Effect of reducing anatomic dead space on arterial PCO2 during CO2 inhalation

Carotid body-denervated (CBD) ponies have a less than normal increase in arterial PCO2 (PaCO2) when inspired CO2 (PICO2) is increased, even when pulmonary ventilation (VE) and breathing frequency (f) are normal. We studied six tracheostomized ponies to determine whether this change 1) might be due to increased alveolar ventilation (VA) secondary to a reduction in upper airway dead space (VD) or 2) is dependent on an upper airway sensory mechanism. Three normal and three chronic CBD ponies were studied while they were breathing room air and at 14, 28, and 42 Torr PICO2. While the ponies were breathing room air, physiological VD was 483 and 255 ml during nares breathing (NBr) and tracheostomy breathing (TBr), respectively. However, at elevated PICO2, mixed expired PCO2 often exceeded PaCO2; thus we were unable to calculate physiological VD using the Bohr equation. At all PICO2 in normal ponies, PaCO2 was approximately 0.3 Torr greater during NBr than during TBr (P less than 0.05). In CBD ponies this NBr-TBr difference was only evident while breathing room air and at 28 Torr PICO2. At each elevated PICO2 during both NBr and TBr, the increase in PaCO2 above control was always less in CBD ponies than in normal ponies (P less than 0.01). The VE-PaCO2, f-PaCO2, and tidal volume-PaCO2 relationships did not differ between NBr and TBr (P greater than 0.10) nor did they differ between normal and CBD ponies (P greater than 0.10). We conclude that the attenuated increase in PaCO2 during CO2 inhalation after CBD is not due to a relative increase in VA secondary to reducing upper airway VD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of Potentiation by Chlordiazepoxide (Librium) of Depression or Excitation due to Alcohol

A double-blind study was completed comparing the interaction of chlordiazepoxide (Librium), 10 mg. given three times for one day, and 6 oz. of Canadian rye whiskey given over a three-hour period in the evening of the same day. The comparison drug was a placebo. Four evening experiments were conducted using the same six normal subjects and two observers. At the end of the evening, the observers were unable to detect which subjects had had placebo or chlordiazepoxide. It was concluded that chlordiazepoxide, given in this recommended daily dose, did not potentiate what was considered a social quantity of alcohol.     

Genomic organization and chromosomal localization of a new repeat MS7, specific for heterochromatin of sex chromosomes in Microtus species voles of the arvalis group

The tandemly arranged MS4 repeat with monomeric units of 4.1 kb is species-specifically distributed in heterochromatin of sex chromosomes of four common vole species of genus Microtus, group arvalis [1, 2]. In this work, we studied the genomic organization of the MS4 homolog in euchromatin of the X chromosome of M. arvalis. It has been shown by analyzing the phage genomic clones that one MS4 copy makes a part of a monomeric unit exceeding 8.5 kb that also includes a new MS7 repeat and, possibly, LINE fragments. MS7 is located together with MS4 in heterochromatin of common vole sex chromosomes, but in a substantially lesser amount. Probably, as a result of an evolutionary transition of an original repeat from euchromatin of the X chromosome to heterochromatin of the Y chromosome, MS4 underwent multiple amplification, and MS7 spread throughout heterochromatin, being surrounded by the MS4 tandem arrays.     

Targeted over-expression of glutamate transporter 1 (GLT-1) reduces ischemic brain injury in a rat model of stroke

Following the onset of an ischemic brain injury, the excitatory neurotransmitter glutamate is released. The excitotoxic effects of glutamate are a major contributor to the pathogenesis of a stroke. The aim of this study was to examine if overexpression of a glutamate transporter (GLT-1) reduces ischemic brain injury in a rat model of stroke. We generated an adeno-associated viral (AAV) vector expressing the rat GLT-1 cDNA (AAV-GLT1). Functional expression of AAV-GLT1 was confirmed by increased glutamate clearance rate in non-stroke rat brain as measured by in vivo amperometry. AAV-GLT1 was injected into future cortical region of infarction 3 weeks prior to 60 min middle cerebral artery occlusion (MCAo). Tissue damage was assessed at one and two days after MCAo using TUNEL and TTC staining, respectively. Behavioral testing was performed at 2, 8 and 14 days post-stroke. Animals receiving AAV-GLT1, compared to AAV-GFP, showed significant decreases in the duration and magnitude of extracellular glutamate, measured by microdialysis, during the 60 minute MCAo. A significant reduction in brain infarction and DNA fragmentation was observed in the region of AAV-GLT1 injection. Animals that received AAV-GLT1 showed significant improvement in behavioral recovery following stroke compared to the AAV-GFP group. We demonstrate that focal overexpression of the glutamate transporter, GLT-1, significantly reduces ischemia-induced glutamate overflow, decreases cell death and improves behavioral recovery. These data further support the role of glutamate in the pathogenesis of ischemic damage in brain and demonstrate that targeted gene delivery to decrease the ischemia-induced glutamate overflow reduces the cellular and behavioral deficits caused by stroke.     

