communication by care providers and the quality of cooperation. The reliability of most scales is higher than 0.8. The validity of the dimensions is assessed by determining the correlation between the scales on the one hand, and people's experience and a general mark they would assign on the other. We conclude that public trust is a multi-dimensional concept, including not only issues that relate to the patient-doctor relationship, but also issues that relate to health care institutions. The instrument appears to be reliable and valid.     

Class II antigens on canine T lymphocytes

A panel of crossreactive anti-human, -mouse and -rat MHC class II monoclonal antibodies (Mabs) was used to examine MHC class II antigen expression on canine T lymphocytes by cytofluorometry. The presence of MHC class II antigens was demonstrated on activated T lymphoblasts as well as on non-stimulated peripheral blood T lymphocytes. A number of anti-MHC class II Mabs reacted only with activated T lymphoblasts. Immunoprecipitation studies confirmed the Ia-like or MHC class II molecular character of the antigens on canine T cells. The expression of MHC class II antigens on peripheral blood T lymphocytes appeared to be not induced by stimulation of the T cells, as purified T lymphocytes of specific pathogen free dogs reacted with anti-MHC class II Mabs. Moreover, the study indicates that MHC class II antigen expression is present in the neonatal thymus. Lectin stimulated and allogeneically stimulated T lymphoblasts showed a stronger expression of MHC class II antigens in comparison with non-stimulated T cells.     

Connections of the parahippocampal cortex in the cat. II. Subcortical afferents

The organization of subcortical inputs to the parahippocampal cortex, which in the present study in the cat is considered to comprise the entorhinal and perirhinal cortices, was studied by using retrograde and anterograde tracing techniques. The results of the retrograde tracer horseradish peroxidase (HRP), HRP conjugated with wheat germ agglutinine (WGA-HRP), Fast Blue (FB) or Nuclear Yellow (NY] injections indicate that the entorhinal and perirhinal cortices receive inputs from the magnocellular basal forebrain and from distinct portions of the amygdaloid complex, the claustrum, and the thalamus. The two cortices are further projected upon by fibers from the supramamillary region of the hypothalamus, the ventral tegmental area of the mesencephalon, the dorsal raphe nucleus, the nucleus centralis superior, and the locus coeruleus. The entorhinal cortex, in addition, receives projections from the medial septum. As regards the projections from the amygdaloid complex, it was observed that the entorhinal cortex receives its heaviest input from the basolateral amygdaloid nucleus, whereas the perirhinal cortex receives a strong projection from the lateral nucleus and a weaker projection from the basomedial nucleus of the amygdala. Of the thalamic nuclei that project to the parahippocampal cortex, the nucleus reuniens is only connected with the entorhinal cortex, while fibers from the medial geniculate nucleus and the lateral posterior nucleus terminate in the perirhinal cortex. Injections of tritiated amino acid (3H-leucine) were placed in the medial septum, the dorsal and ventral claustrum, the basolateral and basomedial amygdaloid nuclei, and the nucleus reuniens of the thalamus. The results of these experiments demonstrate that, with the exception of the claustrum, these subcortical areas project mainly to the superficial layers I-III and the lamina dissecans of the parahippocampal cortex, and to a lesser degree to the deep layers V and VI.     

Does general practitioner gatekeeping curb health care expenditure?

OBJECTIVES: It is generally assumed that health care systems in which specialist and hospital care is only accessible after referral by a general practitioner (GP) have lower total health care costs. In this study, the following questions were addressed: do health care systems with GPs acting as gatekeepers to specialized care have lower health care expenditure than those with directly accessible specialist care? Does health care expenditure increase more rapidly in countries without a referral system than in those with the GP acting as a gatekeeper? METHODS: Multiple regression analyses on total and ambulatory health care expenditure in 18 OECD countries. RESULTS: Analyses showed only one statistically significant effect (P < 0.05) in countries with gatekeeping GPs: ambulatory care expenditure has increased more slowly than in non-gatekeeping systems. No significant effects of gatekeeping were found on the level of ambulatory care costs, or on the level or growth of total health care expenditure. As in earlier studies, the most important factor influencing aggregate health care costs and their growth is gross national product (GNP), followed by the share of public funding. Relationships that exist at a micro level (such as lower costs with a gatekeeping primary care doctor) did not show up in aggregate data at a macro level. CONCLUSIONS: Gatekeeping systems appear to be better able to contain ambulatory care expenditure. More research is necessary to understand micro level mechanisms and to distinguish the effects of gatekeeping from other structural aspects of health care systems.