Research on brain-dead patients.
Explore the source record for details and available documents.
Brain Death↗
Biomedical subjects
R Baker
Publications and source records attributed to R Baker.
Studies of intestinal lymphoid tissue. XII. Epithelial lymphocyte and mucosal responses to rectal gluten challenge in celiac sprue.
The immunopathologic, structural, and functional changes within rectal mucosa of known celiac sprue subjects were quantitated during local challenge with a peptic-tryptic digest of gluten. In the celiac sprue patients challenged with 2 g of digest, major effects occurred in lamina propria, submucosa, and local microvasculature. The lamina propria swelling was biphasic, starting 1-2 h after challenge with widespread extravascular deposition of fibrinogen, indicative of increased microvascular permeability, receding by 24 h postchallenge. A rapid fall in mast cells together with granule discharge suggested their involvement in this response. The late-phase swelling (48-72 h) was preceded by a rapid influx of neutrophils and basophils, the latter showing evidence of degranulation beyond 72 h. Reestablishment of vessel lumina, a rise in mast cells, and loss of neutrophils indicated tapering of the inflammatory cellular cascade by 96 h. Lymphocytes, first seen to enter the lamina by 2 h postchallenge, increased progressively, thereby resulting in substantial infiltration between 36 and 96 h. A marked rise in epithelial lymphocytes, maximal at 6-8 h, waned by 24 h. Volumes of surface and crypt epithelium remained constant throughout. In another challenge series with 4 g of gluten digest, electrical potential difference across rectal mucosa decreased significantly 12 h postchallenge, but the associated decreases in net sodium and chloride absorptive fluxes were insignificant. It is concluded that rectal mucosa is sensitized to gluten in celiac sprue disease and thus offers a promising and convenient in vivo substrate for investigative and diagnostic purposes.
Adult↗
Novel benzodiazepine receptor partial agonists: oxadiazolylimidazobenzodiazepines.
The synthesis and biochemical evaluation of a series of oxadiazole derivatives of imidazobenzodiazepines related to the benzodiazepine antagonist Ro 15-1788 (2a) are reported. Although the oxadiazole ring is seen as an isosteric replacement for the ester linkage, significant differences in structure-activity trends were observed. Specifically, oxadiazoles 9-12 invariably had increased receptor efficacy (as witnessed by measurements of the GABA shift) relative to the corresponding ester. Additionally, and in direct contrast to the classical agonists such as diazepam, affinity for the benzodiazepine receptor was enhanced by a 7- rather than 8-halo substituent. The results are discussed in terms of a six-point receptor-binding model originally based on the X-ray structure of 2a. For comparison, the crystal structures of two representative oxadiazole derivatives, 10h and 12o, having a 6-oxo and 6-phenyl group, respectively, were determined and the data incorporated into a modified binding model to account for the greater efficacy of these compounds. It is concluded that the antagonist behavior of 2a relies upon the hydrogen-bond-acceptor properties of the ester carbonyl oxygen whereas for the oxadiazole series this site is localized at the imidazole nitrogen.
Animals↗
Effect of thermal injury in the rat on transfer of IgA protein into bile.
Severe thermal injury is associated with bacterial sepsis; the intestine is considered a likely source of invasive organisms. Because IgA antibody in bile accounts for much of the specific immune defense of the upper intestinal tract in the rat, the effect of thermal injury on the quantity of IgA protein in bile was examined. Sprague-Dawley rats received a 20% to 30% body surface area burn under anesthesia. Eighteen hours later the common bile duct was cannulated and bile was collected for three hours. Total IgA protein in bile decreased 90% after thermal injury. The bile volume, the concentration of bile protein, and free secretory component did not change significantly. Although blood flow to the liver 18 hours after thermal injury was not changed, there was a significant reduction in total IgA concentration in the circulation; both monomeric (m-IgA) and polymeric IgA (p-IgA) were decreased. This finding may explain, in part, the reduced concentration of IgA protein in bile. Although not examined in this study, decreased local hepatic synthesis and/or transport of p-IgA across the hepatocyte may also contribute to the reduced IgA levels in bile.
Animals↗
The basis for activity controlled rate variable cardiac pacemakers: an analysis of mechanical forces on the human body induced by exercise and environment.
