bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulators and difficult airway management skills
Authors: Schaefer John J. 
Published: January 2004

SummaryAlthough difficult airway management remains one of the leading factors in anaesthetic deaths, there have been tremendous advances in the field in the last few decades. The question is, are advanced airway management skills being taught and used? Of the numerous training tools available, simulators have the advantages of providing whole‐task learning with the potential to change behaviour and, when applied to large groups of trainees, the possibility of achieving standardized application of the safest practices for a range of scenarios limited only by the creativity of the program designers. Partial‐task trainers include computer‐based software programs and simulators. Full‐scale simulators include a variety of products from several manufacturers. To take full advantage of simulators as educational tools, curricula should be designed around a set of educational objectives that address the objectives of learning in all three skill domains (cognitive, psychomotor, and affective). Simulation experiences using partial‐task or whole‐task trainers should be coupled whenever feasible with a structured clinical experience in airway management. This can best be achieved through a dedicated airway management rotation. Monitored procedure logs may also be used. Whether using a simulator or in a clinical rotation, experiences should be graded, for example, gaining experience in an adult population before gaining experience in paediatrics and in each population mastering airway management skills for common scenarios before advancing to more complicated techniques such as fibreoptic bronchoscopy.
Teaching consultants airway management skills
Authors: Nargozian Charles 
Published: January 2004

SummaryAirway management skills are integral to the practice of anaesthesiology and also to the practice of emergency medicine and allied health professions such as respiratory care, emergency medical technology, and emergency and critical care nursing. The basic information to be taught is the same but the level of detail will vary depending on the audience. The learning process usually involves progression from didactic lessons to skills training on inanimate models to supervised clinical practice. Modalities that may be used for skills training include cadavers, recently dead patients, videotapes, mannequins, simulators and virtual reality trainers. To maintain knowledge and skills, review and possible retraining should be conducted on an approximately annual basis.
Airway structure, function and development in health and disease
Authors: Shaffer Thomas H. , Wolfson Marla R. , Panitch Howard B. 
Published: January 2004

SummaryUntil they are fully mature, the airways are highly susceptible to damage. Factors that may contribute to vulnerability of immature airways and the occurrence of bronchopulmonary dysplasia (BPD) in preterm neonates include decreased contractility of smooth muscles of the airway, which leads to generation of lower forces, and immaturity of airway cartilage, leading to increased compressibility of developing airways. Mechanical ventilation has little effect on adult airways, but affects the dimensions and mechanical properties of preterm and newborn airways. Techniques for clinical evaluation of airway function include: (i) measurements of airway function during tidal breathing (airway resistance and reactivity are significantly elevated in infants with BPD); (ii) forced expiratory flow measurements [small‐airway obstruction in infants with BPD is indicated by markedly reduced maximal volume measurements (Vmax)]; (iii) radiography procedures (plain radiographs, fluoroscopy, computed tomography and virtual bronchoscopy); and (iv) endoscopy procedures (rigid or flexible bronchoscopy, with or without measurement of oesophageal pressure). Imaging has demonstrated an excessively decreased airway cross‐sectional area during exhalation in infants with BPD and acquired tracheomegaly in very preterm infants who had received mechanical ventilatory support. To further advance our understanding of how the airways develop, and to design less damaging protocols for mechanical ventilation in preterm neonates, basic laboratory studies of airway ultrastructure need to be performed and the results correlated with clinical pulmonary function studies.
Pattern of mtDNA Variation in Three Populations from São Tomé e Príncipe
Authors: Trovoada M. J. , Pereira L. , Gusmão L. , Abade A. , Amorim A. , Prata M. J. 
Published: January 2004

SummaryWe have analysed the matrilineal genetic composition of three self‐reported ethnic groups from São Tomé e Príncipe (Gulf of Guinea), an African archipelago whose settlement begun in the late fifteenth century. Sequence data from the hypervariable segments I (HVS‐I) and II (HVS‐II) were obtained for 30 Angolares, 35 Forros and 38 Tongas. The repertory of mtDNA lineages in São Tomé e Príncipe denoted a fully African maternal pool, primarily arisen from a Central/Southwestern substratum. The absence of any lineages of putative European descent means that the European impact at the mitochondrial pool was virtually nil. Angolares showed a clear reduction of mtDNA diversity and a slight genetic differentiation relative to Tongas or Forros, whereas the latter two groups did not present any signs of genetic boundaries between each other. The data obtained here reinforce the depiction of genetic substructuring in São Tomé e Príncipe previously derived from Y‐chromosome STRs. In addition, the crossing of mtDNA and Y‐STR information led to the inference that the female mediated gene flow within the archipelago was less restricted than the male, a pattern that could be framed in the cultural traditions and socio‐historical interactions among the groups.
The folding landscape of Streptomyces griseus protease B reveals the energetic costs and benefits associated with evolving kinetic stability
Authors: Truhlar Stephanie M.E. , Cunningham Erin L. , Agard David A. 
Published: January 2004

