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Biomedical subjects

C T Chang

Publications and source records attributed to C T Chang.

At least 37 records · Page 2Linked to original sources

Peripheral venopuncture as temporary vascular access in rhabdomyolysis-induced acute renal failure related to frog leaps: case report.

Rhabdomyolysis, or acute muscle destruction, may be accompanied by myoglobinemia, myoglobinuria, and an elevated serum creatine kinase level. The disorder has many potential causes, the most common one in otherwise healthy people being severe exercise. Rhabdomyolysis has many complications, but the most important one is acute renal failure. We describe a man with rhabdomyolysis-induced acute renal failure occurring after frog leaps. During 3 dialytic sessions, we practiced direct puncture of peripheral veins of the antecubital fossa as temporary vascular access for this patient. His renal function improved, after which he was discharged with a smooth clinical course.

Acute Disease↗

Improved cyclosporine bioavailability in black pediatric liver transplant recipients after administration of the microemulsion formulation.

Black transplant recipients are associated with low cyclosporine bioavailability, which may contribute to the poorer clinical outcomes observed with these patients. In this analysis, we compared cyclosporine exposure in black (n = 9) and nonblack (n = 18) pediatric maintenance liver transplant recipients by using steady-state pharmacokinetic profiles obtained after administration of the original and microemulsion formulations of cyclosporine. Treatment with the original cyclosporine formulation resulted in lower mean dose-normalized, area under the concentration-versus-time curve values for black compared with nonblack pediatric liver transplant recipients. On conversion to the microemulsion formulation of cyclosporine, black and nonblack patients experienced increases in cyclosporine bioavailability of 102% and 39%, respectively (P =.009 and P =.001). Because the increase in mean bioavailability was substantially greater for blacks, area under the concentration-versus-time curve values for this pediatric subpopulation became similar to those levels obtained for nonblacks receiving the microemulsion formulation for cyclosporine. When patients were further stratified by age, ethnic differences in bioavailability with the original formulation of cyclosporine were most apparent in the 1- to 5-year age group. Conversion to the microemulsion formulation resulted in a 164% increase (P =.05) in bioavailability for black patients within this age group such that, again, these levels became similar to area under the concentration-versus-time curve values obtained for young nonblacks receiving cyclosporine for microemulsion. Improvements in cyclosporine bioavailability after administration of the microemulsion formulation of cyclosporine may translate to improved long-term graft and patient outcomes for black pediatric liver transplant recipients.

Adolescent↗

Cyclosporine bioavailability of Neoral and Sandimmune in white and black de novo renal transplant recipients. Neoral Study Group.

Black renal transplant recipients have inferior graft outcomes when compared to whites. The relative bioavailability of cyclosporine (CsA) with the Sandimmune (SIM) formulation is lower in black recipients when compared to whites. To study relative CsA bioavailability in the Neoral formulation, 18 black and 78 white de novo renal transplant recipients were randomized in a multicenter, double-blind, parallel group study to receive either SIM or Neoral capsules twice a day for 12 weeks. After an overnight fast, CsA whole blood levels (TDx) were collected during 12 hours after the morning dose and 12 hours after the evening dose with a standardized meal. Pharmacokinetic profiles were obtained at the end of weeks 1, 4, 8, and 12. Initial CsA dose was 5 mg/kg twice a day; subsequent doses were titrated to target trough CsA levels. Area under the blood concentration vs. time curve (AUC), peak blood concentration (Cmax) and time to Cmax(Tmax) were obtained from 16 black and 73 white patients. Food conditions (fed and fasting) were averaged, and data was dose-normalized. For black recipients, Neoral was significantly more bioavailable than SIM only during week 1; there was also a consistent trend to higher cyclosporine bioavailability at weeks 4, 8, and 12. For whites, there were significant differences in favor of Neoral at all time periods. No significant differences in relative bioavailability were noted between races for either SIM or Neoral except for a higher Cmax in white patients given Neoral. Neoral is better absorbed than SIM in both blacks and whites. These data suggest that Neoral is the superior CsA preparation for all racial groups.

Adult↗

Small functional adrenal cortical adenoma: treatment with CT-guided percutaneous acetic acid injection--report of three cases.

