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Biomedical subjects

R Granger

Publications and source records attributed to R Granger.

At least 19 recordsLinked to original sources
PubMed2001

Intraoperative decrease in pulse oximeter readings following injection of isosulfan blue.

PURPOSE: Sentinel lymph node mapping, involving injection of isosulfan blue dye around a tumour, is beginning to be used in patients with carcinoma of the breast. Absorption of the dye into the circulation may interfere with pulse oximetry, causing falsely low readings. This report describes changes in pulse oximeter readings following injection of isosulfan blue for sentinel lymph node mapping in a patient with carcinoma of the breast. CLINICAL FEATURES: An 83-yr-old female patient underwent sentinel node biopsy of the axilla followed by partial mastectomy for carcinoma of the left breast. Isosulfan blue was injected in the area of the tumour in the left breast. The SpO2 began to decrease 15 min after dye injection, reaching a nadir of 89-90% 30 min after injection. Arterial blood gas analysis showed normal arterial partial pressure of oxygen. Pulse oximeter readings did not return to normal until more than six hours after dye injection. CONCLUSION: Review of the literature reveals a small number of case reports of similar occurrences of low pulse oximeter readings following injection of isosulfan blue or patent blue dye for lymphatic mapping. Data from these reports and the case described here suggest that the latency, magnitude and duration of effect on pulse oximeter readings following injection of these dyes is highly variable. It is important to rule out other causes of low pulse oximeter readings when this effect occurs; normal oxygenation can be verified with arterial blood gas analysis. Co-oximetry can be done to rule out methemoglobinemia as a cause of decreased SpO2.

Adenocarcinoma↗
PubMed2000

Origins and distribution of cholinergically induced beta rhythms in hippocampal slices.

Regional variations and substrates of high-frequency rhythmic activity induced by cholinergic stimulation were studied in hippocampal slices with 64-electrode recording arrays. (1) Carbachol triggered beta waves (17.6 +/- 5.7 Hz) in pyramidal regions of 75% of the slices. (2) The waves had phase shifts across the cell body layers and were substantially larger in the apical dendrites than in cell body layers or basal dendrites. (3) Continuous, two-dimensional current source density analyses indicated apical sinks associated with basal sources, lasting approximately 10 msec, followed by apical sources and basal sinks, lasting approximately 20 msec, in a repeating pattern with a period in the range of 15-25 Hz. (4) Carbachol-induced beta waves in the hippocampus were accompanied by 40 Hz (gamma) oscillations in deep layers of the entorhinal cortex. (5) Cholinergically elicited beta and gamma rhythms were eliminated by antagonists of either AMPA or GABA receptors. Benzodiazepines markedly enhanced beta activity and sometimes introduced a distinct gamma frequency peak. (6) Twenty Hertz activity after orthodromic activation of field CA3 was distributed in the same manner as carbachol-induced beta waves and was generated by a current source in the apical dendrites of CA3. This source was eliminated by high concentrations of GABA(A) receptor blockers. It is concluded that cholinergically driven beta rhythms arise independently in hippocampal subfields from oscillatory circuits involving (1) bursts of pyramidal cell discharges, (2) activation of a subset of feedback interneurons that project apically, and (3) production of a GABA(A)-mediated hyperpolarization in the outer portions of the apical dendrites of pyramidal neurons.

Acetylcholine↗
PubMed1999

A distinct member of the aspartic proteinase gene family from the human malaria parasite Plasmodium falciparum.

A gene (hap) transcribed during the intra-erythrocytic life cycle stages of the human malaria parasite Plasmodium falciparum was cloned and sequenced. It was found to encode a protein belonging to the aspartic proteinase family but which carried replacements of catalytically crucial residues in the hallmark sequences contributing to the active site of this type of proteinase. Consideration is given as to whether this protein is the first known parasite equivalent of the pregnancy-associated glycoproteins that have been documented in ungulate mammals. Alternatively, it may be operative as a new type of proteinase with a distinct catalytic mechanism. In this event, since no counterpart is known to exist in humans, it affords an attractive potential target against which to develop new anti-malarial drugs.

Amino Acid Sequence↗
PubMed1999

The effects of retroperitoneal carbon dioxide insufflation on hemodynamics and arterial carbon dioxide.

