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Biomedical subjects

S Wilson

Publications and source records attributed to S Wilson.

At least 181 records · Page 10Linked to original sources

Convergent inductive signals specify midbrain, hindbrain, and spinal cord identity in gastrula stage chick embryos.

In the chick embryo, neural cells acquire midbrain, hindbrain, and spinal cord character over a approximately 6 hr period during gastrulation. The convergent actions of four signals appear to specify caudal neural character. Fibroblast growth factors (FGFs) and a paraxial mesoderm-caudalizing (PMC) activity are involved, but neither signal is sufficient to induce any single region. FGFs act indirectly by inducing mesoderm that expresses PMC and retinoid activity and also directly on prospective neural cells, in combination with PMC activity and a rostralizing signal, to induce midbrain character. Hindbrain character emerges from cells that possess the potential to acquire midbrain character upon exposure to higher levels of PMC activity. Induction of spinal cord character appears to involve PMC and retinoid activities.

Animals↗

The long-acting beta2-agonist salmeterol xinafoate: effects on airway inflammation in asthma.

Salmeterol xinafoate is an inhaled long-acting beta2-adrenoceptor agonist recently introduced for the treatment of asthma. Both in vitro and animal studies suggest that it may have anti-inflammatory activities of benefit in this disease. To assess this directly, the effects of 6 weeks' treatment with salmeterol on indices of clinical activity, airway dysfunction and inflammation in subjects with stable atopic asthma were investigated. In a double blind study, asthmatic patients were randomized to 6 weeks' treatment with either salmeterol 50 microg twice daily (n=14) or placebo (n=12). They underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy immediately before starting treatment and again after 6 weeks. Treatment with salmeterol improved clinical indices of asthma activity, but there were no changes in BAL differential cell counts or mediator levels, and no change in T-cell numbers or activation status. In the biopsy specimens there were no changes in numbers of inflammatory cells, sub-basement membrane collagen deposition or mast cell degranulation. Regular treatment with salmeterol improves clinical indices of asthma but has no effect on the underlying inflammatory process. These findings strengthen guideline recommendations that long-acting beta2-agonists should not be prescribed as sole antiasthma medication.

Adolescent↗

Comforting strategies used during nasogastric tube insertion.

Nasogastric tube insertion is a procedure that commonly involves discomfort, yet requires the cooperation of the conscious patient. This study employed qualitative ethology to investigate how comforting strategies were used during the insertion of nasogastric tubes in trauma care. Practitioners used eight direct and indirect comforting strategies in uniquely patterned styles (technical, affective and blended). In addition, a form of 'team comforting' was implemented as multiple trauma team members made a concerted effort to complete the procedure. Further study is needed to explicate how the nurse's style affects the behavioural state displayed by the patient.

Emergency Nursing↗

Evaluation of cerebral perfusion pressure changes in laboring women: effects of epidural anesthesia.

OBJECTIVE: To compare the effect of epidural anesthesia on cerebral perfusion pressure in laboring women. STUDY DESIGN: Maternal cerebral blood flow velocity was assessed in seven laboring patients with continuous epidural anesthesia and 15 without, using transcranial Doppler. Maternal cerebral blood flow velocity was assessed during the first stage at the trough of a contraction, at the peak of a contraction and at the second stage during pushing over the course of four contractions. Calculated estimated cerebral perfusion pressure: eCPP = Vmean/(Vmean - Vdiastolic) x (mean BP - diastolic BP), where V is velocity and BP is blood pressure; modified from Aaslid and colleagues. An index of cerebrovascular resistance, the resistance area product, was calculated: RAP = mean BP/mean velocity. We calculated an index of cerebral blood flow (cerebral blood flow index): CBF index = eCPP/RAP. RESULTS: In non-epidural patients, the eCPP fell significantly at the peak of a contraction and during pushing. Cerebrovascular resistance, RAP, rose significantly during the peak of a contraction, although cerebral blood flow did not change. In patients undergoing epidural anesthesia, the stages of labor had no significant effect on eCPP or RAP; however, these values were lower than those in patients without epidural anesthesia. CONCLUSIONS: The epidural group had a lower eCPP and RAP and cerebral blood flow index compared to the non-epidural group. In the non-epidural group, the mean arterial pressure was higher in all stages of labor with a trend towards an increase in eCPP and cerebral blood flow index.

Adult↗

Implementation of on-site screening sigmoidoscopy positively influences utilization by primary care providers.

