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Biomedical subjects

K K Chan

Publications and source records attributed to K K Chan.

At least 19 recordsLinked to original sources
PubMed1992

Allatostatin-immunoreactive neurons projecting to the corpora allata of adult Diploptera punctata.

A monoclonal antibody against allatostatin I was used to demonstrate the allatostatin-immunoreactive pathways between the brain and the corpus cardiacum-corpus allatum complex in the adult cockroach Diploptera punctata. The antibody was two to three orders of magnitude more sensitive to allatostatin I than to the other four known members of the allatostatin family. Whole and sectioned brains in which immunoreactivity was localized with horseradish peroxidase-H2O2-diaminobenzidine reaction showed strongly immunoreactive cells in the pars lateralis of the brain with axons leading to and arborizing in the corpus cardiacum and the corpus allatum. Although many neurosecretory cells of the pars intercerebralis project to the corpora allata only, four strongly immunoreactive cells were evident here (two pairs on either side), and these did not project to the corpus cardiacum and corpus allatum but rather terminated within the protocerebrum in areas in which lateral cells also formed arborizations. Immunoreactivity was found in many other cells in the brain, especially in the tritocerebrum.

Amino Acid Sequence↗
PubMed1992

Psychiatric morbidity in a general medical ward. Hong Kong's experience.

The psychiatric morbidity of a general hospital's male medical ward in Hong Kong was studied using a one-stage single-rater method. Medical diagnoses were made according to ICD-9 on 91.5% of patients and 24% were diagnosed with DSM-III. The most common mental disorders included substance use disorder, dementia, and delirium. Of all the patients, 8.5% were not medically diagnosable and 5.3% were given only psychiatric diagnoses, the majority of which were substance use disorders.

Adolescent↗
PubMed1992

Hydrazine--a possible cause of isoniazid--induced hepatic necrosis.

Pharmacokinetic parameters of isoniazid, hydrazine (a metabolite of isoniazid), rifampicin and pyrazinamide in a 74-year-old man with pulmonary tuberculosis who died of submassive hepatic necrosis eight days after starting antituberculosis therapy were compared with those of other elderly patients who did not develop hepatotoxicity. Steady-state plasma hydrazine and rifampicin concentrations in this patient exceeded twice the mean +/- 2 SD value for the group of patients without hepatotoxicity, while concentrations for isoniazid and pyrazinamide were comparable. The findings suggest that HYD may have a role in isoniazid-induced hepatic necrosis.

Age Factors↗
PubMed1991

Phase I and pharmacologic evaluation of intraperitoneal 5-fluoro-2'-deoxyuridine.

Intraperitoneal (i.p.) 5-fluoro-2'-deoxyuridine (Floxuridine, FUdR, FdUrd) was evaluated in a phase I study at a starting level of 500 mg given on 1 day in 2 I 1.5% dialysate. Escalations within patients were allowed every other cycle. A total of 23 patients (age, 32-78 years) received 108 treatment courses. Local tolerance at all dose levels was excellent, with no cases of drug-related peritonitis being observed. Nausea and vomiting increased in severity in relation to dose and was universal at greater than 3,000 mg x 3 days. One patient each developed grade 1 mucositis as well as diarrhea at a dose of 3,000 mg x 3 days and leukopenia and thrombocytopenia at 5,000 mg x 3 days. Peritoneal fluid (PF) and plasma (PL) FdUrd profiles were monitored by an HPLC method in 13 subjects, with 7 being studied serially at 2-4 increment doses for up to 6 h. Profiles that exhibited apparent linear pharmacokinetics gave PF drug levels 2-4 logs higher than the PL counterparts, with the latter essentially declining in parallel to the former, indicating that the disposition of FdUrd from the peritoneal compartment is rate-determining. The mean terminal half-life for PF FdUrd was found to be 115 min and mean peritoneal clearance was 25 ml/min. The vast differences in drug levels and AUC found between the PF and the PL profiles suggests a high systemic clearance of FdUrd, which was confirmed in two patients receiving 2 g FdUrd by short i.v. infusion. A disproportionate increase in the plasma FdUrd levels and the corresponding AUC values was found with increasing dose, suggesting a disproportionate increase in the systemic partitioning of FdUrd when doses were escalated within a patient. Substantial levels of peritoneal 5-fluorouracil (FUra) were also detected in most of the subjects. Thus, FdUrd was found to have several desirable properties for i.p. administration: (1) a 2- to 4-log pharmacologic advantage. (2) the absence of local toxicities, and (3) a favorable antitumor spectrum and some evidence of antitumor effects in this phase I and pharmacology study. A 3,000-mg dose given in 2 1 1.5% dialysate for 3 consecutive days exhibited antitumor activity and produced no systemic toxicity except nausea and vomiting, which was controlled by antiemetics. This dose schedule is therefore recommended for phase II trials directed against small-volume disease in the peritoneal cavity, such as may be found in some stages of ovarian and gastrointestinal cancers.(ABSTRACT TRUNCATED AT 400 WORDS)

Ascitic Fluid↗
PubMed1991

Short-duration (three cycles) cisplatin combination chemotherapy with alkylating agent consolidation in advanced epithelial ovarian cancer.

