Biomedical subjects

M Gallagher

Publications and source records attributed to M Gallagher.

At least 109 records · Page 6Linked to original sources

PubMed1996

In vitro autoradiography of ionotropic glutamate receptors in hippocampus and striatum of aged Long-Evans rats: relationship to spatial learning.

Using in vitro autoradiography, we investigated [3H] alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, [3H]kainate and [3H]N-methyl-D-aspartate binding in two forebrain regions, the hippocampus and striatum, of young (four months of age) and aged (24-25 months of age) Long-Evans rats that had previously been tested for spatial learning ability in the Morris water maze. Although there was substantial preservation of binding in the aged rats, reductions in binding were present in the aged rats that were specific to ligand and anatomical region. In the hippocampus of aged rats, [3H] alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate binding in CA1 and [3H]kainate binding in CA3 were reduced. In contrast, N-methyl-D-aspartate binding was not significantly different between age groups. There was evidence of sprouting in the dentate gyrus molecular layer of aged rats, indicated by changes in the topography of [3H]kainate binding. Binding density was analysed with respect to patch/matrix compartmentalization in the striatum. The most striking result was a large decrease in N-methyl-D-aspartate binding in aged rats that was not limited to any dorsal/ventral or patch/matrix area of the striatum. Additionally, [3H]kainate binding in striatal matrix was modestly reduced in aged rats. Of these age effects, only N-methyl-D-aspartate binding in the striatum and [3H]kainate binding in the CA3 region of the hippocampus were correlated with spatial learning, with lower binding in the aged rats associated with better spatial learning ability. Age-related alterations in ionotropic glutamate receptors differ with respect to the receptor subtype and anatomical region examined. The age effects were not necessarily indicative of cognitive decline, as only two age-related binding changes were correlated with spatial learning. Interestingly, in these instances, lower binding in the aged rats was associated with preserved spatial learning, suggesting a compensatory reduction in receptor binding in a subpopulation of aged rats.

Aging↗

PubMed1996

Detection of adrenomedullin, a hypotensive peptide, in amniotic fluid and fetal membranes.

OBJECTIVE: Our purpose was to determine whether adrenomedullin, a multifunctional regulatory peptide involved in blood flow regulation and growth stimulation and with antimicrobial activity, was a component of amniotic fluid from second-trimester human fetus and to determine the source of this peptide. STUDY DESIGN: A prospective descriptive study was performed on 134 patients undergoing amniocentesis after genetic counseling, ultrasonography, and informed consent. Adrenomedullin expression was determined by immunocytochemical analysis, Western blot analysis, reverse transcriptase-polymerase chain reaction, and in situ reverse transcriptase-polymerase chain reaction in fetal membranes and with radioimmunoassay in amniotic fluids. RESULTS: Radioimmunoassay of the 134 amniotic fluid specimens revealed adrenomedullin-like immunoreactivity in all of them, ranging in concentration from 10 to 300 fmol/25 microliters (170 +/- 62 fmol/25 microliters). Immunocytochemical analysis, Western blot analysis, reverse transcriptase-polymerase chain reaction, and in situ reverse transcriptase-polymerase chain reaction further established the expression of adrenomedullin protein and messenger ribonucleic acid in fetal amniotic membranes, suggesting that this organ is the source of amniotic adrenomedullin. CONCLUSIONS: Our results clearly demonstrate the presence of adrenomedullin in second-trimester human amniotic fluid and adrenomedullin messenger ribonucleic acid and protein in amniotic membranes, suggesting that adrenomedullin is a hormone involved in the maintenance of normal pregnancy. Further studies with these molecular tools are in progress to determine the precise role of this hormone and whether adrenomedullin plays a role in the pathogenesis of various disorders of pregnancy.

Adrenomedullin↗

PubMed1996

The regulation of hippocampal dynorphin by neural/neuroendocrine pathways: models for effects of aging on an opioid peptide system.

