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Biomedical subjects

K K Chan

Publications and source records attributed to K K Chan.

At least 145 records · Page 8Linked to original sources
PubMed1990

Early second surgery in ovarian cancer--improving the potential for cure or another unnecessary operation?

The presence and amount of residual disease after primary surgery is a major adverse prognostic factor in epithelial ovarian cancer [EOC]. Rapid initial cytoreduction employing second surgery early in the primary chemotherapeutic management of patients with gross residual disease has been advocated as a means of improving outcome. To evaluate the prognostic value of such an approach we have reviewed the outcome of 24 patients with gross residual disease, who were debulked to less than 2 cm residuum at a second operation, performed after three cycles of cis-platinum-based chemotherapy (a median of 14 weeks from the initial laparotomy), and compared this with an historical series of 195 patients with residual disease (70 patients with less than 2 cm residuum) who received cis-platinum but no early secondary surgery. In the control series, stage and residual disease status were important prognostic factors. There was no significant difference in patient or disease characteristics between those patients in the early second surgery group and control patients with greater than 2 cm disease (n = 125). Initially the survival curve for the early second surgery group was similar to the less than 2 cm disease group, but at about 18 months, there was a rapid deterioration until the survival parallels that of the patients with bulky disease at presentation. Early secondary surgery did not significantly prolong survival in patients with greater than 2 cm of residual disease.

Aged↗
PubMed1990

Selective salvage surgery in gastrointestinal and gynaecological cancer.

The role of reoperation with intent to excise locally recurrent disease has been evaluated in a selected group of 64 patients originally treated for primary gastrointestinal or gynaecological cancer. In 16 (25%), surgery was successful in eradicating all known sites of disease and was associated with a median survival of 23 months. Patients most suitable for reoperation were those with non-specific gastrointestinal symptoms or asymptomatic local disease. Nevertheless, those with specific symptoms may have treatable local disease or even benign conditions, and thus all with suspected local recurrence should be evaluated with a view to salvage surgery.

Colorectal Neoplasms↗
PubMed1989

Analysis of 4-hydroxycyclophosphamide by gas chromatography-mass spectrometry in plasma.

A sensitive and specific method for the quantitative analysis of 4-hydroxycyclophosphamide/aldophosphamide has been developed using gas chromatography-mass spectrometry and a deuterium-labeled analogue as the internal standard. The labile 4-hydroxycyclophosphamide/aldophosphamide and the internal standard in plasma were first converted into the more stable cyanohydrin adducts before extraction. The isolated adducts were silylated and the products analyzed by gas chromatography-mass spectrometry. The assay was found to be linear from 50 to 5000 ng/ml in plasma with a routine detection limit of 50 ng/ml. The within- and between-run standard deviations at 100 ng/ml on eight replicate determinations were found to be 6.2 and 11.9%, respectively. The extraction recovery was ca. 80%. This analytical method was used to evaluate the stability of 4-hydroxycyclophosphamide/aldophosphamide in fresh rat and pooled human plasma and to measure plasma 4-hydroxycyclophosphamide/aldophosphamide concentrations in the rat.

Animals↗
PubMed1989

Ultrasound-induced damage of veins in pig ears, as revealed by scanning electron microscopy.

Pig ear veins have been treated in situ with ultrasound at a frequency of 750 kHz and intensity of 1.5 W cm-2 (spatial average) during which the temperature in the surrounding tissues rose to 52-54 degrees C. The veins were examined by scanning electron microscopy. Gaps developed between the endothelial cells, which showed many fine perforations in their membranes. Extensive blood clots were observed in which erythrocytes had become more spherical and showed damaged membranes. Effects on membranes were also found with HeLa cells heated to 50 degrees C, and have been previously described by others in heat-treated blood vessels.

Animals↗
PubMed1989

Mode of action of the dual-action cephalosporin Ro 23-9424.

Ro 23-9424 is a broad-spectrum antibacterial agent composed of a cephalosporin and a quinolone moiety. Its biological properties were compared with those of its two components and structurally related cephalosporins and quinolones. Like ceftriaxone and cefotaxime but unlike its decomposition product, desacetyl cefotaxime, Ro 23-9424 bound at less than or equal to 2 micrograms/ml to the essential penicillin-binding proteins 1b and 3 of Escherichia coli and 1, 2, and 3 of Staphylococcus aureus. In E. coli, Ro 23-9424 produced filaments exclusively and decreased cell growth; cefotaxime produced both filaments and lysis. Like its decomposition product fleroxacin but unlike quinolone esters, Ro 23-9424 also inhibited replicative DNA biosynthesis in E. coli. In an E. coli strain lacking OmpF, growth continued after addition of Ro 23-9424, decreased after addition of cefotaxime, and stopped immediately after addition of fleroxacin. The results, together with the chemical stability of Ro 23-9424 (half-life, approximately 3 h at pH 7.4 and 37 degrees C), suggest that in E. coli the compound acts initially as a cephalosporin with intrinsic activity comparable to that of cefotaxime but with poorer penetration. Subsequent to the decomposition of Ro 23-9424 to fleroxacin and desacetyl cefotaxime, quinolone activity appears. The in vitro antibacterial activity reflects both mechanisms of action.

