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Biomedical subjects

S Davis

Publications and source records attributed to S Davis.

At least 73 records · Page 4Linked to original sources
PubMed2000

Plasticity at hippocampal to prefrontal cortex synapses: dual roles in working memory and consolidation.

The involvement of the hippocampus and the prefrontal cortex in cognitive processes and particularly in learning and memory has been known for a long time. However, the specific role of the projection which connects these two structures has remained elusive. The existence of a direct monosynaptic pathway from the ventral CA1 region of the hippocampus and subiculum to specific areas of the prefrontal cortex provides a useful model for conceptualizing the functional operations of hippocampal-prefrontal cortex communication in learning and memory. It is known now that hippocampal to prefrontal cortex synapses are modifiable synapses and can express different forms of plasticity, including long-term potentiation, long-term depression, and depotentiation. Here we review these findings and focus on recent studies that start to relate synaptic plasticity in the hippocampo-prefrontal cortex pathway to two specific aspects of learning and memory, i.e., the consolidation of information and working memory. The available evidence suggests that functional interactions between the hippocampus and prefrontal cortex in cognition and memory are more complex than previously anticipated, with the possibility for bidirectional regulation of synaptic strength as a function of the specific demands of tasks.

Animals↗
PubMed2000

Magnetic resonance-based vertebral morphometry of the thoracic spine: age, gender and level-specific influences.

OBJECTIVE: The aim of this study was to examine age, gender, and segmental trends in thoracic vertebral body shape, utilising thoracic spine magnetic resonance images involving an age range spanning the life span. DESIGN: A quantitative, cross-sectional, retrospective study design involving a sample of convenience. BACKGROUND: Thoracic vertebral shape data are commonly derived from radiographic resources. The non-ionising properties of magnetic resonance imaging and availability of digital data for image analysis suggest potential for MR-based morphometric studies. For the thoracic spine, there is limited vertebral shape data on males, while few studies have examined the pattern of age-related changes across the life span. METHODS: Morphometry was performed on 220 mid sagittal T1-weighted MR images using image analysis software. Three indices of vertebral shape were utilised: the antero-posterior height ratio or anterior wedge index, mid-posterior height ratio or biconcavity index, and ratio of posterior vertebral height to mid antero-posterior diameter or compression index. RESULTS: Different segmental patterns were noted for the vertebral shape indices. Significantly lower mean values were noted in males for the compression index. Age trends were significant, with a linear age-related decline demonstrated for the anterior wedge and biconcavity indices, and a quadratic trend noted for the compression index. CONCLUSIONS: Thoracic vertebral body shape may be uniquely described using specific shape indices, for examining various segmental, gender and age-associated changes. RELEVANCE: These results suggest the importance of defining specific reference criteria for thoracic vertebral body shape indices, particularly age-related data encompassing a wide age range. Magnetic resonance studies enable interpretation of vertebral shape data in relation to the wide spectrum of pathologies afflicting the thoracic spine, without the concerns of ionising radiation.

Adolescent↗
PubMed2000

Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression.

The relationship of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) to antidepressant response was examined in 95 elderly patients receiving a protocolized treatment for depression with paroxetine or nortriptyline. Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations. Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele. There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression (HRSD) scores or anxiety symptoms. During acute treatment with paroxetine, mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele, despite equivalent paroxetine concentrations. Onset of response to nortriptyline was not affected. Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor.

Adrenergic alpha-Agonists↗
PubMed2000

The role of local estrogen biosynthesis in males and females.

Natural (human) and experimental (mouse) models of estrogen insufficiency have revealed hitherto unexpected roles for estrogens in both males and females. In postmenopausal women, and in men, estrogen no longer has a major role as a circulating hormone, but rather it functions locally as a paracrine or even 'intracrine' factor in tissue sites where it is formed. As a consequence, the tissue-specific nature of aromatase production assumes physiological and pathophysiological significance. The availability of circulating precursors is also important in sites where there is no local supply of C19 precursors, particularly in elderly women. The potential clinical significance of these findings in terms of the development of new therapeutic modalities is discussed.

