Human caudal appendage diagnosed prenatally with ultrasound.
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Adult↗
Biomedical subjects
C Hsu
Publications and source records attributed to C Hsu.
Maternal urine beta-core hCG fragment level and small for gestational age neonates.
OBJECTIVE: To determine whether second-trimester urine beta-core fragments of hCG predict small for gestational age (SGA) neonates. METHODS: Spot urine beta-core levels were measured in 733 nonhypertensive women with singleton pregnancies who presented for amniocentesis and had karyotypically normal fetuses. The beta-core level was standardized to urine creatinine and expressed as multiples of the median. The area under a receiver operating characteristics curve was used to determine the screening efficiency of the urine analyte for prediction of small for gestational age (SGA) births. In a subgroup of cases, serum markers (alpha-fetoprotein [AFP], hCG, and unconjugated estriol) were compared using stepwise regression analysis to urine beta-core fragment for SGA prediction. RESULTS: There were 23 (3.0%) SGA neonates. The mean +/- standard deviation (SD) gestation at urine collection was 16.4 +/- 1.3 weeks and collection to delivery interval was 23.0 +/- 2.2 weeks. Mean beta-core (+/- SD) fragment levels were significantly higher in those who later had SGA infants compared with appropriately grown infants (2982.8 ng/mg creatinine versus 1447.4 ng/mg creatinine, P <.001). Stepwise logistic regression found that urine beta-core fragment and serum AFP were the only significant predictors of SGA, with statistically significant chi(2) values (P <.001 and P =.038, respectively). The urine analyte was significantly superior. Second-trimester urine beta-core fragment had a 78.3% sensitivity and 70% specificity for SGA prediction. Exclusion of preeclamptic cases resulted in a sensitivity of 84.2% and a specificity of 71.2%. CONCLUSION: Second-trimester elevated maternal urine beta-core fragment of hCG predicted SGA infants, and was superior to other serum analytes in that prediction.
Adult↗
Excess disability during morning care in nursing home residents with dementia.
Excess disability was examined in 17 nursing home residents with dementia by comparing their performance of morning care tasks under two activities of daily living (ADL) caregiving approaches-a dependence-supportive one under usual care and an independence-supportive one under functional rehabilitation. The results suggest that excess disability in severely cognitively impaired and functionally disabled residents can be reduced by increasing opportunities for independent activity, and substituting nondirective and directive verbal assists for physical assists. Further, the findings indicate that increased independence in ADL can be achieved without increasing disruptive behaviors and can foster appropriate requests for task-related help during caregiving. Functional rehabilitation, however, requires more time than usual care.
Activities of Daily Living↗
Middle cerebral artery Doppler velocimetric deceleration angle as a predictor of fetal anemia in Rh-alloimmunized fetuses without hydrops.
OBJECTIVE: The purpose of this study was to evaluate the screening performance of a new middle cerebral artery Doppler velocimetric index for the prediction of fetal anemia. STUDY DESIGN: Doppler velocimetry of the middle cerebral artery was performed before cordocentesis in 24 Rh-alloimmunized fetuses without hydrops on 52 occasions. The angle between the line describing the average slope during the diastolic phase of the cardiac cycle and the vertical, the middle cerebral artery standardized deceleration angle, was measured. The deceleration angle values were expressed in multiples of the median for gestational age. The screening performances of deceleration angle for the prediction of anemia (difference between expected mean hemoglobin level and measured value >/=2 g/dL) and severe anemia (hemoglobin deficit >/=5 g/dL) were determined. RESULTS: The mean (+/-SD) gestational age at cordocentesis was 28.6 +/- 5.7 weeks' gestation. The risk of fetal anemia increased with decreasing deceleration angle values. The sensitivity and false-positive rate for the detection of anemia in cases with no previous transfusions (one measurement per patient) were 72.0% and 13.3%, respectively; among those with one previous transfusion the values were 90.0% and 0.0%, respectively. For severe anemia the corresponding values were 100% and 0%, respectively, among those with no previous transfusions and 100.0% and 16.7%, respectively, among those with one previous transfusion. There was no risk of severe anemia when the angle was >0.9 multiples of the median. The risk of anemia was significantly reduced with an angle greater than the median for gestational age (deceleration angle >1.0 multiples of the median; relative risk, 0.09; 95% confidence interval, 0.02-0.37). The risk was significantly increased with an angle less than the median for gestational age (deceleration angle <1.0 multiples of the median; relative risk, 30.0; 95% confidence interval, 5.9-158.4). CONCLUSION: The risk of fetal hydrops is remote in the absence of severe anemia. With a new Doppler velocimetric index in the middle cerebral artery the risk of severe anemia was found to be low when the deceleration angle was >0.9 multiples of the median. Anemia can also be predicted with this index. The high sensitivities and acceptable false-positive rates support the potential clinical applicability of the method to reduce the reliance on cordocentesis in Rh alloimmunization. Our findings appear to validate the utility of the deceleration angle for the prediction of fetal anemia.