Two patients with Conn syndrome and one patient with Cushing syndrome underwent computed tomography (CT)-guided tumor ablation with a total of 5-11 mL of 50% acetic acid injected into their adrenal nodule (1.3-3.3 cm in diameter). No major complications were encountered during or after the procedure. All patients were symptom free with normal laboratory test results for at least 1-year follow-up. CT images showed complete cystic change with tumor size regression. Our preliminary results suggest that percutaneous acetic acid injection is a safe and effective alternative for treatment of small functional adrenal cortical adenoma.

Acetic Acid↗

Safety of withdrawing inhaled nitric oxide therapy in persistent pulmonary hypertension of the newborn.

OBJECTIVE: Because of case reports describing hypoxemia on withdrawal of inhaled nitric oxide (I-NO), we prospectively examined this safety issue in newborns with persistent pulmonary hypertension who were classified as treatment successes or failures during a course of I-NO therapy. METHODS: Randomized, placebo-controlled, double-masked, dose-response clinical trial at 25 tertiary centers from April 1994 to June 1996. Change in oxygenation and outcome (death and/or extracorporeal membrane oxygenation) during or immediately after withdrawing I-NO were the principal endpoints. Patients (n = 155) were term infants, <3 days old at study entry with echocardiographic evidence of persistent pulmonary hypertension of the newborn. Exclusion criteria included previous surfactant treatment, high-frequency ventilation, or lung hypoplasia. Withdrawal from treatment gas (0, 5, 20, or 80 ppm) started once treatment success or failure criteria were met. Withdrawal of treatment gas occurred at 20% decrements at <4 hours between steps. RESULTS: The patient profile was similar for placebo and I-NO groups. Treatment started at an oxygenation index (OI) of 25 +/- 10 (mean +/- SD) at 26 +/- 18 hours after birth. For infants classified as treatment successes (mean duration of therapy = 88 hours, OI <10), decreases in the arterial partial pressure of oxygen (PaO(2)) were observed only at the final step of withdrawal. On cessation from 1, 4, and 16 ppm, patients receiving I-NO demonstrated a dose-related reduction in PaO(2) (-11 +/- 23, -28 +/- 24, and -50 +/- 48 mm Hg, respectively). For infants classified as treatment failures (mean duration of therapy = 10 hours), no change in OI occurred for the placebo group (-13 +/- 36%, OI of 31 +/- 11 after the withdrawal process); however a 42 +/- 101% increase in OI to 46 +/- 21 occurred for the pooled nitric oxide doses. One death was possibly related to withdrawal of I-NO. CONCLUSION: For infants classified as treatment successes, a dose response between the I-NO dose and decrease in PaO(2) after discontinuing I-NO was found. A reduction in I-NO to 1 ppm before discontinuation of the drug seems to minimize the decrease in PaO(2) seen. For infants failing treatment, discontinuation of I-NO could pose a life-threatening reduction in oxygenation should extracorporeal membrane oxygenation not be readily available or I-NO cannot be continued on transport.

Administration, Inhalation↗

Novel protein kinase C inhibitors: alpha-terthiophene derivatives.

A series of alpha-terthiophene derivatives were prepared and their protein kinase C inhibitory activity were evaluated. The aldehyde derivatives were most potent inhibitors (IC50 < 1 microM). alpha-Terthiophene monoaldehyde was inactive in the inhibitions of protein kinase A, mitogen activated protein kinase and protein tyrosine kinase.

Enzyme Inhibitors↗

Is the short insulin tolerance test safe and reproducible?

