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L Chan

Publications and source records attributed to L Chan.

At least 199 records · Page 11Linked to original sources
PubMed1997

Factors predicting prolonged mechanical ventilation in critically injured patients: introducing a simplified quantitative risk score.

Our objective was to identify a set of readily available and easily obtainable parameters that would predict prolonged mechanical ventilation in the critically injured patient. A surgical intensive care unit of an academic Level I trauma center. Prospectively collected data were retrospectively analyzed on all critically injured patients receiving mechanical ventilation for more than 2 days between January and December 1994. Prolonged mechanical ventilation (PMV) was defined as the need for mechanical ventilatory support for more than 7 days. One hundred and nineteen patients entered the final analysis. Of these, 63 remained on the ventilator for 7 days or less and 56 for more than 7 days. The Injury Severity Score (ISS), partial arterial oxygen tension (PaO2)/inspired fraction of oxygen (FiO2), net fluid balance, and use of Swan-Ganz were significantly different between the two groups when calculated 48 hours after surgical intensive care unit admission. Furthermore, we dichotomized these four variables across cutpoints that were determined by statistical analysis (ISS more or less than 20, PaO2/FiO2 more or less than 250, fluid retention more or less than 2000 cc, and presence or absence of Swan-Ganz). Again, significantly more patients required PMV if they had any one of the following: Swan-Ganz, ISS more than 20, PaO2/FiO2 less than 250, or fluid retention more than 2000 cc at 48 hours. An easily calculated five-point risk score (0-4 points) for predicting PMV based on these four variables was developed. Among the 35 patients at the extremes of the risk score (0 or 4 points), 33 (94.3%) were correctly prognosticated as to their needs for PMV. The need for an easily calculated score, which is derived from readily available parameters and can reliably identify patients with prolonged needs for ventilatory support, is obvious in the trauma setting. We describe a five-point risk score by which we can predict the need for PMV early in the course of the disease. Resource utilization and personnel allocation issues, as well as important therapeutic procedures, can be planned based on this score.

Adolescent↗
PubMed1997

Evaluation of adnexal masses using three-dimensional ultrasonographic technology: preliminary report.

The purpose of the current study was to demonstrate the ability of three-dimensional ultrasonographic technology to enhance the morphologic scoring system and further improve the ability to differentiate benign from malignant ovarian masses. We performed conventional two-dimensional and three-dimensional transabdominal and transvaginal ultrasonography on eight women with adnexal masses. All patients underwent exploratory laparotomy or diagnostic laparoscopy. The three-dimensional ultrasonographic findings were compared with the two-dimensional ultrasonograms, the intraoperative observations, and gross and histopathologic findings. The morphologic scoring system as described by Sassone and coworkers was adopted, with scores of less than 9 suggestive of benign lesions, and this system was applied in both the two-dimensional and three-dimensional ultrasonographic examinations. The morphologic scores were subsequently compared. The images were dissected in the XYZ planes, and the areas suggestive of malignancy, as suggested by two-dimensional ultrasonography, were determined to be either negative or positive and confirmatory. In each of the eight adnexal masses, three-dimensional ultrasonography confirmed the preoperative diagnoses. The morphologic scores did not differ between two-dimensional and three-dimensional ultrasonograms for the benign cysts. In one case of benign solid fibroma, both the two-dimensional and three-dimensional gray scale morphologic scores were falsely positive at greater than 9. In one case of malignant serous papillary cystadenocarcinoma the two-dimensional morphologic score was a 9, where- as the three-dimensional score was 13. This difference in scores can be attributed to the additional views available with three-dimensional volume scanning, which allowed better characterization of the pathologic conditions. In addition, three-dimensional sonographic technology had the added advantage of high-speed image acquisition and recording to decrease the time of scanning to improve patient comfort. Furthermore, three-dimensional ultrasonography allowed the real-time analysis of the acquired image data to be conducted at a later time when the patient is off the examination table. Our preliminary results suggest that three-dimensional transvaginal ultrasonographic technology can enhance and facilitate the morphologic evaluation of both benign and malignant adnexal masses.

