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Biomedical subjects

A Lee

Publications and source records attributed to A Lee.

At least 253 records · Page 14Linked to original sources
PubMed1999

Neuroanatomical basis of maternal memory in postpartum rats: selective role for the nucleus accumbens.

The experience of interacting with pups causes long-term changes in mothers' brains that mediate long-term changes in maternal behavior. As little as 1 hr of pup experience postpartum results in enhanced maternal responses to pups 10 days later. This experiment investigated the effects of lesions in multiple neural sites that have been implicated either in the actual expression of maternal behavior or in learning and memory within other behavioral contexts on the initiation and the long-term experience-based retention of maternal behavior. Electrolytic lesions were performed either before or after a 1-hr or 24-hr maternal experience. Rats sustaining lesions of the nucleus accumbens (NACC), whether administered before parturition and experience or immediately after a brief experience, failed to show a maternal experience effect. NACC lesions sustained 24 hr after a maternal experience did not disrupt long-term retention of the maternal behavior.

Animals↗
PubMed1999

Heterogeneity of HLA-DR2 haplotypes in Caucasoid Americans, African Americans, Chinese Americans, Native Americans and Xiamen Chinese.

HLA-DR, -DQ specificities were determined by PCR amplification with SSOP in 4560 individuals: Caucasoid Americans (CA), African Americans (AA), Chinese Americans (ChA), Native Americans (NA) and Xiamen Chinese (XC). DR2 subtypes were compared amongst the five ethnic populations. The DRB1*1501-DRB5*0101 haplotype was found to be the most frequent in all populations except African Americans, in which DRB1*1503-DRB5*0101 was the predominant haplotype, accounting for 65% of DR2 subtypes. In contrast to Caucasoid Americans, the DRB1*1602 is strongly associated with the DRB5*0101 allele in Chinese populations. The presence of DRB5*0203 and DRB1*1602-DRB5*0101 haplotypes in Chinese populations, especially in Xiamen Chinese, suggests that various DR2 haplotypes may be generated via multiple gene conversion events together with point mutations and reciprocal recombination. The strong DR and DQ associations are found in DRB1*1501/DQB1*0602 (66.22%) for CA, DRB1*1503/DQB1*0602 (56.58%) for AA, DRB1*1501/DQB1*0602 (30.20%) and DRB1*1602/DQB1*0502 (15.76%) for ChA, DRB1* 1501/DQB1*0602 (41.55%) and DRB1*1602/DQB1*0301 (40.25%) for NA, and DRB1*1501/DQB1*0602 (30.26%) and DRB1*1602/DQB1*0502 (25.81%) for XC.

Alleles↗
PubMed1999

Addition of physicians to paramedic helicopter services decreases blunt trauma mortality.

BACKGROUND: The authors hypothesized that the addition of critical care physicians to the flight crew of paramedic helicopter services would decrease mortality in blunt trauma, and that this would be due to the greater procedural capability and clinical judgement of the physician. METHODS: Retrospective comparison was undertaken of patients flown directly from the accident scene over a 28-month period by the paramedic-staffed Westpac Hunter region helicopter to John Hunter Hospital, and the physician-staffed NRMA CareFlight helicopter to Westmead or Nepean Hospitals. Inclusion criteria were blunt trauma and an Injury Severity Score of > 10. Mortality was compared by trauma score-injury severity score (TRISS) methodology. RESULTS: There were 140 patients in the paramedic treatment group and 67 in the physician group. There were no significant differences between the groups in age, mechanism of injury, distance transported, response, scene or transport times. Physicians intubated a greater proportion of patients (51 vs 10%; P < 0.001) including all patients with a Glasgow Coma Score of < 9. Physicians gave significantly greater volumes of fluids to hypotensive patients (median: 5035 vs 1475 mL: P < 0.001) and performed thoracic decompressions on a larger proportion of patients (12 vs 1%; P < 0.01). The Z statistic for the physician treatment group was 2.72 (P < 0.01 ) compared with -1.16 (P = 0.25) in the paramedic group. The adjusted W statistic was 13.44 (95% CI: 7.80-19.08) suggesting that there would be between eight and 19 extra survivors per 100 patients treated in the physician group compared with the paramedic group. CONCLUSIONS: Physicians perform a greater number of procedures at accident scenes without increasing scene time. This results in significantly lower mortality. Critical care physicians should be added to paramedic helicopter services for scene response to blunt trauma.

Adolescent↗
PubMed1999

Carbachol-induced sustained tonic contraction of rat detrusor muscle.

