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PubMed1975

Autoradiographic studies of the projections of the midbrain reticular formation: descending projections of nucleus cuneiformis.

The descending projections of nucleus cuneiformis in the cat were traced by autoradiography in the transverse and sagittal planes following stereotaxically placed injections of 3H-leucine. Many descending axons are organized into distinct fiber systems, of which the largest and most well-defined crosses directly in the midbrain and descends through the ventromedial tegmentum of the brain stem. This fiber system first terminates profusely in n. reticularis tegmenti pontis and then proceeds through the rhombencephalic tegmentum emitting transversely oriented branches to n. reticularis pontis caudalis and gigantocellularis, the raphe magnus and the facial nucleus...

Animals↗
PubMed1982

Reevaluation of projections from the mesencephalic trigeminal nucleus to the medulla and spinal cord: new projections. a combined retrograde and anterograde horseradish peroxidase study.

Microinjection of horseradish peroxidase (HRP) into the medullary parvocellular reticular formation (NPvc) resulted in retrograde labeling of neurons throughout the mesencephalic trigeminal nucleus (Mes V). Labeled cells were large and ovoid and were distributed primarily in the expanded pontine part of the nucleus. However, none of the small neurons in Mes V were labeled. Injections of HRP made into adjacent brainstem structures including the nucleus gigantocellularis, ventrolateral reticular formation, vestibular complex, and the spinal trigeminal nucleus failed to label neurons in Mes V. Injections made into the medullary raphe and into regions reported to receive inputs from Mes V--spinal cord, nucleus tractus solitarius, hypoglossal nucleus, and facial nucleus--were also not followed by transport to Mes V. Anterograde axonal transport of HRP from the region of reticular formation innervated by Mes V also labeled axons projecting to Mes V and to visceral and somatic sensorimotor nuclei in the lower brainstem. Recent reports of afferents from the amygdala to Mes V suggest that reflexes involving the mesencephalic trigeminal nucleus might be modulated by signals from limbic and autonomic as well as somatic centers in the brain.

Animals↗
PubMed1987

Distribution and size of thalamic neurons projecting to layer I of the auditory cortical fields of the cat compared to those projecting to layer IV.

The distribution of thalamocortical neurons projecting to layer I of the cat auditory cortical fields was examined by the horseradish peroxidase (HRP) method. After HRP injection into layer I of the primary auditory cortex (AI), HRP-labeled neuronal cell bodies were distributed mainly in the medial, dorsal, and ventrolateral divisions of the medial geniculate nucleus (MGN) and suprageniculate nucleus (Sg), and additionally in the lateral and medial divisions of the posterior group of the thalamus (Pol and Pom), lateroposterior thalamic nucleus (Lp), and nucleus of the brachium of the inferior colliculus (BIN). After HRP injection into layer I of the second auditory cortex (AII), labeled neurons were seen mainly in the medial, dorsal, and ventrolateral divisions of the MGN and Sg and additionally in the Pom, Lp, and BIN. After HRP injection into layer I of the anterior auditory field (AAF), labeled neurons were located mainly in the medial and dorsal divisions of the MGN, Sg, Pol, and BIN, and additionally in the ventrolateral divisions of the MGN, Pom, and Lp. After HRP injection into layer I of the dorsal part of the posterior ectosylvian gyrus (Epd), labeled neurons were observed chiefly in the medial and dorsal divisions of the MGN, Sg, and Lp and additionally in the ventrolateral division of the MGN, Pom, and BIN. After HRP injection into layer I of the ventral part of the posterior ectosylvian gyrus (Epv), labeled neurons were distributed chiefly in the medial and dorsal divisions of the MGN and Pol and additionally in the ventrolateral division of the MGN, Sg, and BIN. Thus no labeled neurons were found in the ventral division of the MGN after HRP injection into layer I of all auditory cortical fields examined in the present study. The average soma diameters of neurons that were labeled after HRP injection into layer I were statistically smaller than those of neurons that were labeled after HRP injection into layer IV.

