Therapeutic drug monitoring of phenytoin. Rationale and current status.
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Humans↗
Biomedical subjects
T Chang
Publications and source records attributed to T Chang.
Emphysematous pyelonephritis in a polycystic kidney. Demonstration by ultrasound and computed tomography.
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Emphysema↗
Pyeloduodenal fistula: report of 2 cases.
Pyeloduodenal fistula is a rare event, which can occur spontaneously or be caused by trauma. We present two such cases, of which, one was complicated by percutaneous nephrolithotomy for a right renal stone and the other occurred spontaneously from right renal and perirenal abscesses. Its etiology, pathogenesis, clinical manifestations, diagnosis and treatment are discussed. We emphasize that with the increasing use of interventional uroradiologic procedures, particularly percutaneous nephrolithotomy, we may encounter more traumatic pyeloduodenal fistulae.
Abscess↗
[Duplex Doppler ultrasound of internal jugular vein ectasia. Case report].
A seven-year-old boy, who complained of painless swelling mass over the right neck on exertion, was diagnosed as right internal jugular vein ectasis by the duplex Doppler ultrasound. The caliber of the right internal jugular vein was prominently dilated when Valsalva maneuver was done, the duplex Doppler ultrasound showed an essentially flat wave from that indicated the swelling mass to be a venous structure. The clinical manifestation, etiology, pathological findings and diagnostic methods of the internal jugular vein ectasia were reviewed with emphasis on the advantages of duplex Doppler ultrasound in confirming the diagnosis.
Child↗
Preservation of sexual function in men during radical pelvic surgery.
Recent neuroanatomical findings making it possible to intraoperatively identify the branches of the pelvic plexus that innervate the corpora cavernosa have been used to modify standard radical prostatectomy and cystoprostatectomy to prevent postoperative sexual dysfunction.
Cystostomy↗
Development of a radioimmunoassay for the anthrapyrazole chemotherapy agent CI-937 and the pharmacokinetics of CI-937 in rats.
The anthracyclines daunorubicin and doxorubicin are cancer chemotherapy agents that complex DNA and are widely utilized clinically. Cumulative cardiotoxicity, however, limits their prolonged use. The novel anthrapyrazole agent, CI-937, which has shown exceptional in vivo anticancer activity and reduced cardiotoxicity in preclinical models has been developed at the Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co. Due to an inability to extract CI-937 reproducibly from biological fluids, high-performance liquid chromatography is not a feasible analytical method. We developed a radioimmunoassay by conjugating CI-937 to porcine thyroglobulin to elicit rabbit antibody which was used with a radioiodinated derivative. The assay was validated for rat plasma using 50 microliters of sample with a resulting limit of quantitation of 100 pg/ml. By dilution of samples the assay can quantitate CI-937 levels up to 16 micrograms/ml. The antiserum is very specific as evidenced by cross-reactivities of less than 0.4% for structural analogues and less than 0.004% for any of the commonly used cancer chemotherapy agents. Analysis of plasma samples from rats treated with a single 5 mg/kg i.v. dose indicated that CI-937 is rapidly cleared from plasma and is extensively bound to tissues.
Animals↗
Attenuation of low dose phenobarbital induction of hepatic microsomal aminopyrine N-demethylase activity in rats by cimetidine.
Cimetidine, a substituted imidazole, is an inhibitor of hepatic cytochrome P-450-mediated drug metabolism in rats and humans. We investigated the effect of cimetidine on phenobarbital induction of hepatic microsomal aminopyrine N-demethylase activity in the rat. Phenobarbital induction of aminopyrine N-demethylase was log-linear in the range of 1-6 mg/kg/day and the ED50 was approximately 3 mg/kg/day. Cimetidine 75 mg/kg (four times a day) attenuated the induction of aminopyrine N-demethylase activity by 58% in low dose (3 mg/kg/day) but not in high dose (40 mg/kg/day) phenobarbital treated rats. This result could not be explained by residual inhibition of enzyme activity by cimetidine and suggests that cimetidine affects the induction of hepatic cytochrome P-450 by low dose phenobarbital.