OBJECTIVE: To investigate the underlying contractile mechanism of the sustained tonic contraction (SuTC) induced by repetitive carbachol application in rat detrusor muscles. MATERIALS AND METHODS: Longitudinal muscle strips with no mucosa were obtained from the anterior wall of the urinary bladder in 12-week-old Sprague-Dawley rats. Carbachol (5 micromol/L) was applied repetitively to induce SuTC. The carbachol-induced SuTC was assessed in the presence of various Ca2+-channel blockers and drugs affecting intracellular Ca2+ concentration. RESULTS: The first application of carbachol elicited a large phasic contraction followed by a tonic contraction (TC); the carbachol-induced contraction was completely reversed by washing out the solution. However, the initial phasic contraction was not reproduced after a second or further application of carbachol. There was consistently only a SuTC with no phasic contraction. The amplitude of the SuTC was 85% of the TC induced by the first carbachol application. The application of atropine (1 micromol/L) to the bath completely blocked SuTC. The carbachol-induced SuTC was insensitive to nicardipine (5 micromol/L) and extracellular polyvalent cations (1 mmol/L, La3+, Co2+, Cd2+, Ni2+ ). Moreover, a similar SuTC was induced even after the complete elimination of extracellular Ca2+ by adding 2 mmol/L EGTA to the Ca2+-free Tyrode solution. To exclude intracellular Ca2+ sources related to the sarcoplasmic reticulum (SR), the effects of SR Ca2+ pump inhibitors, cyclopiazonic acid (CPA, 10 micromol/L) and thapsigargin (0.5 micromol/L) were tested. The carbachol-induced SuTC was insensitive to pretreatment with CPA and/or thapsigargin. To deplete the ryanodine-sensitive Ca2+ pool, muscle strips were repetitively stimulated with caffeine (10 mmol/L) in the presence of 10 micromol/L ryanodine, which did not affect the carbachol-induced SuTC. CONCLUSIONS: Although the characteristics of the carbachol-induced SuTC have not been defined, these results show that a significant proportion of the carbachol-induced contraction in rats is contributed by the SuTC, which is present even in the complete absence of external Ca2+. The SuTC was not affected by limiting the contributions of internal Ca2+ sources. This suggests that the SuTC in rat bladders is unrelated to known Ca2+ mobilization mechanisms.

Animals↗
PubMed1999

Characterization of Helicobacter felis by pulsed-field gel electrophoresis, plasmid profiling and ribotyping.

BACKGROUND: Helicobacter felis, an organism naturally infecting both canine and feline gastric mucosa, has been largely used as in animal models to study the ecology and treatment of human Helicobacter pylori infections. H. felis has not yet been studied at the genetic level. METHODS: The aims of this study were to modify an in situ DNA isolation method suitable for H. felis and, by the use of pulsed-field gel electrophoresis (PFGE), plasmid profiling, and ribotyping, to determine the degree of genetic variation among H. felis strains isolated from cats and dogs from various geographic locations, and to determine the genome size of H. felis. Furthermore, the ability of these new H. felis strains to colonize mice was tested. RESULTS: Most H. felis strains were distinguishable from each other, and 20 distinct PFGE types were detected. Four pairs of strains within a country and animal species produced identical patterns. All strains tested were found to carry several plasmids and plasmid profiling was equally discriminatory to PFGE. Ribotyping was not able to discriminate all the strains. CONCLUSIONS: The genome size of H. felis was found to be approximately 1.6 Mb.

Animals↗
PubMed1999

Application of artificial neural networks for detection of abnormal fetal heart rate pattern: a comparison with conventional algorithms.

Cardiotocography signals were sampled during labour in 53 patients. A recurrent artificial neural network with hidden layer feedback was trained and performance was compared with that of several conventional systems. Correct and false positive rates of all systems tested were calculated. To ensure that the performance of neural networks was not just caused by using different cut-off levels, the threshold used for conventional methods were also adapted and optimised. The correct positives rate of neural networks was between 0.72 and 0.9, and the false positive rate between 0.2 and 0.4. Before optimising, conventional algorithms produced a very low correct positive (0.02-0.5) and a low false positive rate (0.0-0.08). After adjusting the parameters, the tested neural networks still performed better than optimised conventional systems.

Journal Article↗
PubMed1999

Inhibition of hypervigilance in the treatment of traumatic simple phobias: three case examples.