We conducted tests on six healthy volunteers and six pacemaker patients. With the aid of three straight line frequency acceleration pickups attached to the body, the mechanical signals were recorded on the three axes during different activities. Along with standardized exercise on bicycle and treadmill ergometers, we tested the influence of household activities and interference influences. The results were analyzed in terms of the amplitude and frequency content of the signals. For walking activities, we found a signal amplitude increasing in a largely linear fashion with the walking speed, the signal amplitudes being approximately twice as high on the vertical axis as on the other two axes. Exercise on the bicycle ergometer produced mechanical signals of clearly lower amplitude than comparable walking activities. The Fast-Fourier analysis showed amplitude peaks in the low frequency range of 1 to 4 Hz for all forms of physiological exercise, while interference influences showed amplitude peaks mainly in the range above 8 Hz. The use of a straight line-frequency acceleration pickup and a corresponding low pass filter might be a way of reducing the effect of unphysiological interference influences on an activity controlled pacemaker system. A sensor measuring on the horizontal axis appears to be the most favorable compromise for the various types of exercise. However, due to the considerable difference in signal amplitude for different types of exercise of the same intensity, an activity controlled pacemaker system cannot entirely meet metabolic conditions and requirements.
Activities of Daily Living↗
Do inhibitors of lipoxygenase and cyclooxygenase block neonatal hypoxic pulmonary vasoconstriction?
Lipoxygenase products have been suggested as mediators of the hypoxic pulmonary pressor response in newborn animals. Data supporting this suggestion are equivocal, since lipoxygenase and leukotriene receptor antagonists that have been used may produce vasodilation because of phosphodiesterase inhibition. We used a leukotriene receptor antagonist L 649923, which appears not to have smooth muscle relaxant activity. L 649923 blocks pressor responses to leukotriene D4 (LTD4) without diminishing the pressor response to hypoxia. Also, BW 755C did not block the pressor response to hypoxia in newborn sheep and goats, whereas the pressor response to LTD4 (75 ng/kg) was depressed significantly. In newborn sheep there was an augmented response to hypoxia with BW 755C, which is consistent with cyclooxygenase inhibition. Finally, the thromboxane receptor antagonist SQ 29548 was investigated in both species. With this agent the pressor response to LTD4 in contrast to that of hypoxia was completely inhibited. We conclude that thromboxanes are involved in the pressor response to LTD4 in newborn lambs and goats. These data do not support the view that leukotrienes are involved in the ovine or caprine neonatal pulmonary pressor response to hypoxia.
4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
Correlation between blood eosinophilia and airways hyper-responsiveness in rats.
The injection of Sephadex particles intravenously into rats produced a specific blood eosinophilia and an hyper-responsiveness of the airways to 5-hydroxytryptamine (5-HT). The rats given Sephadex had an hyper-sensitivity to the respiratory effects of 5-HT in vivo with a shift to the left of the intravenous dose response curve. In vitro lung strips from rats given Sephadex were hyper-reactive to 5-HT in that the strips from these rats and control rats responded over the same dose range of 5-HT but the slope of the dose response curve and the maximum response were greater in the strips from the Sephadex treated rats. The levels of hyper-sensitivity in vivo and of hyper-reactivity in vitro both correlated with the numbers of blood eosinophils.
Animals↗
Evidence for glycine as an inhibitory neurotransmitter of vestibular, reticular, and prepositus hypoglossi neurons that project to the cat abducens nucleus.
The localization and distribution of brain-stem afferent neurons to the cat abducens nucleus has been examined by high-affinity uptake and retrograde transport of 3H-glycine. Injections of 3H-glycine selectively labeled (by autoradiography) only neurons located predominantly in the ipsilateral medial vestibular and contralateral prepositus hypoglossi nuclei, and in the contralateral dorsomedial reticular formation, the latter corresponding to the location of inhibitory burst neurons. The specificity of uptake and retrograde transport of 3H-glycine was indicated by the absence of labeling of the dorsomedial medullary reticular neurons ipsilateral and in close proximity to the injection site, where local uptake by diffusion could have occurred. The selectivity of uptake and transport was demonstrated by the absence of retrograde labeling following injections of 3H-GABA or 3H-leucine into the abducens nucleus. The immunohistochemical localization of glycine and GABA revealed a differential distribution of the 2 inhibitory neurotransmitter candidates in the extraocular motor nuclei. Glycine-immunoreactive staining of synaptic endings in the abducens nucleus was dense with a widespread soma-dendritic distribution but was sparse in the trochlear and oculomotor nuclei. By contrast, GABA-immunoreactive staining within the oculomotor and trochlear nuclei was associated with synaptic endings that were particularly prominent on the somata of motoneurons. GABA-immunoreactive staining in the abducens nucleus, however, was sparse. These differences between glycine- and GABA-immunoreactive staining in the extraocular motor nuclei were correlated with differences in the immunoreactivity of axons in the descending (glycine) and ascending (GABA) limbs of the medial longitudinal fasciculus. Glycine-immunoreactive neurons, furthermore, were observed in the same locations as neurons that were labeled autoradiographically by retrograde transport of 3H-glycine from the abducens nucleus. Electrophysiological recordings from abducens motoneurons and internuclear neurons revealed a marked reduction in the slow positivity of the orthodromic extracellular potential elicited by ipsilateral vestibular nerve stimulation following systemic administration of strychnine, an antagonist of glycine. Intracellular recordings demonstrated that the vestibular-evoked disynaptic inhibitory postsynaptic potentials in abducens neurons were effectively blocked by strychnine but were unaffected by picrotoxin, an antagonist of GABA.(ABSTRACT TRUNCATED AT 400 WORDS)
Abducens Nerve↗
Nonphenylketonuric hyperphenylalaninemia.