Animals↗
PubMed1991

Gracile projection to the cat medial accessory olive: ultrastructural termination patterns and convergence with spino-olivary projection.

The caudal medial accessory subdivision of the inferior olive (cMAO) receives information from the hindlimb from both the gracile nucleus and the lumbosacral spinal cord. This study determined which elements in cMAO serve as the postsynaptic targets of the gracile projection and whether these elements also receive input from the lumbosacral spinal cord. Gracile axons were labeled in cats by anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), visualized with tetramethylbenzidine. Convergence of gracile and lumbosacral axons was evaluated by labeling in the same animal, one pathway by WGA-HRP and the other by degeneration. In cMAO, gracile axons synapse with equal probability on dendritic spines and distal dendritic shafts. This termination pattern contrasts markedly with that of other somatosensory inputs to the inferior olive and may account for the greater heterogeneity in responses to somatosensory stimuli displayed by neurons in cMAO. The distal dendritic shafts receiving gracile input were more likely than dendritic spines to receive convergent input from putative inhibitory synapses. The most likely source of these inhibitory synapses is the parasolitary nucleus, a structure that has been shown by others to receive input from the cerebellum. Thus the parasolitary nucleus may serve as an inhibitory relay between the cerebellum and cMAO. The dendritic spines in cMAO that receive input from the gracile nucleus often receive additional input from the lumbosacral spinal cord. This convergence of somatosensory axons on dendritic spines may provide a mechanism through which the unusually complex receptive fields of neurons in cMAO are generated.

Animals↗
PubMed1991

Short term changes in cardiovascular risk factors in the Di.S.Co. Intervention Project. Research Group of the DI.S.Co. Project.

The Di.S.Co. Project--Sezze District Community Control--is aimed at achieving in the general population the prevention of chronic diseases through community intervention. Two areas are enrolled, one for intervention (25,706 subjects) and one for reference (12,655 subjects). In 1983 the first survey was conducted on a sample of males and females aged 20-69, and some risk factors for cardiovascular diseases were measured. In 1986 a second screening was conducted on the same sample examined in 1983 and in a new one to evaluate the effect of community treatment during the three-year intervention. The main net differences obtained in the treatment area against controls (by the paired analysis), adjusted by the initial levels of the risk factors considered, were: in males body mass index: -1.3% and number of cigarettes smoked per day: -5.1%; in females systolic blood pressure: -2.1%, body mass index: -3.2% and number of cigarettes smoked per day: -34.4%. The theoretical probability of death from atherosclerotic cardiovascular diseases in 25 years was estimated by the multiple logistic function and in three years it increased by 1% in males, while for females it decreased by 6.5%.

Adult↗
PubMed1983

Demonstration of spinocerebellar projections in cat using anterograde transport of WGA-HRP, with some observations on spinomesencephalic and spinothalamic projections.

Wheat germ agglutinin-horseradish peroxidase (WGA-HRP) conjugate was injected into the lumbar or cervical spinal cord of adult cats in order to examine its usefulness as an anterograde tracer of long ascending spinal tracts. Heavily labeled fibers and terminal-like structures were found in restricted regions of the granular layer of the cerebellar cortex in all animals. The terminal-like structures showed features characteristic of mossy fiber rosettes. Many labeled terminals were found in regions anatomically and physiologically defined as cerebellar hind limb regions after lumbar cord injections. Relatively few labeled terminals were found in both hind limb and in forelimb regions after cervical cord injections. Although the cervical spinal cord is known to project to both hind limb and forelimb regions, it cannot be entirely excluded that some of the labeling in the hind limb regions was derived from uptake by fibers of passage. In addition to labeling in the cerebellar cortex, labeled fibers and terminals were also observed in the cerebellar medial and interposed nuclei, regardless of whether the injections had been made into the lumbar or the cervical spinal cord. Several midbrain and thalamic regions were found to contain labeled fibers and terminal-like profiles in all cases. In the midbrain the periaqueductal gray, the nucleus of Darkschewitsch and the posterior pretectal nucleus contained fairly dense labeling. Labeling was more scattered in the cuneiform nucleus, the mesencephalic reticular formation, the superior colliculus and in the magnocellular part of the medial geniculate body.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Computer assisted data analysis in intensive care: the ICDEV project--development of a scientific database system for intensive care (Intensive Care Data Evaluation Project).