OBJECTIVE: In traumatic simple phobia (TSP) fear of retraumatisation tends to be enduring and may show little reduction with time despite frequent and prolonged exposure. This paper describes how hypervigilant behaviour may account for this enduring response by interfering with exposure. METHOD: Three case histories illustrating the clinical features of TSP and its treatment using in vivo exposure coupled with direct inhibition of hypervigilance are presented. RESULT: In all three cases, reduction of anxiety occurred with spontaneous generalisation of improvement. CONCLUSIONS: The efficacy of in vivo therapeutic exposure for fear of retraumatisation may be enhanced by the use of strategies to inhibit hypervigilant behaviour.

Accidents, Traffic↗
PubMed1999

Mitochondrial redox state in the critically ill.

Abnormal oxygen use and organ failure in the critically ill may result from 'poisoning' of mitochondrial function. Measurement of arterial ketone body ratio (AKBR) has been proposed to reflect mitochondrial redox state and may provide a useful marker to monitor mitochondrial function in the critically ill. We measured AKBR (acetoacetate to beta-hydroxybutyrate) and plasma lactate concentrations in 20 critically ill patients, on 3 consecutive days after admission to the intensive care unit. Nine (45%) patients died (five with sepsis) within the 30-day follow-up period. AKBR increased significantly over the 3 days of the study in patients who died (P = 0.034) and decreased in those who survived (P < 0.0001). In addition, there was a significant difference between survivors and non-survivors (P = 0.015). We conclude that serial AKBR measurement may be useful in the management of septic patients.

3-Hydroxybutyric Acid↗
PubMed1999

The use of nonpharmacologic techniques to prevent postoperative nausea and vomiting: a meta-analysis.

UNLABELLED: We assessed the efficacy of nonpharmacologic techniques to prevent postoperative nausea and vomiting (PONV) by systematic review. These studies included acupuncture, electroacupuncture, transcutaneous electrical nerve stimulation, acupoint stimulation, and acupressure. Of the 24 randomized trials retrieved by a search of articles indexed on the MEDLINE and EMBASE databases (1980-1997), 19 were eligible for meta-analysis. The primary outcomes were the incidence of nausea, vomiting, or both 0-6 h (early efficacy) or 0-48 h (late efficacy) after surgery. The pooled relative risk (RR) and numbers needed to treat (NNT) were calculated. In children, no benefit was found. Some results in adults were significant. Nonpharmacologic techniques were similar to antiemetics in preventing early vomiting (RR = 0.89 [95% confidence interval 0.47-1.67]; NNT = 63 [10-infinity]) and late vomiting (RR = 0.80 [0.35-1.81]; NNT = 25 [5-infinity]) in adults. Nonpharmacologic techniques were better than placebo at preventing early nausea (RR = 0.34 [0.20-0.58]; NNT = 4 [3-6]) and early vomiting in adults (RR = 0.47 [0.34-0.64]; NNT = 5 [4-8]). Nonpharmacologic techniques were similar to placebo in preventing late vomiting in adults (RR = 0.81 [0.46-1.42]; NNT = 14 [6-infinity]). Using nonpharmacologic techniques, 20%-25% of adults will not have early PONV compared with placebo. It may be an alternative to receiving no treatment or first-line antiemetics. IMPLICATIONS: This systematic review showed that nonpharmacologic techniques were equivalent to commonly used antiemetic drugs in preventing vomiting after surgery. Nonpharmacologic techniques were more effective than placebo in preventing nausea and vomiting within 6 h of surgery in adults, but there was no benefit in children.

Acupressure↗
PubMed1999

Comparison of 7 versus 10 days of antibiotic therapy for hospitalized patients with uncomplicated community-acquired pneumonia: a prospective, randomized, double-blind study.

The objective of this study was to compare the outcome of 7 versus 10 days of antibiotic therapy for inpatients with moderately severe community-acquired pneumonia (CAP). A prospective, randomized, double-blind study with a follow-up period of 42 days was conducted. Fifty-two veterans were treated with 2 days of cefuroxime at 750 mg intravenously every 8 hours followed by group 1, 8 days oral therapy, and group 2, 5 days oral therapy followed by 3 days of placebo. Oral therapy consisted of cefuroxime axetil at 500 mg every 12 hours. No difference was seen in cure rates: 20 of 22 (90.9%) patients in group 1 and 21 of 24 (87.5%) patients in group 2. There were no late recurrences. Potential US cost-savings is $27.2 million. Inpatients with moderately severe CAP can be treated with 2 days of intravenous antibiotics followed by 5 additional days of oral antibiotics. Longer treatment duration prolongs the cost of care, without increasing the cure rate or decreasing the pneumonia recurrence rate.

