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Biomedical subjects

A C Chang

Publications and source records attributed to A C Chang.

At least 109 records · Page 6Linked to original sources
PubMed1995

Successful use of transesophageal echocardiography during extracorporeal membrane oxygenation in infants after cardiac operations.

We report the use of transesophageal echocardiography in infants after cardiac operations while supported on extracorporeal membrane oxygenation. In all patients transesophageal echocardiography provided valuable information when standard transthoracic echocardiographic evaluation was limited by poor acoustic windows. This report describes the application of transesophageal echocardiography during extracorporeal membrane oxygenation after cardiac operations.

Cardiac Surgical Procedures↗
PubMed1995

Identification of patients with hypertrophic cardiomyopathy at high risk for sudden death.

Patients with hypertrophic cardiomyopathy are at increased risk for sudden death. Recent studies have improved our ability to risk-stratify such patients and have elucidated several potential mechanisms of sudden death and syncope. Certain noninvasive tests, such as signal-averaged electrocardiography and measurements of cardiac autonomic function and QT/QT dispersion, are often abnormal in hypertrophic cardiomyopathy, but are not useful for risk stratification. Myocardial ischemia determined by exercise thallium scintigraphy, however, identifies young patients with hypertrophic cardiomyopathy who are at high risk for cardiac arrest and syncope. Nonsustained ventricular tachycardia on ambulatory Holter monitoring in the absence of symptoms of impaired consciousness is associated with a benign prognosis and is not predictive of sudden death. Conversely, ventricular tachycardia induced at electrophysiologic study identifies adult patients with hypertrophic cardiomyopathy who subsequently experience sudden death. Finally, characterization of the natural history of the genetic defects will increasingly become an integral part of risk evaluation in hypertrophic cardiomyopathy.

Adult↗
PubMed1995

Pulmonary vascular resistance in infants after cardiac surgery: role of carbon dioxide and hydrogen ion.

OBJECTIVE: The objective of this study was to describe the effects of altering arterial PCO2 and pH on pulmonary vascular resistance in infants after cardiopulmonary bypass for cardiac surgery. DESIGN: Prospective study (with each patient as his or her own control). SETTING: Cardiac intensive care unit in a children's hospital. PATIENTS: We studied 15 infants (ages ranging from 0.4 to 15.6 months; median 5.7) who were mechanically ventilated during the immediate postoperative period after corrective cardiac surgery. INTERVENTIONS: The study was designed to have the following three stages: In the baseline stage, the initial postoperative hemodynamic parameters were stabilized and body temperature was normalized. In the hypercarbia stage, with FIO2 at 0.40, the rate of ventilation was decreased to produce an end-tidal CO2 level of > 55 torr (> 7.3 kPa). This stage established a clinical model of increased pulmonary vascular resistance. With the minute ventilation held constant in order to maintain a constant PaCO2, the arterial pH was increased by administration of a 4-mEq/kg iv dose of sodium bicarbonate (sodium bicarbonate stage). Arterial blood gas and hemodynamic determinations were obtained after a 10-min stabilization period at each stage. Drug infusions were not altered during the study period. MEASUREMENTS AND MAIN RESULTS: In the hypercarbia stage (stage 2), the mean PaCO2 increased from 36 +/- 5 torr (4.8 +/- 0.7 kPa) (at baseline) to 55 +/- 16 torr (7.3 +/- 2.1 kPa) (p < .01). As a result, the mean arterial pH decreased from 7.48 +/- 0.05 to 7.31 +/- 0.03 (p < .01). During this stage, the mean pulmonary arterial pressure increased from 21 +/- 6 to 30 +/- 8 mm Hg (p < .01) but the cardiac index remained unchanged (3.7 +/- 1.2 to 3.8 +/- 1.2 L/min/m2). Pulmonary vascular resistance index increased from 4.1 +/- 2.0 to 6.0 +/- 3.1 U.m2 (p < .01). After the administration of sodium bicarbonate (stage 3), the arterial pH increased to 7.44 +/- 0.06 (p < .05), while the PaCO2 was unchanged. The pulmonary vascular resistance index decreased to 3.1 +/- 1.5 U.m2 (from 6.0 +/- 3.1 U.m2; p < .01) as a result of both a decrease in mean pulmonary arterial pressure (to 26 +/- 6 mm Hg; p < .01) and a concomitant increase in cardiac index to 5.1 +/- 1.6 L/min/m2 (p < .01). CONCLUSIONS: Increasing the arterial pH by the administration of sodium bicarbonate both lowers the pulmonary arterial pressure and increases the cardiac index, resulting in a decrease in pulmonary vascular resistance. These changes were observed without alteration in PaCO2. Metabolic alkalosis may have a role in the treatment of increased pulmonary vascular resistance in infants after cardiopulmonary bypass for cardiac surgery.