Anemia↗
Blockage of N-methyl-D-aspartate receptors decreases testosterone levels and enhances postnatal neuronal apoptosis in the preoptic area of male rats.
Sexual dimorphism has been found in the preoptic area of the hypothalamus (POA), a major site of glutamate actions via N-methyl-D-aspartate (NMDA) receptors. The sexually dimorphic nucleus of the preoptic area (SDN-POA) of male rats exhibits about seven-fold greater nuclear volume than that of females. A naturally occurring neonatal neuronal apoptosis, that can be prevented by testosterone, may contribute to this sexual difference in SDN-POA nuclear volume. Since activation of NMDA receptors in the POA induces GnRH secretion, it may be involved in both elevation of serum testosterone and prevention of neuronal death in the SDN-POA. In the present study, protein expression of NMDA receptors in the POA of male and female fetuses was quantified on the day preceding the fetal testosterone peak (embryonic day 16; ED 16). Rats were then distributed in four groups: (1) untreated males, (2) untreated females, (3) males pretreated with MK-801 (a noncompetitive NMDA receptor antagonist), and (4) females pretreated with MK-801. Serum levels of testosterone were estimated on the afternoon of ED 18. Expression of Bcl-2 and Bax, as well as neuronal apoptosis in SDN-POA, were observed on postnatal day 8. The results showed that (1) expression of NMDA receptors in the POA of male fetuses was higher than that of females on ED 16; (2) levels of testosterone were lower in MK-801 pretreated male fetuses than in intact males on ED 18; (3) expression of Bcl-2 in the POA of MK-801 pretreated male rats was significantly less than that of control males; (4) the apoptotic incidence in the SDN-POA of MK-801 pretreated male rats was significantly greater than in control males, while there was no significant difference in apoptotic incidence in the SDN-POA between MK-801 pretreated and intact females. These results suggest that the NMDA receptor is highly expressed in prenatal male fetuses, and that it might play an important role in the elevation of testosterone levels. Moreover, activation of NMDA receptors may protect SDN-POA neurons from naturally occurring neuronal death, by modulating testosterone and/or Bcl-2 expression.
Animals↗
Attenuation of sepsis-induced apoptosis by heat shock pretreatment in rats.
Apoptosis is a process by which cells undergo a form of non-necrotic cellular suicide. Although it is a programmed process, apoptosis can be induced by various stressors. During sepsis, apoptosis has been regarded as an important cause of cell death in the immune system, leading to unresponsiveness to treatment. This study was designed to investigate how prior heat shock induction can influence the rate of apoptosis in animals that have experienced sepsis. Sprague-Dawley rats were used, and experimental sepsis was induced by cecal ligation and puncture (CLP). Animals in the heated group were anesthetized and received heat shock by whole-body hyperthermia. They were sacrificed 9 h and 18 h after CLP as early and late sepsis, respectively. Apoptosis was evaluated by "DNA ladder" detection in agarose electrophoresis and Tdt-mediated dUTP nick end-labeling (TUNEL) assay. Hsp72 was detected by Western blot analysis. The results showed that the DNA ladder was detected most clearly in the thymus at the late phase of sepsis with time course dependence, while it showed less clearly in heat shock treated animals. Histopathological study by TUNEL assay obtained similar results in the thymus, where the cortex was more susceptible to apoptosis than the medulla. The Western blot analysis showed that the heat shock induced Hsp72 concomitant with an increase in Bcl-2:Bax ratio. In conclusion, heat shock pretreatment prevents rats from sepsis-induced apoptosis that may account for the better outcome of experimental sepsis. An increase in the Bcl-2:Bax ratio may in part explain the molecular mechanism of the effect of heat shock pretreatment.