BACKGROUND: Laparoscopic techniques are being increasingly used for retroperitoneal surgery. However, hemodynamic and ventilatory efforts of retroperitoneal carbon dioxide (CO2) insufflation have not been studied. We hypothesized that differences in absorptive surface, anatomy, and compartment compliance could result in different hemodynamic and ventilatory effects between retroperitoneal and intraperitoneal insufflation. METHODS: Pigs (n = 7) were anesthetized and stabilized. The peritoneal cavity was incrementally insufflated with CO2 to a maximum pressure of 25 cm H2O and the gas released. Hemodynamics and arterial blood gas values were recorded initially, at each level of insufflation, and following the pneumoperitoneum release until baseline values were reached. This insufflation protocol was repeated in the retroperitoneum. RESULTS: Mean arterial pressure (111 mm Hg, 95% confidence interval 99 to 156) and cardiac output (3.7 L/min, 2.8 to 5.2) did not change with increasing insufflation pressure of either intraperitoneum or retroperitoneum. PaCO2 was directly related to insufflation pressure in both spaces, increasing from 41.2 mm Hg (37.3 to 43.4) at baseline to 57.7 mm Hg (47.6 to 82.1) at insufflation pressure of 25 cm H2O. After release of the insufflation gas, time to return to baseline PaCO2 was slightly less from the retroperitoneal space (73 minutes, 45 to 105) than the intraperitoneal (107 minutes, 35 to 175). CONCLUSIONS: The effects of CO2 insufflation on hemodynamics and PaCO2 are the same in the retroperitoneal and intraperitoneal spaces.

Animals↗
PubMed1998

Regulation of arousal and attention in preschool children exposed to cocaine prenatally.

Four lines of evidence suggest a plausible link between prenatal cocaine exposure (CE) and specific effects on the mechanisms subserving arousal and attention regulation in infants and preschool-aged children. These are (1) the association of prenatal CE with alterations in monoaminergic system ontogeny; (2) neurobehavioral effects of prenatal CE in animals consistent with an enduring increased level of activity in response to novelty and inhibited exploration and altered responses to stress, suggesting overarousal in the face of novel/stressful situations and disrupted attention and exploration; (3) altered norepinephrine system function in cocaine-exposed human infants; and (4) neurobehavioral findings in infants and preschool-aged children suggestive of disrupted arousal regulation in the face of novelty, increased distractibility, and consequent impaired attention to novel, structured tasks. This paper summarizes findings on response to novel challenges from a cohort of prenatally cocaine-exposed infants and preschool-aged children followed longitudinally since birth. Arousal regulation in the face of novel challenges is operationalized behaviorally as state and emotional reactivity and neurophysiologically as the startle response and heart rate variability. Across different ages and tasks, behavioral and neurophysiological findings suggest that prenatally cocaine-exposed children are more likely to exhibit disrupted arousal regulation. Because the regulation of arousal serves as a gating mechanism to optimize orientation and attention, arousal regulation has important implications for ongoing information processing, learning, and memory. Furthermore, impaired arousal regulation predisposes children to a lower threshold for activation of "stress circuits" and may increase their vulnerability to the developmentally detrimental effects of stressful conditions particularly when such children are also exposed to the chaotic environmental conditions often characterizing substance-abusing families.

Adult↗
PubMed1997

Evidence that a positive modulator of AMPA-type glutamate receptors improves delayed recall in aged humans.

Elderly subjects (65-76 years) were tested for recall of nonsense syllables prior to and after oral administration of 1-(quinoxalin-6 ylcarbonyl)piperidine (CX516), a centrally active drug that enhances currents mediated by AMPA-type glutamate receptors. A significant and positive drug effect was found for delayed (5 min) recall at 75 min posttreatment; average scores for the highest dose group were more than twofold greater than for the placebo group. The drug had no evident influence on heart rate or self-assessment of several psychological variables.

Aged↗
PubMed1997

Enhancement by an ampakine of memory encoding in humans.

Acentrally active drug that enhances AMPA receptor-mediated currents was tested for its effects on memory in humans. Evidence for a positive influence on encoding was obtained in four tests: (i) visual associations, (ii) recognition of odors, (iii) acquisition of a visuospatial maze, and (iv) location and identity of playing cards. The drug did not improve scores in a task requiring cued recall of verbal information. The selectivity of drug effects on memory was confirmed using tests of visual recognition, motor performance, and general intellectual functioning. These results suggest that positive modulators of AMPA receptors selectively improve at least some aspects of memory.

Adult↗
PubMed1997

Triazolam impairs delayed recall but not acquisition of various everyday memory tasks in humans.