Carbon Dioxide↗
PubMed1995

Milrinone: systemic and pulmonary hemodynamic effects in neonates after cardiac surgery.

OBJECTIVE: To evaluate the hemodynamic effects of intravenous milrinone in neonates with low cardiac output after cardiac surgery. DESIGN: Prospective cohort study. SETTING: Pediatric cardiac intensive care unit. PATIENTS: Ten neonates with low cardiac output (cardiac index of < or = 3.0 L/min/m2) after corrective cardiac surgery were enrolled in the study. The neonates' ages ranged from 3 to 27 days (median 5) and their weights ranged from 2.0 to 4.8 kg (median 3.7). The diagnoses were: transposition of the great arteries (n = 6, including two with ventricular septal defect), tetralogy of Fallot (n = 2), truncus arteriosus (n = 1), and total anomalous pulmonary venous connection (n = 1). INTERVENTIONS: Milrinone was intravenously administered in three stages: a) baseline stage, in which patients had a stable hemodynamic status, ventilation and gas exchange, hemostasis, and body temperature; b) loading stage, in which a 50 microgram/kg intravenous loading dose of milrinone was administered over 15 mins; and c) infusion stage, in which milrinone was continuously infused at 0.50 microgram/kg/min for 30 mins. MEASUREMENTS AND MAIN RESULTS: The mean heart rate increased after the loading stage (149 +/- 13 to 163 +/- 12 beats/min, p < .01) but slowed during the infusion stage (154 +/- 11 beats/min, p < .01 vs. loading stage). Both right and left atrial pressures were lowered in all ten neonates. Compared with baseline, mean arterial pressure decreased after the loading stage (66 +/- 12 to 57 +/- 10 mm Hg, p < .01) but did not decrease further at the infusion stage (59 +/- 12 mm Hg); changes in mean pulmonary arterial pressure were comparable. Cardiac index increased from a baseline mean of 2.1 +/- 0.5 to 3.0 +/- 0.8 L/min/m2 (p < .01) with the loading stage, and was maintained at 3.1 +/- 0.6 L/min/m2 during the infusion stage. Systemic vascular resistance index decreased below baseline values with loading, from 2136 +/- 432 to 1336 +/- 400 dyne.sec/cm5.m2 (p < .01), and pulmonary vascular resistance index also decreased with loading dose of milrinone, from 488 +/- 160 to 360 +/- 120 dyne.sec/cm5.m2 (p < .01). There was no change in the rate pressure index, an indirect measurement of myocardial oxygen consumption, throughout the study. CONCLUSIONS: Administration of milrinone in neonates with low cardiac output after cardiac surgery lowers filling pressures, systemic and pulmonary arterial pressures, and systemic and pulmonary vascular resistances, while improving cardiac index. Milrinone increases heart rate without altering myocardial oxygen consumption. While milrinone appears to be effective and safe during short-term use, the relative distribution of inotropic and vasodilatory properties of milrinone remains to be elucidated.

Cardiac Output, Low↗
PubMed1995

Relief of left ventricular outflow tract obstruction following inadvertent left ventricular apical pacing in a patient with hypertrophic cardiomyopathy.