Adult↗
PubMed1999

Measuring the inappropriate utilization of accident and emergency services?

Accident and Emergency (A&E) departments are increasingly popular venues for primary care, causing a serious threat to healthcare quality. This paper reports the development of a comprehensive research method for identifying primary care patients attending A&E. Patients were randomly selected from the four A&E departments across different time periods and different regions in Hong Kong. The definition of GP cases was based on a retrospective record review conducted by a panel of emergency physicians using the standard laid down by the Hong Kong College of Family Physicians. The patients sampled were similar in sex and age distribution to A&E attendees for the whole territory. The level of GP cases was found to be 57 per cent, with a significantly higher proportion of patients in the younger age group. The high level of use reflects the lack of a well co-ordinated development of primary care services and interfacing with secondary care.

Adolescent↗
PubMed1999

Use of a genetic approach to evaluate the consequences of inhibition of efflux pumps in Pseudomonas aeruginosa.

Drug efflux pumps in Pseudomonas aeruginosa were evaluated as potential targets for antibacterial therapy. The potential effects of pump inhibition on susceptibility to fluoroquinolone antibiotics were studied with isogenic strains that overexpress or lack individual efflux pumps and that have various combinations of efflux- and target-mediated mutations. Deletions in three efflux pump operons were constructed. As expected, deletion of the MexAB-OprM efflux pump decreased resistance to fluoroquinolones in the wild-type P. aeruginosa (16-fold reduction for levofloxacin [LVX]) or in the strain that overexpressed mexAB-oprM operon (64-fold reduction for LVX). In addition to that, resistance to LVX was significantly reduced even for the strains carrying target mutations (64-fold for strains for which LVX MICs were >4 microg/ml). We also studied the frequencies of emergence of LVX-resistant variants from different deletion mutants and the wild-type strain. Deletion of individual pumps or pairs of the pumps did not significantly affect the frequency of emergence of resistant variants (at 4x the MIC for the wild-type strain) compared to that for the wild type (10(-6) to 10(-7)). In the case of the strain with a triple deletion, the frequency of spontaneous mutants was undetectable (<10(-11)). In summary, inhibition of drug efflux pumps would (i) significantly decrease the level of intrinsic resistance, (ii) reverse acquired resistance, and (iii) result in a decreased frequency of emergence of P. aeruginosa strains highly resistant to fluoroquinolones in clinical settings.

Anti-Infective Agents↗
PubMed1999

Isolation of recombinant protective Helicobacter pylori antigens.

A total of seven clones producing both new and previously described Helicobacter pylori proteins were isolated from a library of H. pylori genomic DNA. The screening approach by which these proteins were detected relied on the use of antisera raised in mice vaccinated with Helicobacter felis sonicate plus cholera toxin, a regimen which protects mice from H. pylori challenge. This strategy was designed to maximize the possibility of obtaining antigens which might be capable of conferring protection from H. pylori infection. Two of the clones were shown to encode the urease enzyme and the heat shock protein HspB, which have already been identified as protective antigens. The other five clones were sequenced, protein coding regions were deduced, and these sequences were amplified by PCR for incorporation into Escherichia coli expression vectors. The proteins produced from these expression systems were purified to allow testing for protective efficacy in an H. pylori mouse model. All five proteins were able to facilitate the clearance of a challenge with H. pylori, as judged by an assay of gastric urease activity and light microscopy on stomach sections. These results clearly indicate that the screening strategy has successfully identified candidate vaccine antigens.

Animals↗
PubMed1999

A genetic basis for atrophy: dominant non-responsiveness and helicobacter induced gastritis in F(1) hybrid mice.

BACKGROUND: The importance of host factors in helicobacter induced gastritis has been shown in animal models. Infection of most mouse strains with Helicobacter felis results in a functional atrophic gastritis, while other strains remain gastritis free. AIMS: To investigate these host factors further by using genetic crosses of responder and non-responder mice. METHODS: F(1) hybrids of the non-responder CBA/Ca strain and three strains of mice known to develop H felis induced gastritis were infected for three months with H felis. Gastritis was assessed by histopathology and serum antibody responses by ELISA. RESULTS: Infection of CBA/Ca mice and F(1) hybrids induced little or no gastritis. Analyses of the antibody responses in these mice revealed virtually undetectable anti-helicobacter antibody levels despite colonisation with high numbers of H felis. In contrast, infection of H felis responsive strains induced gastritis and a significant humoral immune response. CONCLUSIONS: The non-responsiveness of CBA/Ca mice to H felis infection is dominantly inherited. The lack of gastritis in CBA mice and their offspring is probably due to active suppression of the immune response normally mounted against H felis. Investigation of these mechanisms will provide important insights relevant to induction of gastric atrophy and cancer in humans.