Aminopyrine N-Demethylase↗
Quantitative whole-body autoradiographic determination of tacrine tissue distribution in rats following intravenous or oral dose.
Tacrine (1,2,3,4-tetrahydro-9-acridinamine) has been employed in diverse clinical situations but has recently been of considerable interest for the treatment of cognitive deficits associated with senile dementia (Alzheimer's disease). The present studies examined tissue distribution of radiolabeled tacrine by quantitative whole-body autoradiography. Tacrine radioequivalents were widely distributed to tissue following iv or peroral dose, with an apparently prolonged absorption phase following po dose. The presence of high levels of activity in kidneys and ureters indicates a major role for urinary excretion, but there is also evidence for biliary excretion and direct secretion of compound or metabolites into the intestinal lumen. Tacrine was rapidly taken up into the brain and demonstrated regional localization to cortex, hippocampus, thalamus, and striatum. Although the inhibition of acetylcholinesterase by tacrine is well documented, regional uptake in brain did not correlate consistently with distribution of the enzyme, supporting suggestions by others that the alleged action of tacrine in treatment of senile dementia may be by mechanisms other than cholinesterase inhibition.
Administration, Oral↗
CT of pineal tumors and intracranial germ-cell tumors.
We reviewed 59 cases of pineal tumors and intracranial germ-cell tumors. Most pineal tumors occurred in the first three decades of life, with the exception of pineocytomas, which were seen at a mean age of 34. A male preponderance was noted in the various pineal tumors, except for pineocytomas. The most common tumor of the pineal region was germinoma, which usually showed high density with homogeneously intense enhancement after IV administration of contrast medium. An increased prevalence of pineal calcification was also a feature of pineal germinomas. No characteristic CT features could be found to differentiate among pineal choriocarcinoma, germinoma, embryonal carcinoma, yolk-sac tumor, pineocytoma, and pineoblastoma. CT is useful in detecting intracranial tumors, but the definite diagnosis should depend on pathologic examination and detection of tumor markers in the serum and CSF.
Adolescent↗
In vitro metabolism of isoxicam by horseradish peroxidase.
1. Disposition studies in vivo in animals and man indicate that hydroxylation of the isoxazole methyl group of isoxicam is the major route of metabolism. 2. Recently, N-methylsaccharin, saccharin, and an open-ring sulphonamide have been identified as additional isoxicam metabolites. 3. Attempts to form these metabolites in vitro with hepatic microsomal incubations were unsuccessful. However, incubations of isoxicam with purified horseradish peroxidase resulted in the formation of N-methylsaccharin and the open-ring sulphonamide in good overall yield (28% in 1 h). 4. A possible mechanism for HP-catalysed conversion of isoxicam to N-methylsaccharin and open-ring sulphonamide is presented.
Animals↗
Lack of dose proportional pharmacokinetics for CI-937, an anthrapyrazole DNA intercalator, in mice.
The time course of CI-937, an anthrapyrazole DNA intercalator, was studied in plasma of mice after single intravenous doses of 1.2, 8, 12, and 15 mg/kg (1/10 the LD10, 2/3 the LD10, LD10, and LD50). CI-937 concentrations in plasma were determined by a sensitive radioimmunoassay capable of quantifying 0.1 ng/ml. Area under the plasma concentration-time curve increased less than proportionally to dose. Time-averaged plasma clearance was dose-dependent, increasing from 31.1 to 63.6 ml/min/kg over the 1.2 to 12 mg/kg dose range. Terminal half-life in plasma ranged from 11 to 25 days. Fraction plasma protein bound was 69 to 76% from 10 to 10,000 ng/ml, which suggests the nonlinear behavior was not due to saturable protein binding. Potential mechanisms include autoinduction of metabolism and dose-dependent reabsorption from the gastrointestinal tract or kidneys.
Animals↗
Carp gamma-crystallins with high methionine content: cloning and sequencing of the complementary DNA.