Forty-eight patients with advanced epithelial ovarian cancer were treated with a two-part cytotoxic regimen consisting of three cycles of cisplatin-based induction therapy followed by five cycles of escalating doses of cyclophosphamide, all given at 3-weekly intervals. The total cisplatin dose was 225 mg/m2. Seventeen patients with optimal primary surgery received chemotherapy only, while 17 of the 31 patients with suboptimal primary surgery underwent optimal interval cytoreductive surgery at the end of induction (cisplatin) therapy. Median survival for all patients was 15.4 months. Median survival was 15 months for patients with optimal primary surgery and 22 months for patients who had optimal secondary cytoreduction. Only 10 patients suffered WHO grade 3 or greater toxicity during therapy. This study suggests that the total dose of cisplatin can be reduced for patients with advanced ovarian carcinoma, resulting in reduced overall toxicity, without compromising response or response duration. A randomized trial to test this concept is now underway.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Retrospective analysis of 318 cases of uterine sarcoma.

A study of data from 318 cases of uterine sarcoma presenting during a 10-year period (1967-1976) is reported. All but 6 of the patients had at least a 5-year follow-up (98% 5-year follow-up). Overall 5-year survival was 31%, with the major prognostic indicator being tumour stage. Despite the tendency for mixed mesodermal tumours to present in older women with more advanced disease, survival was not statistically different to those patients with leiomyosarcomas. Thus, the propensity for tumour dissemination in leiomyosarcomas should not be underestimated. Leiomyosarcomas are less likely to present with abnormal symptoms than are other sarcomas, and their occurrence as an incidental finding on histological examination underlines the need for an adequate inspection of the intra-abdominal contents at hysterectomy. The tendency to treat all sarcomas as if they were endometrial tumours may be fallacious, and an alternative classification (such as the TNM system) may be required. Recurrence of tumour tended to be at distant sites (distant:pelvic recurrence rate 3:1). Adjuvant radiotherapy is unlikely to alter distant disease foci, and thus the development of combination chemotherapeutic regimens using agents which have shown to result in tumour response seem warranted. Such trials will need to be organised on a multicentre basis to attain statistically evaluable numbers of patients.

Adult↗
PubMed1991

Pharmacokinetics of multiple daily transdermal doses of nicotine in healthy smokers.

The plasma concentration-time profiles and pharmacokinetics were characterized for nicotine and its major metabolite, cotinine, after multiple daily application of a nicotine user-activated transdermal therapeutic system (UATTS) to nine healthy smokers. The volunteers abstained from smoking 24 hr prior to and during the course of the study. A 10-cm2 system (designed to deliver 75 micrograms/cm2/hr) was applied every 24 hr for 5 days, with serial blood samples taken on Days 1 and 5 and after system removal on Day 5. Generally, the nicotine UATTS was well tolerated. Predose nicotine concentrations on Days 3 to 5 indicated that steady state was reached by Day 3. The nicotine pharmacokinetic parameters for Day 1 and Day 5 were similar: the mean (SD) AUC(0-24) values for Days 1 and 5 were 271.7 (50.7) and 311.7 (55.0) ng.hr/ml, the mean (SD) Cmax values were 16.3 (2.6) and 16.8 (2.9) ng/ml, and the median (range) Tmax values on Days 1 and 5 were 12 (9-24) hr and 12 (0-24) hr, respectively. There was only slight or no accumulation of nicotine after multiple dosing as indicated by the Day 5 to Day 1 AUC and Cmax ratios of 1.15 (0.09) and 0.98 (0.06), respectively. Overall, the UATTS system maintained relatively constant plasma nicotine concentrations and is suitable for once-daily application.

Administration, Cutaneous↗
PubMed1990

Feasibility and outcome of complete secondary tumor resection for patients with advanced ovarian cancer.

From November 1981 to July 1985, 124 women with International Federation of Gynecology and Obstetrics (FIGO) stage III ovarian cancer were treated in prospective studies of surgery and chemotherapy in our institution. Patients with no macroscopic cancer after primary surgery (n = 16) received five cycles of adjuvant cis-platinum; those with residual cancer after primary laparotomy (n = 108) underwent a second surgical debulking after three or five cycles of cis-platinum-based cytoreductive chemotherapy. Total macroscopic tumor clearance was achieved in 26 of these 108 patients. Fourteen patients with total tumor excision at primary laparotomy remain in complete clinical remission a minimum of 36 months after diagnosis, but the median progression-free interval for the other two groups was 9 and 17 months, respectively. The survival for women who have total tumor clearance only at secondary surgery after chemotherapy is inferior to that for women with primary macroscopic tumor excision followed by chemotherapy.

Adult↗
PubMed1990

Cephalosporin 3'-quinolone esters with a dual mode of action.