A double-blind test battery was administered to 24 human subjects (8 control, 16 drug) to assess the effects of 0.125 mg triazolam (oral) on memory encoding and retention across delay intervals ranging from seconds to 1 week after presentation. Although the drug reduced immediate psychomotor performance, it did not impair recall of previously learned information, nor did it significantly impair encoding of new information. The drug enhanced immediate recall of the location and identity of playing cards, without affecting 4-h delayed recall. The drug treatment impaired correct recall of object names after a delay of 20 min. At 4 h delay, the drug impaired olfactory recognition and free-recall of object names. At both 1 day and 1 week delay, the drug impaired recall of biographical information and correct identification of picture-photographer pair associations. The drug also impaired the daily improvement of the drug group as compared with the control group in a geometric puzzle solving task. The time course of these memory impairments compares well with the known effects of triazolam on long-term potentiation (LTP), a candidate biological mechanism underlying telencephalic memory formation and expression.

Adolescent↗
PubMed1997

A profile of the behavioral changes produced by facilitation of AMPA-type glutamate receptors.

A newly developed group of benzoylpiperidine drugs that enhance AMPA-receptor-gated currents ("ampakines") has been shown to improve memory encoding in rats across a variety of experimental paradigms. The present experiments were intended to i) provide a partial profile of the behavioral changes produced by ampakines, ii) test if two ampakines (BDP-12 and BDP-20) that differ significantly in their effects on AMPA receptor kinetics produce similar behavioral profiles, and iii) determine if physiological potency is reflected in behavioral potency. BDP-20 reduced two measures of exploratory activity in aged rats but increased speed of performance in a radial maze; the drug also caused substantially improved retention of spatial information. These results are similar to those obtained with BDP-12, an analog that differs from BDP-20 in its effects on ligand binding to the AMPA receptor and on the physiological responses of the receptors to glutamate. BDP-20 was approximately ten-fold more potent in behavioral effects than BDP-12, which agrees with the relative potencies of the two drugs as assessed with excised patches and excitatory synaptic responses. These findings indicate that ampakines, though differing in their effects on AMPA-receptor-mediated responses, have similar effects at the behavioral level.

Animals↗
PubMed1996

Distinct memory circuits composing the hippocampal region.

The very different anatomical designs of the adjacent circuitries of the cortico-hippocampal pathway, along with their somewhat different synaptic plasticity mechanisms, suggest a nearly serial pathway of distinct memory circuits each contributing its own specialized processing operation to overall hippocampal function. Modeling and formal theoretical analysis of the prominent anatomical design features of particular circuits (piriform/entorhinal cortex; hippocampal field CA3; hippocampal field CA1) are found to identify potential emergent function not readily arrived at in the absence of these formal models, and yet which once derived can be seen potentially to confer unique capabilities to an integrated hippocampal mechanism for processing memories during behavior.

Animals↗
PubMed1996

Facilitation of glutamate receptors reverses an age-associated memory impairment in rats.

The accuracy of memory for recent events is reported to decay between young adulthood and middle age in humans (Crook et al., 1990; Crook and West, 1990; Thomas et al., 1977) due to impairments in acquisition and/or retention (Craik, 1977; Huppert and Kopelman, 1989). Effects of this kind are also found in comparisons of middle-aged (12-18 months) vs. young adult (3 months) rats in tests requiring retention of recently sampled spatial cues (Kadar et al., 1990a; Kadar et al., 1990b; Goudsmit et al., 1990; Weiss and Thompson, 1991). The causes of such changes in memory processing are unknown but might be expected to involve age-related losses in forebrain glutamate receptors (Bahr et al., 1992; Magnusson and Cotman, 1993; Wenk et al., 1991); these receptors mediate fast excitatory transmission in many brain regions and play an essential role in the production of long-term potentiation (LTP), a form of synaptic plasticity that has been implicated in memory encoding (Landfield and Lynch, 1977; Moore et al., 1993). In the present communication we report results indicating that a drug that enhances AMPA-type glutamate receptors acts centrally to selectively increase hippocampal spatial cell firing and improves both acquisition performance and memory retention in middle-aged rats to levels equivalent to those found in young adult animals.

Age Factors↗
PubMed1996

Psychological effects of a drug that facilitates brain AMPA receptors.

The effects of 1-(quinoxalin-6-ylcarbonyl)piperidine (CX516), a centrally active compound that facilitates AMPA receptor-mediated synaptic responses, were tested in human subjects. Separate tests of delayed recall were given prior to and nearly 3 h after administration of placebo (n = 12) or drug (n = 36). Control subjects exhibited poorer performance in the second session than in the first while subjects given 600-1200 mg of the drug did not. There were no pre- vs post-treatment differences in immediate recall in either group. The drug did not reliably affect self-assessment scores for any of several psychological variables but did disrupt the normally present correlations for within-subject changes in the variables. These results suggest that AMPA receptor modulators may (1) improve memory under some circumstances and (2) produce psychological effects that are subtle or not related to specific mood states.