Animals↗
PubMed1999

Effect of AMPK activation on muscle glucose metabolism in conscious rats.

The effect of AMP-activated protein kinase (AMPK) activation on skeletal muscle glucose metabolism was examined in awake rats by infusing them with 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR; 40 mg/kg bolus and 7.5 mg. kg-1. min-1 constant infusion) along with a variable infusion of glucose (49.1 +/- 2.4 micromol. kg-1. min-1) to maintain euglycemia. Activation of AMPK by AICAR caused 2-deoxy-D-[1,2-3H]glucose (2-DG) uptake to increase more than twofold in the soleus and the lateral and medial gastrocnemius compared with saline infusion and occurred without phosphatidylinositol 3-kinase activation. Glucose uptake was also assessed in vitro by use of the epitrochlearis muscle incubated either with AICAR (0.5 mM) or insulin (20 mU/ml) or both in the presence or absence of wortmannin (1.0 microM). AICAR and insulin increased muscle 2-DG uptake rates by approximately 2- and 2.7-fold, respectively, compared with basal rates. Combining AICAR and insulin led to a fully additive effect on muscle glucose transport activity. Wortmannin inhibited insulin-stimulated glucose uptake. However, neither wortmannin nor 8-(p-sulfophenyl)-theophylline (10 microM), an adenosine receptor antagonist, inhibited the AICAR-induced activation of glucose uptake. Electrical stimulation led to an about threefold increase in glucose uptake over basal rates, whereas no additive effect was found when AICAR and contractions were combined. In conclusion, the activation of AMPK by AICAR increases skeletal muscle glucose transport activity both in vivo and in vitro. This cellular pathway may play an important role in exercise-induced increase in glucose transport activity.

AMP-Activated Protein Kinases↗
PubMed1999

Airway epithelial tight junctions and binding and cytotoxicity of Pseudomonas aeruginosa.

The role of tight junctions in the binding and cytoxicity of Pseudomonas aeruginosa to apical or basolateral membranes of lung airway epithelial cells was tested with fluorescence microscopy on living cells. Binding of noncytotoxic P. aeruginosa strain O1 was assessed with P. aeruginosa that expressed green fluorescent protein. Binding of cytotoxic P. aeruginosa strain 6206 was assessed with FITC-labeled P. aeruginosa; cytotoxicity was determined from nuclear uptake of the impermeant dye propidium iodide. The role of direct contact of P. aeruginosa to epithelial cells was tested with filters with small (0.45-micrometer) or large (2.0-micrometer) pores. High transepithelial resistance (R(t)) Calu-3 and cultured bovine tracheal monolayers (R(t) > 1,000 Omega. cm(2)) bound P. aeruginosa very infrequently (<1 P. aeruginosa/100 cells) at the apical membrane, but P. aeruginosa bound frequently to cells near "free edges" at holes, wounds, islands, and perimeters; cytotoxicity required direct interaction with basolateral membranes. Wounded high R(t) epithelia showed increased P. aeruginosa binding and cytotoxicity at the free edges because basolateral membranes were accessible to P. aeruginosa, and dead and living cells near the wound bound P. aeruginosa similarly. Compared with high R(t) epithelia, low R(t) CFT1 (R(t) = 100-200 Omega. cm(2)) and EGTA-treated Calu-3 monolayers were 25 times more susceptible to P. aeruginosa binding throughout the monolayer. Cytotoxicity to CFT1 cells (throughout the confluent monolayer, not only at the free edge) occurred after a shorter delay (0.25 vs. 2.0 h) and then five times faster than to Calu-3 cells, indicating that the time course of P. aeruginosa cytotoxicity may be limited by the rate of gaining access through tight junctions and that this occurred faster in low R(t) than in high R(t) airway epithelia. Cytotoxicity appeared to occur in a sequential process that led first to a loss of fura 2 and a later uptake of propidium iodide. P. aeruginosa bound three times more frequently to regions between cells (tight junctions?) than to cell membranes of low R(t) CFT1 cells.

Animals↗