INTRODUCTION: Patient Data Management Systems (PDMS) for ICUs collect, present and store clinical data. Various intentions make analysis of those digitally stored data desirable, such as quality control or scientific purposes. The aim of the Intensive Care Data Evaluation project (ICDEV), was to provide a database tool for the analysis of data recorded at various ICUs at the University Clinics of Vienna. SETTINGS: General Hospital of Vienna, with two different PDMSs used: CareVue 9000 (Hewlett Packard, Andover, USA) at two ICUs (one medical ICU and one neonatal ICU) and PICIS Chart+ (PICIS, Paris, France) at one Cardiothoracic ICU. CONCEPT AND METHODS: Clinically oriented analysis of the data collected in a PDMS at an ICU was the beginning of the development. After defining the database structure we established a client-server based database system under Microsoft Windows NI and developed a user friendly data quering application using Microsoft Visual C++ and Visual Basic; RESULTS: ICDEV was successfully installed at three different ICUs, adjustment to the different PDMS configurations were done within a few days. The database structure developed by us enables a powerful query concept representing an 'EXPERT QUESTION COMPILER' which may help to answer almost any clinical questions. Several program modules facilitate queries at the patient, group and unit level. Results from ICDEV-queries are automatically transferred to Microsoft Excel for display (in form of configurable tables and graphs) and further processing. CONCLUSIONS: The ICDEV concept is configurable for adjustment to different intensive care information systems and can be used to support computerized quality control. However, as long as there exists no sufficient artifact recognition or data validation software for automatically recorded patient data, the reliability of these data and their usage for computer assisted quality control remain unclear and should be further studied.

Austria↗
PubMed1999

Project neighborhoods in action: an HIV-related intervention project targeting drug abusers in Washington, DC.

Project Neighborhoods in Action was a human immunodeficiency virus (HIV) outreach and intervention program that was conducted with injection drug users and crack users in several inner-city neighborhoods in the District of Columbia. Study participants were placed randomly in either a standard intervention or an enhanced intervention condition, with more than 800 persons being assigned to each group. Drug use frequency dropped from 15.2 days to 12.4 for alcohol (P<.0001), 2.1 days to 1.6 for marijuana (P<.003), 13.0 days to 8.8 days for crack (P<.0001), 2.4 days to 1.5 days for cocaine (P<.0001), 19.7 days to 15.6 for heroin (P<.0001), and 5.2 days to 3.4 for speedball (P<.0001). Drug injecting decreased from an average of 90.8 times to 66.9 (P<.0001), with both direct sharing and indirect sharing rates decreasing significantly as well (from 2.4 to 1.1 times for the former [P<.002] and from 12.0 to 8.1 times for the latter [P<.0004]). The number of sexual partners dropped from a mean of 1.6 to 1.1 (P<.0001). The number of drug-injecting sexual partners went from 0.3 to 0.2 (P<.01). Having sex while high decreased from 11.2 times to 7.9 (P<.0001). Trading sex for drugs and/or money declined from 1.9 times to 1.3 (P<.001). Protected sex increased from 29.5% to 63.7% (P<.0001), and the number of unprotected sexual acts dropped from 9.6 to 7.2 (P<.0001). Only a few differences were observed for standard versus enhanced intervention respondents, with no particular pattern formed. We were left with the impression that the standard intervention and enhanced intervention used in this program were about equally effective at reducing the involvement of drug abusers in HIV-related risky behaviors.