Adult↗
PubMed1995

Necrotizing fasciitis in childhood.

Necrotizing fasciitis is a rare entity in the pediatric population. Five cases of this soft tissue infection were treated at the authors' institution between January and December 1993. Three of the children were profoundly neutropenic secondary to chemotherapy. All five were treated with aggressive surgical debridement, frequent dressing changes, broad-spectrum antibiotics, and nutritional support. In addition, the patients with neutropenia received a combination of granulocyte-colony stimulating factor and granulocyte transfusions. One child died of overwhelming sepsis and bone marrow graft failure. The others eventually made a complete recovery. Necrotizing fasciitis may be becoming a more common problem in children. Aggressive chemotherapeutic regimens and more frequent use of bone marrow transplantation could be a factor in this. Early diagnosis and aggressive surgical therapy is critical. However, mortality may be significant, especially in patients with neutropenia. Leukocyte response to the infection may be a prognostic marker. Pseudomonas and enteric gram-negative organisms are seen frequently in immunocompromised children with necrotizing fasciitis. Antimicrobial selection should supply adequate coverage of these organisms.

Adolescent↗
PubMed1994

Non-Hebbian properties of long-term potentiation enable high-capacity encoding of temporal sequences.

A hypothesis commonly found in biological and computational studies of synaptic plasticity embodies a version of the 1949 postulate of Hebb that coactivity of pre- and postsynaptic elements results in increased efficacy of their synaptic contacts. This general proposal presaged the identification of the first and still only known long-lasting synaptic plasticity mechanism, long-term potentiation (LTP). Yet the detailed physiology of LTP induction and expression differs in many specifics from Hebb's rule. Incorporation of these physiological LTP constraints into a simple non-Hebbian network model enabled development of "sequence detectors" that respond preferentially to the sequences on which they were trained. The network was found to have unexpected capacity (e.g., 50 x 10(6) random sequences in a network of 10(5) cells), which scales linearly with network size, thereby addressing the question of memory capacity in brain circuitry of realistic size.

Algorithms↗
PubMed1993

Simulated dendritic spines influence reciprocal synaptic strengths and lateral inhibition in the olfactory bulb.

Whereas many theories have been proposed for the function of dendritic spines in axodendritic processing, the influence of spines on reciprocal dendrodendritic processing has received relatively little attention. Mitral cells in the olfactory bulb, for example, synapse on granule cell spines (gemmules) which are in turn presynaptic to reciprocal inhibitory synapses back onto the same mitral cells. The postulate that these synapses respond with synaptic strengths graded by presynaptic depolarization results in a sensitivity of the reciprocal response to the local depolarization in the spine head. A biophysical computer simulation was performed to study this effect and the effect of changing the spine neck diameter and cytoplasmic resistance on the reciprocal and lateral inhibitory responses given graded dendrodendritic synapses. Since spine head local potentials are larger than similar inputs on dendritic shafts, spines facilitate the graded reciprocal response even for low levels of activity. Spine heads also reduce the synaptic current, lowering the contribution to the rest of the granule dendritic tree and thus reducing lateral inhibition. In addition, an increase in the effective spine neck axial resistance further increases the reciprocal synaptic response and decreases the lateral inhibitory response. Short-term, reversible, and long-term methods of implementing this resistance-based dendrodendritic plasticity are discussed as well as the partial dependence of the reciprocal increase/lateral decrease effect on a broad synaptic gradation. Candidate memory operations by the bulb are also discussed, including a possible recognition memory pass/block function.

Computer Simulation↗
PubMed1993

A drug that facilitates glutamatergic transmission reduces exploratory activity and improves performance in a learning-dependent task.

A recently developed benzamide compound which facilitates glutamate receptor-mediated synaptic responses was used to test behavioral consequences of enhanced glutamatergic transmission. The drug was found to depress exploratory activity by rats in a novel environment. At a dose below threshold for causing such effects, drug-treated and control rats exhibited no evident behavioral differences during the acquisition phase of a radial maze experiment. Yet, when tested 2.5 h later, experimental animals were more likely than controls to choose maze arms that had not been entered during the acquisition session, suggesting that the drug enhanced retention of information about prior choices and the maze environment.

Animals↗