Adipose Tissue↗
PubMed2000

Comparison of powder and aerosol formulations of salmeterol in the treatment of asthma.

BACKGROUND: The efficacy and safety of the aerosol metered-dose inhaler (MDI) formulation of salmeterol for asthma symptoms have been established. Recently, salmeterol has been introduced as a micronized powder formulation administered via a breath-activated multidose powder inhaler (Diskus). OBJECTIVE: A multicenter, randomized, double-blind, double-dummy, parallel-group, placebo-controlled study involving 498 adolescents and adults with mild-to-moderate asthma was conducted to compare the efficacy and safety of salmeterol powder 50 microg twice daily via Diskus, salmeterol aerosol 42 microg twice daily via MDI, and placebo. METHODS: Patients were randomized to one of the three treatment groups for 12 weeks. Efficacy was assessed by serial measurements of forced expiratory volume in one second (FEV1) over 12 hours, daily peak expiratory flow (PEF), self-rated asthma symptom scores, nighttime awakenings, and supplemental albuterol use. Safety of each treatment was evaluated by monitoring vital signs, electrocardiograms, Holter monitoring, and occurrence of adverse events. RESULTS: As compared with placebo, both salmeterol powder and aerosol produced significant improvement in FEV1 and PEF and decreased nighttime awakenings and supplemental albuterol use. There were no significant differences in the efficacy of the two salmeterol formulations. The magnitude of improvement in pulmonary function was undiminished over the 12-week study. Both formulations of salmeterol were well tolerated, with safety profiles not significantly different from placebo. CONCLUSION: Results of this study indicate that salmeterol, administered either as a powder 50 microg twice daily via Diskus or as an aerosol 42 microg twice daily via MDI, produces clinically significant and comparable improvement in pulmonary function and is well tolerated in patients with mild-to-moderate persistent asthma.

Adolescent↗
PubMed2000

Morning urinary assessment of nocturnal melatonin secretion in older women.

We evaluated the feasibility of using morning urine samples in epidemiological studies aimed at clarifying the relationship between nocturnal melatonin levels and breast cancer risk. Initially, a laboratory-based study of 29 women (40- 70 yr old) was performed to examine the correlation between plasma melatonin levels in hourly nocturnal blood samples and both melatonin and its major enzymatic metabolite, 6-hydroxymelatonin-sulfate (6-OHMS) in morning urine samples. In a companion field study, morning urine samples were collected from 203 healthy women to assess similarities and differences in laboratory versus field measures. Taken together, our results indicate: 1) levels of melatonin and of creatinine-corrected 6-OHMS in the first morning void urine are strongly correlated with total nocturnal plasma melatonin output (P < 0.001) and also with peak nocturnal melatonin values (P < 0.001); 2) similar ranges for 6-OHMS were found in the laboratory and the field; and 3) neither menopausal status nor hormonal replacement therapy altered 6-OHMS values in morning void urine. The inclusion of morning urine samples in epidemiological studies of cancer could allow cost-effective, widespread testing of the role played by melatonin in human health and disease.

Adult↗
PubMed2000

The central domain of bovine submaxillary mucin consists of over 50 tandem repeats of 329 amino acids. Chromosomal localization of the BSM1 gene and relations to ovine and porcine counterparts.