Sixteen subjects with nonphenylketonuric hyperphenylalaninemia were followed up during a period of years. Dietary treatment did not seem to influence the outcome, and no relationship between blood phenylalanine and intellectual outcome was demonstrable.
Adolescent↗
The accuracy of a practice-based immunisation register.
Explore the source record for details and available documents.
Child↗
The dephosphorylation of inositol 1,4-bisphosphate to inositol in liver and brain involves two distinct Li+-sensitive enzymes and proceeds via inositol 4-phosphate.
1. Hydrolysis of both enantiomers of inositol 1-phosphate and both enantiomers of inositol 4-phosphate to inositol is inhibited by LiCl in liver and brain. 2. The phosphatase activity is predominantly soluble. 3. Inositol 1,4-bisphosphate is also hydrolysed by the soluble fraction of liver and brain. 4. Bisphosphatase activity is inhibited by LiCl, but is less sensitive than monophosphatase activity. 5. The product of bisphosphatase in liver and brain is inositol 4-phosphate.
Animals↗
Behavior of neurons in the abducens nucleus of the alert cat--III. Axotomized motoneurons.
The effects of peripheral and central VIth nerve axotomy on abducens nucleus synaptic potentials of vestibular origin and the ultrastructure of intracellularly labeled abducens motoneurons were examined in the anesthetized cat. Subsequent experiments explored the activity of identified abducens motoneurons during spontaneous and vestibular induced eye movements in alert cats prepared for chronic recordings of eye movements, single units and field potentials. Following axotomy the typical disynaptic inhibition of abducens motoneurons induced by electrical stimulation of the ipsilateral vestibular nerve either disappeared or was reduced for 5-30 days. Disynaptic activation produced by contralateral VIIIth nerve stimulation was apparently not affected. These changes were accompanied at the ultrastructural level by a decrease of axosomatic pleiomorphic synaptic endings. No changes were observed in either the number or distribution of synaptic endings on proximal and distal dendrites. Although not expected by results obtained in acute experiments, axotomized motoneurons showed a decreased excitability in the behavioral paradigm. Amplitude of the abducens antidromic field potential was significantly reduced 4-6 days following axotomy and frequent failures were observed in the antidromic somadendritic invasion of single motoneurons. Somatic invasion was obtained by the simultaneous presentation of appropriate visual and/or vestibular synaptic activity. Chronic recordings of field potentials showed their amplitude to recover in 30-40 days. The spontaneous and vestibular induced activity of identified axotomized motoneurons during this period of time differed in several aspects from controls. Motoneurons could not maintain tonic activity during eye fixations and they showed short, low frequency, bursts of activity that followed, rather than preceded, on-directed saccades. In some cases axotomized motoneurons fired during horizontal off-directed and vertical saccades. Position and velocity gains of axotomized motoneurons were lower than control values. The effects of central axotomy were always larger and of longer duration than those following peripheral axotomy. Structural and functional properties influenced by axotomy seemed to recover in 2-3 months, but with independent time courses. The present results differ in many aspects from those described after axotomy in spinal and hypoglossal motoneurons. In addition, they point out that behavior or axotomized neurons in chronic preparations are not predictable on the basis of those described in acute experiments.
Abducens Nerve↗
2-Methyl-1,3-dioxaazaspiro[4.5]decanes as novel muscarinic cholinergic agonists.
Many nonquaternary ammonium muscarinic agonists have been developed over the last few years, but most of the existing compounds (e.g., arecoline, RS-86, AF-30) behave as weak partial agonists at cholinergic receptors in tissues of limited receptor reserve. The current paper describes the synthesis and biochemical assessment of analogues of AF-30 designed to have sufficient conformational freedom to allow greater receptor flexibility and hence activation. The new compounds and important standards were tested in a new biochemical assay designed to measure both receptor affinity and intrinsic activity of each compound and for their ability to stimulate phosphatidylinositol turnover in rat cerebral cortex. Two azaspirodecanes (5a and 5b) were shown to have far greater predicted efficacy than AF-30.
Animals↗
REHAB: a new assessment instrument for chronic psychiatric patients.
