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Biomedical subjects

K K Chan

Publications and source records attributed to K K Chan.

At least 199 records · Page 11Linked to original sources
PubMed1981

Adriamycin and methyl-CCNU combination therapy in hepatocellular carcinoma: clinical and pharmacokinetic aspects.

Twenty-one patients with unresectable hepatocellular carcinoma (hepatoma) were treated with adriamycin (15-45 mg/m2 q21 D) and methyl-CCNU (75-150 mg/m2 q 63 D) with dosage adjusted for hepatic dysfunction. Objective response frequency was 14% with all responses occurring in patients with normal pretreatment bilirubin levels. Median survival of all patients was 87 days. Initial bilirubin levels greater than 2 mg/dl predicted for decreased survival (median 30 days vs. 115 days, P less than 0.05). Only moderate hematologic toxicity was observed. Plasma profiles of Adriamycin and adriamycinol were determined during 11 courses of Adriamycin administration in seven of these patients. Despite moderately elevated transaminase levels (all cases) and bilirubin levels (three cases), plasma Adriamycin profiles in hepatoma patients were not elevated (terminal half-life of 30 hours) and were indistinguishable from that of non-hepatoma patients with normal liver functions. However, delayed appearance of peak levels and prolongation of terminal half-lives were routinely observed for adriamycinol, a major metabolite of Adriamycin. This resulted ina significant increase in the CXT (concentration X time) ratio of adriamycinol/Adriamycin in hepatoma patients compared with nonhepatoma patients (2.36 +/- 2.12 vs 0.76 +/- 0.31, (P less than 0.05). We conclude that the combination of relatively mild toxicity and normal Adriamycin disposition indicates unusual tolerance to Adriamycin therapy for patients with hepatoma and cirrhosis. As a result, severe dosage adjustments of Adriamycin may not be indicated for all such patients having only moderate hepatic dysfunction.

Adult↗
PubMed1981

Fluorinated retinoic acids and their analogues. 2. Synthesis and biological activity of aromatic 4-fluoro analogues.

Ethyl (E,Z,E,E)-3,7-dimethyl-4-fluoro-9-(4-methoxy-2,3,6-trimethylphenyl)nonatetraenoate (10a) has been found to cause a marked regression of chemically induced skin papillomas in mice. A new synthesis of this compound was achieved by condensation of 4-fluoro aldehyde 7 or 8 with the aromatic phosphonium salt 9a. Several analogues (101-e) having different substituted aromatic moieties were also prepared and tested for their antipapilloma effect. The monochloro analogue 10b was shown to have comparable activity to the parent compound 10a.

Animals↗
PubMed1980

Distribution of adriamycin in cancer patients: tissue uptakes, plasma concentration after IV and hepatic IA administration.

Twenty patients with solid tumors received 30 mg/M2 of adriamycin. Various tissue samples were intraoperatively obtained from 18 patients, about 1.5--5 hours after an intravenous (IV) bolus dose. Normal liver showed the highest levels of adriamycin uptake (2.3--19.8 micrograms/g); lymph nodes were second; muscle and bone marrow, next; fat and skin had the lowest adriamycin uptake (0.04--0.40 microgram/g). Tumor tissue, excluding that with much necrosis and hemorrhaging, had adriamycin concentrations which approximated those of the liver (1.1--9.2 micrograms/g). Six patients, all with hepatic malignancies, had prolonged plasma concentration studies after IV administration; 5 also had adriamycin administered directly into the hepatic artery catheter. Adriamycin-plasma-time courses were similar, whether the drug was administered by bolus directly into the hepatic artery or peripheral vein. The concentration of metabolites after hepatic intraarterial administration was definitely higher than that after IV administration. Patients with hepatic dysfunction had delayed plasma clearance and secondarily elevated levels approximately 160 and 300 minutes after administration.

Adult↗
PubMed1980

Effect of cardiopulmonary bypass on cefazolin disposition.

Cefazolin kinetics was studied in 8 patients the day before (PREOP), during (SURG), and the day after (POSTOP) cardiopulmonary bypass (CPB) surgery. PREOP (48.6 ml/min) and POSTOP (46.6 ml/min) total body clearances were of the same order and both were greater than the SURG (27.4 ml/min) total body clearance. Since cefazolin is almost entirely eliminated by the kidney, the lower SURG clearance is a result of reduced renal elimination, as confirmed by measuring cefazolin SURG (28.7 ml/min) and POSTOP (52.9 ml/min) renal clearance. The reduction in cefazolin renal elimination was the same throughout the surgical procedure, including the period of extracorporeal circulation. Cefazolin distribution was altered by the operative procedure as evidence by a higher SURG steady-state volume of distribution. This increase in apparent cefazolin distribution volume brought about by surgery was not seen with cephalothin, which was investigated by us in a similar group of patients. The different effect of CPB surgery on cefazolin and cephalothin distribution may be due to differences in plasma protein binding.