According to the generally accepted mechanism by which bacterial enzymes react with cephalosporins, opening of the beta-lactam ring can lead to the expulsion of a 3'-substituent. A series of dual-action cephalosporins was prepared in which antibacterial quinolones were linked to the cephalosporin 3'-position through an ester bond in the expectation that, in addition to exerting their own beta-lactam activity, these cephalosporins would act as prodrugs for the second antibacterial agent. Compared to parent cephalosporins in which the 3'-substituent was acetoxy, the bifunctional cephalosporins exhibited a broadened antibacterial spectrum, suggesting that a dual mode of action may indeed be operative.

Animals↗
PubMed1990

Effects of first-pass metabolism on metabolite mean residence time determination after oral administration of parent drug.

Metabolite kinetics after oral drug administration can be determined, without separate metabolite administration, using the concepts of mean residence time (MRT). The MRT of parent drug and metabolite after oral administration of the parent drug, MRTp,p(oral) and MRTm,p(oral), can be calculated directly from the drug and metabolite profiles. The difference between MRTm,p(oral) and MRTp,p(oral), termed Delta MRT, yields an estimate of MRT of metabolite when the metabolite is given as an iv bolus, MRTm,m(iv). The calculation is simple for drugs that are known to undergo, negligible first-pass metabolism. Correction can also be made when extent of first-pass metabolism is known. Ambiguity is encountered, however, when the degree of first-pass metabolism is unknown. When the delta MRT is negative, then first-pass metabolism must be considered. A positive value of delta MRT, on the other hand, is not a definitive indication of the absence of first-pass metabolism. It may occur in the presence or absence of first-pass metabolism. Ignoring the possibility of first-pass metabolism when a positive value of delta MRT occurs may lead to an incorrect estimate of MRTm,m(iv). The estimation error is relatively small, however, when MRTm,m(iv) much greater than MRTp,p(iv), even when first-pass metabolism is extensive. This situation may apply to the administration of a prodrug.

Biotransformation↗
PubMed1990

Application of radiotelemetric technique in evaluating diclofenac sodium absorption after oral administration of various dosage forms in healthy volunteers.

A radiotelemetric technique with the Heidelberg capsule (HC) was used to improve the quality of data generated in a bioavailability study involving an enteric-coated (EC) formulation. Further, changes in plasma levels of the drug from other dosage forms were related to changes in pH environment as determined by the HC. Eight healthy male subjects received the following treatments, 15 min after a light breakfast, according to a randomized, four-way crossover design: (A) HC and 75 mg of a diclofenac sodium aqueous buffered solution: (B) HC and one 75-mg Voltaren EC tablet; (C) HC and one 100-mg Voltaren slow-release (SR) tablet; and (D) HC alone. Each treatment was separated by a 1-week washout period. Two additional subjects subsequently received Treatment B only. Multiple peaks were observed in the drug plasma level-time profiles for the buffered aqueous solution which, in all cases, occurred before gastric emptying of the HC. The multiple peaks were not observed for the Voltaren SR tablet, but a variable absorption lag time occurred which coincided with the gastric residence time of the SR tablet. For the EC tablet the variability of individual plasma level-time profiles was drastically reduced when the time after dosing was adjusted to coincide with gastric emptying of the HC. Finally, the lag time between gastric emptying of the EC tablet and the onset of drug absorption was consistently at 1 hr for all subjects. This lag time was longer than the in vitro disintegration or dissolution times measured under USP conditions.

Administration, Oral↗
PubMed1990

Pharmacokinetics of Ro 23-9424, a dual-action cephalosporin, in animals.

Ro 23-9424 is a dual-action cephalosporin with an aminothiazolylmethoxyimino-type side chain at the 7 position and fleroxacin esterified at the 3' position. The new compound has broad and potent antibacterial activity in vitro and in vivo, reflecting contributions from both the beta-lactam moiety and the quinolone moiety. In animals, the ester bond potentially could be hydrolyzed enzymatically or nonenzymatically, to yield the active metabolites desacetylcefotaxime and fleroxacin. The extent to which Ro 23-9424 acts in vivo as a true dual-action cephalosporin, or acts as a combination of active metabolites, is therefore a function of its pharmacokinetic properties. To investigate these properties, Ro 23-9424 was administered as a single intravenous dose of 20 mg/kg of body weight to mice, rats, dogs, and baboons. Timed plasma samples were assayed by an ion-paired high-pressure liquid chromatography method that allowed detection of both intact Ro 23-9424 and fleroxacin. The pharmacokinetic parameters of Ro 23-9424 were similar to published results for cefotaxime, while concentrations of fleroxacin in plasma were low and fairly constant (about 1 to 3 micrograms/ml) in all species, suggesting that excretion of the intact molecule is a major route of elimination for Ro 23-9424, as it is for cefotaxime. For technical reasons, urinary recovery of Ro 23-9424 was not quantitated, but intact Ro 23-9424 was found in high concentrations (greater than 400 micrograms/ml) in mouse urine aspirated directly from the bladder. In all species, low concentrations of free fleroxacin in plasma persisted after the elimination of Ro 23-9424 was complete, but fleroxacin did not accumulate unduly in a 14-day multiple-dose experiment in baboons. Thus, it seems likely that the activity seen in vivo is primarily due to intact Ro 23-9424, although the low levels of free fleroxacin may also have some therapeutic significance.

Animals↗
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↗