The Psychotropic Self/Imaginary: Subjectivity and Psychopharmaceutical Use Among Heroin Users with Co-Occurring Mental Illness

Many people diagnosed with mental illnesses struggle with illicit drug addiction. These individuals are often treated with psychiatric medications, yet little is known about how they experience this treatment. Research on the subjective experience of psychiatric medication use highlights the complex, contradictory, and ambiguous feelings often associated with this treatment. However, for those with mental illness and addiction, this experience is complicated by the need to manage both psychiatric medication and illicit drug use. Using ethnographic data from a study of heroin use in Northeast Ohio, we explore this experience by expanding the pharmaceutical self/imaginary (Jenkins, Pharmaceutical Self: The Global Shaping of Experience in an Age of Psychopharmacology, School for Advanced Research Press, Santa Fe, NM, 2010b) to include psychopharmaceuticals and illicit drugs, what we call the psychotropic self/imaginary. Through this lens we explore the ways participants interpret and manage their psychotropic drug use in relation to sociocultural, institutional, and political–economic contexts. This analysis reveals how participants seek desired effects of legally prescribed and illicit drugs to treat mental illness, manage heroin addiction, and maintain a perceived “normal” self. Participants manage their drug use using active strategies, such as selective use of psychiatric medications, in the context of structural constraints, such as restricted access to mental health care, and cultural contexts that blur distinctions between “good” medicines and “bad” drugs.     

A Comprehensive Assessment of the Precision and Agreement of Anterior Corneal Power Measurements Obtained Using 8 Different Devices

Purpose

To comprehensively assess the precision and agreement of anterior corneal power measurements using 8 different devices.

Methods

Thirty-five eyes from 35 healthy subjects were included in the prospective study. In the first session, a single examiner performed on each subject randomly measurements with the RC-5000 (Tomey Corp., Japan), KR-8000 (Topcon, Japan), IOLMaster (Carl Zeiss Meditec, Germany), E300 (Medmont International, Australia), Allegro Topolyzer (Wavelight AG, Germany), Vista (EyeSys, TX), Pentacam (Oculus, Germany) and Sirius (CSO, Italy). Measurements were repeated in the second session (1 to 2 weeks later). Repeatability and reproducibility of corneal power measurements were assessed based on the intrasession and intersession within-subject standard deviation (Sw), repeatability (2.77Sw), coefficient of variation (COV), and intraclass correlation coefficient (ICC). Agreement was evaluated by 95% limits of agreement (LoA).

Results

All devices demonstrated high repeatability and reproducibility of the keratometric values (2.77Sw<0.36D, COV<0.3%, ICC>0.98). Repeated-measures analysis of variance with Bonferroni post test showed statistically significant differences (P<0.01) among mean keratometric values of most instruments; the largest differences were observed between the EyeSys Vista and Medmont E300. Good agreement (i.e., 95%LoA within ±0.5D) was found between most instruments for flat, steep and mean keratometry, except for EyeSys and Medmont. Repeatability and reproducibility of vectors J₀ and J₄₅ was good, as the ICCs were higher than 0.9, except J₄₅ of Medmont and Pentacam. For the 95% LoAs of J₀ and J₄₅, they were all ≤ ±0.31 among any two paired devices.

Conclusions

The 8 devices showed excellent repeatability and reproducibility. The results obtained using the RC-5000, KR-8000, IOLMaster, Allegro Topolyzer, Pentacam and Sirius were comparable, suggesting that they could be used interchangeably in most clinical settings. Caution is warranted with the measurements of the EyeSys Vista and Medmont E300, which should not be used interchangeably with other devices due to lower agreement.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01587287","term_id":"NCT01587287"}}NCT01587287     

CD14 C-159T and early infection with Pseudomonas aeruginosa in children with cystic fibrosis

Early acquisition of Pseudomonas aeruginosa is associated with a poorer prognosis in patients with cystic fibrosis. We investigated whether polymorphisms in CD14, the lipopolysaccharide receptor, increase the risk of early infection. Forty-five children with cystic fibrosis were investigated with annual bronchoalveolar lavage (BAL) and plasma sCD14 levels. Plasma sCD14 levels were significantly lower in children from whom P.aeruginosa was subsequently isolated (492.75 μg/ml vs. 1339.43 μg/ml, p = 0.018). Those with the CD14 -159CC genotype had a significantly increased risk of early infection with P.aeruginosa suggesting that CD14 C-159T plays a role in determining the risk of early infection with P.aeruginosa.