We previously elucidated five distinct protein domains (I-V) for bovine submaxillary mucin, which is encoded by two genes, BSM1 and BSM2. Using Southern blot analysis, genomic cloning and sequencing of the BSM1 gene, we now show that the central domain (V) consists of approximately 55 tandem repeats of 329 amino acids and that domains III-V are encoded by a 58.4-kb exon, the largest exon known for all genes to date. The BSM1 gene was mapped by fluorescence in situ hybridization to the proximal half of chromosome 5 at bands q2. 2-q2.3. The amino-acid sequence of six tandem repeats (two full and four partial) were found to have only 92-94% identities. We propose that the variability in the amino-acid sequences of the mucin tandem repeat is important for generating the combinatorial library of saccharides that are necessary for the protective function of mucins. The deduced peptide sequences of the central domain match those determined from the purified bovine submaxillary mucin and also show 68-94% identity to published peptide sequences of ovine submaxillary mucin. This indicates that the core protein of ovine submaxillary mucin is closely related to that of bovine submaxillary mucin and contains similar tandem repeats in the central domain. In contrast, the central domain of porcine submaxillary mucin is reported to consist of 81-amino-acid tandem repeats. However, both bovine submaxillary mucin and porcine submaxillary mucin contain similar N-terminal and C-terminal domains and the corresponding genes are in the conserved linkage regions of the respective genomes.

Amino Acid Sequence↗
PubMed2000

Dysfunctional regulation of alphaCaMKII and syntaxin 1B transcription after induction of LTP in the aged rat.

Syntaxin 1B and alphaCaMKII are two genes that are upregulated after the induction of LTP and appear to underlie different mechanisms of synaptic plasticity. alphaCaMKII is directly implicated in strengthening the synapses that have been modified, whereas syntaxin 1B has been implicated in a mechanism for the propagation of synaptic plasticity within neural circuits. In these experiments we have investigated whether the regulation of these genes is altered after the induction of LTP in aged rats. We found, three hours after the induction of LTP in the dentate gyrus, that aged rats could be subgrouped into those in which LTP was maintained and those in which LTP had decayed back to basal levels. Both genes were upregulated in young adult rats, whereas there was a differential pattern of LTP-induced expression in the aged rats. Dendritic alphaCaMKII was upregulated in aged rats only when LTP was maintained. In contrast, regulation of syntaxin 1B and alphaCaMKII was absent in the granule cell bodies of the aged rats regardless of whether LTP was maintained or not. These results suggest that molecular mechanisms implicated in two aspects of hippocampal synaptic plasticity malfunction during normal ageing and therefore may have some contributory role in the decline in memory function routinely observed in ageing.

Aging↗
PubMed2000

Influence of age and gender on thoracic vertebral body shape and disc degeneration: an MR investigation of 169 cases.

There are limited data detailing the pattern of age and gender-related changes to the thoracic vertebral bodies and intervertebral discs. A retrospective MR investigation, involving T1-weighted midsagittal images from 169 cases, was undertaken to examine age influences on the anterior wedge (anteroposterior height ratio or Ha/Hp), biconcavity (midposterior height ratio or Hm/Hp), and compression indices (posterior height/anteroposterior diameter or Hp/D) of the thoracic vertebral bodies. Disc degenerative changes in the annulus, nucleus, end-plate and disc margin were noted on T2-weighted sagittal images for the 169 cases, based on a 3-level grading system. A linear age-related decline in the Ha/Hp and Hm/Hp indices was noted. The Hp/D index increased during the first few decades of life, then decreased gradually thereafter. The prevalence of abnormal findings in the annuli, nuclei and disc margins increased with increasing age, particularly in the mid and lower thoracic discs. Greater disc degenerative changes were observed in males. These findings provide further insight into the nature of thoracic vertebral shape changes across the lifespan, and the typical patterns of degeneration of the thoracic intervertebral discs.

Adolescent↗
PubMed2000

Arachnoiditis ossificans and syringomyelia: a unique case report.

A 62-year-old male presented with progressive quadriparesis. Magnetic resonance imaging of the spine revealed a spinal cord syrinx but failed to detect extensive arachnoiditis ossificans noted on insertion of a syringopleural shunt. A postoperative computed tomography scan clearly demonstrated the abnormality and its extent. We present a rare case of syringomyelia resulting from spinal arachnoiditis ossificans and review the relevant literature.

