Conventional chest physiotherapy compared to other airway clearance techniques for cystic fibrosis.

Background: Cystic fibrosis is an inherited life-limiting disorder, characterised by pulmonary infections and thick airway secretions. Chest physiotherapy has been integral to clinical management in facilitating removal of airway secretions. Conventional chest physiotherapy techniques (CCPT) have depended upon assistance during treatments, while more contemporary airway clearance techniques are self-administered, facilitating independence and flexibility.

Development of a large-scale obstetric quality-improvement program that focused on the nulliparous patient at term.

Objective: The purpose of this study was to identify an appropriate population and a balanced set of maternal and neonatal measures to drive a hospital network obstetric quality improvement program.

Study Design: Sutter Health, a large Northern California health care system with>40,000 births annually, served as the site for this project. We chose to focus on the standardized nulliparous patients: term, singleton, and vertex.

Cesarean delivery rates and neonatal morbidity in a low-risk population.

Objective: To estimate the relationship between case-mix adjusted cesarean delivery rates and neonatal morbidity and mortality in infants born to low-risk mothers.

Methods: This retrospective cohort study used vital and administrative data for 748,604 California singletons born without congenital abnormalities in 1998-2000. A total of 282 institutions was classified as average-, low-, or high-cesarean delivery hospitals based on their cesarean delivery rate for mothers without a previous cesarean delivery, in labor at term, with no evidence of maternal, fetal, or placental complications.

Respiratory physiotherapy vs. suction: the effects on respiratory function in ventilated infants and children.

Objective: To assess and compare the effects of physiotherapy and suction on expired tidal volume (V(TE)), respiratory compliance (C(rs)), resistance (R(rs)) and arterial blood gases.

Design: Randomised cross-over study comparing outcomes after both treatments on the same day.

Setting: Intensive tertiary care units, Great Ormond Street Hospital, London.

The influence of physiotherapy and suction on respiratory deadspace in ventilated children.

Objective: To assess and compare the effects of respiratory physiotherapy and suction on deadspace volumes, carbon dioxide elimination (VCO(2)), end tidal CO(2) (ETCO(2)), and arterial partial pressure of carbon dioxide (PaCO(2)) in ventilated infants and children.

Design: Randomised crossover study. Participants received both treatments with a washout interval of more than 90 min.

The folding and design of repeat proteins: reaching a consensus.

Although they are widely distributed across kingdoms and are involved in a myriad of essential processes, until recently, repeat proteins have received little attention in comparison to globular proteins. As the name indicates, repeat proteins contain strings of tandem repeats of a basic structural element. In this respect, their construction is quite different from that of globular proteins, in which sequentially distant elements coalesce to form the protein.

Design of stable alpha-helical arrays from an idealized TPR motif.

The tetratricopeptide repeat (TPR) is a 34-amino acid alpha-helical motif that occurs in over 300 different proteins. In the different proteins, three to sixteen or more TPR motifs occur in tandem arrays and function to mediate protein-protein interactions. The binding specificity of each TPR protein is different, although the underlying structural motif is the same.

The influence of endotracheal tube leak on the assessment of respiratory function in ventilated children.

Objective: The use of respiratory mechanics to optimise ventilator settings has become more common since the integration of pressure and flow transducers into modern ventilators. However, values of respiratory resistance (R(rs)) and compliance (C(rs)) can be overestimated in the presence of tracheal tube leak and clinical decisions based on these figures would be misinformed. This study aimed to assess the influence of tracheal tube leak on measurements of C(rs), R(rs) and expired tidal volume (V(TE)) in ventilated children in order to establish when such measurements were reliable in this population.

Effect of delayed sternal closure after cardiac surgery on respiratory function in ventilated infants.

Objective: Studies examining the effect of sternal closure on respiratory function have not been published, and currently there is little evidence to guide ventilation management immediately after closure. The aim of this study was to establish the impact of delayed sternal closure on expired tidal volume, respiratory system compliance, and CO2 elimination immediately after the procedure in infants who had undergone open heart surgery.

Design: Prospective study of respiratory function before and after delayed sternal closure.

A comparison of experimental and computational methods for mapping the interactions present in the transition state for folding of FKBP12.

The folding pathway of FKBP12, a 107 residue α/β protein, has been characterised in detail using a combination of experimental and computational techniques. FKBP12 follows a two-state model of folding in which only the denatured and native states are significantly populated; no intermediate states are detected. The refolding rate constant in water is 4 s(-1) at 25 °C.

Maternal and fetal outcomes in pregnancies affected by von Willebrand disease type 2.

We report a case series that lends support for both the maternal and neonatal safety of vaginal delivery in pregnancies complicated by heritable von Willebrand disease types 2A and 2B. With proper hematologic support, a cesarean delivery may be indicated only for obstetric reasons.

Prevention of early-onset invasive neonatal group B streptococcal disease in a private hospital setting: the superiority of culture-based protocols.

Objective: In a large private tertiary care hospital we compared the two different approaches to group B streptococcal screening and intrapartum chemoprophylaxis suggested by The American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the Centers for Disease Control and Prevention: risk factor-based protocol and culture-based protocol.

Study Design: A 2-year baseline period was followed by sequential prospective observational studies of the impacts of two different group B streptococcal management protocols, 3 years with the risk-based approach and 2 years with the culture-based approach of universal screening at 35 to 37 weeks' gestation.

Results: During the baseline period the rate of early-onset group B streptococcal infection was 1.

