13 research outputs found
Brain lactic alkalosis in Aicardi-Goutières Syndrome
Aicardi-Goutières syndrome is a rare progressive encephalopathy characterized by
acquired microcephaly, basal ganglia calcification, and chronic CSF
lymphocytosis, raised levels of interferon alpha in CSF and plasma and
chill-blain type lesions. A possible mechanism of injury is cytokine related
microangiopathy. We report brain imaging and proton (1H) and phosphorus-31 (31P)
magnetic resonance spectroscopy (MRS) findings during the first year after birth
in two patients. In patient 1 the evolution of brain metabolite ratios and
intracellular pH obtained from serial 1H (long TE) and 31P MRS studies are
described; in patient 2 a single 1H (short TE) MRS study is described. Imaging
findings included basal ganglia calcifications, cerebral atrophy, and
leukodystrophy. The MRS results demonstrated that Aicardi-Goutières syndrome is
associated with reduced NAA/Cr, reflecting decreased neuronal/axonal density or
viability, increased myo-inositol/Cr, reflecting gliosis or osmotic stress and a
persisting brain lactic alkalosis. A brain lactic alkalosis has also been
observed in those infants surviving perinatal hypoxia-ischaemia but with a poor
neurodevelopmental outcome. A possible mechanism leading to brain alkalosis is
up-regulation of the Na+/H+ transporter by focal areas of ischaemia related to
the microangiopathy or by pro-inflammatory cytokines. Such brain alkalosis may be
detrimental to cell survival and may increase glycolytic rate in astrocytes
leading to an increased production of lactate
Genetic prevention, carrier screening and the role of citizens: the legitimisation of libertarian paternalist policies by deliberative democracy
In this paper, first we recall some paradigmatic ways of implementing carrier screening policies in a community. Then we move on to a proposal concerning a possible bottom-up solution based on deliberative democracy (and thus on real citizens’ participation in decisional processes) that should legitimate libertarian paternalist strategies concerning which genetic screenings should be made and which policies should be adopted by the institution
Heparin-binding protein in sputum as a marker of pulmonary inflammation, lung function, and bacterial load in children with cystic fibrosis
Pathophysiology of Alpha-1 Antitrypsin Lung Disease
Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder characterized by low serum levels of alpha-1 antitrypsin (AAT). Loss of AAT disrupts the protease-antiprotease balance in the lungs, allowing proteases, specifically neutrophil elastase, to act uninhibited and destroy lung matrix and alveolar structures. Destruction of these lung structures classically leads to an increased risk of developing emphysema and chronic obstructive pulmonary disease (COPD), especially in individuals with a smoking history. It is estimated that 3.4 million people worldwide have AATD. However, AATD is considered to be significantly underdiagnosed and underrecognized by clinicians. Contributing factors to the diagnostic delay of approximately 5.6 years are: inadequate awareness by healthcare providers, failure to implement recommendations from the American Thoracic Society/European Respiratory Society, and the belief that AATD testing is not warranted. Diagnosis can be attained using qualitative or quantitative laboratory testing. The only FDA approved treatment for AATD is augmentation therapy, although classically symptoms have been treated similarly to those of COPD. Future goals of AATD treatment are to use gene therapy using vector systems to produce therapeutic levels of AAT in the lungs without causing a systemic inflammatory response