Adult↗
PubMed1997

Production of rabbit polyclonal antibody against apobec-1 by genetic immunization.

Circulating apolipoprotein B (apoB) exists in two forms; apoB-100 and apoB-48. ApoB-48 is a truncated form of apoB resulting from RNA editing. The editing enzyme, called apobec-1, converts a cytidine (C) at nucleotide 6666 in apoB 100 mRNA to a uridine (U) and changes a CAA codon to an in-frame stop codon, UAA. We have produced a specific rabbit polyclonal antiserum against apobec-1 by genetic immunization. The cDNA of mouse apobec-1 was inserted downstream and in-frame at the BamH I site in the last exon of human growth hormone cDNA driven by a cytomegalovirus promoter. This plasmid was injected together with another plasmid expressing granulocyte macrophage colony-stimulating factor into the thigh muscles of a rabbit. The resulting antiserum demonstrated high specificity on Western blots, and inhibited the apoB mRNA editing activity of mouse liver extract in a dose-dependent manner. This report demonstrates that DNA immunization is a powerful technique that can be readily applied to other sparse or difficult-to-purify proteins in lipid metabolism.

APOBEC-1 Deaminase↗
PubMed1996

Control of apolipoprotein B mRNA editing: implication of mRNA dynamics at various maturation stages.

Apolipoprotein (apo) B mRNA editing is a genetic regulatory mechanism whereby nucleotide 6666 in apo-B-100 mRNA is converted from a C to a U. The end result of this change is the creation of a premature stop codon so that the translation product of the edited (apoB-48) mRNA contains 2152 amino acids residues instead of 4536 residues in the product (apoB-100) encoded by the unedited mRNA. ApoB mRNA editing is a post-transcriptional process that is expressed in a tissue-specific manner. Here we present a model for the control of apoB mRNA editing. The three variables in the model include editing activity, apoB mRNA transcription rate and mRNA degradation rate at various maturation stages for the mRNA, and a simple formula can be used to quantify the degree of apoB mRNA editing with respect to these variables at different apoB mRNA maturation stages. Time-dependent equations were solved numerically. Using this model, it can be shown that, in addition to editing activity, the degradation kinetics of apoB mRNA can also serve as an efficient modulator of the degree of editing. The rate of apoB mRNA transcription has a transient effect on the degree of editing; varying the apoB mRNA degradation constant tends to change the degree of editing only at the specific maturation stage. This model can render some previously proposed hypothesis (e.g. coupling of mRNA editing to splicing/polyadenylation) unnecessary and provides a rational basis for the design of experiments on specific aspects of apoB mRNA editing in the future; it may also be applicable to other types of RNA editing.

Animals↗
PubMed1996

Transcription of the human hepatic lipase gene is modulated by multiple negative elements in HepG2 cells.

The expression of the hepatic lipase (HL) gene is highly tissue specific. In order to identify cis-acting elements which regulate the expression of this gene in the liver, multiple deletion mutants of the 5'-flanking region of the HL gene fused to the human growth hormone gene were transfected in HepG2 cells, which normally produce HL. Transient expression assays indicated the presence of negative (at nucleotides (nt) -1576(/)-1342 and -623(/)-407) and positive (at nt -1862(/)-1576 and -50(/)-9) regulatory elements. Transfection of HeLa cells, which do not produce HL, with the same deletion constructs resulted in a similar pattern of promoter activities. However, additional negative (nt -138/-50) and positive (nt -407(/)-138) elements were found. DNase I footprint analysis of the proximal and distal HLpromoter sequences with HepG2 and HeLa cell nuclear extracts identified seven protected regions: A, nt -1540(/)-1527; B, -1505(/)-1473; C, -1467(/)-1460; D, -592(/)-577; E, -565(/)-545; F, -234(/)-220; and G, -70(/) -48. Sites A, B, C, D and E were located within regions containing negative regulatory elements. In order to determine which nuclear factor interacts with the negative elements, sites B, D and E were mutated and the effects of mutation on competition in a gel retardation assay and on promoter activity were studied. When the binding motif for AP1 in sites B, D and E was mutated, the specific DNA-protein complexes were not competed with the mutant oligonucleotides and promoter activity increased twofold. The magnitude of the increase is less than expected from the deletion analysis, and simultaneous mutations did not cause further increase in promoter activity, which suggests that other sites are involved in this negative modulation. These results suggest that the transcription of the HLgene in HepG2 cells is negatively modulated by multiple cis-acting negative elements and AP1-like nuclear factor may play some role in this modulation.