Previous research has demonstrated increased messenger RNA expression and peptide content in an opioid system localized to hippocampal dentate granule cells in aged rats. This altered regulation of dynorphin was correlated with the emergence of an age-related impairment in spatial learning. Considerable evidence exists for additional effects of aging on systems that provide input to the dynorphin-containing dentate granule cells. Such changes have been well documented for loss of perforant path innervation from entorhinal cortex, deterioration in septohippocampal cholinergic neurons, and high amounts of glucocorticoids that have, among their targets, receptors located in the dentate gyrus. Similar to the effects of aging on hippocampal dynorphin, age-related changes in each of these systems correlate with the severity of spatial learning impairment in aged rats. This raises the possibility that dysregulation of dynorphin in the aged brain is a reactive response to antecedant change(s) in this circuitry, a hypothesis that was examined by separately manipulating in young rats the three neural/neuroendocrine systems identified above. Of the three models examined only removal of the perforant path reproduced the effect of aging on dynorphin in the hippocampal formation. An immunotoxin was used in Experiment 1 to selectively remove septo-hippocampal cholinergic neurons in young rats. No alteration in hippocampal opioid peptides was produced by this treatment. Experiment 2 examined effects of exposure to excess corticosterone. Adrenalectomized rats exhibited a significant decrease in hippocampal dynorphin-A (1-8) content, which was reversed by corticosterone replacement at a concentration approximating normal basal levels. Dynorphin-A (1-8) content, however, was not reliably increased by exposure to excess corticosterone. In contrast, perforant path removal was found to reproduce the effect of aging on dynorphin content; either aspiration of the entorhinal cortex or knife-cut transections of the perforant path reliably increased hippocampal dynorphin content. These results support the conclusion that age-related deterioration in the septohippocampal cholinergic system and evaluated exposure to corticosterone are not sufficient to induce an elevation in hippocampal dynorphin content. Only removal of the perforant path innervation was found to reproduce the elevation in hippocampal dynorphin content observed in aged rats with hippocampal-dependent learning impairment.

Adrenalectomy↗

PubMed1996

The amygdala and emotion.

The amygdala complex has long been known as part of the neural circuitry critical for emotion. Beyond its role in emotional reactivity, studies of animal models and patients with amygdala damage demonstrate its importance in emotional learning, whereby cues acquire significance through association with rewarding or aversive events. Although its function in associative learning has become well established, other recent research has advanced the concept that the amygdala regulates additional cognitive processes, such as memory or attention. For example, a correspondence in the function of the amygdala has recently been shown in the modulation of memory in humans and laboratory animals. The use of animal models has progressively defined the circuitry for these functions within the amygdala and its interconnections with other brain systems, including pathways through which the amygdala modulates memory and regulates attention. These various lines of research are progressively advancing our understanding of the amygdala's role in providing linkages between affect and cognition.

Amygdala↗

PubMed1996

Intact spatial learning in both young and aged rats following selective removal of hippocampal cholinergic input.

Studies using the selective cholinergic immunotoxin 192 IgG-saporin have demonstrated that lesions of the cholinergic input to the hippocampus from the medial septum/vertical limb of the diagonal band (MS/VDB) do not disrupt spatial learning in the water maze in young rats. However, age-related deficits in spatial learning correlate with the integrity of cholinergic neurons in the MS/VDB, suggesting that these neurons may be more crucial for spatial learning in aged rats. To investigate this hypothesis directly, we selectively lesioned these neurons in aged rats that demonstrated relatively intact spatial learning in an initial screening as well as in a comparison set of young rats. Intact and lesioned rats of both ages rapidly acquired a new place discrimination in a different spatial environment. These results indicate that the cholinergic input to the hippocampus is not differentially involved in spatial learning in aged rats.

Aging↗

PubMed1996

Rapid reverse transcription-PCR detection of hepatitis C virus RNA in serum by using the TaqMan fluorogenic detection system.

We describe the application of a new fluorogenic probe-based PCR assay (TaqMan; Perkin Elmer Corp./Applied Biosystems, Foster City, Calif.) for the detection of hepatitis C virus RNA in serum and plasma. This assay allows for the direct direction of specific PCR products within minutes of completion of the PCR by monitoring the increase in fluorescence of a dye-labeled oligonucleotide probe. We evaluated this assay by comparing the results obtained by nested PCR with those obtained by TaqMan PCR. Test samples included two separate dilutions series of plasma samples from experimentally infected chimpanzees and a panel of 48 serum specimens from patients with community-acquired hepatitis C virus. The quantity of HCV RNA in each chimpanzee plasma sample was determined by using branched DNA (bDNA) signal amplification assay (Quantiplex HCV RNA assay; Chiron Corp., Emeryville, Calif.). Both PCR assays demonstrated similar levels of detection and could reliably detect 13 bDNA genome equivalents per sample. We found an overall concordance of 88% between results of two PCR assays with the community-acquired panel, which resolved to 100% when discrepant samples were retested by nested PCR. TaqMan compared favorably with nested PCR with key advantages of speed, increased throughput, and decreased opportunity for false-positive results because of elimination of second-round amplification.