Dual chamber (DDD) pacing improves symptoms and relieves left ventricular (LV) outflow obstruction in hypertrophic cardiomyopathy. The ventricular lead is usually positioned at the right ventricular apex (RVA). We report a patient in whom the ventricular lead had inadvertently penetrated the septum, resulting in DDD pacing from the LV apex. However, after 3 months, obstruction was reduced and symptoms were improved. Pacing from LV apex and RVA resulted in comparable hemodynamic improvement. This case suggests that the asynchronous wave of septal contraction, originating from the apex, irrespective of ventricular site, accounts for the reduction in LV outflow obstruction.

Adult↗
PubMed1995

Alterations in p53 and p16INK4 expression and telomere length during spontaneous immortalization of Li-Fraumeni syndrome fibroblasts.

Normal cells have a strictly limited growth potential and senesce after a defined number of population doublings (PDs). In contrast, tumor cells often exhibit an apparently unlimited proliferative potential and are termed immortalized. Although spontaneous immortalization of normal human cells in vitro is an extremely rare event, we observed this in fibroblasts from an affected member of a Li-Fraumeni syndrome kindred. The fibroblasts were heterozygous for a p53 mutation and underwent senescence as expected at PD 40. In four separate senescent cultures (A to D), there were cells that eventually recommenced proliferation. This was associated with aneuploidy in all four cultures and either loss (cultures A, C, and D) or mutation (culture B) of the wild-type (wt) p53 allele. Loss of wt p53 function was insufficient for immortalization, since cultures A, B, and D subsequently entered crisis from which they did not escape. Culture C has continued proliferating beyond 400 PDs and thus appears to be immortalized. In contrast to the other cultures, the immortalized cells have no detectable p16INK4 protein. A culture that had a limited extension of proliferative potential exhibited a progressive decrease in telomere length with increasing PD. In the culture that subsequently became immortalized, the same trend occurred until PD 73, after which there was a significant increase in the amount of telomeric DNA, despite the absence of telomerase activity. Immortalization of these cells thus appears to be associated with loss of wt p53 and p16INK4 expression and a novel mechanism for the elongation of telomeres.

Animals↗
PubMed1994

kappa Opioid receptor selective affinity labels: electrophilic benzeneacetamides as kappa-selective opioid antagonists.

2-(3,4-Dichlorophenyl)-N-methyl-N-[1-(3- or 4-substituted phenyl)-2-(1-pyrrolidinyl)ethyl]-acetamides 3-6 were synthesized as kappa-selective affinity labels and evaluated for opioid activity. In smooth muscle preparations, the non-electrophilic parent compound (+)-S-2 and the affinity labels 3-6 behaved as kappa agonists in that they were potently antagonized by norbinaltorphimine (norBNI). In addition to the high binding affinity and selectivity of the 3-isothiocyanate 3 (DIPPA) to kappa opioid receptors, wash studies have suggested that this involves covalent binding. In the mouse tail-flick assay, the 3- and 4-substituted isomers (3 and 5, respectively) produced long-lasting antagonism of the antinociceptive effect of the kappa opioid agonist, (+/-)-trans-2-(3,4-dichlorophenyl)-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]acetamide ((+/-)-U50,488). In contrast, the non-electrophilic parent compound (+)-S-2 and the fumaramate derivative 4 were devoid of antagonist activity in the tail-flick assay. At substantially different doses, DIPPA (3) and the 4-isothiocyanate 5 also produced antinociception in the mouse abdominal stretch assay. In addition, DIPPA and the 3-fumaramate methyl ester 4 had improved in vivo kappa-selectivities compared to the unsubstituted parent compound (+)-S-2 and the para-substituted derivative 5. The improved kappa-selectivities of 3 and 4 and the different agonist and antagonist potencies of 3 and 5 may be explained respectively by the existence of multiple kappa agonist binding sites and distinct agonist and antagonist binding sites. In view of the antagonist selectivity and the apparent irreversible binding of DIPPA to kappa receptors, it may serve as a useful pharmacologic or biochemical tool to investigate kappa opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1994

Constitutive activation of integrin alpha 4 beta 1 defines a unique stage of human thymocyte development.