The short insulin tolerance test (SITT) is described as a simple method to measure insulin sensitivity. To investigate the safety and reproducibility of the SITT, 16 healthy volunteers underwent two SITTs within 1 week. Intravenous insulin (0.05 U kg(-1) body weight) was injected into an antecubital vein. Blood samples were collected from the contralateral antecubital vein. The insulin-induced glucose disposal rate (Kitt) was calculated from the slope of the regression line of the logarithm of blood glucose against time during the first 3-15 min. Plasma glucose concentrations fell below 2.8 mmol l(-1) in 4 of the 32 tests and below 2.2 mmol I(-1) in 1 of these 4. Five subjects had mild hypoglycaemic symptoms, three of whom had plasma glucose concentrations below 2.8 mmol l(-1) in at least one SITT. The mean Kitt was 4.2% min(-1) (range 0.8-8.4) for the first test and 3.4% min(-1) (range 0.1-6.8) for the second test. The mean within-subject coefficient of variation was 30.7%. We conclude that SITT should be applied with caution especially on insulin sensitive subjects and has poor reproducibility using 0.05 U kg(-1) body weight of insulin injection, venous sampling, uncontrolled physical activity and uncontrolled dietary composition. Whether 0.1 U kg(-1) body weight of insulin injection and arterialized venous blood sampling as in the original description of this test can improve the reproducibility of the SITT needs further investigation.

Adult↗

Thermal modeling of laser welding for titanium dental restorations.

STATEMENT OF PROBLEM: Concerns of laser welding for titanium dental prostheses are the limited depth of laser beam penetration and extensive surface damage. PURPOSE: This study used numerical heat transfer simulation to explain this behavior and offers an alternate multiple-pulsed method. MATERIAL AND METHODS: A one-dimensional finite difference analysis was used to simulate heat transfer in pure titanium and gold during laser welding with a custom-constructed software program. RESULTS: The thermal gradient profiles revealed the problem to be inherent in titanium's low thermal conductivity; gold did not have this problem. Time-elapsed multiple pulses on titanium relieved this problem by giving the energy time to diffuse into the depth of the material. CONCLUSIONS: With single-pulse laser irradiation on titanium, an increase in power could not greatly increase melting depth. The excess energy only vaporized the material surface.

Computer Simulation↗

Optimal selection procedures for abbreviated area under the curve (AAUC) of blood concentration versus time for drug blood concentration levels.

It has become common to collect blood samples from patients for phase II/III clinical trials to investigate pharmacokinetic/pharmacodynamic relationships. However, the frequency of blood samples drawn from patients is limited due to clinical or pharmacoeconomic reasons. We discuss some sampling schemes for an immunosuppressive drug in phase III studies. Selection criteria and statistical approaches are discussed to select blood-sampling time points in four scenarios from a single study and from combined multiple studies: (1) Area under the curve (AUC) only without constraint, (2) AUC and Cmax simultaneously without constraint, (3) AUC only with constraint(s), and (4) AUC and Cmax simultaneously with constraint(s).

Area Under Curve↗

Purification and properties of beta-N-Acetylhexosaminidase from cabbage.

beta-N-Acetylhexosaminidase was purified from the extract of cabbage by sequential steps of ammonium sulfate fractionation, chromatofocusing, DEAE-Sepharose CL-6B ion exchange chromatography and Sephacryl S-200 HR gel filtration. By these steps, the purity of the enzyme increased by 256 fold with a recovery of 8%. The purified enzyme was homogeneous as examined by native PAGE. It showed an optimal pH of 4, an optimal temperature of 60 degrees C and a Km of 0.94 mM for hydrolysis of pNp-beta-GlcNAc. The molecular mass of the enzyme determined from filtration through Sephacryl S-200 was 150 kDa. Three subunits with molecular mass of 64, 57 and 51 kDa were observed as determined by SDS-PAGE. NBS (0.025 mM), DEPC (3 mM) and WRK (30 mM) significantly inhibited the activity of the enzyme. The enzyme also showed activity toward pNp-beta-GalNAc, N,N'-diacetylchitobiose, N,N',N"-triacetylchitotriose and N,N',N",N"'-tetraacetyl chitotetraose but showed no activity toward pNp-alpha-GlcNAc, chitin and ethylene glycol chitin.

Brassica↗

Evidence for increased functional vascular Na+/K+ pump activity in the obese Zucker rat.