Anti-Infective Agents↗
PubMed1989

Full-frame transform compression of CT and MR images.

Compression algorithms based on full-frame discrete cosine transforms have achieved compression ratios as high as 10:1 to 20:1 with almost imperceptible image degradation, when applied to projection radiographs digitized with 2,048 X 2,048 X 8-bit matrices. Compared with such radiographs, images obtained with computed tomography (CT) and magnetic resonance (MR) are smaller in size, have lower signal-to-noise ratios, and, in the case of CT, have a larger dynamic range. These differences result in qualitatively different spectral properties. The authors studied the efficiency of the full-frame technique when applied to CT and MR images. They achieved excellent results, with compression ratios in the neighborhood of 5:1. The study was performed with the use of a hardware implementation of the authors' algorithm, which can compress a 512 X 512 X 12-bit image in less than 1.5 seconds.

Algorithms↗
PubMed1989

Neoadjuvant (cytoreductive) chemotherapy combined with intervention debulking surgery in advanced, unresected epithelial ovarian cancer.

Thirty-six patients with epithelial ovarian cancer, incompletely resected at primary laparotomy, were treated with one of two intensive cis-platinum-based combination chemotherapy regimens. The intention was to perform further surgical debulking (intervention debulking surgery) after three cycles in patients responding to treatment. Intervention debulking surgery was carried out in 28 of 36 patients (78%) at a median interval of 12.7 weeks from primary diagnosis. Omentectomy and total abdominal hysterectomy were the most commonly performed procedures at intervention debulking. As a result of such surgery, 16 of the 28 women (57%) were left with no macroscopic residual disease, five (18%) had less than 1 cm, four (14%) less than 2 cm residuum, and three (11%) remained with more extensive disease. Post-intervention debulking surgical complications were few, with a median postoperative hospital stay of 10 days and a median interval of 21 days from debulking surgery to resumption of chemotherapy. Neoadjuvant (cytoreductive) chemotherapy combined with early secondary surgical debulking is feasible, with little severe morbidity, and can leave a high proportion of patients free of macroscopic disease. The effect of such a program on patient survival is now being tested in a randomized study.

Adult↗
PubMed1989

Survival after negative second-look laparotomy.

Complete pathological responses, as defined by multiple negative intraperitoneal biopsies at second-look laparotomy, were recorded in 22 of 120 patients with epithelial ovarian cancer. Patients had been previously treated with either high-dose single agent cisplatinum (19) or total abdominal and pelvic irradiation (3). Nine of 21 (43%) evaluable patients developed recurrent disease after 'negative' second-look laparotomy. The median time to relapse was 15 months (3-19) and the median survival after relapse, 4 months (1-6). One patient remains alive with evidence of disease.

Adolescent↗
PubMed1988

Metabolic interaction between methotrexate and 4'-(9-acridinylamino)methanesulfon-M-anisidide in the rabbit.

