BackgroundUltrasound (US) assessment of intravascular volume may improve volume management of dialysis patients. We investigated the relationship of intravascular volume evaluated by inferior vena cava (IVC) US to net volume changes with intermittent hemodialysis (HD) in critically ill patients.MethodsA retrospective cohort of 113 intensive care unit patients in 244 encounters had clinical assessment of intravascular volume followed by US of respiratory/ventilatory variation of IVC diameter, and had HD within 24 h. IVC collapsibility index (IVC CI)=(IVCmax–IVCmin)/IVCmax*100%. Volume management was guided by clinical data plus IVC US findings. Intradialytic hypotension (IDH) was categorized by severity from none to inability to tolerate HD.ResultsLinear regression correlating n-weighted proportions of encounters achieving net volume removal of ≥0.5 L, ≥1.0 L, ≥1.5 L, and ≥2.0 L strongly correlated across the range of IVC CI (R2=0.87–0.64). Sensitivity and specificity analysis showed IVC CI was a better predictor than IVCmax of achieving net ultrafiltration (UF) volumes. Mean central venous pressure, pulmonary artery occlusion pressure, and cardiac output were poor predictors by logistic regression and receiver operating curve analyses. IVC CI <20% was the approximate optimal cutoff for achieving ≥0.5 L to ≥2.0 L net UF volumes. Net volume change achieved tended to be less than recommended and may have been limited by the development of IDH. Severity of IDH did not correlate with UF rate in mL/kg/h. χ2 analysis showed pre-US clinical intravascular volume assessments had poor concordance with IVC CI categories.ConclusionIVC US may be a useful tool for predicting whether critically ill patients will achieve volume removal with HD.
Apolipoprotein E (apo E) is responsible for the binding of very low density lipoprotein and chylomicron remnants to cellular receptors thereby removing them from circulation. We have isolated and determined the sequence of a cDNA encoding 285 amino acids and the entire 3' untranslated region of 112 nucleotides of mouse apo E. The remaining coding sequence was determined by sequencing mouse liver mRNA. Comparisons with rat and human apo E sequences showed a high degree of conservation although there were regions in each species that were characterized by unique insertions and deletions. Analysis of the sequence homologies within apo E revealed that the entire sequence is made up of repetitive units. The most primitive unit appeared to be an li-nucleotide repeat within higher order repeats of 22 or 33 nucleotides. The li-nucleotide unit -TCGGACGAGGC-is read in all three reading frames, and when tandemly repeated, it encodes the highly conserved amino acid sequence Xaa-We postulate that apo E and those other apolipoproteins related to it have arisen by duplications and subsequent modifications of this or a closely related l1-nucleotide ancestral sequence.Apolipoprotein E (apo E) plays a central role in mammalian lipoprotein metabolism by serving both as a structural component for a diverse group of lipoprotein types and as a mediator of lipoprotein catabolism by specific cell surface receptors (1-3). Mature human apo E is a 299-amino acid polypeptide of known sequence (4), and the nucleotide sequences of human and rat apo E cDNA clones have been reported (5)(6)(7). Apo E as well as other apolipoproteins contain 11-or 22-amino acid repeated regions as dominant features (8-12). These appear to encode largely amphipathic a-helices, which have been implicated in lipid binding (13,14). The mouse is being utilized as a model in the study of lipid transport and metabolism because of the advantages it offers for genetic analysis (15). We report here the nucleotide sequence of mouse apo E mRNA and a detailed analysis of internal homology within the sequence. We also present evidence that apo E and other members of the apolipoprotein gene family may have evolved from a tandemly repeated 11-base-pair unit, with each successive unit being read in a different reading frame. After three such units, the translational repeat length of 11 amino acids would also repeat, as has been observed in modern day apolipoproteins.EXPERIMENTAL PROCEDURES The cDNA library construction and screening were as described (16). DNA sequencing was done by both the dideoxy chain termination (17) and the chemical cleavage methods (18). Synthetic oligonucleotides used as sequencing primers were synthesized and purified following the protocol of Matteucci and Caruthers (19).Apo E mRNA was sequenced as follows: A 14-base oligonucleotide corresponding to the 5' end of the cDNA clone (nucleotides 89-102) was labeled with 32P at its 5' end by kinase treatment and annealed to mouse liver poly (A)' RNA at a molar ratio of approximately 1:1 [oligonucleot...
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