Biomedical subjects
Publications and source records attributed to C Hsu.
Self-assembly of millimeter-scale polyhedra, with surfaces patterned with solder dots, wires, and light-emitting diodes, generated electrically functional, three-dimensional networks. The patterns of dots and wires controlled the structure of the networks formed; both parallel and serial connections were generated.
Phosphine (PH(3)), from hydrolysis of aluminum, magnesium and zinc phosphide, is an insecticide and rodenticide. Earlier observations on PH(3)-poisoned insects, mammals and a mammalian cell line led to the proposed involvement of oxidative damage in the toxic mechanism. This investigation focused on PH(3)-induced oxidative damage in rats and antioxidants as candidate protective agents. Male Wistar rats were treated ip with PH(3) at 2 mg/kg. Thirty min later the brain, liver, and lung were analyzed for glutathione (GSH) levels and lipid peroxidation (as malondialdehyde and 4-hydroxyalkenals) and brain and lung for 8-hydroxydeoxyguanosine (8-OH-dGuo) in DNA. PH(3) caused a significant decrease in GSH concentration and elevation in lipid peroxidation in brain (36-42%), lung (32-38%) and liver (19-25%) and significant increase of 8-OH-dGuo in DNA of brain (70%) and liver (39%). Antioxidants administered ip 30 min before PH(3) were melatonin, vitamin C, and beta-carotene at 10, 30, and 6 mg/kg, respectively. The PH(3)-induced changes were significantly or completely blocked by melatonin while vitamin C and beta-carotene were less effective or inactive. These findings establish that PH(3) induces and melatonin protects against oxidative damage in the brain, lung and liver of rats and suggest the involvement of reactive oxygen species in the genotoxicity of PH(3).
The optimal treatment of localized large-cell lymphoma of the stomach remains controversial. In particular, the role of surgical resection of the primary tumor needs to be clearly defined. We have reviewed all patients with a diagnosis of gastric lymphoma and treated in our institutions between 1988 and 1998. Patients fulfilling the following criteria were included in this study: (1) histologically proven large-cell lymphoma of the stomach; (2) adequate pathological materials and complete clinical information for analysis; (3) clinical stage I/II disease according to the Musshoff modification of Ann Arbor system; and (4) received primary chemotherapy alone with anthracycline- or anthracenedione-containing regimens (group A) or curative surgery followed by adjuvant chemotherapy (group B). There were 38 and 21 patients in group A and group B, respectively. All pertinent clinicopathologic features were similar between the two groups of patients, except that patients of group A had significantly more stage II-2 disease (P = 0.004). Of group A, among 36 patients who could be evaluated for response to chemotherapy, there were 29 complete and 1 partial responses, with an overall response rate of 83.3% (95% CI, 71.1-95.5%). The projected 5-year relapse-free survival (RFS) and overall survival (OS) were 86.0% (95% CI, 73.3-98.7%) and 72.6% (95% CI, 57.0-88.2%), respectively. On the other hand, the projected 5-year RFS and OS of group B were 77.9% (95% CI, 58.0-97.8%) and 77.8% (95% CI, 57.9-97. 7%), respectively, not significantly different from that of group A. Our data suggest that systemic chemotherapy alone may be a reasonable alternative treatment for stage I/II large-cell lymphoma of the stomach. Resection of the primary tumor before systemic chemotherapy does not appear to improve the cure rate of this group of patients.
The present study was designed to investigate the role of NF-kappaB in influencing the outcome of sepsis modulated by previous heat shock treatment. Sepsis was induced in rats by cecum ligation and puncture (CLP) method, which manifests two distinct clinical phases: an initial hyperdynamic phase (9 h after CLP, early sepsis) followed by a hypodynamic phase (18 h after CLP, late sepsis). Rats of heated group were treated by whole body hyperthermia 24 h prior to the CLP operation. Lymphocytes were collected during the early and late sepsis phases. The expressions of Hsp72, p65 and I-kappa B were evaluated by Western blot and immunochemical analysis. NF-kappaB activity was detected by EMSA. The results showed that NF-kappaB activation was initiated during early sepsis and apparently suppressed during late stage of sepsis. Previously treated by heat shock, late-sepsis rats emerged with high preservation of p65 expression and NF-kappaB activity, while Hsp72 was over-expressed. In conclusion, down-regulation of NF-kappaB activity during late sepsis could be attenuated by pretreatment of heat shock through the preservation of p65 expression. The results may provide a mechanistic explanation for the improved outcome to polymicrobial sepsis of rats that are preconditioned with heat shock, as well as a novel highlight for therapeutic intervention of severe infection.
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.