The renewed interest in the care and treatment of chronic psychiatric patients has led to an awareness of the need for improved assessment methods for this group. This article describes the development of REHAB, a behavior rating scale for use with people with chronic psychiatric disability, which has been carefully designed with respect to content, format, and ease of use. The article also draws together the various factor-analytic, reliability, validity, and sensitivity-to-change studies that provide the basic psychometric evidence for the scale's value. REHAB is presented as an integrated package of materials with special attention paid to training of raters and simplicity of interpretation. It has been used for a variety of different assessment purposes, in both research and clinical settings.
Deinstitutionalization↗
The effect of four narcotics on cholecystokinin octapeptide stimulated gallbladder contraction.
In an attempt to find the ideal analgesic to treat biliary tract pain we compared the effects of saline and equianalgesic doses of morphine, pentazocine, pethidine, and butorphanol on CCK-OP stimulated gallbladder emptying in healthy volunteers. Morphine produced a profound delay in gallbladder emptying while the other narcotics produced a significant delay in comparison to saline, but less than morphine. None of the drugs affected common bile duct diameter, bilirubin, liver enzymes or amylase. We recommend avoiding the use of morphine in the treatment of biliary and pancreatic pain, but although pethidine, pentazocine and butorphanol may be potentially detrimental we could find no definite superiority of one versus the others.
Adolescent↗
Token economy in a hospital rehabilitation system.
A ward-based token economy programme which formed one part of a larger rehabilitative service for long-stay psychiatric patients is described. The clinical effectiveness of the programme is examined by the use of various nursing, psychological and psychiatric assessments before and after the patients' treatment on the ward, and the progress of former patients is followed-up as they move to different parts of the rehabilitation service. Significant clinical gains in patients' psychiatric symptomatology and problem behaviour on the ward are reported, although there were indications that improvement was not fully maintained as the patients moved on to other parts of the service. Comparison of the present clinical programme with the earlier research programmes on the ward indicated that the present regime was superior. The advantages and problems of token economy as a rehabilitative facility are discussed, outlining the various different roles for token economy with psychiatric rehabilitation. Finally, the future of token economy for long-stay patients is considered, questioning whether it might more appropriately be replaced by other structured ward programmes.
Adult↗
Immunologic diversity among serogroup 1 Legionella pneumophila urinary antigens demonstrated by monoclonal antibody enzyme-linked immunosorbent assays.
We tested urine specimens from 222 patients with serogroup 1 Legionella pneumophila pneumonia in two enzyme-linked immunosorbent assays (ELISAs) which used different monoclonal antibodies (A and B) as detector antibodies. Of 171 specimens which contained enough antigen to be detected in the ELISAs, 169 reacted in only one of the two assays. A total of 25 patients whose infections were acquired in any of three Indianapolis hospitals excreted antigen reactive with monoclonal antibody B, but 18 patients who were treated for infections acquired elsewhere reacted with monoclonal antibody A. The urinary antigen ELISA reactivity patterns correlated with the reactivity patterns of L. pneumophila isolates when a separate panel of seven monoclonal antibodies was used. The isolate patterns, in turn, correlated well with environmental isolate patterns from two of the hospitals with nosocomial cases. We conclude that at least two different epitopes exist on the antigen molecules in urine from patients with serogroup 1 L. pneumophila pneumonia and that the subtyping of urinary antigens can be useful epidemiologically.
Animals↗
Specificity of FPL 57231 for leukotriene D4 receptors in fetal pulmonary circulation.
The effects of leukotriene D4 and the putative leukotriene receptor antagonist FPL 57231 were studied on the pulmonary circulation of alpha-chloralose-anesthetized fetal lambs close to term. At constant pulmonary inflow leukotriene D4 (LTD4, 0.1-10 micrograms), as bolus injections, caused dose-dependent increases in pulmonary vascular resistance. FPL 57231 (1.0-10 mg/kg) not only blocked the pressor responses to LTD4 but also lowered the normal pulmonary vascular resistance in a dose-dependent fashion. However, FPL 57231 also decreased the pulmonary pressor response to U 46619, a thromboxane A2 mimic, as well as the pressor response to phenylephrine HCl. Furthermore, the pressor responses to LTD4 were markedly reduced by cyclooxygenase inhibition. In preliminary experiments we demonstrated that the phenidone derivative, BW755C, which is a dual inhibitor of both cyclooxygenase and 5-lipoxygenase enzymes, did not block the pressor response to hypoxia. We conclude that FPL 57231 decreases fetal pulmonary vascular resistance by nonspecific mechanisms. Also the action of LTD4, is indirect and by way of the cyclooxygenase system. Although exogenous leukotrienes are able to produce a marked pulmonary pressor response, endogenous leukotrienes are probably not responsible for the hypoxic pulmonary pressor response of the fetal lung or its normally high pulmonary vascular resistance.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