Animals↗
An assessment of quality control testing in an emergency department (ED) maintained arterial blood gas analyzer
Emergency medicine by its nature requires the immediacy of laboratory testing. Point of care testing (POCT) affords the ED the fastest access to important laboratory data. To the best of the authors' knowledge, maintenance of an arterial blood gas (ABG) analyzer as a POCT device by ED personnel has not been studied. OBJECTIVE: To determine the accuracy of POCT quality control testing of an ED maintained ABG Analyzer (Gem Premier)-Instrumentation Laboratory). METHODS: We compared comprehensive quality control data obtained when the ABG analyzer was maintained by the Department of Clinical Laboratories with data obtained from the same analyzer when it was maintained by ED attending physicians. Each parameter measured by the ABG analyzer was tested using unknown control samples supplied by the College of American Pathologists. These two groups of data were then compared to the total number of obtained values submitted to the College of American Pathologists. RESULTS: Each parameter measured (n = 7) showed no difference between the two groups in regard to overall pass rate. All values for the two groups fell within the limits of acceptability when compared to all other samples analyzed by the College of American Pathologists (range 159-208 other labs). CONCLUSIONS: ED attendings are capable of quality control maintenance of an ABG analyzer as a POCT device under the quality control testing parameters set forth by the College of American Pathologists.
Journal Article↗
Diagnostic odor recognition
Many diseases, toxic ingestions, and intoxications have characteristic odors. These odors may provide diagnostic clues that affect rapid treatment long before laboratory confirmation or clinical deterioration. Odor recognition skills, similar to auscultation and palpation skills, require teaching and practical exposure. Dr. Goldfrank and colleagues recognized the importance of teaching odor recognition to emergency service providers. They proposed the "sniffing bar" method for odor recognition training. OBJECTIVES: (1) To identify the recognition rates of medically important odors among emergency care providers. (2) To investigate the effectiveness of teaching odor recognition. Hypothesis: The recognition rates of medically important odors will increase after teaching exposure. METHODS: The study exposed emergency care providers to 11 tubes of odors. Identifications of each substance were recorded. After corrective feedback, subjects were re-tested on their ability to identify the odors. Analysis of odor recognition improvement after teaching was done via chi-square test. RESULTS: Improvement in identification after teaching was seen in all odors. However, the improvement was significant only in the lesscommon substances because their initial recognition was especially low. Significant changes may improve with a larger sample size. Subjects often confuse the odors of alcohol with acetone, and wintergreen with camphor. CONCLUSIONS: The recognition rates are higher for the more-common odors, and lower for the less-common odors. Teaching exposures to the less well-known odors are effective and can significantly improve the recognition rate of these substances. Because odor recognition may affect rapid diagnosis and treatment of certain medical emergencies such as toxic ingestion, future studies should investigate the correlation between odor recognition and the ability to identify corresponding medical emergencies.
Journal Article↗
Shaken. Not stirred-temperature change and heat loss during delivery of IV fluids
Microwave-heated intravenous fluids are used in the rewarming of hypothermic patients. OBJECTIVES: To study the effect of both shaking of the microwaved bag and heat loss during delivery. METHODS: Twenty 1-liter normal saline bags were heated individually in a commercial microwave, immediately randomized into a "shaken" or a "non-shaken" group. The temperature of the fluid was recorded initially out of the bag and then at one-minute intervals by a blinded observer as the fluid ran "wideopen" through ambient temperature tubing. RESULTS: No statistically significant temperature difference occurred in any of the measured time intervals between the shaken and the non-shaken bags. Seventy percent of the overall temperature losses occurred in the first three minutes out of the microwave for both groups. CONCLUSIONS: Absence of shaking of the microwaved fluids does not produce "hot spots." Higher initial temperatures out of the bag should be considered as well as warming of the IV tubing.