The nucleotide sequences of gamma-crystallin cDNAs cloned from the common carp (Cyprinus carpio) have been determined. The amino-acid sequences derived consist of two polypeptides with 177 and 172 amino-acid residues for gamma-m1 and gamma-m2, respectively. They exhibit unusually high methionine contents: 12.4% for gamma-m1 and 14% for gamma-m2. Comparison of both fish gamma-crystallins with bovine gamma-II crystallin reveals that they are similar in structure. The striking features of both fish gamma-crystallins are as follows. (1) Both of them retain the 'conserved' residues, i.e., Tyr-6, Glu-7, Gly-13, Ser-34 and their equivalents in other motifs. (2) they possess the second aromatic residue at position 11. Both of these structural features are considered to be the major factors in stabilizing the folded hairpin structure of the protein. (3) The variable residues in the core region of C-terminal domain are almost all sulfur-containing amino acids, i.e., methionine or cysteine. (4) 30% of the surface hydrophobic groups are composed of methionine. The last two unusual features have been found so far only in these two fish gamma-crystallins. The high methionine content may make an important contribution to the protein stability of fish gamma-crystallins.
Amino Acid Sequence↗
Guided-wave measurement of the one-way speed of light.
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Journal Article↗
Enhanced pirmenol elimination by rifampin.
The potential for drug-drug interaction between pirmenol, an extensively metabolized antiarrhythmic agent, and rifampin, a potent inducer of hepatic drug-metabolizing enzymes, was evaluated in 12 healthy adults. After administration of a single 150-mg oral dose of pirmenol on day 1, pirmenol plasma and urine concentrations were determined for 72 hours postdose. On days 4 through 17, subjects received 600 mg of rifampin once daily. On day 15, subjects were given a second single 150-mg oral dose of pirmenol concomitantly with rifampin, and plasma and urine concentrations were again determined. Coadministration of rifampin with pirmenol resulted in significant (P less than .005) changes in pirmenol pharmacokinetic parameters. A sixfold decrease in pirmenol AUC and sevenfold increase in the apparent plasma clearance of pirmenol were found. Elimination half-life decreased more than twofold. Based on these findings, pirmenol dosage adjustment will be required when pirmenol is given to patients concurrently receiving rifampin. These results suggest that the administration of pirmenol with other agents that induce hepatic enzymes may result in accelerated pirmenol clearance.
Adult↗
Quantitative whole-body autoradiographic analysis of the tissue distribution of orally-administered [14C]cholesterol in hypercholesterolemic rats.
The cholesterol-fed rat model has been used to examine the distribution of radiolabeled cholesterol by whole-body autoradiographic and quantitative videodensitometric methods. Animals were fed a hypercholesterolemic diet for 7 days, and were subsequently killed at 3, 6, 12, 24, or 72 h following a single oral dose of [14C]cholesterol. Maximum blood and tissue levels were observed at 12 h, while liver and adrenals were the most intensely labeled tissues. Liver maintained consistently high levels over the course of the study, while activity in other tissues declined moderately by 72 h, indicating the long half-life of cholesterol radioequivalents in tissue. The results of these experiments suggest that autoradiographic examination of cholesterol distribution in animals treated with pharmaceutical agents designed to modify cholesterol absorption or clearance will be useful in providing supplemental or confirmatory information on the drugs' mode of action.
Animals↗
Pharmacokinetics of intravenous and oral enoxacin in healthy volunteers.