BACKGROUND & AIMS: Sigmoidoscopy is an effective screening strategy for colorectal cancer that is not widely used by primary care providers. The aim of this study was to assess the impact of "academic detailing" in the form of an outreach educational seminar combined with implementation of on-site sigmoidoscopy services performed by university-based gastroenterologists on provider compliance. METHODS: A controlled trial was initiated at 9 urban neighborhood health centers, including 4 intervention and 5 comparison sites. Baseline data on provider attitudes and practice patterns were collected using a validated questionnaire. Outcome measures included a year 1 follow-up survey of provider attitudes and quarterly review of screening sigmoidoscopy referrals using appointment logs to assess utilization. RESULTS: Overall self-reported compliance rates for screening sigmoidoscopy increased by 36% (baseline, 24%; year 1, 60%) for the intervention group vs. only 7% (baseline, 19%; year 1, 26%) for the comparison group (P = 0. 001). When stratified by site, compliance rates increased at each intervention site (range, 7%-92%) but at only 2 control sites. Use of screening sigmoidoscopy was also significantly greater at the intervention sites (47% vs. 4%; P </= 0.001). CONCLUSIONS: An outreach educational seminar combined with implementation of on-site sigmoidoscopy services is an effective strategy for enhancing provider utilization of screening sigmoidoscopy.

Adult↗

Phase I study of combination therapy with intravenous cidofovir and oral ganciclovir for cytomegalovirus retinitis in patients with AIDS.

Ganciclovir and cidofovir, two antiviral agents used in the treatment of cytomegalovirus (CMV) retinitis, have a synergistic effect inhibiting CMV replication in vitro. In a phase I study, seven patients with AIDS-related CMV retinitis were treated with cidofovir (5 mg/kg intravenously every 2 weeks) combined with ganciclovir (1 g orally three times a day). During a median of 5.5 months (range, 1-12 months) of combined therapy, only one patient had retinitis progression, and only two of 28 blood cultures (specimens of which were obtained on a monthly basis) yielded CMV. Dose-limiting adverse ocular effects (anterior uveitis [two patients] and hypotony [two patients]) occurred in three of seven patients. The results suggest that combination therapy with intravenous cidofovir and oral ganciclovir (a regimen that does not require indwelling central venous catheter access) might enhance clinical efficacy. Less frequent administration of cidofovir in combination with oral ganciclovir should be prospectively studied to determine if the incidence of treatment-associated toxicity might be reduced.

AIDS-Related Opportunistic Infections↗

Effect of nitric oxide, perfluorocarbon, and heliox on minute volume measurement and ventilator volumes delivered.

OBJECTIVE: To determine the effect of heliox, nitric oxide (NO), and perfluorocarbon on differential pressure pneumotachometer characteristics and to determine the effect of heliox on volumes delivered by the Siemens S900C (S900C), and Servo Ventilator 300 (SV300) ventilators. DESIGN: Prospective, laboratory study. SETTING: Pulmonary laboratory of a tertiary care, nonprofit children's hospital. APPARATUS: SV300, S900C ventilator, differential pressure pneumotachometer. INTERVENTIONS: Dual pneumotachometers were connected in series to a 0.5-L calibration syringe and a 1-L anesthesia bag creating a closed system. Calibration of the pneumotachometers was done in room air at ambient temperature with 100 strokes. Accepted accuracy of measured volumes is within 0.5%. Flow-conductance curves were constructed using 100 strokes each for heliox (70:30 mixture), NO, and perfluorocarbon. Expired gases of room air and a 70:30 mixture of heliox from the above ventilators were collected into a nondiffusing gas collection bag, and the volume was measured in a chain-compensated gasometer. Ten sets of 500-mL breaths (20 breaths each set) and 100-mL breaths (40 breaths each set) were collected. The paired Student's t-test was used to detect significant differences in measured volumes, with significance defined as p < .01. MEASUREMENTS AND MAIN RESULTS: Volumes measured with the pneumotachometer using 25 ppm of NO, 50 ppm of NO, and perfluorocarbon were within +0.25%, -0.7%, and +0.4%, respectively (p = .155, p = .001, p = .06). Heliox decreased the conductance of the pneumotachometer, thereby increasing the measured volume by 15% (p < .001). However, heliox did not affect its linearity. Heliox had no affect on volumes delivered by the S900C. However, the SV300 delivered 7.9% less volume of heliox at a set tidal volume of 500 mL and 10.8% less at a set tidal volume of 100 mL. CONCLUSIONS: A 70:30 mixture of heliox caused a significantly overestimated gas volume measured and, therefore, an underestimated gas volume delivered by SV300. NO at 25 ppm and perfluorocarbon did not interfere with the accuracy of a differential pressure pneumotachometer. However, at 50 ppm, NO caused a difference in measured gas volume that was statistically, but not clinically, significant. Application of pneumotachometers in critically ill children receiving heliox requires recalibration. Heliox did not affect volumes delivered with the S900C ventilator. Although volumes delivered with the SV300 were significantly reduced by heliox, the difference can be corrected easily by increasing minute ventilation until expired tidal volume equals desired tidal volume.