Base Sequence↗
PubMed1996

Macrophage-mediated 15-lipoxygenase expression protects against atherosclerosis development.

Oxidative modification of LDL increases its atherogenicity, and 15-lipoxygenase (15-LO) has been implicated in the process. To address this issue, we generated transgenic rabbits that expressed 15-LO in a macrophage-specific manner and studied their susceptibility to atherosclerosis development when they were fed a high-fat, high-cholesterol (HFHC) diet (Teklad 0533 rabbit diet 7009 with 10% corn oil and 0.25% cholesterol) for 13.5 wk. Transgenic and nontransgenic rabbits developed similar degrees of hypercholesterolemia and had similar levels of triglyceride, VLDL, LDL, and HDL. Quantitative morphometric analysis of the aortic atherosclerosis indicated that the transgenic animals (n = 19) had significantly smaller lesion areas (9.8+/-6.5%, mean+/-SD) than their littermate controls (n = 14, 17.8+/-15.0%) (P < 0.05). In a subgroup (n = 9) of transgenic rabbits that received the HFHC diet plus the antioxidant N',N '-diphenyl-phenylenediamine (1%), the extent of lesion involvement (9.8+/-7.5%) did not differ from the subgroup (n = 10) that received the regular HFHC diet (9.7+/-5.9%). Since the results were unexpected, we repeated the experiments. Again, we found that the nontransgenic littermates (n = 12) had more extensive lesions (11.6+/-10.6%) than the transgenic rabbits (n = 13; 9.5+/-7.8%), although the difference was not significant. In a third set of experiments, we crossed 15-LO transgenic rabbits with Watanabe heritable hyperlipidemic (WHHL) rabbits and found that the lesion area in the 15-LO transgenic/heterozygous WHHL rabbits (n = 14) was only about one third (7.7+/-5.7%) that found in nontransgenic heterozygous WHHL littermate controls (n = 11, 20.7+/-19.4%) (P < 0.05). These data suggest that overexpression of 15-LO in monocytes/macrophages protects against lipid deposition in the vessel wall during early atherogenesis in these rabbit models of atherosclerosis.

Animals↗
PubMed1996

Ubiquitin-proteasome pathway mediates intracellular degradation of apolipoprotein B.

Newly synthesized apolipoprotein B (apoB) is degraded by a proteolytic process in the pre-Golgi compartment that can be inhibited by N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal (ALLN) but not by several other protease inhibitors. We have tested the hypothesis that the ubiquitin-proteasome pathway is involved in the intracellular degradation of apoB in liver cells. We found that inhibitors of proteasomes blocked the degradation of apoB in cultured human hepatoma (HepG2) cells. Protein degradation by proteasomes is ATP-dependent, and ATP depletion by dinitrophenol and 2-deoxyglucose also inhibited apoB degradation in these cells. Furthermore, the intracellular human apoB isolated by immunoprecipitation was shown to react specifically with anti-ubiquitin antibody by immunoblotting. This result was corroborated by sequential immunoprecipitation of [35S]methionine-labeled proteins by anti-human apoB and anti-ubiquitin antisera. In contrast, secreted apoB was not ubiquitinated. The amount of intracellular ubiquitinated apoB was increased by the proteasome inhibitors, ALLN and carbobenzoxyl-leucinyl-leucinyl-norvalinal-H (MG115). Our findings suggest that the ubiquitin-proteasome pathway is one mechanism for the intracellular degradation of apoB.