Aged↗
PubMed1980

A comparison between midline and mediolateral episiotomies.

A randomised prospective study of 407 primiparous patients compared the consequences of midline and mediolateral episiotomies. The patients' estimates of the pain from their episiotomies were similar. Anal sphincter injury was significantly more common after a midline procedure but no rectovaginal fistulae occurred. Scarring was less noticeable after the midline incision and intercourse began earlier.

Adult↗
PubMed1980

Compensatory adrenal hypertrophic response in fetuses of calorie-malnourished rats.

Fetuses of ad libitum fed and calorie-restricted rats were unilaterally adrenalectomized on day 19. By day 20 ad libitum fed fetuses exhibited compensatory adrenal hypertrophy, but calorie-restricted fetuses did not. As this may be due to the elevated corticosteroid levels of the calorie-restricted dams, unilateral adrenalectomy was performed on fetuses of control and restricted rats bilaterally adrenalectomized on day 15. Fetuses of restricted and control rats exhibited compensatory hypertrophy. One effect of calorie restriction may be to increase the amount of maternal corticosteroids acting on the fetus.

Adrenal Cortex↗
PubMed1980

Metabolism of methotrexate in man after high and conventional doses.

Methotrexate has been found to be extensively metabolized to 7-hydroxymethotrexate in patients receiving conventional doses (less than 10 mg/kg) and high doses (greater than 10 mg/kg). Twelve hours after administration, plasma levels of this metabolite in several patients treated with low doses exceeded those of methotrexate. No 7-hydroxymethotrexate was found in CSF after CNS administration of methotrexate; however, small amounts of the metabolite was found in the CSF after intravenous high dose infusion. We conclude that methotrexate is significantly metabolized in man at all doses used clinically.

Chromatography, High Pressure Liquid↗
PubMed1979

Outcome of normal and dysfunctional labor in different racial groups.

Spontaneous labor in patients of different racial groups has been studied relating progress and outcome to whether labor was dysfunctional as defined by the partogram and action line. Forty-three percent of primigravidas and 17.6 to 25.8% of multigravidas passed the action line and had a lower admission cervical dilatation and a longer observed first stage than those patients whose labor progress remained to the left of the action line. White and black primigravidas whose labor progressed to the right of the action line had lower 1 and 5 minute Apgar scores and delivered heavier babies than those to the left. The cesarean section rates were 1.6% and 1.4% (left) and 7.6% and 18.2% (right) in white and black primigravidas, respectively. The cesarean section rate was significantly higher in black primigravidas irrespective of the relationship to the action line due to the high incidence of the complications of hypertension such as fetal distress and abruptio placentae in those in normal labor as well as those in dysfunctional labor due to cephalopelvic disproportion in those patients whose cervimetric progress went to the right of the action line.

Age Factors↗
PubMed1979

Quantitative thin-layer chromatography: thin-film fluorescence scanning analysis of adriamycin and metabolites in tissue.

A rapid, non-hydrolytic thin-film fluorescence scanning method is described for the quantitation of adriamycin and metabolites in tissues. Adriamycin, with daunomycin added as the internal standard, was extracted from tissue homogenate which contained 500 micrograms of oxalic acid, with ice-cold 0.5 N hydrochloric acid--85% isopropanol, separated by thin-layer chromatography, and quantitated in situ via a fluorescence scanning technique. This method has a sensitivity to 0.05 microgram per gram of tissue.

Animals↗
PubMed1979

Cephalothin kinetics: before, during, and after cardiopulmonary bypass surgery.

Cephalothin kinetics was studied in 5 patients the day before (PREOP), during (SURG), and the day after (POSTOP) cardiopulmonary bypass surgery. The PREOP (114 ml/min) and SURG (94 ml/min) renal clearances were of the same order but both were less than POSTOP renal clearance (248 ml/min). Cephalothin total body clearance during operation was lower (p less than 0.01) than PREOP or POSTOP clearance, with decreased metabolic clearance the primary cause. There was reduction in cephalothin elimination throughout the surgical procedure, not only in the period of extracorporeal circulation, indicating that general anesthesia had a significant influence on drug disposition. The metabolite deacetylcephalothin was rapidly formed on all 3 days and its kinetic behavior paralleled that of the parent drug.