Adult↗
PubMed1978

Natural history of myocardial infarction in the coronary drug project: long-term prognostic importance of serum lipid levels. Coronary Drug Project Research Group.

The relation between baseline fasting serum lipid levels (serum cholesterol and triglycerides) and 5 year rates for four end points--mortality from all causes, mortality from coronary heart disease, sudden death due to coronary heart disease and incidence of nonfatal myocardial infarction plus coronary death--was studied in 2,789 men. These were patients in the Coronary Drug Project placebo group who were 30 to 64 years old on entry and had recovered from one or more previous documented myocardial infarctions. Serum cholesterol was significantly related to all four end points, in both univariate and multivariate regression analyses (with control of 38 or 39 other factors in the latter). This significant relation of cholesterol to these end points was shown at low, medium and high levels of serum triglycerides. In contrast, baseline fasting serum triglyceride levels were not positively related to any of these end points. In these postmyocardial infarction patients, findings indicative of cardiovascular status at baseline evaluation, particularly the state of the myocardium, were more powerful prognosticators than serum cholesterol. These findings underscore the importance of efforts to prevent the first coronary episode. They also indicate the possibility after recovery from acute myocardial infarction of improving long-term prognosis through reduction of serum cholesterol.

Adult↗
PubMed1981

Hypoalgesia induced by blockade of noradrenergic projections to the raphe magnus: reversal by blockade of noradrenergic projections to the spinal cord.

Previous studies have demonstrated that microinjection of noradrenergic (NA) antagonists such as phentolamine in the nucleus raphe magnus (NRM) produces hypoalgesia. This hypoalgesia appears to result from disinhibition of raphe-spinal serotonergic neurons since it is blocked by intrathecally injected methysergide. The present studies demonstrate that the hypoalgesia produced by microinjection of phentolamine in the NRM is also abolished by intrathecal administration of phentolamine. The results suggest that the hypoalgesia produced by microinjection of NA antagonists in the NRM is also mediated, at least in part, by the activation of spinally projecting NA neurons. Such hypoalgesia does not appear to be mediated by activation of enkephalinergic neurons since intrathecal injection of the opiate antagonist naloxone did not attenuate the hypoalgesia.

Animals↗
PubMed1985

Anatomical and physiological properties of the projection from the sensory cortex to the motor cortex in normal cats: the difference between corticocortical and thalamocortical projections.

Details of the distribution of terminal sites of the projection fibers from area 2 of the sensory cortex to the motor cortex were studied and compared with the distribution of terminals from the ventrolateral (VL) nucleus of the thalamus to the motor cortex. The results obtained were as follows: Intracortical microstimulation (ICMS) in area 2 produced measurable short-latency EPSPs only in neurons located in layers II and III of the motor cortex, whereas VL stimulation produced short-latency EPSPs in neurons throughout the depths of the motor cortex. The time from the beginning to the peak of the EPSPs was not significantly different for area 2- and VL-elicited EPSPs suggesting that there was no systematic difference between effective terminal sites for both inputs. However, there was a difference when a given neuron received both inputs suggesting that there was a segregation between the two inputs within a given cell. The majority of area 2-elicited EPSPs were smooth and monophasic, but some (40%) of them showed double peaks indicating that some neurons received mono- and disynaptic inputs from area 2. Intracellular injections of HRP suggested that neurons receiving input from area 2 were predominantly multipolar non-pyramidal neurons in layers II and III whereas neurons receiving thalamic input were pyramidal as well as non-pyramidal cells. Field potentials in the motor cortex evoked by area 2 stimulation did not change polarity in the depths of the cortex and therefore, differed from the VL-evoked potentials suggesting differences in the mechanisms of generating the electrical fields. It is concluded that association fibers effective for producing EPSPs terminate primarily on non-pyramidal cells in layer II and III whereas VL fibers terminate not only on pyramidal but also on non-pyramidal cells in layers III and V. This study provided a basis for examining the modifiability of association fibers after elimination of VL input to the motor cortex which is reported in the following paper.