Adenosine Triphosphate↗
PubMed1996

Complete phenotypic characterization of apobec-1 knockout mice with a wild-type genetic background and a human apolipoprotein B transgenic background, and restoration of apolipoprotein B mRNA editing by somatic gene transfer of Apobec-1.

We have produced gene knockout mice by targeted disruption of the apobec-1 gene. As recently reported by Hirano et al. (Hirano, K.-I., Young, S. G., Farese, R. V., Jr., Ng, J., Sande, E., Warburton, C., Powell-Braxton, L. M., and Davidson, N. O. (1996) J. Biol. Chem. 271, 9887-9890), these animals do not edit apolipoprotein (apo) B mRNA or produce apoB-48. In this study we have performed a detailed analysis of the lipoprotein phenotypic effects of apobec-1 gene disruption that were not examined in the previous study. We first analyzed the plasma lipoproteins in knockout animals with a wild-type genetic background. Although there was no difference in plasma cholesterol between apobec-1(-/-), +/-, or +/+ mice, there was a marked (176%) increase in plasma apoB-100, from 1.8 +/- 1.2 mg/dl in apobec-1(+/+) mice to 2.7 +/- 0.6 mg/dl in apobec-1(+/-) and 5.0 +/- 1.4 mg/dl in apobec-1(-/-) mice. Plasma apoE was similar in these animals. By fast protein liquid chromatography (FPLC) analysis, there was a significant decrease in plasma high density lipoprotein (HDL) cholesterol in apobec-1(-/-) mice. We further fractionated the plasma lipoproteins into d < 1.006, 1.006-1.02, 1.02-1.05, 1.05-1.08, 1.08-1.10, and 1.10-1.21 g/ml classes, and found a marked (30-40%) reduction in the cholesterol and protein content in the (d 1.08-1.10 and 1.10-1.21) HDL fractions, corroborating the FPLC data. SDS-gel analysis revealed an absence of apoB-48, an increase in apoB-100 in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions, and a small decrease in apoA-I in the HDL fractions in the apobec-1(-/-) samples. We next raised the basal plasma apoB levels in the apobec-1(-/-) animals by cross-breeding them with human apoB transgenic (TgB) mice. The plasma apoB-100 was 3-fold higher in apobec-1(-/-)/TgB+/- mice (26.6 +/- 18.3 mg/dl) than in apobec-1(+/+)/TgB+/- mice (9.8 +/- 3.9 mg/dl, p < 0.05). The apobec-1(-/-)/TgB+/- mice had a plasma cholesterol levels of 170 +/- 28 mg/dl and triglyceride levels of 106 +/- 31 mg/dl, which are 80% and 58% higher, respectively, than the corresponding values of 94 +/- 21 mg/dl and 67 +/- 11 mg/dl in apobec+/+/TgB+/- mice. By FPLC, the apobec-1(-/-)/TgB+/- animals developed markedly elevated plasma LDL cholesterol (518.5 +/- 329.5 microg/ml) that is 373% that of apobec1(+/+)/TgB+/- mice (139.0 +/- 87.0 microg/ml) (p < 0.05). The elevated plasma triglyceride was accounted for mainly by a 97% increase in VLDL triglyceride in the apobec1(-/-)/TgB+/- mice. We conclude that apobec-1(-/-) animals have a distinctive lipoprotein phenotype characterized by significant hyperapoB-100 and HDL deficiency in mice with a wild-type genetic background. Furthermore, the abolition of apoB mRNA editing elevates plasma total cholesterol and LDL cholesterol in apobec-1(-/-) animals with a TgB background. Finally, to exclude the possibility that absence of apoB mRNA editing was a secondary effect of chronic Apobec-1 deficiency, we treated apobec-1(-/-) mice with a replication-defective mouse Apobec-1 adenoviral vector and found that we could acutely restore apoB mRNA editing in the liver. These experiments indicate that Apobec-1 is an essential component of the apoB mRNA editing machinery and absence of editing in the knockout animals is a direct consequence of the absence of functional Apobec-1.