Arachnoiditis↗
PubMed2000

Echoplanar magnetic resonance imaging in acute stroke.

Echoplanar magnetic resonance imaging (EPI) enables rapid, non-invasive imaging and analysis of cerebral pathophysiology in acute stroke. It represents an important clinical advance over computed tomography (CT) and conventional magnetic resonance (MR) scanning. It can rapidly delineate infarcted cerebral tissue and distinguish acute from chronic stroke. In addition, EPI has the potential to quickly determine the presence and degree of potentially viable brain tissue in the ischaemic penumbra. Thrombolysis is thought to reperfuse the penumbra and hence reduce infarct size. The thrombolytic agent tissue plasminogen activator (t-PA) improves outcome in ischaemic stroke when administered within the first 3 hours of onset. However, there is a significant risk of haemorrhage, and the time window for benefit may well exceed 3 hours in some patients. Hence, by facilitating diagnosis of 'at-risk' tissue in the ischaemic penumbra, a major clinical role of EPI may well become the rational selection of patients for acute interventional stroke therapy.

Brain↗
PubMed2000

Design of the blockade of the glycoprotein IIb/IIIa receptor to avoid vascular occlusion (BRAVO) trial.

BACKGROUND: Platelets play a key role in the pathogenesis of atherosclerosis, thrombosis, and acute coronary and cerebrovascular syndromes. Inhibition of platelet function by acetylsalicylic acid (aspirin) has been shown to reduce the incidence atherothrombotic events in patients with coronary, cerebrovascular, or peripheral vascular disease. Thienopyridine agents, however, including ticlopidine and clopidogrel, inhibit the adenosine diphosphate receptor and have modestly superior effects compared with aspirin on reduction of death, myocardial infarction, and stroke among a broad group of patients with vascular disease. More effective antithrombotic agents are still required to treat patients at high risk for recurrent vascular events. METHODS: Lotrafiban, a selective, nonpeptide antagonist of the human platelet fibrinogen receptor (glycoprotein [GP] IIb/IIIa [alphaIIb/beta3 integrin]), blocks the binding of fibrinogen to the GP IIb/IIIa receptor, which is the final common pathway of platelet aggregation. Lotrafiban at doses of up to 50 mg twice daily was well-tolerated in a 12-week, double-blind, placebo-controlled, dose-ranging study in patients with recent myocardial infarction, unstable angina, transient ischemic attack, or stroke when added to aspirin therapy. On the basis of these results, a dosing regimen was selected for the phase III Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial based on pharmacodynamics and drug tolerability. In the pivotal BRAVO study, lotrafiban therapy is being evaluated in patients who have had a recent myocardial infarction, unstable angina, transient ischemic attack, or ischemic stroke, or who present at any time after a diagnosis of peripheral vascular disease combined with either cardiovascular or cerebrovascular disease. RESULTS: The efficacy evaluation will be based on a composite end point of clinical events (death by any cause, myocardial infarction, stroke, recurrent ischemia requiring hospitalization, or urgent ischemia-driven revascularization). The target enrollment is 9200 patients worldwide. Approximately 700 centers will participate and will be distributed within 30 countries across North America, Europe, Australia, and Asia.

Administration, Oral↗
PubMed2000

Alcohol consumption and urinary concentration of 6-sulfatoxymelatonin in healthy women.

Consumption of alcoholic beverages may suppress circulating melatonin levels at night, possibly resulting in an increase in circulating estrogen. An increased estrogen burden could increase the risk of breast cancer. This study was designed to investigate whether alcohol consumption is associated with a decrease in nighttime melatonin levels in a group of healthy women. A total of 203 randomly selected healthy women between the ages of 20 and 74 years were recruited for a broader study of the effects of exposure to power-frequency magnetic fields on nocturnal levels of urinary 6-sulfatoxymelatonin. For the purposes of this analysis, data collection consisted of the following during two seasons of the year: (1) an in-person interview, (2) a daily activity diary, and (3) nocturnal urine collection for each of 3 consecutive nights. We found that the nocturnal urinary concentration of the primary metabolite of melatonin (6-sulfatoxymelatonin) decreased in a dose-dependent manner with increasing consumption of alcoholic beverages in the preceding 24-hour period, after taking into account the independent effects on melatonin of age, hours of darkness, use of medications that affect melatonin levels, and body mass index. A categorical analysis revealed no effect of one drink, but a 9% reduction with two drinks, a 15% reduction with three drinks, and a 17% reduction with four or more drinks. It remains unknown whether such a change could affect estrogen levels or breast cancer risk.