AbstractLike most extracellular bacterial proteases, Streptomyces griseus protease B (SGPB) and α‐lytic protease (αLP) are synthesized with covalently attached pro regions necessary for their folding. In this article, we characterize the folding free energy landscape of SGPB and compare it to the folding landscapes of αLP and trypsin, a mammalian homolog that folds independently of its zymogen peptide. In contrast to the thermodynamically stable native state of trypsin, SGPB and αLP fold to native states that are thermodynamically marginally stable or unstable, respectively. Instead, their apparent stability arises kinetically, from unfolding free energy barriers that are both large and highly cooperative. The unique unfolding transitions of SGPB and αLP extend their functional lifetimes under highly degradatory conditions beyond that seen for trypsin; however, the penalty for evolving kinetic stability is remarkably large in that each factor of 2.4–8 in protease resistance is accompanied by a cost of ∼105 in the spontaneous folding rate and ∼5–9 kcal/mole in thermodynamic stability. These penalties have been overcome by the coevolution of increasingly effective pro regions to facilitate folding. Despite these costs, kinetic stability appears to be a potent mechanism for developing native‐state properties that maximize protease longevity.
Validation of helical tilt angles in the solution NMR structure of the Z domain of Staphylococcal protein A by combined analysis of residual dipolar coupling and NOE data
Authors: Zheng Deyou , Aramini James M. , Montelione Gaetano T. 
Published: January 2004

AbstractStaphylococcal protein A (SpA) is a virulence factor from Staphylococcus aureus that is able to bind to immunoglobulins. The 3D structures of its immunoglobulin (Ig) binding domains have been extensively studied by NMR and X‐ray crystallography, and are often used as model structures in developing de novo or ab initio strategies for predicting protein structure. These small three‐helix‐bundle structures, reported in free proteins or Ig‐bound complexes, have been determined previously using medium‐ to high‐resolution data. Although the location and relative orientation of the three helices in most of these published 3D domain structures are consistent, there are significant differences among the reported structures regarding the tilt angle of the first helix (helix 1). We have applied residual dipolar coupling data, together with nuclear Overhauser enhancement and scalar coupling data, in refining the NMR solution structure of an engineered IgG‐binding domain (Z domain) of SpA. Our results demonstrate that the three helices are almost perfectly antiparallel in orientation, with the first helix tilting slightly away from the other two helices. We propose that this high‐accuracy structure of the Z domain of SpA is a more suitable target for theoretical predictions of the free domain structure than previously published lower‐accuracy structures of protein A domains.
Nucleotide recognition in the ATP‐grasp protein carbamoyl phosphate synthetase
Authors: Kothe Michael , Powers‐Lee Susan G. 
Published: January 2004

AbstractSynthesis of carbamoyl phosphate by carbamoyl phosphate synthetase (CPS) requires the coordinated utilization of two molecules of ATP per reaction cycle on duplicated nucleotide‐binding sites (N and C). To clarify the contributions of sites N and C to the overall reaction, we carried out site‐directed mutagenesis aimed at changing the substrate specificity of either of the two sites from ATP to GTP. Mutant design was based in part on an analysis of the nucleotide‐binding sites of succinyl‐CoA synthetases, which share membership in the ATP‐grasp family with CPS and occur as GTP‐ and ATP‐specific isoforms. We constructed and analyzed Escherichia coli CPS single mutations A144Q, D207A, D207N, S209A, I211S, P690Q, D753A, D753N, and F755A, as well as combinations thereof. All of the mutants retained ATP specificity, arguing for a lack of plasticity of the ATP sites of CPS with respect to nucleotide recognition. GTP‐specific ATP‐grasp proteins appear to accommodate this substrate by a displacement of the base relative to the ATP‐bound state, an interaction that is precluded by the architecture of the potassium‐binding loop in CPS. Analysis of the ATP‐dependent kinetic parameters revealed that mutation of several residues conserved in ATP‐grasp proteins and CPSs had surprisingly small effects, whereas constructs containing either A144Q or P690Q exerted the strongest effects on ATP utilization. We propose that these mutations affect proper movement of the lids covering the active sites of CPS, and interfere with access of substrate.
Structural alteration of cofactor specificity inCorynebacterium2,5‐diketo‐D‐gluconic acid reductase
Authors: Sanli Gulsah , Banta Scott , Anderson Stephen , Blaber Michael 
Published: January 2004