Animals↗
PubMed1986

Neural projections subserving the initiation of a specific motivated behavior in the rat: new projections from the subfornical organ.

The activation of neurons in the subfornical organ (SFO) by angiotensin II in the blood is known to stimulate thirst. The projections of these neurons were examined with anterograde and retrograde axonal transport methods, and were found to end in specific parts of the prefrontal cortex, septal region, substantia innominata, medial preoptic area, zona incerta and lateral hypothalamic area. These regions in turn are thought to be involved in arousal, somatomotor control and cognitive functions, essential components of the initiation and procurement phases of motivated behavior.

Animals↗
PubMed1987

Reorganization of the projection from the sensory cortex to the motor cortex following elimination of the thalamic projection to the motor cortex in cats; Golgi, electron microscope and degeneration study.

Changes of terminal connections of projection fibers from area 2 of the sensory cortex to the motor cortex following chronic lesion in the thalamus were examined using the electron microscope. The lesioned areas included nucleus ventralis anterior, n. ventralis lateralis and rostral part of n. ventralis posterolateralis. The synaptic sites were identified using the Golgi impregnation method to identify postsynaptic neurons in the motor cortex and the axonal degeneration method to identify presynaptic terminals of fibers originating from area 2. The following results were obtained. (1) The number of degenerating terminals per unit area in the motor cortex was increased to nearly twice that in normal animals. (2) The number of degenerating terminals synapsing with stellate cells was not increased but stayed more or less the same as in normal animals. (3) The number of degenerating terminals contacting pyramidal cells increased substantially, to more than twice that in normal animals. (4) These newly formed synapses were found on proximal dendritic shafts of the pyramidal cells in both layers III and V, suggesting that these synapses occupied the spaces where the thalamocortical terminals were located. (5) The functional significance of these newly formed synapses was discussed in relation to the recovery of motor function following thalamic lesion.

Animals↗
PubMed1995

A retrograde double-labeling study of uni- and bilaterally projecting retinal ganglion cells that project to the superior colliculi after unilateral eye removal at birth in the albino rat.

By injecting Fluoro-Gold and Evans-Blue into the right and left superior colliculi of the normal adult albino rats, bilaterally projecting retinal ganglion cells were labeled in the ventrotemporal crescent accounting for 37.9% of all the labeled cells, whereas in 0- and 5-day unilaterally enucleated rats these were found in the lower half of the retina accounting for 64.8% and 80.6%, respectively. Furthermore, they tended to have larger somata (type I cells).

Animals↗
PubMed1986

Eight-year follow-up results from the Rome Project of Coronary Heart Disease Prevention. Research Group of the Rome Project of Coronary Heart Disease Prevention.

The Rome Project of Coronary Heart Disease Prevention is a primary preventive trial carried out among 6,027 working men ages 40-59; 3,131 constituted the treatment group and the remaining 2,896 the control group. The preventive action aimed at reducing mean levels of serum cholesterol (generally through dietary prescription and, in a small number of subjects, by drug treatment), high blood pressure (by drugs), smoking habits (by advice to reduce or stop smoking), overweight (by means of diet), and sedentary lifestyle by increased physical activity). The treatment was carried out during a 6-year period and consisted of individual sessions administered to about one-third of higher-risk subjects, while mass education was administered to all men allocated to treatment. No intervention was offered to the control group. The mean changes in levels of the main coronary risk factors in the treatment vs the control group were computed in different ways. Net changes in the treatment group after 6 years, after adjustment for several confounding variables, were -0.71% for body weight, +0.77% for the cigarette consumption, -3.00% for systolic blood pressure, -5.39% for serum cholesterol, and -18% for the estimated multivariate coronary risk. After 8 years of observation, mortality from all causes was lower by 9.8% (one-tailed P = 0.140) in the treatment than in the control group, whereas mortality from coronary heart disease was lower by 23.7% (one-tailed P = 0.059). The incidence of fatal plus nonfatal coronary heart disease events (hard criteria), which could be measured only for the first 6 years, was reduced by 30.9% (one-tailed P = 0.005) in the treatment as compared with the control group.