Airway Resistance↗

Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor.

The cysteinyl leukotrienes (CysLTs) have been implicated in the pathophysiology of inflammatory disorders, in particular asthma, for which the CysLT receptor antagonists pranlukast, zafirlukast, and montelukast, have been introduced recently as novel therapeutics. Here we report on the molecular cloning, expression, localization, and pharmacological characterization of a CysLT receptor (CysLTR), which was identified by ligand fishing of orphan seven-transmembrane-spanning, G protein-coupled receptors. This receptor, expressed in human embryonic kidney (HEK)-293 cells responded selectively to the individual CysLTs, LTC(4), LTD(4), or LTE(4), with a calcium mobilization response; the rank order potency was LTD(4) (EC(50) = 2.5 nM) > LTC(4) (EC(50) = 24 nM) > LTE(4) (EC(50) = 240 nM). Evidence was provided that LTE(4) is a partial agonist at this receptor. [(3)H]LTD(4) binding and LTD(4)-induced calcium mobilization in HEK-293 cells expressing the CysLT receptor were potently inhibited by the structurally distinct CysLTR antagonists pranlukast, montelukast, zafirlukast, and pobilukast; the rank order potency was pranlukast = zafirlukast > montelukast > pobilukast. LTD(4)-induced calcium mobilization in HEK-293 cells expressing the CysLT receptor was not affected by pertussis toxin, and the signal appears to be the result of the release from intracellular stores. Localization studies indicate the expression of this receptor in several tissues, including human lung, human bronchus, and human peripheral blood leukocytes. The discovery of this receptor, which has characteristics of the purported CysLT(1) receptor subtype, should assist in the elucidation of the pathophysiological roles of the CysLTs and in the identification of additional receptor subtypes.

Amino Acid Sequence↗

A mutant HemA protein with positive charge close to the N terminus is stabilized against heme-regulated proteolysis in Salmonella typhimurium.

The HemA enzyme (glutamyl-tRNA reductase) catalyzes the first committed step in heme biosynthesis in the enteric bacteria. HemA is mainly regulated by conditional protein stability; it is stable and, consequently, more abundant in heme-limited cells but unstable and less abundant in normally growing cells. Both the Lon and ClpAP energy-dependent proteases contribute to HemA turnover in vivo. Here we report that the addition of two positively charged lysine residues to the third and fourth positions at the HemA N terminus resulted in complete stabilization of the protein. By contrast, the addition of an N-terminal myc epitope tag did not affect turnover. This result confirms the importance of the N-terminal sequence for proteolysis of HemA. This region of the protein also contains a proline flanked by hydrophobic residues, a motif that has been suggested to be important for Lon-mediated proteolysis of UmuD. However, mutation of this motif did not affect the turnover of HemA protein. Cells expressing the stabilized HemA[KK] mutant protein display substantial defects in heme regulation.

ATP-Dependent Proteases↗

A major sporting event does not necessarily mean an increased workload for accident and emergency departments. Euro96 Group of Accident and Emergency Departments.

AIM: To determine whether there were any changes in attendance at accident and emergency departments that could be related to international football matches (Euro96 tournament). METHOD: Fourteen accident and emergency departments (seven adjacent to and seven distant from a Euro96 venue) provided their daily attendance figures for a nine week period: three weeks before, during, and after the tournament. The relation between daily attendance rates and Euro96 football matches was assessed using a generalised linear model and analysis of variance. The model took into account underlying trends in attendance rates including day of the week. RESULTS: The 14 hospitals contributed 172 366 attendances (mean number of daily attendances 195). No association was shown between the number of attendances at accident and emergency departments and the day of the football match, whether the departments were near to or distant from stadia or the occurrence of a home nation match. The only observed independent predictors of variation were day of the week and week of the year. Attendance rates were significantly higher on Sunday and/or Monday; Monday was about 9% busier than the daily average. Increasing attendance was observed over time for 86% of the hospitals. CONCLUSION: Large sports tournaments do not increase the number of patients attending accident and emergency departments. Special measures are not required for major sporting events over and above the capacity of an accident and emergency department to increase its throughput on other days.