Insulin is known to stimulate Na+/K+ ATPase and to relax vascular smooth muscle. We hypothesized that vascular tone in the obese Zucker (fa/fa) rat, a hyperinsulinemic model in which hypertension can develop, may be influenced by insulin's ability to stimulate Na+/K+ ATPase at the vascular level. We studied isometric preparations of tail and femoral arteries from 10-wk-old, male obese Zucker rats, which were hyperinsulinemic but still normotensive vs. lean controls. Sensitivity to potassium-induced relaxations, an index of vascular Na+/K+ ATPase activity was significantly greater in the obese Zucker rat than control. Sensitivity to transmural-nerve-stimulation-induced contractions was decreased in the femoral and tail arteries from obese rats as compared with lean controls. Insulin (50 to 200 mU/ml) mimicked potassium-induced relaxations in the femoral artery, an effect that was significantly greater in the obese group. These data suggest that in the young hyperinsulinemic Zucker rat, insulin has a stimulatory effect on the vascular Na+/K+ pump, which may be associated with a decreased presynaptic adrenergic influence on vascular tone. Development of resistance to these vascular relaxant effects of insulin with advancing age might contribute to the onset of hypertension in this model.

Animals↗

Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose-response, multicenter study. The I-NO/PPHN Study Group.

OBJECTIVES: To assess the dose-related effects of inhaled nitric oxide (I-NO) as a specific adjunct to early conventional therapy for term infants with persistent pulmonary hypertension (PPHN), with regard to neonatal outcome, oxygenation, and safety. METHODS: Randomized, placebo-controlled, double-masked, dose-response, clinical trial at 25 tertiary centers from April 1994 to June 1996. The primary endpoint was the PPHN Major Sequelae Index ([MSI], including the incidence of death, extracorporeal membrane oxygenation (ECMO), neurologic injury, or bronchopulmonary dysplasia [BPD]). Patients required a fraction of inspired oxygen [FIO2] of 1.0, a mean airway pressure >/=10 cm H2O on a conventional ventilator, and echocardiographic evidence of PPHN. Exogenous surfactant, concomitant high-frequency ventilation, and lung hypoplasia were exclusion factors. Control (0 ppm) or nitric oxide (NO) (5, 20, or 80 ppm) treatments were administered until success or failure criteria were met. Due to slowing recruitment, the trial was stopped at N = 155 (320 planned). RESULTS: The baseline oxygenation index (OI) was 24 +/- 9 at 25 +/- 17 hours old (mean +/- SD). Efficacy results were similar among NO doses. By 30 minutes (no ventilator changes) the PaO2 for only the NO groups increased significantly from 64 +/- 39 to 109 +/- 78 Torr (pooled) and systemic arterial pressure remained unchanged. The baseline adjusted time-weighted OI was also significantly reduced in the NO groups (-5 +/- 8) for the first 24 hours of treatment. The MSI rate was 59% for the control and 50% for the NO doses (P = .36). The ECMO rate was 34% for control and 22% for the NO doses (P = .12). Elevated methemoglobin (>7%) and nitrogen dioxide (NO2) (>3 ppm) were observed only in the 80 ppm NO group, otherwise no adverse events could be attributed to I-NO, including BPD. CONCLUSION: For term infants with PPHN, early I-NO as the sole adjunct to conventional management produced an acute and sustained improvement in oxygenation for 24 hours without short-term side effects (5 and 20 ppm doses), and the suggestion that ECMO use may be reduced.

Administration, Inhalation↗

Lymphoepithelioma-like carcinoma of the uterine cervix: association with Epstein-Barr virus and human papillomavirus.

BACKGROUND: The presence of Epstein-Barr virus (EBV) has not been documented in previous reports of lymphoepithelioma-like carcinoma (LELC) of the uterine cervix by either polymerase chain reaction or in situ hybridization, and the histogenesis of the tumor remains unknown. Additionally, a relationship between human papillomavirus (HPV) and cervical LELC also has not been reported. METHODS: In this article, the authors describe the clinical and histopathologic findings for 15 patients with cervical carcinoma that had a histologic pattern of LELC. The polymerase chain reaction detected the presence of EBV and HPV DNA sequences in cervical LELC. RESULTS: All 15 tumors showed a typical syncytial growth pattern of undifferentiated cells with prominent lymphocytic infiltration. The detection rate of the EBV gene sequence in tissue samples from patients with LELC was more frequent than that in control patients with squamous cell carcinoma of the cervix (11 of 15 patients, 73.3%, vs. 4 of 15 patients, 26.7%; P = 0.01). However, the detection rate of HPV-16 and HPV-18 DNA was significantly lower in patients with LELC tumors than in patients with cervical squamous cell carcinoma (3 of 15 patients, 20.0%, vs. 12 of 15 patients, 80.0%; P = 0.001). After a median follow-up of 3.9 years (range, 1.8-5.3 years), the 15 patients showed no evidence of disease or metastasis after radical hysterectomy or radiotherapy. CONCLUSIONS: The finding of EBV associations in cervical LELC supports the hypothesis that EBV may be involved in the pathogenesis of tumors that arise in the cervix. It is possible that cervical LELC may follow a different pathway in the pathogenesis of LELC in Asian women as compared with the more common forms of squamous cell carcinoma.