APOBEC-1 Deaminase↗
PubMed1996

Structure-function relationship of lipoprotein lipase-mediated enhancement of very low density lipoprotein binding and catabolism by the low density lipoprotein receptor. Functional importance of a properly folded surface loop covering the catalytic center.

We examined the structure-function relationship of human lipoprotein lipase (hLPL) in its ability to enhance the binding and catabolism of very low density lipoproteins (VLDL) in COS cells. Untransfected COS cells did not bind to or catabolize normal VLDL. Expression of wild-type hLPL by transient transfection enhanced binding, uptake, and degradation of the VLDL (a property of LPL that we call bridge function). Heparin pretreatment and a monoclonal antibody ID7 that blocks LDL receptor-binding domain of apoE both inhibited binding, and apoE2/E2 VLDL from a Type III hyperlipidemic subject did not bind. However, LDL did not reduce 125I-VLDL binding to the hLPL-expressing cells, whereas rabbit beta-VLDL was an effective competitor. By contrast, LDL reduced uptake and degradation of 125I-VLDL to the same extent as excess unlabeled VLDL or beta-VLDL. These data suggest that binding occurs by direct interaction of VLDL with LPL but the subsequent catabolism of the VLDL is mediated by the LDL receptor. Mutant hLPLs that were catalytically inactive, S132A, S132D, as well as the partially active mutant, S251T, and S172G, gave normal enhancement of VLDL binding and catabolism, whereas the partially active mutant S172D had markedly impaired capacity for the process; thus, there is no correlation between bridge function and lipolytic activity. A naturally occurring genetic variant hLPL, S447-->Ter, has normal bridge function. The catalytic center of LPL is covered by a 21-amino acid loop that must be repositioned before a lipid substrate can gain access to the active site for catalysis. We studied three hLPL loop mutants (LPL-cH, an enzymatically active mutant with the loop replaced by a hepatic lipase loop; LPL-cP, an enzymatically inactive mutant with the loop replaced by a pancreatic lipase loop; and C216S/C239S, an enzymatically inactive mutant with the pair of Cys residues delimiting the loop substituted by Ser residues) and a control double Cys mutant, C418S/C438S. Two of the loop mutants (LPL-cH and LPL-cP) and the control double Cys mutant C418S/C438S gave normal enhancement of VLDL binding and catabolism, whereas the third loop mutant, C216S/C239S, was completely inactive. We conclude that although catalytic activity and the actual primary sequence of the loop of LPL are relatively unimportant (wild-type LPL loop and pancreatic lipase loops have little sequence similarity), the intact folding of the loop, flanked by disulfide bonds, must be maintained for LPL to express its bridge function.

Animals↗
PubMed1996

Mouse microsomal triglyceride transfer protein large subunit: cDNA cloning, tissue-specific expression and chromosomal localization.

Microsomal triglyceride transfer protein (MTP) catalyzes the transfer of triglyceride, cholesteryl ester, and phospholipid between membranes. It is essential for the secretion of apolipoprotein B from the cell. Mutations in MTP are a major cause of abetalipoproteinemia. The mouse is a popular animal model for lipoprotein metabolism. We have cloned and sequenced mouse MTP cDNA. The DNA-deduced amino acid sequence indicates that mouse MTP contains 894 amino acids; the mouse protein shows 93, 86, and 83% sequence identity to the hamster, human, and bovine sequences, respectively. Northern blot analysis indicates that mouse MTP mRNA is expressed at high levels in the small intestine and at substantially lower levels in the liver and that it is not detectable in six other tissues examined. The mouse MTP gene has been localized to the distal region of chromosome 3 by Southern blots of interspecific backcross panels using progeny derived from matings of (C57BL/6J x SPRET/Ei)F1 x SPRET/Ei. Comparison of MTP sequences from human, bovine, hamster, and mouse indicates that the C-terminal region of MTP is better conserved than its N-terminal region.