Our understanding of thymocyte development and of the positive and negative selection events involved in shaping the repertoire of mature T lymphocytes has been greatly facilitated by the use of transgenic and gene knockout animals. Much less is known about the factors that control the homing and population of the thymus by T cell precursors and the subsequent migration of developing thymocytes through the thymic architecture. As the integrins represent a candidate group of cell surface receptors that may regulate thymocyte development, we have analyzed the expression and function of alpha 4 beta 1 and alpha 5 beta 1 on human thymocytes. A major portion of double positive (CD4+ CD8+) human thymocytes express alpha 4 beta 1 in a constitutively active form and adhere to fibronectin and vascular cell adhesion molecule 1. alpha 4 beta 1 expression is similar on adherent and nonadherent populations, thus, activity reflects the receptor state and not simple expression. The adherent cells are immature, expressing high levels of CD4/CD8 and low levels of CD3 and CD69. In contrast, nonadherent cells possess the phenotype of thymocytes after positive selection, expressing intermediate levels of CD4 and/or CD8 and high levels of CD3 and CD69. The adherent population fails to respond to activation with anti-CD3 and fibronectin, whereas nonadherents exhibit an alpha 5 beta 1-dependent proliferation. Differential regulation of alpha 4 beta 1 and alpha 5 beta 1 receptors may provide a mechanism controlling cellular traffic, differentiation, and positive selection of thymocytes.

Antibodies↗
PubMed1994

Assignment of two alpha 2 adrenoceptor subtype genes to murine chromosomes.

Subtype-specific probes to the murine homologs of the human ADRA2B and ADRA2C genes were prepared by PCR amplification and used to map these two genes to mouse chromosomes 2 and 5, respectively. Both genes mapped in regions of mouse chromosomes consistent with their map location in humans. These mapping results provide additional insights into the linkage relationships among members of this important gene family.

Animals↗
PubMed1994

Management and outcome of low birth weight neonates with congenital heart disease.

In 100 consecutive neonates with birth weights < or = 2500 gm (range, 540 to 2500 gm; median, 2200 gm), major congenital heart disease (excluding patent ductus arteriosus, isolated atrial septal defect, and ventricular septal defect) was diagnosed between January 1987 and January 1991; 46 had ductus-dependent lesions. Of the 100 neonates, 30 had genetic aberrations or significant associated congenital anomalies. The four most common cardiac diagnoses were tetralogy of Fallot with or without pulmonary atresia (n = 16); coarctation of the aorta (n = 12); transposition of the great arteries (n = 11); and common atrioventricular canal (n = 11). The hospital survival rate for the entire group of 100 neonates was 70%. The patients were separated into three groups on the basis of the time of intervention. Group 1 (early intervention) included 62 infants. These neonates (including 31 with ductus-dependent lesions) had surgical or catheter intervention during the initial hospitalization (median age, 9 days), all at weights < or = 2500 gm. The hospital survival rate was 81% (50/62); survival rates for palliation (78%, 18/23) and for correction (82%, 32/39) were similar. There were 26 neonates in group 2 (late intervention). These neonates did not have surgical intervention during the initial hospitalization. All were managed medically; survivors were discharged and had surgical procedures later (at a median age of 4.3 months). Six neonates (23%) died during medical management; all 20 survivors returned and had surgical procedures, with 90% survival. Overall survival rate for this group was 69% (18/26). The remaining 12 patients (group 3) had complicating features that precluded intervention; none survived. On the basis of these results, we conclude that early intervention, even with corrective surgery, can be performed in low birth weight neonates with an acceptable mortality rate. Prolonged medical therapy to achieve further weight gain did not appear to improve the survival rate.

Cardiac Catheterization↗
PubMed1994

Radiofrequency catheter atrioventricular node ablation in patients with permanent cardiac pacing systems.