Adult↗
PubMed2000

Estimation of skeletal muscle interstitial adenosine during forearm dynamic exercise in humans.

It has been proposed that adenosine is a metabolic signal that triggers activation of muscle afferents involved in the exercise pressor reflex. Furthermore, exogenous adenosine induces sympathetic activation that mimics the exercise pressor reflex, and blockade of adenosine receptors inhibits sympathetic activation induced by exercise. Thus, we hypothesize that adenosine is released locally by the muscle during exercise. We used microdialysis probes, placed in the flexor digitorium superficialis muscle, to estimate muscle interstitial adenosine levels in humans. We estimated resting in vivo muscle interstitial adenosine concentrations (0.292+/-0.058 micromol/L, n=4) by perfusing increasing concentrations of adenosine to determine the gradient produced in the dialysate. Muscle interstitial adenosine concentrations increased from 0.23+/-0.04 to 0.82+/-0.14 micromol/L (n=14, P<0.001) during intermittent dynamic exercise at 50% of maximal voluntary contraction. Lactate increased from 0.8+/-0.1 to 2.3+/-0.3 mmol/L (P<0.001). Lower intensity (15% maximal voluntary contraction) intermittent dynamic exercise increased adenosine concentrations from 0.104+/-0.02 to 0.42+/-0.16 micromol/L (n=7). The addition of ischemia to this low level of exercise produced a greater increase in adenosine (from 0.095+/-0.02 to 0.48+/-0.2 micromol/L) compared with nonischemic exercise (0. 095+/-0.02 to 0.25+/-0.12 micromol/L). These results indicate that microdialysis is useful in estimating adenosine concentrations and in reflecting changes in muscle interstitial adenosine during dynamic exercise in humans.

Adenosine↗
PubMed2000

Forced expiratory flows and volumes in infants. Normative data and lung growth.

Forced expiratory flows (FEF) can be measured in infants from lung volumes initiated near total lung capacity. In order to establish reference values and to evaluate lung growth, we obtained measurements in 155 healthy subjects between 3 and 149 wk of age. Forced vital capacity (FVC) was highly correlated with body length; however, after accounting for length, age was also significant. When subjects were divided at the median age (40 wk) younger compared with older subjects had a significantly larger slope for length (3.7 versus 2.8; p = 0.002). The flow parameters (FEF(50), FEF(75), FEF(85), and FEF(25-75)) were highly correlated with length, and those infants whose mothers smoked had lower flows. For FEF(75), male subjects had lower flows than female subjects. The relationship between FEF and volume was assessed using FEV(0.5)/FVC, which decreased with increasing length. Smaller subjects emptied their lung volume proportionately faster. We conclude that our study provides reference values for this age group and demonstrates that smoke-exposed infants and male subjects have decreased FEF. In addition, our findings indicate that lung volume increases most rapidly during the first year of life and that airways are large relative to lung volume very early in life.

Anthropometry↗
PubMed2000

Medial displacement of grommets: an unwanted sequel of grommet insertion.

Grommet insertion is one of the commonest surgical procedures performed in the UK. We have come across three cases in which grommets have displaced medially in the middle ear after establishing a satisfactory post-insertion position. We suggest that an abnormally long myringotomy incision and improper placement of the grommet are responsible for this unwanted outcome.

Child↗