Animals↗
PubMed1996

Functional lecithin:cholesterol acyltransferase deficiency and high density lipoprotein deficiency in transgenic mice overexpressing human apolipoprotein A-II.

The concentration of high density lipoproteins (HDL) is inversely related to the risk of atherosclerosis. The two major protein components of HDL are apolipoprotein (apo) A-I and apoA-II. To study the role of apoA-II in lipoprotein metabolism and atherosclerosis, we have developed three lines of C57BL/6 transgenic mice expressing human apoA-II (lines 25.3, 21.5, and 11.1). Northern blot experiments showed that human apoA-II mRNA was present only in the liver of transgenic mice. SDS-polyacrylamide gel electrophoresis and Western blot analysis demonstrated a 17.4-kDa human apoA-II in the HDL fraction of the plasma of transgenic mice. After 3 months on a regular chow, the plasma concentrations of human apoA-II were 21 +/- 4 mg/dl in the 25.3 line, 51 +/- 6 mg/dl in the 21.5 line, and 74 +/- 4 mg/dl in the 11.1 line. The concentration of cholesterol in plasma was significantly lower in transgenic mice than in control mice because of a decrease in HDL cholesterol that was greatest in the line that expressed the most apoA-II (23 mg/dl in the 11.1 line versus 63 mg/dl in control mice). There was also a reduction in the plasma concentration of mouse apoA-I (32 +/- 2, 56 +/- 9, 91 +/- 7, and 111 +/- 2 mg/dl for lines 11.1, 21.5, 25.3, and control mice, respectively) that was inversely correlated with the amount of human apoA-II expressed. Additional changes in plasma lipid/lipoprotein profile noted in line 11.1 that expressed the highest level of human apoA-II include elevated triglyceride, increased proportion of total plasma, and HDL free cholesterol and a marked (>10-fold) reduction in mouse apoA-II. Total endogenous plasma lecithin:cholesterol acyltransferase (LCAT) activity was reduced to a level directly correlated with the degree of increased plasma human apoA-II in the transgenic lines. LCAT activity toward exogenous substrate was, however, only slightly decreased. The biochemical changes in the 11.1 line, which is markedly deficient in plasma apoA-I, an activator for LCAT, are reminiscent of those in patients with partial LCAT deficiency. Feeding the transgenic mice a high fat, high cholesterol diet maintained the mouse apoA-I concentration at a normal level (69 +/- 14 mg/dl in line 11.1 compared with 71 +/- 6 mg/dl in nontransgenic controls) and prevented the appearance of HDL deficiency. All this happened in the presence of a persistently high plasma human apoA-II (96 +/- 14 mg/dl). Paradoxical HDL elevation by high fat diets has been observed in humans and is reproduced in human apoA-II overexpressing transgenic mice but not in control mice. Finally, HDL size and morphology varied substantially in the three transgenic lines, indicating the importance of apoA-II concentration in the modulation of HDL formation. The LCAT and HDL deficiencies observed in this study indicate that apoA-II plays a dynamic role in the regulation of plasma HDL metabolism.

Animals↗
PubMed1996

Reversal of hypercholesterolemia in low density lipoprotein receptor knockout mice by adenovirus-mediated gene transfer of the very low density lipoprotein receptor.