Following successful RF ablation of the atrioventricular node (AVN), temporary pacing is necessary prior to insertion of a permanent pacemaker. The risks and inconvenience of temporary pacing could be avoided if a permanent pacemaker is already in place. This study reports the feasibility of RF ablation of the AVN in 27 patients (age 55 +/- 17 years, 15 males) with hypertrophic cardiomyopathy and pacemakers. Indications for AVN ablation were drug refractory atrial fibrillation in 24 patients, and rapid AVN conduction preventing septal pre-excitation by DDD pacemaker, inserted for relief of left ventricular outflow obstruction, in three cases. Sixteen patients had DDD devices and 11 patients had VVI devices. During RF ablation, each pacemaker was programmed to VVI at 50 beats/min. The ablation catheter was manipulated with fluoroscopic control to avoid close contact with or disturbance of the pacing leads. In 16 patients, RF ablation was performed immediately following pacemaker implantation but in the remaining patients, the AVN was ablated 6-32 months after pacemaker implantation. The power applied was 25-50 watts for a duration of 15-60 seconds. AV block was achieved in all cases but required 34 +/- 36 applications for 16.5 +/- 17.8 min/case. RF ablation consistently caused reversion to magnet rate in one patient and temporarily inhibited appropriate pacemaker discharge in another. However, no other pacemaker or lead malfunction was detected so that temporary pacing was not required in any case. At 6 +/- 3 months follow-up, all pacemakers were functioning normally without alteration in pacing parameters from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Recombinant E. coli-derived tissue factor pathway inhibitor reduces coagulopathic and lethal effects in the baboon gram-negative model of septic shock.

Excessive coagulation is a typical response to the vascular injury occurring in gram negative sepsis. This study evaluated the pharmacological effects of the use of a recombinant Escherichia coli derived form of tissue factor pathway inhibitor (ala-TFPI) in a baboon model of septic shock. Several doses of ala-TFPI were administered either 30 or 120 min after the initiation of a lethal intravenous infusion of E. coli into baboons. Treatment at 30 min with either 2.7 or 7.4 mg/kg of ala-TFPI resulted in the same survival rates and attenuation of both the coagulation response and cellular injury, as measured by clinical chemistry. When administration of ala-TFPI was delayed for 120 min, a dose of ala-TFPI protein continued to provide a benefit to survival. Ala-TFPI reduced the drop in mean systemic arterial pressure compared to control baboons in addition to partially attenuating the coagulopathic response. Baboons given ala-TFPI also maintained lower levels of plasma interleukin-6 (IL-6) and thrombin-antithrombin. These results suggest that the site of action of the protein may involve the later stage components of the coagulation and inflammatory pathways.

Animals↗
PubMed1994

Study of septic shock in the non-human primate: relationship of pathophysiological response to therapy with anti-TNF antibody.

Therapy with anti-TNF antibody is reported to be effective in preventing morbidity and mortality in baboons given lethal infusions of Escherichia coli. Treated animals survived, and organ histopathology was absent when antibody was administered early after lethal infusions of E. coli. The present study explored the relationship between antibody dosage, pathophysiology, and survivability from shock. When antibody dose was decreased lungs, kidneys, adrenals, spleen, and liver were injured as shown by increased vascular congestion, hemorrhage, edema, and necrosis of tissues. Survival was also affected. All animals treated with 15 mg/kg antibody survived as reported earlier; less than 60% survived with 7.5 mg/kg; 9% survived with 5.0 mg/kg, and all died with 1.5 mg/kg. Serum concentrations of interleukin-6 (IL-6) increased markedly as dose of antibody decreased. The increases in concentrations of IL-6 were associated with increases in morbidity and mortality following E. coli administration.

Adrenal Glands↗
PubMed1994

Retrospective description and experimental reconstitution of three different responses of the baboon to lethal E. coli.