The interaction between methotrexate (MTX) and a new acridine antitumor agent and potent aldehyde oxidase inhibitor, 4'-(9-acridinylamino)methanesulfon-m-anisidide (mAMSA), was investigated both in vivo and in vitro. New Zealand White male rabbits were used for the former experiments under three pharmacokinetic designs: (a) a zero order infusion of mAMSA at 9 mg/h to steady state followed by a single i.v. bolus dose of MTX at 50 mg/kg while maintaining the infusion; (b) a zero order infusion of MTX at 7 mg/h to steady state followed by a single i.v. bolus dose of mAMSA at 5 mg/kg while maintaining the infusion, and (c) a zero order infusion of MTX at 3 mg/h to steady state followed by a zero order infusion of mAMSA at 3 mg/h while maintaining the MTX infusion. In (a) while the mean AUC for MTX (15815 +/- 1317 microMmin) with mAMSA (+mAMSA) remained essentially unchanged relative to that without mAMSA (-mAMSA) at the same dose (14832 +/- 5151 microMmin), the mean AUC of the metabolite 7-hydroxymethotrexate (7-OH MTX) decreased from 9338 +/- 3057 (n = 6, -mAMSA) to 5794 +/- 1371 microMmin (n = 6, +mAMSA). Urinary excretion of 7-OH MTX also decreased from 40.3 +/- 9.5% (n = 6) (-mAMSA) to 23.8 +/- 6.1% dose (n = 6) (P less than 0.01) (+mAMSA) in 8 h with essentially no change in MTX excretion. The fractional rate conversion of MTX to this metabolite (fmi) also decreased from 0.60 +/- 0.19 (n = 6) to 0.40 +/- 0.10 (n = 6) (P less than 0.05). No change in terminal half-lives of MTX and 7-OH MTX was apparent. In (b) MTX steady state levels increased with the concomitant decrease in 7-OH MTX levels in the presence of mAMSA such that their concentration ratios (7-OH MTX/MTX) decreased to 43, 54, 75, and 76% of the pre-mAMSA values, respectively, in four rabbits. In the presence of mAMSA, clearance of MTX at steady state decreased significantly relative to those without mAMSA. Similar results were also observed in (c) except that the perturbation of MTX metabolism was more profound consistent with the experimental setting. No change in protein binding of MTX or the metabolite was apparent in the presence of mAMSA. Rabbit liver homogenate was used in the in vitro experiments which yielded a classical competitive inhibition on the double-reciprocal plot when conversion of MTX to 7-OH MTX was monitored.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗
PubMed1988

Analysis of clomesone in plasma by gas chromatography-electrolytic conductivity detection.

A sensitive and specific gas chromatographic (GC) method with electrolytic conductivity detection (ELD) for the analysis of clomesone (2-chloroethylmethylsulfonylmethane sulfonate), a new experimental antitumor alkylating agent, in plasma has been developed for the first time. Clomesone in plasma containing suitable internal standard was extracted with methylene chloride. After evaporation, the residue was analyzed by GC-ELD. Either a 15-m wide-bore DB-17 or a DB-1 column with the corresponding internal standards of propachlor or butachlor, respectively, was used. For the DB-1 column with butachlor as the internal standard, the routine assay limit was 20 ng/ml with linearity from 10 to 2000 ng/ml monitored. The within-run coefficient of variation of eight replicates at 50 ng/ml was 8.0% and the between-run coefficient of variation was 11% at 120 ng/ml. Using this assay procedure, the stability in several aqueous media and protein binding of clomesone were evaluated. In fresh mouse plasma, the half-life of clomesone was less than 1 h, although in aged pooled human plasma the drug was more stable. The mean protein binding value in mouse and human plasma was about 81-85%.

Animals↗
PubMed1988

The effect of the gene for microphthalmia (mi) on the dorsal lateral geniculate nucleus of the cinnamon mouse.

The dystrophic retina of the cinnamon mouse homozygous for the gene for microphthalmia (mi/mi) has a population of large ganglion cells. Unilateral enucleation and examination of the dorsal lateral geniculate nucleus using the Fink-Heimer technique showed that, while there was continuing degeneration argyrophilia in the dorsal lateral geniculate nucleus secondary to the retinopathy, there was additional degeneration attributable to enucleation. In addition, the pattern of degeneration indicated that the axon terminals were less mature than those of the cinnamon and heterozygous (mi/+) mice. Quantitative study of the dorsal lateral geniculate nucleus in the homozygous (mi/mi) mouse showed that the nucleus is small with fewer neurons and that the markers for protein metabolism, namely volume of nucleoli and cytoplasmic RNA, are reduced when compared to the cinnamon and heterozygous (mi/+) mice. It is concluded that the portion of the retino-geniculate pathway represented by the large ganglion cells in the retina, develops in the absence of patterned visual stimuli, but is less mature and has a more limited functional activity than controls.

Aging↗
PubMed1988

Picture archiving and communication systems (PACS) for radiological images: state of the art.

Implementation of a Picture Archiving and Communication System (PACS) is a system integration task and requires the knowledge of multidisciplinary fields. This paper reviews current PACS development with emphasis on radiological images. The following topics are covered: methods of image acquisition, image compression, storage, display, communication, and image database structure. Methods of implementation of PACS in a clinical environment as well as current operational PACS in hospitals are reviewed. A survey of private industry participating in PACS research and development are also given.

Hospital Information Systems↗
PubMed1988

Survival following intestinal obstruction in ovarian cancer.