Journal Article↗
The effect of carbonated beverages on colorimetric end-tidal CO(2) determination
Esophageal intubation is a significant complication of attempted airway control. Colorimetric end-tidal CO(2) monitors are highly sensitive and specific for detecting the presence of CO(2). There are reports of false-positive end-tidal CO(2) readings from esophageal intubations in patients who had ingested carbonated beverages. OBJECTIVE: To determine whether carbonated gastric contents can affect colorimetric end-tidal CO(2) readings. METHODS: End-tidal CO(2) was measured in sacrificed piglets at measured time intervals after instillation of 5-, 10-, 15-, and 20-mL aliquots of Diet Coke were placed into the stomach via a 28-French orogastric tube followed by esophageal intubation. The stomach was completely evacuated prior to each instillation and rechecked for baseline CO(2). RESULTS: Compiled data from three piglets (20-30 kg). Piglets were not ventilated or moved and determinations were measured at 20 degrees while supine. All data collected within 2 hours postmortem (table 24-1). CONCLUSIONS: The colorimetric end-tidal CO(2) turned "yellow" and did not change to blue with extended insufflations. The CO(2) of a small quantity of carbonated beverage in the stomach could be "blown off" by multiple insufflations. We conclude that esophageal intubation in the setting of recent ingestion of a carbonated beverage may result in a false-positive end-tidal CO(2) determination.
Journal Article↗
Ultrasonography evaluation of retrobulbar hematoma in bovine orbits
As the proptotic eye is pushed anteriorly against the canthis, pressure within the eye increases until there is inadequate perfusion of the eye due to the pressure effects. computed tomography (CT) scan of the orbit is the most common method of diagnosing a retrobulbar hematoma. In the trauma/emergency department setting, where the wait for a CT scan may present significant delay, bedside ultrasonography may aid in the rapid diagnosis and treatment of a retrobulbar hematoma. OBJECTIVE: To establish concordance between orbital CT scan and a bedside sonographic orbital evaluation of a retrobulbar hematoma. METHODS: Eighteen of 22 bovine orbits were injected with a 10-mL mixture of calcium-treated banked blood and contrast into the retro-orbital space thereby effecting a retrobulbar hematoma. Each orbit was studied with CT and evaluated by a neuroradiologist. Four orbits were left intact as controls. Each orbit underwent an ultrasonographic evaluation. The ultrasonographer was first allowed to study an orbit with a documented hematoma and a control. Thereafter, he was blinded to the orbits containing hematoma, did not physically examine each orbit, and completed each exam in a darkened room. The CT results were correlated with the ultrasound findings. RESULTS: 15 of 18 orbits (83%) were correctly identified as containing hematoma by ultrasound. All four intact orbits were correctly identified as being free of hematoma (kappa 0.6). CONCLUSIONS: Bedside ultrasonography may aid in the rapid diagnosis of a retrobulbar hematoma.
Journal Article↗
Efficacy of the porcine model for demonstrating pericardial effusion with real-time ultrasound
Ultrasound in emergency medicine (EM) is an invaluable tool for emergent evaluation of pericardial effusion and tamponade. The training in the recognition of such has relied on ultrasonic images or videotapes. OBJECTIVE: To evaluate the efficacy of demonstrating pericardial effusion and tamponade using real-time ultrasound. METHODS: A convenience sample of 10 Yorkshire swine were anesthetized, sedated, intubated, and monitored as per an approved EM training protocol. Using EKG guidance and a subxiphoid approach, an 18-gauge spinal needle was advanced into the pericardium until a current of injury was detected. After a slight withdrawal of the needle, an aliquot of 50-100 mL of normal saline was instilled to produce a pericardial effusion. Ultrasound was used before and after the instillation of fluid into the pericardium. The effusion was confirmed by subsequent pericardiocentesis or by visual inspection on thoracotomy. RESULTS: The instillation saline, detection of effusion, and subsequent confirmation by ultrasound, pericardiocentesis, or visual inspection were successfully performed in 10/10 pigs. Under ultrasound, one pig had a preexisting effusion. Another had much less fluid visualized. On thoracotomy, the saline was found to have leaked into the adjacent lung parenchyma. CONCLUSIONS: We conclude that the porcine model is an adequate model to demonstrate pericardial effusion using real-time ultrasound.