Adult↗
PubMed1995

A therapeutic preschool for abused children: the KEEPSAFE Project. Kempe Early Education Project Serving Abused Families.

Twenty-four children attended a therapeutic preschool for physically and sexually abused children, the Kempe Early Education Project Serving Abused Families (KEEPSAFE), over a 3-year period from 1985-1988. The program provided early education and therapy for abused children so that they could improve developmentally, socially, and emotionally, with the aim that the children would be suitable to enter the public education system. The therapeutic preschool was combined with a home visitation program for the child's parents or primary caretaker, focusing on improving the quality of interaction between the adult and child. The majority of children made developmental gains at a faster rate than would normally be expected as measured by the McCarthy Scales of Children's Abilities and the Peabody Picture Vocabulary Test. Although all 24 children were thought at onset of intervention to be unable to participate in a public school setting, after 12 months in the program over 79% were staffed into the public school system eight (33.3%) into a regular classroom. Three others (12.5%) needed residential care, and two were too young to enter public school. Even though a therapeutic preschool is expensive in terms of the high staff to child ratio needed, it is likely to be beneficial in improving the developmental skills of abused children.

Child Abuse↗
PubMed1988

Heterotopically transplanted embryonic olfactory bulb projection neurons form selective and appropriate axonal projections over considerable distances in adult host brains.

Embryonic olfactory primordia were transplanted into the region of the septum, the adjacent lateral ventricle (LV) and olfactory tubercle (Tu) in adult host rats. After a minimum of 7 weeks, wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP) were injected into the host anterior olfactory nucleus (AO). The injection retrogradely labeled the neural cell bodies in the large neuron area (the mitral and tufted cells) of the olfactory bulb (OB) transplant. In addition, the anterogradely labeled fibers projected from the host AO to the transplant. These results indicated that the transplanted mitral and tufted neurons were able to grow axons selectively to an appropriate host terminal region (the AO) and receive fibers from the AO, even when the transplant itself was in an inappropriate host site, at a considerable distance from the host AO.

Animals↗
PubMed1981

Practical aspects of decision making in clinical trials: the coronary drug project as a case study. The Coronary Drug Project Research Group.

Arriving at a decision for early termination of a treatment group or of an entire clinical trial, due to either beneficial or adverse results, is a complex process. It may involve, among other things, the necessity to (1) determine whether the observed treatment differences are likely to represent real effects and are not due to chance; (2) weigh the importance of many different response variables, some possible trending in favor of the treatment and some against it; (3) adjust for differences in distributions of baseline characteristics among the treatment groups; (4) discern possible biases (due to the study not being double-blind) in the medical management of patients or in the diagnosis of events; and (5) evaluate treatment effects in subgroups of the study participants. Experiences in the Coronary Drug Project are described in making decisions for early termination of treatment groups. Special methods applied in conjunction with reaching these decisions included: (1) analyses designed to detect possible biases in diagnosing a major endpoint--nonfatal myocardial infarction, e.g.--biases that may have arisen because of unblinding by side effects of the estrogen treatment group; (2) a simulation study to assess the statistical significance of mortality differences between the dextrothyroxine and placebo participants in certain subgroups identified a posteriori; and (3) the development, on the basis of the accumulated data, or new hypotheses relating to treatment differences in specific subgroups and the testing of these hypotheses a few months later on the basis of new events occurring during that interval.

Clinical Trials as Topic↗