The effect of learning on ventilatory responses to inspiratory threshold loading in COPD

BACKGROUND: Progressive threshold loading (PTL) is a common test of respiratory muscle endurance. Healthy naive subjects improve endurance with successive exposures to PTL by altering their breathing responses, thus necessitating a familiarization period before reproducible measures can be obtained. This study sought to determine whether a similar "learning effect" is evident in patients with COPD, and what the mechanism of any such effect may be. METHODS: Ten subjects with COPD (FEV1 34+/-13% predicted) underwent PTL on four occasions (>24 h apart). During PTL measurements were obtained of breathing pattern and maximum threshold pressure (Pthmax) achieved. Maximum inspiratory pressure (PImax) was measured on each occasion. RESULTS: Over the four tests PImax improved by 21+/-16% (SD) (P<0.05) and Pthmax by 32+/-21% (P<0.05) with a plateau in these measures achieved by test three. Pthmax/PImax was unchanged, being 61+/-11% at test one and 67+/-12% at test four. In contrast to healthy subjects, PTL was not associated with increased expiratory time or decreased end-expiratory lung volume. CONCLUSIONS: In contrast to PImax and Pthmax, which changed with successive tests, a single measure of the ratio Pthmax/PImax may present a useful guide to the endurance capacity of the respiratory muscles in patients with COPD.     

Simethicone use during gastrointestinal endoscopy: Position statement of the Gastroenterological Society of Australia

Concern has been raised regarding the use of simethicone, a de‐foaming agent, during endoscopic procedures. Following reports of simethicone residue in endoscope channels despite high level disinfection, an endoscope manufacturer recommended that it not be used due to concerns of biofilm formation and a possible increased risk of microorganism transmission. However, a detailed mucosal assessment is essential in performing high‐standard endoscopic procedures. This is impaired by bubbles within the gastrointestinal lumen. The Gastroenterological Society of Australia's Infection Control in Endoscopy Guidelines (ICEG) Committee conducted a literature search utilizing the MEDLINE database. Further references were sourced from published paper bibliographies. Following a review of the available evidence, and drawing on extensive clinical experience, the multidisciplinary ICEG committee considered the risks and benefits of simethicone use in formulating four recommendations. Published reports have documented residual liquid or crystalline simethicone in endoscope channels after high level disinfection. There are no data confirming that simethicone can be cleared from channels by brushing. Multiple series report benefits of simethicone use during gastroscopy and colonoscopy in improving mucosal assessment, adenoma detection rate, and reducing procedure time. There are no published reports of adverse events related specifically to the use of simethicone, delivered either orally or via any endoscope channel. An assessment of the risks and benefits supports the continued use of simethicone during endoscopic procedures. Strict adherence to instrument reprocessing protocols is essential.     

Catheter‐associated bloodstream infection incidence and outcomes in congenital cardiac surgery

Objective: Catheter‐associated bloodstream infections complicate and prolong hos‐ pitalizations. The incidence of catheter‐associated bloodstream infections in children undergoing congenital cardiac surgery has not been reported. This study sought to define the incidence of catheter‐associated bloodstream infections after congenital cardiac surgery in neonates and infants ≤12 months old and compare hospital out‐ comes and costs to those who underwent surgery and did not have a catheter‐associ‐ ated bloodstream infections.
Design: Retrospective review of hospital admissions between October 2013 and November 2015 for neonates and infants ≤12 months old at admission with ICD‐9 codes for congenital cardiac surgery from discharge data from Vizient Clinical Data Base/Resource Manager (formerly University HealthSystem Consortium), an ana‐ lytic platform for performance improvement. Hospitals were included if they had >100 congenital cardiac surgery admissions during the study period. Admissions were stratified by age at admission: Neonates (<1 month) and Infants (1‐12 months). Established database flags for catheter‐associated bloodstream infections were uti‐ lized. Length of stay, mortality, and direct costs were compared between admissions with and without catheter‐associated bloodstream infections using t test or χ², as appropriate.
Results: Catheter‐associated bloodstream infections incidence after congenital car‐ diac surgery was higher in Neonates than Infants (1.5 vs 0.8%, P = .024). Length of stay and direct costs were significantly higher for patients with catheter‐associated bloodstream infections in both groups. Mortality was higher in the Infant group with catheter‐associated bloodstream infections compared to those without catheter‐as‐ sociated bloodstream infections.
Conclusion: Neonates develop catheter‐associated bloodstream infections at nearly twice the rate of older infants. For those who develop infection, mortality is 2‐8‐fold greater and hospital costs are 4‐6‐fold higher, which further highlight the importance of catheter‐associated bloodstream infections prevention in this population.     

Aquaporin 1 regulates GTP-induced rapid gating of water in secretory vesicles

The swelling of secretory vesicles has been implicated in exocytosis, but the underlying mechanism of vesicle swelling remains largely unknown. Zymogen granules (ZGs), the membrane-bound secretory vesicles in exocrine pancreas, swell in response to GTP mediated by a G(alpha)i3 protein. Evidence is presented here that the water channel aquaporin-1 (AQP1) is present in the ZG membrane and participates in rapid GTP-induced vesicular water gating and swelling. Isolated ZGs exhibit low basal water permeability. However, exposure of granules to GTP results in a marked potentiation of water entry. Treatment of ZGs with the known water channel inhibitor Hg2+ is accompanied by a reversible loss in both the basal and GTP-stimulatable water entry and vesicle swelling. Introduction of AQP1-specific antibody raised against the carboxyl-terminal domain of AQP1 blocks GTP-stimulable swelling of vesicles. Our results demonstrate that AQP1 associated at the ZG membrane is involved in basal as well as GTP-induced rapid gating of water in ZGs of the exocrine pancreas.     

Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation

Life-threatening complications such as graft versus host disease and infection remain major barriers to the success of allogeneic hemopoietic stem cell transplantation (SCT). While pretransplantation conditioning and posttransplantation immunosuppression are important risk factors for infection, the reasons that similarly immunosuppressed transplant recipients show marked variation in frequency of infection after allogeneic SCT are unclear. Mannose-binding lectin (MBL) deficiency is a risk factor for infection in other situations where immunity is compromised. We investigated associations between MBL2 gene polymorphisms and risk of major infection following allogeneic SCT. Ninety-seven related allogeneic donor-recipient pairs were studied. Clinical data including survival, days of fever, graft versus host disease incidence and severity, and infection were collected by case note review. Five single-nucleotide polymorphisms in the MBL2 gene were genotyped using the polymerase chain reaction and sequence-specific primers. MBL2 coding mutations were associated with an increased risk of major infection following transplantation. This association was seen for donor (P =.002, odds ratio [OR] 4.1) and recipient (P =.04, OR 2.6) MBL2 genotype. MBL2 promoter variants were also associated with major infection. The high-producing haplotype HYA was associated with a markedly reduced risk of infection (recipient HYA P =.0001, OR 0.16; donor HYA P =.001, OR 0.23). Donor MBL2 coding mutations and recipient HYA haplotype were independently associated with infection in multivariate analysis. These results suggest that MBL2 genotype influences the risk of infection following allogeneic SCT and that both donor and recipient MBL2 genotype are important. These findings raise the possibility that MBL replacement therapy may be useful following transplantation.     

Effectiveness of Acute Asthma Care Among Inner-city Adults

BACKGROUND: Acute asthma often requires expensive emergency department visits and hospitalizations, especially among economically disadvantaged inner-city adults. However, few studies have examined approaches for improving acute asthma care in this population. METHODS: We conducted a cohort study involving patients who were discharged from a public hospital emergency department following acute asthma care between March 31, 1997, and August 5, 1999, to identify processes of care effective for improving peak expiratory flow rate at a 2- to 3-week follow-up. Adult patients who met the predetermined criteria for asthma, who underwent a baseline peak expiratory flow rate reading, and who did not have concurrent acute sinusitis or pneumonia were eligible (N = 448). Of the 365 patients enrolled in the study, 309 (84.7%) completed it. We used a multiple linear regression analysis adjusted for patient risk to assess the association between acute asthma care processes derived from the National Asthma Education Prevention Program guidelines (inhaled beta2-agonists, inhaled corticosteroids, systemic corticosteroids, asthma care follow-up, and patient asthma education) and percentage peak expiratory flow rate change at follow-up. RESULTS: Systemic corticosteroids had a significant effect for increasing percentage peak expiratory flow rate change at the 2- to 3-week follow-up for all asthma exacerbation severity levels (beta = 26.1; 95% confidence interval, 1.8-50.5; P =.04) and severity levels specified by the National Asthma Education Prevention Program guidelines (beta = 31.6; 95% confidence interval, 8.1-55.1; P =.01). CONCLUSION: Outpatient systemic corticosteroids were effective for improving lung function 2 to 3 weeks after acute asthma care, and their use should reduce asthma-related morbidity, especially among economically disadvantaged inner-city adults.     

A model for amyloid fibril formation in immunoglobulin light chains based on comparison of amyloidogenic and benign proteins and specific antibody binding.

In an attempt to understand the mechanism of amyloid fibril formation in light chain amyloidosis, the properties of amyloidogenic (SMA) and benign (LEN) immunoglobulin light chain variable domains (VL) were compared. The conformations of LEN and SMA were measured using secondary and tertiary structural probes over the pH range from 2 and 8. At all pH values, LEN was more stable than SMA. The CD spectra of LEN at pH 2 were comparable to those of SMA at pH 7.5, indicating that the low pH conformation of LEN closely resembles that of SMA at physiological pH. At low pH, a relatively unfolded intermediate conformation is populated for SMA and rapidly leads to amyloid fibrils. The lack of such an intermediate with LEN, is attributed to sequence differences and accounts for the lack of LEN fibrils in the absence of agitation. A kappa IV-specific monoclonal antibody that recognizes the N-terminal of SMA caused unraveling of the fibrils to the protofilaments and was observed to bind to one end of SMA protofilaments by atomic force microscopy. The antibody result indicates that each protofilament is asymmetric with different ends. A model for the formation of fibrils by SMA is proposed.     

Clinical outcomes following stent implantation in internal mammary artery grafts.

We evaluated our experience with percutaneous coronary intervention (PCI) of internal mammary artery (IMA) grafts. From the institution's database we identified 288 patients with 311 IMA lesions. Of these, 82 (26.4%) had stents placed during PCI. Angiographic success was 92%. Mortality at 1 month was 1.7%, myocardial infarction (MI) 15.7%, and target lesion revascularization (TLR) 0.4%. Cumulative 1-year event rates were mortality 6.4%, MI 20.4%, and TLR 8.0%. TLR rates were significantly higher in the stented lesions than lesions treated with angioplasty alone (19.2% vs. 4.9%; P = 0.004). The higher TLR rate in stented lesions was most apparent at the anastomotic site (25.0% vs. 4.2%; P = 0.006). Percutaneous revascularization of IMA grafts can be performed safely with high procedural success and excellent short- and long-term results. Stenting, particularly at the anastomotic site, was associated with significantly greater rates of TLR than angioplasty alone.