We have used the technique of adenovirus-mediated gene transfer to study the in vivo function of the very low density lipoprotein receptor (VLDLR) in low density lipoprotein receptor (LDLR) knockout mice. We generated a replication-defective adenovirus (AdmVLDLR) containing mouse VLDLR cDNA driven by a cytomegalovirus promoter. Transduction of cultured Hepa (mouse hepatoma) cells and LDLR-deficient CHO-ldlA7 cells in vitro by the virus led to high-level expression of immunoreactive VLDLR proteins with molecular sizes of 143 kDa and 161 kDa. Digestion of the cell extract with the enzymes neuraminidase, N-glycanase, and O-glycanase resulted in the stepwise lowering of the apparent size of the 161-kDa species toward the 143-kDa species. LDLR (-/-) mice fed a 0.2% cholesterol diet were treated with a single intravenous injection of 3 x 10(9) plaque-forming units of AdmVLDLR. Control LDLR (-/-) mice received either phosphate-buffered saline or AdLacZ, a similar adenovirus containing the LacZ cDNA instead of mVLDLR cDNA. Comparison of the plasma lipids in the 3 groups of mice indicates that in the AdmVLDL animals, total cholesterol is reduced by approximately 50% at days 4 and 9 and returned toward control values on day 21. In these animals, there was also a approximately 30% reduction in plasma apolipoprotein (apo) E accompanied by a 90% fall in apoB-100 on day 4 of treatment. By FPLC analysis, the major reduction in plasma cholesterol in the AdmVLDLR animals was accounted for by a marked reduction in the intermediate density lipoprotein/low density lipoprotein (IDL/LDL) fraction. Plasma VLDL, IDL/LDL, and HDL were isolated from the three groups of animals by ultracentrifugal flotation. In the AdmVLDLR animals, there was substantial loss (approximately 65%) of protein and cholesterol mainly in the IDL/LDL fraction on days 4 and 9. Nondenaturing gradient gel electrophoresis indicates a preferential loss of the IDL peak although the LDL peak was also reduced. When 125I-IDL was administered intravenously into animals on day 4, the AdmVLDLR animals cleared the 125I-IDL at a rate 5-10 times higher than the AdLacZ animals. We conclude that adenovirus-mediated transfer of the VLDLR gene induces high-level hepatic expression of the VLDLR and results in a reversal of the hypercholesterolemia in 0.2% cholesterol diet-fed LDLR (-/-, mice. The VLDLR overexpression appears to greatly enhance the ability of these animals to clear IDL, resulting in a marked lowering of the plasma IDL/LDL. Further testing of the use of the VLDLR gene as a therapeutic gene for the treatment of hypercholesterolemia is warranted.

Adenoviridae↗
PubMed1996

Paramedic vs private transportation of trauma patients. Effect on outcome.

BACKGROUND: Prehospital emergency medical services (EMS) play a major role in any trauma system. However, there is very little information regarding the role of prehospital emergency care in trauma. To investigate this issue, we compared the outcome of severely injured patients transported by paramedics (EMS group) with the outcome of those transported by friends, relatives, bystanders, or police (non-EMS group). DESIGN: We compared 4856 EMS patients with 926 non-EMS patients. General linear model analysis was performed to test the hypothesis that hospital mortality is the same in EMS and non-EMS cases, controlling for the following confounding factors, which are not affected by mode of transportation: age, gender, mechanism of injury, cause of injury, Injury Severity Score (ISS), and severe head injury. Crude, specific, and adjusted mortality rates and relative risks were also derived for the EMS and non-EMS groups. SETTING: Large, urban, academic level I trauma center. PATIENTS: All patients meeting the criteria for major trauma. RESULTS: The two groups were similar with regard to mechanism of injury and the need for surgery or intensive care unit admission. The crude mortality rate was 9.3% in the EMS group and 4.0% in the non-EMS group (relative risk, 2.32; P < .001). After adjustment for ISS, the relative risk was 1.60 (P = .002). Subgroup analysis showed that among patients with ISS greater than 15, those in the EMS group had a mortality rate twice that of those in the non-EMS group (28.8% vs 14.1%). After controlling for confounding factors, the adjusted mortality among patients with ISS greater than 15 was 28.2% for the EMS group and 17.9% for the non-EMS group (P < .001). CONCLUSIONS: Patients with severe trauma transported by private means in this setting have better survival than those transported via the EMS system. Large prospective studies are needed to identify the factors responsible for this difference.

Adult↗
PubMed1996

Cerebellar Doppler velocimetry in the appropriate- and small-for-gestational-age fetus.