AbstractCorynebacterium2,5‐Diketo‐D‐gluconic acid reductase (2,5‐DKGR) catalyzes the reduction of 2,5‐diketo‐D‐gluconic acid (2,5‐DKG) to 2‐Keto‐L‐gulonic acid (2‐KLG). 2‐KLG is an immediate precursor toL‐ascorbic acid (vitamin C), and 2,5‐DKGR is, therefore, an important enzyme in a novel industrial method for the production of vitamin C. 2,5‐DKGR, as with most other members of the aldo‐keto reductase (AKR) superfamily, exhibits a preference for NADPH compared to NADH as a cofactor in the stereo‐specific reduction of substrate. The application of 2,5‐DKGR in the industrial production of vitamin C would be greatly enhanced if NADH could be efficiently utilized as a cofactor. A mutant form of 2,5‐DKGR has previously been identified that exhibits two orders of magnitude higher activity with NADH in comparison to the wild‐type enzyme, while retaining a high level of activity with NADPH. We report here an X‐ray crystal structure of theholoform of this mutant in complex with NADH cofactor, as well as thermodynamic stability data. By comparing the results to our previously reported X‐ray structure of theholoform of wild‐type 2,5‐DKGR in complex with NADPH, the structural basis of the differential NAD(P)H selectivity of wild‐type and mutant 2,5‐DKGR enzymes has been identified.
Effect of a single dose of the selectin inhibitor TBC1269 on early and late asthmatic responses
Authors: Avila P. C. , Boushey H. A. , Wong H. , Grundland H. , Liu J. , Fahy J. V. 
Published: January 2004

SummaryBackground
Selectins participate in the initial phase of leucocyte migration from circulation to inflamed tissues and may play a role in inflammatory cellular influx into airways in asthma. In the sheep asthma model, TBC1269, a pan‐selectin antagonist, reduced late allergen response by 74%.Objective
To determine whether a single dose of TBC1269 inhibits early (EAR) and late (LAR) asthmatic responses, and whether it inhibits sputum leucocyte influx after inhalation allergen challenge in atopic asthmatic subjects treated with bronchodilators only.Methods
Twenty‐one asthmatic subjects (mean±SD, age=32.5±6.7 years, 8 males, FEV1 percent predicted=84±15%) with known late asthmatic response based on a screening inhalation allergen challenge were randomly assigned to receive intravenous treatment with either placebo (n=11) or TBC1269 (n=10, 30 mg/kg) infused over 15 min immediately prior to a second (post‐treatment) allergen challenge at least 4 weeks after the screening challenge. After each challenge, EAR and LAR were monitored for 7 h. In addition, sputum was induced 1 day before and 1 day after each allergen challenge.Results
TBC1269 did not attenuate the EAR compared with placebo (largest fall in FEV1 within 1 h of 34.1±13.9% vs. 31.8±12.2% for TBC1269 and placebo groups respectively, P=0.61) or the LAR (largest fall in FEV1 between 3 and 7 h of 39.3±15.3% vs. 32.6±13.8%, P=0.24). TBC1269 had only minor effects on allergen‐induced sputum eosinophilia.Conclusion
We conclude that TBC1269 administered before allergen challenge as a single intravenous dose does not attenuate early or late asthmatic responses to allergen in asthmatic subjects.
Early and late bronchoconstrictions, airway hyper‐reactivity, leucocyte influx and lung histamine and nitric oxide after inhaled antigen: effects of dexamethasone and rolipram
Authors: Toward T. J. , Broadley K. J. 
Published: January 2004