In a randomized, crossover study single 200 and 800 mg doses of enoxacin were administered intravenously and orally to eight healthy normal volunteers. Plasma and urinary enoxacin concentrations and urinary concentrations of its oxo-metabolite were determined by high-performance liquid chromatography. At the end of a 1 h intravenous infusion period, mean enoxacin plasma concentrations were 1.8 and 6.6 mg/l for the 200 and 800 mg doses, respectively. Disappearance of enoxacin from the systemic circulation appeared to follow first order kinetics with harmonic mean elimination half lives of 3.3 and 4.7 h for the 200 and 800 mg dose groups, respectively. However, enoxacin kinetics were dose-dependent over the dose range tested. Total body clearance decreased and elimination half-life increased with increasing dose. The volume of distribution was large (2.8 l/kg) and independent of dose. Absorption of orally administered enoxacin was rapid, with mean peak plasma concentrations (1.0 and 3.8 mg/l) appearing one to two hours postdose. Absolute oral bioavailability averaged 89%, and was independent of the dose administered. Cumulative enoxacin urinary recovery accounted for 51-53% of the dose irrespective of dose or route of administration. Enoxacin renal clearance exceeded creatinine clearance indicating that urinary excretion of enoxacin involved both glomerular filtration and tubular secretion. Urinary excretion of the oxo-metabolite averaged 16% and 11% following the 200 and 800 mg dose, respectively. Evidence of dose dependent decrease in enoxacin renal clearance and formation of its oxo-metabolite was observed. Enoxacin was well tolerated during the course of the trial. The present study shows that enoxacin pharmacokinetics can be characterized by apparent first order elimination, large volume of distribution, and dose-dependent increase of half life. Oral absorption of enoxacin is complete over a wide dose range.
Administration, Oral↗
Ocular bruits in ischemic cerebrovascular disease.
A total of 72 ocular bruits in 50 patients with symptoms of atherothrombotic ischemic cerebrovascular disease were studied with continuous-wave Doppler ultrasonography with spectrum analysis (Dopscan). Fourteen patients also had conventional angiography, and 14 had digital subtraction angiography. Ocular bruits by augmentation flow due to occlusion (seven bruits, 9.7%) or tight stenosis (17 bruits, 23.6%) of the contralateral internal carotid artery accounted for only 24 ocular bruits (33.3%). In contrast, siphon stenosis ipsilateral to the ocular bruit was a very common finding. All 14 patients studied with conventional angiography had variable degrees of siphon stenosis ipsilateral to the ocular bruits; there was one angiography failure. We conclude that siphon stenosis can cause ocular bruit alone or can act in combination with augmentation flow by contralateral carotid occlusion or tight stenosis. The difference in their relative occurrence in our patients compared with previous reports probably reflects racial differences in the distribution of stenotic or occluded lesions of the carotid artery between our patients and Caucasian patients. The ocular bruit was the only auscultatory finding in more than a quarter of our patients (14 of 50, 28%).
Aged↗
Metabolic labeling of human thyroglobulin with [35S]sulfate: incorporation into chondroitin 6-sulfate and endoglycosidase-F-susceptible carbohydrate units.
To study the incorporation of sulfate into thyroglobulin, human thyroid tissue was incubated with [35S]sulfate. Labeled thyroglobulin was purified by ammonium sulfate precipitation, gel exclusion chromatography, and equilibrium density gradient centrifugation, the last of these specifically to remove proteoglycans. [35S]Sulfate was found in thyroglobulin with low density, indicating that sulfate was incorporated into newly synthesized molecules before their iodination. Chondroitin ABC lyase and chondroitin AC lyase released equal amounts of [35S]sulfate, demonstrating the presence of chondroitin units, and TLC showed this to be predominantly chondroitin 6-sulfate. Additional [35S]sulfate was released by endoglycosidase-F (Endo-F), but not by Endo-H. The Endo-F-sensitive sulfate-labeled complex carbohydrate units were heterogeneous, one fraction passing through a Concanavalin-A-Sepharose column without delay and another fraction showing weak affinity for the lectin. More than 90% of the incorporated [35S]sulfate was accounted for by the chondroitin ABC lyase and Endo-F-sensitive fractions. Thus, human thyroglobulin contains sulfate in at least three types of carbohydrate units, 1) chondroitin 6-sulfate units, 2) complex units with no affinity for Concanavalin-A (tri- or tetraantennary forms), and 3) complex units with weak affinity for Concanavalin-A (biantennary forms).
Ammonium Sulfate↗