Animals↗

PubMed1996

Policy priorities in diabetes care: a Delphi study.

OBJECTIVES: To produce policy priorities for improving care of diabetes based on the findings of original research into patient and professional opinions of diabetes care in South Tyneside. To judge the feasibility of implementing these priorities as policy. DESIGN: A two round Delphi survey with a panel of 28 ¿experts.¿ In the first round each respondent produced a list of recommendations based on the findings of a report of patients' and professionals' opinions of diabetes care. 20 respondents produced a total of 180 recommendations, reviewed by a monitoring panel to produce a summary list of 28 recommendations. In the second round respondents rated each recommendation on two 5 point Likert scales. SETTING: Mainly Tyneside but also other parts of England. SUBJECTS: 28 healthcare professionals, including patients and patients' representatives. MAIN MEASURES: Voting by experts on how important each recommendation was to improving diabetes care service, and how likely the recommendation was to be implemented in the next five years. RESULTS: There was a high degree of consensus among respondents about recommendations considered important and likely to be implemented--namely, those concerned with improving communications between doctors in hospital and in general practice, and improving communications with patients. Respondents were more pessimistic about the prospects of implementing the recommendations than about their importance. Respondents thought that standards were important for improving care, and half would stop payments to general practice diabetic clinics that did not keep to district standards for diabetes care. For two recommendations a mismatch occurred between the importance of the recommendations and likelihood of implementation. This may reflect the practical problems of implementing recommendations. 18 of the 22 respondents thought that the study was useful in generating recommendations. CONCLUSIONS: The Delphi technique is a useful method for determining priorities for diabetes care and in assessing the feasibility of implementing recommendations.

Attitude of Health Personnel↗

PubMed1995

Effect of accessory pathway location on the efficiency of heating during radiofrequency catheter ablation.

During radiofrequency catheter ablation of accessory pathways there is a poor correlation between applied power and temperature at target sites for catheter ablation. This study was designed to examine the relation between power and temperature during radiofrequency catheter ablation in patients with accessory pathways and to identify the factors that affect the efficiency of heating, defined as the ratio of applied power and temperature. Twenty-nine patients underwent radiofrequency catheter ablation of an accessory pathway. Among 257 energy applications, 108 were applied for ablation of a right-sided accessory pathway, 105 for a left-sided accessory pathway, and 44 for a posteroseptal accessory pathway. During each application of radiofrequency energy, temperature was continually monitored by use of an ablation catheter with a thermistor embedded in the tip of the distal electrode. During some applications of energy, fluctuations in temperature were observed. The average power, impedance, temperature, and efficiency of heating for all applications of radiofrequency energy was 37 +/- 11 W, 100 +/- 9 ohms, 53 +/- 9 degrees C, and 1.7 +/- 0.8 degrees C/W (range 0.9 degrees to 6.6 degrees C/W), respectively. The efficiency of heating varied by location (p < 0.0001), with the greatest efficiency of heating for posteroseptal energy applications (2.3 +/- 1.2 degrees C/W, which were significantly greater than for left-sided (1.8 +/- 0.8 degrees C/W; p < 0.01) or right-sided (1.2 +/- 0.4 degrees C/W; p < 0.0001) applications. Phasic fluctuation in temperature was observed during 127 (49%) energy applications, and the efficiency of heating was 1.5 +/- 0.7 degrees C/W.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Ageing: the cholinergic hypothesis of cognitive decline.

The concept that memory loss in ageing might be attributable to deficiencies in cholinergic function was first proposed two decades ago. This proposal gained additional definition when pathology was found in the basal forebrain cholinergic system of patients with Alzheimer's disease, and substantial deterioration of these neurons was detected in several animal models of ageing. A recently developed method for selectively removing basal forebrain cholinergic neurons using an immunotoxin provides a powerful tool for examining the function of the basal forebrain cholinergic system. This review will address new information that has come from this approach, with an emphasis on understanding the contribution of basal forebrain cholinergic neurons to age-related cognitive impairment.