Athletic Injuries↗

The effects of regular inhaled formoterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma.

The present study was designed to observe the effects of 8 wk of treatment with formoterol (Foradil) 24 microgram, budesonide 400 microgram, and matched placebo inhaled twice a day on inflammatory indices in the bronchial mucosa of 64 patients with mild atopic asthma. Biopsies were obtained at the start and 1 wk before stopping a 9-wk period of treatment, and inflammatory cell numbers were assessed in the submucosa and epithelium by immunohistochemistry. Regular formoterol significantly reduced the number of submucosal mast cells, with a similar trend for eosinophils but not activated T cells. A subgroup analysis conducted in biopsies with >= 10 eosinophils per mm2 revealed a significant reduction in eosinophil numbers when compared with both pretreatment baseline (p < 0.01) and changes after placebo (p < 0.01). Parallel, but less pronounced, effects were observed on mast cell but not on CD25(+) T cell numbers. There was no effect of any of the three treatments on BAL levels of mast cell or eosinophil mediators. We conclude that regular treatment with inhaled formoterol reduces rather than increases inflammatory cells in the mucosa of asthmatic patients. It is possible that these cellular effects of formoterol may contribute to the therapeutic efficacy of this drug when used regularly in the treatment

Administration, Inhalation↗

Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma.

We have shown in nocturnal asthma that alveolar tissue eosinophils are increased at night as compared with the proximal airway, and that they correlate with the overnight decrement in lung function. As the CD4+ cell is thought to be the principal orchestrating cell in eosinophil recruitment, we evaluated its presence in the proximal and distal airways in nocturnal asthma. Eleven patients with nocturnal asthma (NA) and 10 patients with non-nocturnal asthma (NNA) underwent two bronchoscopies with proximal airway endobronchial and distal alveolar tissue transbronchial biopsy in a random order at 4:00 P.M. and at 4:00 A.M. separated by 1 wk. Immunohistochemical staining and morphometric analysis were used to determine the number of CD3+, CD4+, and CD8+ cells and EG2+ eosinophils per mm2 in the epithelium, lamina propria, and alveolar tissue. At 4:00 A.M., the NA group had a significantly greater number of CD4+ cells in the alveolar tissue than the NNA group (9.8 cells/ mm2 [5.6-30.8, interquartile (IQ)] versus 1.5 cells/mm2 [0-6. 3, IQ], p = 0.04). Within the NA group, there were significantly greater numbers of CD3+, CD4+, CD8+, and EG2+ cells in the proximal airway lamina propria than in the distal airway at both 4:00 P.M. and 4:00 A.M. There were no differences within the epithelium between the groups at either time point. Only alveolar tissue, not airway tissue, CD4+ cells correlated inversely with the percentage predicted FEV1 at 4:00 A.M. (r = -0.68, p = 0.0018) and positively with the number of alveolar tissue EG2+ cells (r = 0.66, p = 0.01). These findings suggest that the CD4+ lymphocyte is increased in the alveolar tissue at night in nocturnal asthma as compared with non-nocturnal asthma.

Adult↗

The effects of idazoxan on reaction times, eye movements and the mood of healthy volunteers and patients with upper respiratory tract illnesses.

An experiment was carried out to determine whether idazoxan, a drug which increases the turnover of central noradrenaline, removes the malaise (reduced alertness, slower psychomotor performance) associated with upper respiratory tract illness (URTI). Eighty-one volunteers were tested when healthy and 17 returned to the laboratory when they developed URTIs. Those who remained healthy were then recalled as a control group. Volunteers were tested before and after receiving either idazoxan (40mg) or a lactose placebo. Idazoxan removed the URTI-induced slowing in a simple reaction time task and this group performed at a comparable level to the healthy group. No significant stimulant effect of idazoxan was found in the healthy subjects. The results suggest that at least part of the malaise induced by URTIs may reflect reductions in central noradrenaline and that this can be reversed by compounds such as idazoxan.

