The effect of naloxone on the preoperative gastric volume and pH

The effect of 4 mg oral naloxone on preoperative gastric volume and pH of gastric aspirate was studied in a double-blind, randomized study. Twenty patients received 10 ml of naloxone (4 mg) mixed with 10 ml of orange juice, and 20 patients received 10 ml of isotonic saline mixed with 10 ml of orange juice, 2 h before surgery. Gastric content was obtained immediately after intubation of the trachea. No significant difference in gastric volume and pH of gastric aspirate was found between the two groups. It is concluded that naloxone does not affect gastric emptying and gastric acid secretion to a degree great enough to protect against aspiration of gastric contents into the lungs.     

Quantitative measurement of regional lung gas volume by synchrotron radiation computed tomography

The aim of this study was to assess the feasibility of a novel respiration-gated spiral synchrotron radiation computed tomography (SRCT) technique for direct quantification of absolute regional lung volumes, using stable xenon (Xe) gas as an inhaled indicator. Spiral SRCT with K-edge subtraction using two monochromatic x-ray beams was used to visualize and directly quantify inhaled Xe concentrations and airspace volumes in three-dimensional (3D) reconstructed lung images. Volume measurements were validated using a hollow Xe-filled phantom. Spiral images spanning 49 mm in lung height were acquired following 60 breaths of an 80% Xe-20% O2 gas mixture, in two anaesthetized and mechanically ventilated rabbits at baseline and after histamine aerosol inhalation. Volumetric images of 20 mm lung sections were obtained at functional residual capacity (FRC) and at end-inspiration. 3D images showed large patchy filling defects in peripheral airways and alveoli following histamine provocation. Local specific lung compliance was calculated based on FRC/end-inspiration images in normal lung. This study demonstrates spiral SRCT as a new technique for direct determination of regional lung volume, offering possibilities for non-invasive investigation of regional lung function and mechanics, with a uniquely high spatial resolution. An example of non-uniform volume distribution in rabbit lung following histamine inhalation is presented.     

Whole-exome sequencing of Finnish patients with vascular cognitive impairment

Cerebral small vessel disease (CSVD) is the most important cause of vascular cognitive impairment (VCI). Most CSVD cases are sporadic but familial monogenic forms of the disorder have also been described. Despite the variants identified, many CSVD cases remain unexplained genetically. We used whole-exome sequencing in an attempt to identify novel gene variants underlying CSVD. A cohort of 35 Finnish patients with suspected CSVD was analyzed. Patients were screened negative for the most common variants affecting function in NOTCH3 in Finland (p.Arg133Cys and p.Arg182Cys). Whole-exome sequencing was performed to search for a genetic cause of CSVD. Our study resulted in the detection of possibly pathogenic variants or variants of unknown significance in genes known to associate with CSVD in six patients, accounting for 17% of cases. Those genes included NOTCH3, HTRA1, COL4A1, and COL4A2. We also identified variants with predicted pathogenic effect in genes associated with other neurological or stroke-related conditions in seven patients, accounting for 20% of cases. This study supports pathogenic roles of variants in COL4A1, COL4A2, and HTRA1 in CSVD and VCI. Our results also suggest that vascular pathogenic mechanisms are linked to neurodegenerative conditions and provide novel insights into the molecular basis of VCI.Subject terms: Stroke, Sequencing, Genetics research, Dementia     

Smoking and female infertility: a systematic review and meta-analysis

The high prevalence of smoking among women in their reproductive years continues to be a matter of concern. The negative effects of smoking on general health are well known, but smoking may also affect fertility. The objective of the present study was to perform a systematic review of the literature to determine whether there is an association between smoking and risk of infertility in women of reproductive age, and to assess the size of this effect. In the 12 studies used for this meta- analysis, the overall value of the odds ratio (OR) for risk of infertility in women smokers versus non-smokers was 1.60 [95% confidence interval (CI) 1.34-1.91]. Studies of subfertile women undergoing in-vitro fertilization (IVF) treatment also show a reduction in fecundity among women smokers. A meta-analysis of nine studies found an OR of 0.66 (95% CI 0.49-0.88) for pregnancies per number of IVF- treated cycles in smokers versus non-smokers. Despite the potential limitations of meta-analyses of observational studies, the evidence presented in this review is compelling because of the consistency of effect across different study designs, sample size and types of outcome. However, continued reassurance is needed that the calculated overall effect is not in fact due to confounding variables.      

T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogens

We show here that T cell cross-reactivity between heterologous viruses influences the immunodominance of virus-specific CD8(+) T cells by two mechanisms. First, T cells specific for cross-reactive epitopes dominate acute responses to viral infections; second, within the memory pool, T cells specific for cross-reactive epitopes are maintained while those specific for non-cross-reactive epitopes are selectively lost. These findings suggest an immunological paradigm in which viral infections shape the available T cell repertoire, causing alterations in the hierarchies of both the primary and memory CD8(+) T cell responses elicited by subsequent viral infections. Thus, immunodominance is a function of the host's previous exposure to unrelated pathogens, and this may have an impact on protective immunity and immunopathology.