SummaryBackground
Guinea‐pig models can provide the essential features of asthma, including early‐ (EAR) and late‐ (LAR) phase asthmatic responses, airway hyper‐reactivity (AHR) and inflammatory cell influx; however, these components are rarely demonstrated all in the same model.Objectives
The aim of this study was to establish a conscious guinea‐pig model with these essential features of asthma and to correlate these with bronchoalveolar lavage fluid (BALF) histamine and nitric oxide (NO) levels. The model would be validated from the susceptibility of these parameters to standard anti‐asthmatic agents, the steroid, dexamethasone, and a phosphodiesterase‐4 (PDE4) inhibitor, rolipram.Methods
Guinea‐pigs were sensitized with ovalbumen (OA) (10 μg plus Al2(OH)3 100 mg, intraperitoneal (i.p.)) and 14 days later received inhaled OA (100 μg/mL) or vehicle for 1 h. Airway function was measured by whole‐body plethysmography as specific airway conductance (sGaw). Reactivity to inhaled histamine (nose‐only, 1 mm, 20 s) was recorded 24 h before and at 6, 12 or 24 h after OA challenge. BALF was obtained to determine the total and differential cell counts, NO and histamine.Results
Guinea‐pigs challenged with OA showed an EAR as a fall in (sGaw) (−54.9±10.8%), which resolved by 6 h and was followed by an LAR between 7 and 11 h (−30.2±8.8%). No bronchoconstriction to inhaled histamine occurred before OA challenge but at 6, 12 or 24 h afterwards, sGaw fell significantly, indicating AHR. At 1 h after OA, macrophages, eosinophils and neutrophils significantly increased in BALF. Macrophages and eosinophils increased further up to 24 h (3‐ and 44‐fold), but neutrophils declined to control levels. BALF histamine levels increased at 0.25 h after OA challenge and peaked at 6 h. BALF NO levels initially fell (44%) 1 h after OA exposure and then progressively rose above control levels. Dexamethasone (20 mg/kg, i.p.) and rolipram (1 mg/kg, i.p.) administered 24 and 0.5 h before and 6 h after OA challenge inhibited leucocyte influx, AHR and the early deficiency and later excess of NO. Dexamethasone but not rolipram attenuated the LAR.Conclusions
This model displays many of the features of human asthma with predictable responses to dexamethasone and evidence of anti‐asthmatic activity by the PDE4 inhibitor, rolipram.
Butterbur, a herbal remedy, confers complementary anti‐inflammatory activity in asthmatic patients receiving inhaled corticosteroids
Authors: Lee D. K. C. , Haggart K. , Robb F. M. , Lipworth B. J. 
Published: January 2004

SummaryBackground
The effects of butterbur (BB), a herbal remedy, as add‐on therapy to inhaled corticosteroids in patients with atopic asthma is currently unknown.Objective
We evaluated the effects of BB, given as add‐on therapy to asthmatic patients maintained on inhaled corticosteroids, assessing adenosine monophosphate (AMP) bronchoprovocation (primary outcome variable) along with other surrogate inflammatory markers such as exhaled nitric oxide, serum eosinophil cationic protein and peripheral blood eosinophil count.Methods
Sixteen atopic asthmatic patients with mean (standard error of mean) forced expiratory volume in 1 s (FEV1) of 78 (4)% predicted, maintained on their constant dose of inhaled corticosteroids throughout the study, received twice daily for 1 week either BB 25 mg or placebo (PL), in a double‐blind, cross‐over fashion, with a 1‐week washout period prior to each randomized treatment. Measurements were made at baselines prior to each randomized treatment and following the randomized treatment period.Results
Baseline values for the primary and secondary outcomes were not significantly different prior to BB and PL. AMP provocative concentration causing a 20% reduction from baseline FEV1 (PC20) as doubling dilution change from baseline, significantly improved (P<0.05) with BB, 0.6 (0.2), compared with PL, −0.1 (0.3); a 0.7 doubling dilution difference. Exhaled nitric oxide as change from baseline was significantly reduced (P<0.05) with BB, −1.2 (0.8) p.p.b., compared with PL, 0.5 (0.4) p.p.b. Both serum eosinophil cationic protein and peripheral blood eosinophil count as change from baseline were also significantly suppressed (P<0.05) with BB, −3.9 (3.3) μg/L, −31 (28)×106/L compared with PL, 3.3 (2.5) μg/L, 38 (16)×106/L, respectively.Conclusion
Chronic dosing with BB conferred complementary anti‐inflammatory activity in atopic asthmatic patients maintained on inhaled corticosteroids. Further studies are now required to assess the potential role for BB as either monotherapy in milder patients or add‐on therapy in more severe asthmatics.
Influence of long‐term cigarette smoking on immunoglobulin E‐mediated allergy, pulmonary function, and high‐resolution computed tomography lung densitometry in elderly patients with asthma
Authors: Mitsunobu F. , Ashida K. , Hosaki Y. , Tsugeno H. , Okamoto M. , Nishida N. , Nagata T. , Tanizaki Y. , Tanimoto M. 
Published: January 2004