Journal Article↗
Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters.
It is well established that human serum paraoxonase (PON1) catalyzes the hydrolysis of organophosphate insecticides and nerve agents, as well as that of a number of aromatic carboxylic acid esters. Our laboratory has recently found a new class of PON1 substrates that includes at least 30 lactones and cyclic carbonate esters. The lactone substrates vary in their ring size from 4 to 7 atoms. Substituents on the ring carbons may enhance or reduce the rate of lactone hydrolysis. An appreciable degree of stereospecificity exists with some activities differing up to 9-fold between enantiomers (i.e., S-alpha-hydroxy-gamma-butyrolactone is hydrolyzed 5 to 9 times faster than the R form). Thiolactones are hydrolyzed less efficiently, and some lactams are potent inhibitors. Four lactone-containing drugs-spironolactone, mevastatin, simvastatin, and lovastatin-have been identified as substrates for PON1. All lactone substrates are hydrolyzed by both the Q and R isozymes of human serum PON1. However, some lactone substrates are hydrolyzed faster by the Q than R isozyme, whereas others show a reverse preference. Moreover, these new substrates include homogentisic acid lactone, mevalonic acid lactone, homocysteine thiolactone, and gamma-hydroxybutyric acid lactone-all lactone forms of endogenous compounds. It is reasonable to expect that further investigations may uncover PON1 lactone substrates that are, themselves, endogenous compounds. In this article we characterize the basic enzymatic properties of PON1's newly identified hydrolytic activities with lactone and cyclic carbonate ester substrates and compare these properties with those of representative arylesters and organophosphates.
Aryldialkylphosphatase↗
Susceptibility of rhDNase I to glycation in the dry-powder state.
The accumulated data on the glycation process in rhDNase I, formulated with lactose and stored in the dry-powder state, indicates that this protein becomes covalently modified with lactose at five of the six lysines (2, 50, 77, 157, 260) and to a lesser extent on the amino terminus. Analysis of the three-dimensional protein structure indicates that the reported requirements for the specificity of site reactivity, site accessibility, and the presence of a proton donor/acceptor group near the reaction site, are maintained in this protein. A chemical reaction in the dry-powder state may become permissible simply due to the close packing and resultant high concentrations of the reactant molecules. The reaction between reducing sugar and protein in the dried state indicates that the arrangement of molecules within the dry-powder particle allows for direct contact between all the reactants, including contacts between protein molecules, which may contribute to the completion of the covalent reaction at a surface-accessible reactive site in which the required surrounding microenvironment for self-catalysis is available on only 35% of the individual molecules. These findings should indicate that the use of reducing sugars in the formulation of an excipient for the stabilization of dried protein is not advisable, as reaction clearly occurs between the reducing sugar and protein because of the potentially reactive nature of the proteins' accessible amino groups.
Amino Acid Sequence↗
Evidence that several conserved histidine residues are required for hydrolytic activity of human paraoxonase/arylesterase.
Recent evidence has been acquired that implicates an important role for several histidine residues in the hydrolytic mechanisms of human paraoxonase/arylesterase (PON1). Following titration with diethylpyrocarbonate (DEPC), both human serum and recombinant human type Q PON1 were inhibited in respect to their hydrolytic activity in a dose-responsive manner. Human PON1 treated with varying concentrations lost hydrolytic activity, and with each histidine modified, there was an exponential drop in hydrolytic activity. The reaction was followed spectrophotometrically at 244 nm. Recombinant wild-type and C283A PON1 enzymes inhibited with DEPC and subsequently treated with hydroxylamine had partial restoration of activity. The C283A mutant lacks a free sulfhydryl group, indicating that its inactivation is due to histidine specific modification. The dose response and time course of inactivation as well as the extent of reactivation by hydroxylamine were similar for both the wild-type and mutant recombinant enzymes. Mutants of PON1 containing an asparagine substituted for each of several conserved histidine residues lost hydrolytic activity for each single substitution. The mutants of PON1 constructed and assayed for arylesterase activity were H114N, H133N, and H284N. Each single aminoacid substitution rendered the enzyme catalytically inactive. These two pieces of evidence implicate an important role for several histidine residues in the hydrolytic mechanism of PON1. Although it is unusual for a calcium dependent enzyme to require histidines for its catalytic activity, acquired data suggest such a circumstance.