This paper is divided into a retrospective descriptive section in which we report on three distinctly different and spontaneous responses of the baboon to LD100 Eschericia coli observed over the last 6 years. This section is followed by an experimental section in which we reproduce the immediate and delayed responses based on hypothetical mechanisms. In the descriptive section, we arbitrarily divided all the non-survivor animals on which we had sufficient data into three groups based on duration of survival (i.e., 12 hr or less, immediate, 12 to 30 hr, intermediate, and 30 hr or more, delayed). The natural history and pathophysiology of the 12 hr or less group matched that of capillary leak syndrome with a rapid fall in blood pressure, rise in hematocrit, massive edema, and congestion with leukocyte sequestration in both lung and liver, with only limited adrenal cortical hemorrhage. The 12 to 30 hr group matched the natural history of a consumptive hemorrhagic diatheses with a biophasic blood pressure response, limited change in hematocrit, a severe consumptive coagulopathy, severe adrenal cortical hemorrhage, and a moderate renal cortical tubular necrosis, but limited renal cortical thrombosis. The greater than 30 hr group matched the natural history of a microvascular thrombotic (hemolytic uremic) syndrome with a stable blood pressure, a fall in hematocrit associated with a massive renal cortical thrombosis with a severe medullary, and cortical tubular necrosis. We did not analyze these groups further (i.e., type of intervention etc.) once we found that time of survival correlated with a unique clinical syndrome, because based on these observations, we hypothesized that we could reproduce the immediate capillary leak and pulmonary failure, and the delayed microvascular thrombosis and renal failure syndromes experimentally. We reproduced the immediate (< 12 hr) and delayed (> 30 hr) responses by infusion of either tumor necrosis factor or C4b binding protein with sublethal E. coli. This provides models of the immediate and delayed as well as the intermediate responses to E. coli for study of mechanism and the efficacy of therapeutic interventions.

Animals↗
PubMed1994

In vitro transformation of Li-Fraumeni syndrome fibroblasts by SV40 large T antigen mutants.

Transfection of SV40 early region DNA into normal human diploid fibroblasts (NHDFs) increases their proliferative potential to a limited extent. We have investigated the roles of the SV40 large T antigen (LTAg) regions responsible for binding to the protein products of the retinoblastoma (Rb) and p53 genes in this temporary escape from senescence. Patients encoding LTAg mutants were transfected into NHDFs and into Li-Fraumeni syndrome (LFS) fibroblasts which are heterozygous wild-type (wt)/null-mutant for p53. A LTAg mutated in the p53-binding region (T402DE) had greatly reduced efficiency of focus formation, and a p110Rb-binding mutant was unable to induce any foci. T402DE-induced NHDF foci senesced at the same time as untransfected cells, but the equivalent LFS foci all had increased proliferative potentials, with the greatest increase being seen in clones that lost the wt p53 allele. One LFS clone expressed the T402DE mutant during focus formation, but later lost both the T402DE DNA and the wt p53 allele. We conclude that SV40-induced focus formation in NHDFs requires the LTAg p110Rb-binding region, and is enhanced by loss of normal p53 function. In contrast, increased proliferative potential is primarily due to loss of p53 function.

Antigens, Polyomavirus Transforming↗
PubMed1994

Stability of HBV DNA in cell lines and nude mouse-passaged tissues derived from human hepatocellular carcinoma.

Human hepatitis B virus (HBV) infection has been closely linked to the occurrence of hepatocellular carcinoma (HCC). Hepatoma cell lines and nude mouse-passaged hepatoma tissues were used in this report to study the HBV DNA status in these cells after passage. DNA was extracted from seven hepatoma cell lines and three nude mouse passaged HCC lines. Southern blot hybridization technique was performed with either cloned HBV whole genome or subgenomic DNA fragments as probes to analyze the presence of HBV DNA. Integration of HBV DNA fragments was detected in one mouse passaged tissue, R. Hybridization with HBV subgenomic DNA revealed that there were some DNA rearrangements of the integrated HBV DNA in R. However, the integrated HBV DNA could not be detected in the cell line derived from R after in vitro cultivation for 2 years. Both episomal form and integrated HBV DNA were detected in a cell line NTU-h3. Episomal form HBV DNA ih NTU-h3 changed after several passages. HBV DNA in NTU-h3 was unstable after in vitro cultivation. Therefore, we concluded that the presence of HBV DNA might not be essential for the maintenance of the tumorigenicity of hepatoma and the nude mouse system was more stable for maintaining HBV DNA in HCC.

Animals↗