Aging↗

PubMed1995

Spatial learning in male and female Long-Evans rats.

Male and female Long-Evans rats were tested in the Morris water maze at 6 months of age. A place training procedure, in which rats learned the position of a camouflaged platform, was followed by cue training, in which rats escaped to a visible platform. No sex difference was found in place learning ability. Search accuracy on probe trials, when the platform was unavailable, was also equivalent for the male and female groups. These results contrast with previous studies of rodents at younger ages, which have reported a male advantage in spatial learning. It is suggested that the age at which rats are assessed may be an important factor, possibly reflecting a different course in the relatively protracted maturation of the hippocampus in male and female rats. The results of this investigation are also discussed with reference to studies of sex differences for spatial abilities in humans.

Age Factors↗

PubMed1995

Entorhinal-perirhinal lesions impair performance of rats on two versions of place learning in the Morris water maze.

The effects of entorhinal-perirhinal lesions in rats were studied with 2 versions of a place learning task in the Morris water maze. These lesions impaired performance on a multiple-trial task (3 days of 6 trials and a probe trial). This assessment was followed by a task in which rats were repeatedly trained to find novel locations with a variable delay (30 s or 5 min) imposed between each sample trial and retention test. Entorhinal-perirhinal damage produced a delay-dependent deficit in spatial memory: Rats with lesions were impaired at the 5-min delay relative to the control group and to their own performance at 30 s. These findings are discussed in relationship to memory impairment after entorhinal damage and spatial learning deficits observed after hippocampal damage.

Animals↗

PubMed1995

Taste-potentiated odor conditioning: impairment produced by infusion of an N-methyl-D-aspartate antagonist into basolateral amygdala.

Two experiments examined the effects of infusing an N-methyl-D-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonovalerate(d-APV), on taste-potentiated odor conditioning: a form of learning that is dependent on information processing in 2 sensory modalities. In Experiment 1, rats infused with d-APV were impaired in their acquisition of the potentiated learning to an odor cue. Expression of this learning and acquisition of a simple taste aversion remained intact following drug treatment. In Experiment 2, dose dependence and stereoselectivity were demonstrated for the antagonist compound. These results are consistent with previous studies demonstrating that either basolateral amygdala lesions, or treatment with NMDA antagonists, by other routes (systemic or intraventricular) produce selective deficits in taste-potentiated odor conditioning.

2-Amino-5-phosphonovalerate↗

PubMed1995

Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats.

Male Long-Evans rats were given injections of either 192 IgG-saporin, an apparently selective toxin for basal forebrain cholinergic neurons (LES), or vehicle (CON) into either the medial septum and vertical limb of the diagonal band (MS/VDB) or bilaterally into the nucleus basalis magnocellularis and substantia innominata (nBM/SI). Place discrimination in the Morris water maze assessed spatial learning, and a trial-unique matching-to-place task in the water maze assessed memory for place information over varying delays. MS/VDB-LES and nBM/SI-LES rats were not impaired relative to CON rats in acquisition of the place discrimination, but were mildly impaired relative to CON rats in performance of the memory task even at the shortest delay, suggesting a nonmnemonic deficit. These results contrast with effects of less selective lesions, which have been taken to support a role for basal forebrain cholinergic neurons in learning and memory.

Acetylcholinesterase↗

PubMed1995

A psychiatrist-rated battery of measures for assessing the clinical status of psychiatric inpatients.

Despite the increasing demand for outcome assessment measures, no published reports have provided a standardized way to assess psychiatric inpatients that includes diagnosis and observer ratings of psychopathology. This paper reviews general principles for selecting outcome assessment measures, proposes a battery of instruments based on already available measures to assess clinical status in psychiatric inpatients, reviews methods of implementing the battery in an academic inpatient psychiatric setting, and presents preliminary data on its interrater reliability, construct validity, and range of response to acute hospitalization. Preliminary results suggest that the battery may be useful for resident and medical student education and for enhancing quality assurance and continuous quality improvement.

Comorbidity↗

PubMed1995

Basal forebrain cholinergic lesions disrupt increments but not decrements in conditioned stimulus processing.