Amino Acid Sequence↗
Properties of the retained N-terminal hydrophobic leader sequence in human serum paraoxonase/arylesterase.
Human serum paraoxonase/arylesterase (PON1) is HDL-associated and appears to protect low density lipoproteins (LDL) from oxidation. Mature PON1 retains its N-terminal hydrophobic signal sequence, which may be needed for binding to HDL. By site-directed mutagenesis, we created a mutant PON1 (A19A20) with a cleavable N-terminus to determine if this peptide mediated binding to lipoproteins. As a model system, we studied binding of mutant and wild type PON1s to lipoproteins in fetal bovine serum-containing expression medium and found that the wild type recombinant enzyme associated with lipoproteins whereas the A19A20 mutant did not. These results show that the N-terminus is required for binding to either apolipoproteins or phospholipids. Furthermore, we showed that wild type enzyme can bind to phospholipids directly without apolipoproteins. To determine if lipid binding is a requirement for PON1's protection against LDL oxidation, we used a copper ion-induced oxidation system and found that the wild type enzyme and A19A20 mutant showed similar reductions in both peroxide and aldehyde formation. We conclude that PON1 depends upon its N-terminal hydrophobic peptide for its association with serum lipoproteins.
Animals↗
Sex-specific expression of N-methyl D-aspartate receptor (NMDAR) in the preoptic area of neonatal rats.
The relationship between the N-methyl-D-aspartate receptor (NMDAR) and the sex-specific neurotoxicity of L-glutamate on the preoptic area (POA) of neonatal rats was studied. The NMDAR were semiquantified by western blot analysis. The kinetic change of intracellular calcium and lactate dehydrogenase (LDH) efflux were monitored as rapid and delayed toxic signals, respectively. The results showed that: (1) the NMDAR expression in POA of male rat is higher than that of females; (2) the L-glutamate (500 microM) induced a more significant elevation of intracellular calcium in neuron derived from male rat than that from female; (3) after glutamate-treatment, the LDH efflux in neuronal culture of male rat is higher than that of females. These results suggest that the quantitative difference in NMDAR between male and female rats may contribute to the sex-specific neurotoxicity of L-glutamate on the POA of neonatal rats.
Animals↗
Liver protein kinase A activity is decreased during the late hypoglycemic phase of sepsis.
Changes in protein kinase A (PKA, or cAMP-dependent protein kinase) activity in the rat liver during different metabolic phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into 3 groups: control, early sepsis, and late sepsis. Early and late sepsis refer to those animals killed at 9 and 18 h, respectively, after CLP. Hepatic PKA was extracted and partially purified by acid precipitation, ammonium sulfate fractionation, and diethylaminoethyl (DEAE)-cellulose chromatography. PKA was eluted from DEAE-cellulose column with a linear NaCl gradient. Two peaks of PKA, type I (eluted at low ionic strength) and type II (eluted at high ionic strength), were collected and their activities were determined on the basis of the rate of incorporation of [gamma-32-P]ATP into histone. The results show that during early sepsis, both type I and type II PKA activities remained unchanged. During late sepsis, type I PKA activity was decreased by 40.7-53.6%, whereas type II PKA activity was unaffected. Kinetic analysis of the data on type I PKA during the late phase of sepsis reveals that the Vmax (maximal velocity) values for ATP, cAMP, and histone were decreased by 40.7, 53.6, and 47.3%, respectively whereas the Km (substrate concentration required for half-maximal enzymatic activity) values for ATP, cAMP, and histone were unaltered. These data indicate that type I PKA was inactivated during the late hypoglycemic phase of sepsis in the rat liver. Because PKA-mediated phosphorylation plays an important role in the regulation of hepatic glucose metabolism, an inactivation of PKA may contribute to the development of hypoglycemia during the late phase of sepsis.
Animals↗