Adrenergic alpha-Antagonists↗

Mucosal inflammation in severe glucocorticoid-dependent asthma.

To improve our understanding of the inflammatory mechanisms underlying severe disease, a biopsy study was performed comparing 15 clinically unstable glucocorticoid-dependent asthmatics, 10 mild asthmatics, and 10 control subjects. Compared with mild asthma, severe asthma was characterized by reduced mucosal eosinophilia. Whilst no significant differences were found in the numbers of mast cells, neutrophils, CD3+ and CD4+ T-cells between the three groups, up to a 4-fold increase In the numbers of activated T-lymphocytes bearing the interleukin (IL)-2 receptor (IL-2R) was found in the mucosa in severe asthma compared to mild asthma (p = 0.03) and control subjects (p = 0.003). Compared to control subjects, the mucosa of severe asthmatics contained significantly (p = 0.02) higher numbers of IL-5+ cells, with no differences between mild and severe disease. In contrast, staining for the anti-IL-4 monoclonal antibody 3H4 revealed that biopsies from mild asthmatics contained more IL4+ cells than biopsies from severe asthmatics and control subjects (p = 0.0008). In the severe asthmatics, a close correlation (r(s) = 0.76, p = 0.005) was found between the numbers of IL-2R-bearing cells and the variability in peak expiratory flow. In conclusion, persistent T-cell activation is a prominent feature of severe asthma. These results also indicate that interleukin-5, and not interleukin-4, is upregulated in severe disease.

Administration, Topical↗

A specific sign of pneumoperitoneum on sonography: enhancement of the peritoneal stripe.

OBJECTIVE: Failure to reveal pneumoperitoneum is a recognized weakness of abdominal sonography. Our objective is to describe a reliable and reproducible sign of pneumoperitoneum that was first identified in an animal model and then confirmed in patients who had undergone laparoscopy. SUBJECTS AND METHODS: We injected 300 ml of degassed water into the peritoneal cavity of a 15-kg anesthetized pig. Sonographic images were obtained of the anterior peritoneal area after intraperitoneal injection of a single bubble, a series of bubbles, and, subsequently, a 10-ml bolus of air. Later, abdominal sonography was performed in nine patients who had undergone laparoscopy. Close attention was paid to the anterior peritoneal area and signs of free air observed in the animal model. Ten healthy volunteers functioned as a control group. RESULTS: In the pig, minute amounts of intraperitoneal air showed on sonography as enhancement of the peritoneal stripe. Larger volumes of intraperitoneal air showed as enhancement of the peritoneal stripe associated with dirty shadowing or distal multiple reflection artifacts. The stripe enhanced each time it appeared in the reflection artifact. Intraluminal gas was associated with a normal thin peritoneal stripe, superficial and distinct from the underlying gas artifact. The patients who had undergone laparoscopy showed findings suggestive of small and large pockets of free air, as we saw in the pig model. The control group showed findings consistent with intraluminal gas only. CONCLUSION: On sonography, enhancement of the peritoneal stripe alone or with reflection artifacts involving the peritoneal stripe is an accurate sign of pneumoperitoneum.

Abdominal Pain↗

Hypothalamic orexin expression: modulation by blood glucose and feeding.

Orexins (hypocretins), novel peptides expressed in specific neurons of the lateral hypothalamic area (LHA), stimulate feeding when injected intracerebroventricularly. We investigated their role in feeding in the rat by measuring hypothalamic prepro-orexin mRNA levels under contrasting conditions of increased hunger. Prepro-orexin mRNA levels increased significantly after 48 h of fasting (by 90-170%; P < 0.05) and after acute (6 h) hypoglycemia when food was withheld (by 90%; P < 0.02). By contrast, levels were unchanged during chronic food restriction, streptozotocin-induced diabetes, hypoglycemia when food was available, voluntary overconsumption of palatable food, or glucoprivation induced by systemic 2-deoxy-D-glucose. Orexin expression was not obviously related to changes in body weight, insulin, or leptin, but was stimulated under conditions of low plasma glucose in the absence of food. Orexins may participate in the short-term regulation of energy homeostasis by initiating feeding in response to falls in glucose and terminating it after food ingestion. The LHA is known to contain neurons that are stimulated by falls in circulating glucose but inhibited by feeding-related signals from the viscera; orexin neurons may correspond to this neuronal population.

Animals↗