The relationship between maternal age and uterine dysfunction: a continuous effect throughout reproductive life.

Objective: In a selected low-risk population with spontaneous term labor we sought to determine whether there was a continuous effect of maternal age on uterine function.

Study Design: With our comprehensive computerized database and medical record system, we identified 8496 patients who were nulliparous and in spontaneous labor at term (> or =37 weeks' gestation) with singleton fetuses in vertex presentation. This group was then analyzed according to maternal age for measures of labor dysfunction and rates of operative delivery.

Chest physiotherapy compared to no chest physiotherapy for cystic fibrosis.

Background: Chest physiotherapy is widely used in patients with cystic fibrosis in order to clear mucus from the airways.

Objectives: To determine the effectiveness and acceptability of chest physiotherapy compared to no treatment or spontaneous cough alone to improve mucus clearance in cystic fibrosis.

Search Strategy: Relevant trials are identified in the Cochrane Cystic Fibrosis and Genetic Disorders Group Specialised Register of Controlled Trials.

Does trifluoroethanol affect folding pathways and can it be used as a probe of structure in transition states?

Nonaqueous co-solvents, particularly 2,2,2-trifluoroethanol (TFE), have been used as tools to study protein folding. By analyzing FKBP12, an alpha/beta-protein that folds with two-state kinetics, we have been able to address three key questions concerning the use of TFE. First, does TFE perturb the folding pathway? Second, can the observed changes in the rate of folding and unfolding in TFE be attributed to a change in free energy of a single state? Finally, can TFE be used to infer information on secondary structure formation in the transition state? Protein engineering experiments on FKBP12, coupled with folding and unfolding experiments in 0% and 9.

Mapping the interactions present in the transition state for unfolding/folding of FKBP12.

The structure of the transition state for folding/unfolding of the immunophilin FKBP12 has been characterised using a combination of protein engineering techniques, unfolding kinetics, and molecular dynamics simulations. A total of 34 mutations were made at sites throughout the protein to probe the extent of secondary and tertiary structure in the transition state. The transition state for folding is compact compared with the unfolded state, with an approximately 30 % increase in the native solvent-accessible surface area.

Folding pathway of FKBP12 and characterisation of the transition state.

The folding pathway of human FKBP12, a 12 kDa FK506-binding protein (immunophilin), has been characterised. Unfolding and refolding rate constants have been determined over a wide range of denaturant concentrations and data are shown to fit to a two-state model of folding in which only the denatured and native states are significantly populated, even in the absence of denaturant. This simple model for folding, in which no intermediate states are significantly populated, is further supported from stopped-flow circular dichroism experiments in which no fast "burst" phases are observed.

Reducing cesarean birth rates with data-driven quality improvement activities.

Reduction of cesarean section rates has been a difficult process that has not been easily accomplished by the institution of guidelines. It is more a process of changing physician behavior rather than of medical education. This article analyzed the role of intensive feedback of outcomes to bring about such changes.

Finding evidence to support airway clearance techniques in cystic fibrosis.

Chest physiotherapy, aiming to clear bronchopulmonary secretions, has become a mainstay in the respiratory management of cystic fibrosis (CF). Early diagnosis and new therapeutic interventions have dramatically improved the outlook for patients with this disorder and it is no longer a disease of childhood. Along with these changes chest physiotherapy has also progressed, with the development of several treatment modalities that are more effective and can be performed by the patient without assistance.

Context-dependent nature of destabilizing mutations on the stability of FKBP12.

The context-dependent nature in which mutations affect protein stability was investigated using the FK506-binding protein, FKBP12. Thirty-four mutations were made at sites throughout the protein, including residues located in the hydrophobic core, the beta-sheet, and the solvent-exposed face of the alpha-helix. Urea-induced denaturation experiments were used to measure the change in stability of the mutants relative to that of the wild type (Delta DeltaGU-F).

The use of intravenous immunoglobulin in recurrent pregnancy loss associated with combined alloimmune and autoimmune abnormalities.

Problem: Several studies have evaluated the effect of intravenous gammaglobulin (IVIG) in women with unexplained recurrent spontaneous abortions (RSA). Data regarding the underlying immunologic abnormalities in these patients is scant. This study reports the pregnancy outcome and immunologic changes observed in a large group of women with RSA associated with well-defined alloimmune and autoimmune abnormalities treated with IVIG.

Nuclear regulation of HLA class I genes in human trophoblasts.

Problem: Human trophoblast expression of class I human leukocyte antigen (HLA) genes is unique in that there is no classical gene expression, but nonclassical HLA-G is expressed and only by cytotrophoblast cells. This differential expression of classical versus nonclassical class I genes suggests tissue specific regulation. Recently, a negative regulatory element (NRE), 180 bp 5' to transcription initiation was identified in a murine embryonal carcinoma cell line that markedly inhibited class I gene expression (Flanagan et al.

Expression of the nonclassic histocompatibility antigen HLA-G by preeclamptic placenta.

Objective: Expression of the histocompatibility antigen HLA-G may be required for appropriate invasion and remodeling of uterine spiral arteries. Inappropriate expression of this antigen may result in failure of invasion, leading to partial placental ischemia and gestational disease.

Study Design: To test the hypothesis that the level of expression of HLA-G is reduced in trophoblasts from patients with gestational complications (preeclampsia, intrauterine growth retardation, or gestational hypertension) compared with patients with normal pregnancy, total ribonucleic acid was isolated from the fetal membrane or decidual interface of term placenta from several patient groups.