Adult↗

Pharmacokinetics of an oral solution of the microemulsion formulation of cyclosporine in maintenance pediatric liver transplant recipients.

BACKGROUND: A comparison of the oral bioavailability of cyclosporine from the original formulation (CsA) and from the new formulation, cyclosporine for microemulsion (CsA-ME), was made in pediatric maintenance liver transplant patients within two age groups (group 1, ages 1-5 years; group 2, ages 6-17 years) in an open-label, multicenter, randomized crossover trial. All patients were at least 6 months past transplantation and were receiving CsA maintenance therapy. METHODS: In study period 1 (days 1 through 14), patients were administered either CsA or CsA-ME at the same b.i.d. dosage as their maintenance therapy. Upon entry into period 2 (days 15 through 28), patients were converted to the alternate formulation at a 1:1 mg dose ratio. On day 29, all patients returned to the CsA treatment administered at study entry, with follow-up on day 35. Dosage adjustments were not allowed with either CsA or CsA-ME. Twelve-hour pharmacokinetic profiling was performed at the end of periods 1 and 2. RESULTS: Both the mean area under the concentration-versus-time curve and the mean maximum blood concentration of cyclosporine-both normalized for dose-were significantly increased: by 66% and 109%, respectively, in patients receiving CsA-ME compared with those receiving CsA in group 1 and by 39% and 75%, respectively, in group 2. During this study, liver function remained stable, and serum creatinine and blood pressure did not differ significantly between treatment groups. CONCLUSIONS: This study shows increased bioavailability in all patients converted to CsA-ME, with the greatest increase seen in patients with the lowest initial cyclosporine bioavailability. The tolerability was similar between the two formulations during this study.

Absorption↗

The effect of food on the pharmacokinetics of multiple-dose terbinafine in young and elderly healthy subjects.

Pharmacokinetic (PK) parameters for terbinafine were assessed in 15 elderly and 15 young healthy subjects randomized to receive 250 mg Lamisil once daily for 15 d in a two-period, two-treatment, two-sequence, crossover (fed versus fasted) design within age groups. On each treatment day except days 8 and 15, subjects took Lamisil with food at 8:00 a.m. On days 8 and 15, subjects took the drug under either fed or fasting conditions according to treatment sequence, and 24 h PK profiles were obtained. Two analyses of the pharmacokinetic data were undertaken. In a noncompartmental analysis, AUC0-24h, Cmax, C0h, and tmax were computed for each subject on each of days 8 and 15, and the influences of food condition and age on these variables were assessed by analysis of variance. AUC0-24h and C0h were found to be larger (p < 0.5) among elderly subjects than young subjects on day 15, and tmax was prolonged (p < 0.05) under the fed condition on day 15. Similar trends on day 8, as well as generally higher exposures under the fed condition on both days, were not statistically significant. A three-compartment model fitted to the complete sequence of 33 terbinafine concentrations measured over 29 d for each subject separately permitted a within-subject assessment of the food effect that confirmed prolonged absorption and increased bioavailability (p < 0.05) under the fed condition. Across-subject comparisons of oral clearances estimated with the model also confirmed the increased exposures (lower clearances) among the elderly (p < 0.05). The drug was well tolerated in both age groups. In particular, greater drug exposure in the elderly did not result in greater toxicity, as indicated by the safety evaluations in the study.

Adolescent↗