SummaryBackground
Smoking is the most important cause of chronic obstructive pulmonary disease (COPD). However, the influence of cigarette smoking on the pathogenesis of asthma in the elderly remains controversial. This study attempted to clarify the influence of cigarette smoking on elderly asthmatics.Methods
Forty‐eight asthmatics over 70 years old (25 ex‐smokers and 23 never‐smokers) and 20 patients with COPD over 70 years old (all ex‐smokers) were studied to determine the influence of cigarette smoking on IgE‐mediated allergy (total IgE, IgE antibodies against inhalant allergens, bronchial hyper‐responsiveness (BHR), generation of leukotriene (LT) B4 and C4), pulmonary function, and the relative area of lung showing attenuation values less than −950 Hounsfield units (RA950) on high‐resolution computed tomography scans.Results
The incidence of positive IgE antibodies against inhalant allergens, BHR, and the generation of leukotriene B4 (LTB4) by leucocytes were significantly increased in patients with a history of smoking compared with those without. Residual volume (%RV) was significantly increased, and diffusing capacity for carbon monoxide was significantly decreased in ex‐smokers with asthma and COPD compared with never‐smokers with asthma. Inspiratory RA950 and ratio of expiratory RA950 to inspiratory RA950 were significantly larger in asthmatics with a smoking history than in those without, and in COPD patients than in asthmatics.Conclusion
Cigarette smoking enhances the production of IgE antibodies, BHR, and generation of LTB4 by leucocytes in elderly asthmatics. Increased hyper‐inflation or emphysematous changes of the lungs expressed by increased RA950, closely related to %RV, was more frequently observed in ex‐smokers compared with never‐smokers.
Comparative prevalence of sensitization to common animal, plant and mould allergens in subjects with asthma, or atopic dermatitis and/or allergic rhinitis living in a tropical environment
Authors: Montealegre F. , Meyer B. , Chardon D. , Vargas W. , Zavala D. , Hart B. , Bayona M. 
Published: January 2004

SummaryBackground and objectives
Current information suggests that the expression of allergic diseases is determined by the exposure and nature of the allergen. The objectives of the present study were to determine if the nature of allergenic exposition to animal, plant or fungal allergens influenced the clinical manifestations of atopic dermatitis (AD), allergic rhinitis (AR) or asthma (AS) in patients living in a tropical environment. The prevalence and degree of sensitization to these allergens were analysed by age and gender.Subjects and methods
A total of 1496 atopic cases, grouped according to the primary diagnosis of AD or AR or AS, were skin tested using a standardized allergen panel. Participants were categorized by age groups. The atopic index (AI) and mean weal diameter (MWD) as well as the prevalence of positive skin tests were determined for each of the patient groups and compared by age groups.Results
The prevalence of atopy as well as the AI and the MWD peaked at 6–15 years of age and declined thereafter. In all the patients tested, the prevalence of sensitization was, in decreasing order; dust mites 94.3%, cockroach 41.5%, pets 31.5%, plant allergens 31.1% and fungal 19.4%. Eight hundred and ninety‐three atopic patients were exclusively sensitized only to animal allergens. Of these, 38.4% had AD, 31.3% had AR and 30.5% with AS.Conclusion
These data demonstrate that for patients with AD, AR and AS living in a tropical environment, the prevalence of positive skin reactions to animal allergens is highest followed by plant and fungal allergens. We did not observe any association between the type of allergen and clinical manifestations. The index of atopy was similar for both sexes. The prevalence and degree of sensitization were shown to peak in young adults independent of the allergen in AD and AR patients.