A retrospective survey of 38 ovarian cancer patients who developed radiologically confirmed intestinal obstruction was performed. Twenty-six patients underwent surgery. In the surgical treatment group, obstruction was not due to recurrent disease in six cases. The median survival for the group as a whole was 56 days. Patients in the operative group survived significantly longer than those in the non-operative group. There was an operative mortality of 15% and major postoperative morbidity was seen in 42%. Neither the site of the obstruction nor the type of operation influenced survival. No postoperative chemotherapy responses were seen in previously treated patients.

Adult↗
PubMed1987

Identification and quantitation of alcophosphamide, a metabolite of cyclophosphamide, in the rat using chemical ionization mass spectrometry.

Alcophosphamide was identified in urine obtained from Sprague-Dawley rats treated with a 1:1 mixture of cyclophosphamide and beta-(2H4)cyclophosphamide using chemical ionization mass spectrometry and the ion cluster technique. This compound was also quantified in rat plasma using gas chromatographic-mass spectrometry under ammonia chemical ionization following administration of cyclophosphamide. Apparent terminal half life of 76.2 +/- 13.7 min and area-under-the concentration-time curve value of 24.8 +/- 8.6 micrograms min/ml were obtained for derived alcophosphamide following iv bolus administration of cyclophosphamide. Following co-administrations of unlabeled and beta-(2H4)cyclophosphamide via iv/po and iv/ip routes, apparent terminal half-lives of 68.4 +/- 16.4 and 71.8 +/- 10.1 min were found for the iv portions and 106.7 +/- 25.2 and 73.9 +/- 5.2 min for the non-iv portions, respectively, for the derived alcophosphamide. Phosphoramide mustard was found to be a major circulating and urinary metabolite in the rat following iv administration of preformed alcophosphamide which gave a plasma half-life of 1.9 h.

Animals↗
PubMed1987

In vitro protein binding of diclofenac sodium in plasma and synovial fluid.

The in vitro protein binding behavior of diclofenac sodium (sodium[o-(2,6-dichloroanilino)phenyl]acetate) in plasma and synovial fluid was investigated by equilibrium dialysis. The drug was highly protein bound (approximately 99.5%) and the extent of binding remained constant for drug concentrations of 2-10 micrograms/mL. Comparable results were obtained with human serum albumin solution (45 g/L) indicating that albumin is probably the responsible protein. The extent of binding remained relatively constant for drug concentrations of 0.25-10 micrograms/mL when albumin concentrations were greater than 25 g/L. For albumin concentrations less than 10 g/L, the extent of binding tended to decrease with increased drug concentration. This concentration (10 g/L) is substantially lower than that usually observed in plasma or synovial fluid of arthritic patients. Curvature of the Scatchard plot indicated the existence of two classes of sites. Excellent results were obtained from fitting of the data according to two classes of sites (r2 greater than 0.999). Parameter estimates (SEM) of the number of binding sites, n1 and n2, and the corresponding association constants, k1 and k2, were 2.26 (0.55), 10.20 (0.69), and 1.32 (0.54) X 10(5) M-1, and 3.71 (1.11) X 10(3) M-1, respectively. Simultaneous samples obtained from arthritic patients indicate considerably higher total protein and albumin concentrations in plasma compared with synovial fluid, but the albumin:total protein ratios were essentially the same. There was very little difference in plasma binding in arthritic patients compared with normal subjects. The extent of binding in synovial fluid samples was consistently lower than that for plasma samples (mean +/- SD of 99.5 +/- 0.2% versus 99.7 +/- 0.1%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1987

Evaluation of in vivo drug release by numerical deconvolution using oral solution data as weighting function.

Determination of in vivo drug release using compartmental model analysis is hampered by problems such as flip-flop phenomena and vanishing exponential terms. The usefulness of numerical deconvolution to estimate in vivo drug release was evaluated in this study by means of simulated data comparing solid dosage forms with a solution as a reference standard. Concentration-time data were generated using the standard linear two-compartment body model with various first-order release and absorption rate constants. Random errors of 5 and 10% were added to data sets for further analysis. The results of the study using error-free data afforded excellent agreement with the theoretical values except in one case where the release rate constant was overestimated by 6%. When random error was added to the data, the resulting in vivo release profile showed considerable fluctuation and no single rate constant could be assigned. However, further analysis showed that the method does not create additional error during the calculating process, as previously suggested, but merely reflects the inherent error added to the raw data. If the raw data are poor, no useful information can be obtained without using an arbitrary technique such as smoothing or fitting. In this regard, the time course of drug release obtained after numerical deconvolution merits investigation.

Absorption↗