Adult↗
PubMed1979

5-Azacytidine hydrolysis kinetics measured by high-pressure liquid chromatography and 13C-NMR spectroscopy.

Hydrolysis of 5-azacytidine, an experimental anticancer drug, in aqueous buffers was measured using a high-pressure liquid chromatographic (HPLC) procedure and a 13C-NMR method. The former utilized a 17.5-micron Aminex A-6 strong cation-exchanger column eluted with 0.4 M, pH 4.6 ammonium formate buffer at a flow rate of 0.4 ml/min. The hydrolysis sequence as well as the existence of a labile intermediate, N-formylguanylribosylurea, was unequivocally established using 6-13C-5-azacytidine and NMR spectral techniques. A reversible ring opening step to the N-formylguanylribosylurea with an equilibrium constant of 0.58 +/- 0.03 between pH 5.6 and 8.5, followed by an irreversible formation of guanylribosylurea, was found by HPLC. The data confirm previous assumptions on the hydrolytic kinetics. The pH dependency of hydrolysis was examined, and the hydrolysis profile gave a normal V shape with the most stable pH at 7.0. Rather stable intravenous dosage forms can be formulated.

Azacitidine↗
PubMed1979

Fluorinated retinoic acids and their analogues. 1. Synthesis and Biological activity of (4-methoxy-2,3,6-trimethylphenyl)nonatetraenoic acid analogues.

(4-Methoyx-2,3,6-trimethylphenyl)nonatetraenoic acids, esters, and amides (analogues of retinoic acid) bearing a fluorine atom(s) or a trifluoromethyl group on the polyene side chain were synthesized. The biological activities of these compounds and of 10-, 12-, and 14-fluororetinoic acid esters were evaluated in vivo in a chemically induced mouse papilloma test; the toxicities were assessed in an in vivo mouse hypervitaminosis A test. Antipapilloma activity greater than the parent nonfluorinated ester was found for 1c (ethyl 12-fluororetinoate) and 23 and 39 (aromatic 4- and 6-fluororetinoid esters, respectively). A similar increase in antipapilloma activity was observed for 71 and 72, the aromatic 4- and 6-fluororetinoic acids, respectively, relative to 2 and for 73 (aromatic 4-fluororetinoid amide) relative to 4.

Animals↗
PubMed1979

One-way mixed lymphocyte culture: differences between Chinese and Caucasian stimulator cells.

In "standardized" one-way mixed lymphocyte cultures, a pool of blood lymphocytes from randomly chosen Chinese subjects was a significantly stronger stimulus to Caucasian responder lymphocytes than was a pool of allogeneic cells from Caucasians. In contrast, Chinese lymphocytes did not respond more strongly to Caucasian cells than to Chinese cells. This could not be explained by an inherent racial difference in the capacity of blood lymphocytes to undergo blastogenesis. The implications of these findings for organ transplantation and routine testing of cell-mediated immune function are discussed.

Adult↗
PubMed1978

GLC--mass spectrometry of several important anticancer drugs I: pertrimethylsilylation and O-methoxime formation.

Procedures are reported for the formation of pertrimethylsilyl and pertrimethylsilyl methoxime derivatives of the aglycones of doxorubicin, daunorubicin, carminomycin, chromomycin A3, and mithramycin. The mass spectra are consistent with the formation of these derivatives. Fragmentation patterns highly specific for these derivatives are proposed, and the potential application for the identification of metabolites of these compounds is discussed.

Antibiotics, Antineoplastic↗
PubMed1978

GLC--mass spectrometry of several important anticancer drugs II: doxorubicin and daunorubicin aglycone analogs.

By using previously developed pertrimethylsilylation and methoxime formation procedures, the GLC--mass spectra of pertrimethylsilyl and pertrimethylsilyl methoxime derivatives of 12 doxorubicin and daunorubicin glycone analogs, mostly synthesized in this laboratory, were studied. The fragmentation pathways were readily interpretable, and the patterns were highly specific for corresponding structural changes, thus supporting the previous contention that this method has potential for the identification of doxorubicin and daunorubicin metabolites. Four aglycone metabolites were identified, on the basis of their GLC--mass spectra, in the hydrolysate of the 1-butanol extract of bile obtained from a doxorubicin-treated rabbit.

Animals↗