OBJECTIVE: To compare superior cerebellar artery flow velocity waveforms in the appropriate-for-gestational-age (AGA) and the small-for-gestational-age (SGA) fetus. METHODS: Superior cerebellar artery velocity waveforms were obtained prospectively from 172 AGA fetuses at 17-41 weeks' gestation. The pulsatility index (PI) was used to quantify the waveforms. Superior cerebellar artery velocity waveforms were also obtained from 30 SGA fetuses divided into group A (n = 15), with a normal umbilical artery PI, and group B (n = 15), with an abnormal umbilical artery PI. The transverse cerebellar diameter was measured in all SGA fetuses. RESULTS: The superior cerebellar artery PI was best represented by a second-order polynomial equation [PI = 0.145 + 0.101 x (gestational age) - 0.00197 (gestational age)2]. Small-for-gestational-age fetuses of group A had a superior cerebellar artery PI in the normal range, whereas 13 of 15 fetuses of group B (86.7%) had a PI value less than the individual 95% confidence interval. The transverse cerebellar diameter in group A fetuses was in the normal range in ten of 15 cases, whereas it was in the normal range for all group B fetuses. CONCLUSION: Small-for-gestational-age fetuses with an abnormal umbilical artery PI have "cerebellar-sparing effect," as suggested by a superior cerebellar artery PI less than the normal range and a normal transverse cerebellar diameter.

Arteries↗
PubMed1996

A retrospective review of positive chlamydial cultures in emergency department patients.

This study evaluated the accuracy of diagnosis and treatment of chlamydial infection based solely on clinical presentation in the emergency department (ED). The signs and symptoms of women with chlamydial infection confirmed by cervical culture were identified and compared between appropriately treated and nontreated groups to determine which clinical features tended to lead to the correct or incorrect diagnosis. The study also determined which signs and symptoms were consistently present in the entire study group. Two hundred thirty-three charts of female ED patients with positive cervical chlamydial cultures were obtained via computerized records from the microbiology lab and reviewed retrospectively. Only 20% of the patients were correctly diagnosed as having a sexually transmitted disease and only 24% were properly treated during their initial ED visit. Although abdominal pain and vaginal discharge were the most frequent symptom and sign, only 70% and 54% of all patients had these clinical manifestations, respectively. Patients with vaginal discharge and cervical motion tenderness were significantly (P < .01) more likely to be treated in the ED. Patients with urinary tract symptoms and pregnancy were significantly (P < .01) less likely to be treated in the ED. Cervical cultures should be performed during all pelvic examinations because of the variability in the clinical presentation of chlamydial infection. A follow-up system must be in place to identify positive cultures and locate patients to ensure appropriate treatment.

Adolescent↗
PubMed1996

Drug-drug and drug-disease interactions in the ED: analysis of a high-risk population.

A study was undertaken to determine the potential for adverse drug interactions (ADIs) and drug-disease interactions (DDIs) in a high-risk population of emergency department (ED) patients and to characterize drug-drug and drug-disease interactions in terms of percentage of patients at risk from existing drug regimens, percentage of patients at risk from ED treatment, relation between number of drugs and potential for interactions, types of drugs and diseases posing greatest potential for interaction, and the differences in a general versus community hospital population with respect to these parameters. Records of 205 consecutive patients, 111 from a general hospital teaching facility ED (Facility 1) and 94 from a community hospital ED (Facility 2) were retrospectively reviewed. The records of all patients receiving three or more medications and all patients older than 50 years of age receiving two or more medications were analyzed by two computer programs for the presence of potential drug-drug and drug-disease interactions. A total of 226 potential ADIs were found in 89 patients (47%), with 50% of ADIs being related to ED treatment. A total of 94 potential DDIs were found in 44 patients (21%), with 34% of DDIs being related to ED treatment. The risk of an ADI rose from 13% for patients taking 2 medications to 82% for patients taking 7 or more medications. Eleven medications and four disease categories were identified as having particular potential for interactions. No significant differences were found between the general and the community hospital populations in these respects. ED patients taking three or more medications and patients older than 50 years of age taking two or more medications are at substantial risk for adverse drug-drug and drug-disease interactions. The risk is increased in patients taking particular drugs or having particular disease states.

Adolescent↗