Magnocellular neurons in the basal forebrain provide the major cholinergic innervation of cortex. Recent research suggests that this cholinergic system plays an important role in the regulation of attentional processes. The present study examined the ability of rats with selective immunotoxic lesions of these neurons (made with 192 IgG-saporin) to modulate attention within an associative learning framework. Each rat was exposed to conditioned stimuli (CS) that were either consistent or inconsistent predictors of subsequent cues. Intact control rats showed increased CS associability when that cue was an inconsistent predictor of a subsequent cue, whereas lesioned rats were impaired in increasing attention to the CS when its established relation to another cue was modified. In a separate experiment designed to test latent inhibition, it was shown that removal of the corticopetal cholinergic neurons spared a decrement in associability that occurs when rats are extensively preexposed to a CS prior to conditioning. These data indicate that the cholinergic innervation of cortex is critical for incrementing, but not for decrementing attentional processing. The specific behavioral tests used to assess the role of the basal forebrain cholinergic system in the present study were previously used to identify a role for the amygdala central nucleus in attention (Holland and Gallagher, 1993b). Those studies, together with the results in this report, indicate that regulation of attentional processes during associative learning may be mediated by projections from the amygdala to the basal forebrain cholinergic system.

Animals↗

PubMed1995

Hippocampal lesions disrupt decrements but not increments in conditioned stimulus processing.

Studies recording hippocampal neural activity show widespread registration of events during associative learning. Recent computational models of hippocampal function have stressed its role in attentional processes specified by well-developed modern theories of associative learning. These modeling efforts are largely aimed at accounting for the behavioral outcomes of damage to the hippocampal system in terms of underlying changes in information processing. Two experiments examined the effects of neurotoxic lesions of the hippocampus on changes in attentional processing of a conditioned stimulus (CS) in appetitive Pavlovian conditioning in rats. In Experiment 1, hippocampal lesions eliminated the reduction in associability of a CS usually produced by preexposure to that cue (latent inhibition). In Experiment 2, hippocampal lesions interfered with the loss in associability of a CS normally produced when that CS consistently predicts another event. In contrast, in Experiment 2, hippocampal lesions did not prevent the enhancement of CS associability when a previously consistent predictive relation between two events was made inconsistent. This research supports previous claims that the hippocampus is involved in regulating the processing of CSs in Pavlovian conditioning, and provides new evidence for a hippocampal role in decremental, but not incremental, changes in attention.

Animals↗

PubMed1995

Who should give lifestyle advice in general practice and what factors influence attendance at health promotion clinics? Survey of patients' views.

BACKGROUND: Health promotion activity in general practice has increased greatly since 1990. A large proportion of this work is undertaken by practice nurses. Little is known about patients' views about the providers of health promotion or their views about general practice health promotion clinics. AIM: A study was carried out in 1992 to determine patients' views about the provision of health promotion advice by general practitioners and practice nurses and their views about attending health promotion clinics. METHOD: A postal questionnaire was sent to a random sample of 1750 patients aged 16 years and over from five general practices in south Tyneside. The questionnaire explored patients' preferences regarding health promotion advice from the general practitioner or practice nurse in relation to four areas of lifestyle advice and factors that might encourage patients to attend a health promotion clinic. RESULTS: A response rate of 75% was obtained from 1639 eligible patients. Receiving health promotion advice from either the general practitioner or the practice nurse was the most commonly preferred option expressed by patients overall. The ability of health promotion clinic staff to deal with patients' concerns about their illness and short waiting times were more likely to influence patients' attendance at health promotion clinics than the presence of a general practitioner or practice nurse. CONCLUSION: In the present study, many patients found health advice received from practice nurses and general practitioners equally acceptable. However, it was the ability of health professionals to respond to patients' health concerns in the health promotion clinic rather than the type of health professional running the clinic that was important for patients.

Adolescent↗

PubMed1994

The amygdala complex: multiple roles in associative learning and attention.

Although certain neurophysiological functions of the amygdala complex in learning seem well established, the purpose of this review is to propose that an additional conceptualization of amygdala function is now needed. The research we review provides evidence that a subsystem within the amygdala provides a coordinated regulation of attentional processes. An important aspect of this additional neuropsychology of the amygdala is that it may aid in understanding the importance of connections between the amygdala and other neural systems in information processing.

Amygdala↗