Total parenteral nutrition for a terminally ill patient?
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Abdominal Neoplasms↗
Biomedical subjects
K Chan
Publications and source records attributed to K Chan.
Simultaneous assay for isoniazid and hydrazine metabolite in plasma and cerebrospinal fluid in the rabbit.
A simple procedure for the simultaneous determination of isoniazid and hydrazine metabolite in plasma and cerebrospinal fluid in the rabbit is described. The assay involves organic extraction before and after derivatization of the two compounds and the internal standard, phenelzine. The extract of the derivatized compounds was evaporated to dryness at 40 degrees C and the residue redissolved in the mobile phase (50 microliters). A 25-microliters aliquot was injected into the liquid chromatograph and eluted with acetonitrile-water-triethylamine (70:30:0.4, v/v) containing 5 mM heptanesulphonic acid on a 30-microns C8 precolumn linked to a 10-microns C18 microBondapak column at ambient temperature (25 +/- 1 degree C). The eluate was detected by ultraviolet detection at 320 nm.
Animals↗
Determination of pethidine and its major metabolites in human urine by gas chromatography.
Procedures based on gas chromatography were established to determine pethidine and its major metabolites in human urine. The chromatographic system consisted of a glass column packed with 3% (w/w) SP2250 on Chromosorb W (80-100 mesh) linked to a nitrogen-phosphorus detector. Diethyl ether was used as the extraction solvent. Pethidinic and norpethidinic acids, and their conjugated metabolites (after beta-glucuronidase treatment) were determined after conversion into pethidine and norpethidine by acid-catalysed esterification. The retention times of pethidine, norpethidine and chlorpheniramine (internal standard) were 3.3, 4.5 and 7.5 min, respectively. The amount of unchanged drugs and metabolites excreted varied considerably among the subjects. The mean 24-h urinary recoveries in eight patients of pethidine, norpethidine, pethidinic acid, norpethidinic acid, and the glucuronides of pethidinic and norpethidinic acids were 6.62 +/- 5.05, 4.33 +/- 1.19, 18.9 +/- 6.29, 9.10 +/- 4.26, 15.1 +/- 3.02 and 7.57 +/- 2.28%, respectively. This indicates that the major metyabolic pathways of pethidine in the eight patients were hydrolysis followed by conjugation. Over 60% of the dose was accounted for in 24 h after intramuscular administration of 1 mg/kg pethidine.
Chromatography, Gas↗
A simple method for the preparation of gallium chloride from the citrate solution.
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Citrates↗
Role of adrenoceptors in the potentiation of opioid antinociception by ephedrine and phenylpropanolamine in mice.
Ephedrine and phenylpropanolamine (PPA) (10 mg/kg) pretreatment intraperitoneally (IP) potentiated the antinociceptive effects of subcutaneous (SC) morphine (5 mg/kg) and codeine (60 mg/kg) in mice using the tail-flick method. Prior administration of propranolol (6 mg/kg, SC) 10 min before the sympathomimetics had no effect on this action. Phentolamine (2 mg/kg, SC), on the other hand, abolished the enhancing effects of ephedrine and PPA on opioid antinociception. Prazosin (2 mg/kg, SC) pretreatment did not significantly affect the potentiation of opioid antinociception by ephedrine and PPA, while yohimbine (4 mg/kg, SC) effectively antagonised this enhancing effect. None of the adrenoceptor antagonists had any effect on the tail-flick reaction time on their own in the doses used, and neither did they affect opioid antinociceptive responses. It is concluded that ephedrine and PPA potentiate the antinociceptive effects of morphine and codeine, most probably through an action on alpha 2-adrenoceptors.
Analgesics, Opioid↗
Disposition of propofol infusions for caesarean section.
The disposition of propofol was studied in women undergoing elective Caesarean section. Indices of maternal recovery and neonatal assessment were correlated with venous concentrations of propofol. After induction of anaesthesia with propofol 2.0 mg.kg-1, ten patients received propofol 6 mg.kg-1.hr-1 with nitrous oxide 50 per cent in oxygen (low group) and nine were given propofol 9 mg.kg-1.hr-1 with oxygen 100 per cent (high group). Pharmacokinetic variables were similar between the groups. The mean +/- SD Vss = 2.38 +/- 1.16 L.kg-1, Cl = 39.2 +/- 9.75 ml.min-1.kg-1 and t1/2 beta = 126 +/- 68.7 min. At the time of delivery (8-16 min), the concentration of propofol ranged from 1.91-3.82 micrograms.ml-1 in the maternal vein (MV), 1.00-2.00 micrograms.ml-1 in the umbilical vein (UV) and 0.53-1.66 micrograms.ml-1 in the umbilical artery (UA). Neonates with high UV concentrations of propofol at delivery had lower neurologic and adaptive capacity scores 15 minutes later. The concentrations of propofol were similar between groups during the infusion but they declined at a faster rate in the low group postoperatively. Maternal recovery times did not depend on the total dose of propofol but the concentration of propofol at the time of eye opening was greater in the high group than the low group (1.74 +/- 0.51 vs 1.24 +/- 0.32 micrograms.ml-1, P less than 0.01). The rapid placental transfer of propofol during Caesarean section requires propofol infusions to be given cautiously, especially when induction to delivery times are long.
Adult↗
Stable isotope method for studying transdermal drug absorption: the nicotine patch.
A stable isotope-labeled drug method was used to determine the absolute bioavailability and absorption kinetics of a transdermal nicotine-delivery system (TTS). TTSs are being developed as an adjunct to smoking-cessation therapy. Deuterium-labeled nicotine was infused for 24 hours simultaneously to TTS application in cigarette-abstinent smokers. In 11 subjects with good patch adhesion, an average systemic dose of 19 mg nicotine was delivered, with average absolute bioavailability of 82%. The rate of nicotine absorption was maximal between 6 and 12 hours after TTS application and declined thereafter, plateauing between 16 and 24 hours at 62% of the maximal rate. Ten percent of nicotine was absorbed after the TTS was removed, demonstrating a reservoir for nicotine in the skin. Our study demonstrates the applicability of stable isotope methods in understanding the clinical pharmacology of transdermal drugs.
Administration, Cutaneous↗
Disposition of propofol at caesarean section and in the postpartum period.
We have compared the pharmacokinetics of a bolus dose of propofol 2 mg kg-1 in eight patients undergoing Caesarean section with those in eight postpartum patients undergoing sterilization by mini-laparotomy. The Caesarean section group had a total body clearance of (median) 31.5 (range 24.4-53.3) ml min-1 kg-1, apparent volume of distribution at steady state 5.10 (2.46-6.61) litre kg-1 and mean residence time 161 (52.3-251) min; values for the post-partum group were 33.8 (21.5-47.2) ml min-1 kg-1, 5.17 (3.47-8.09) litre kg-1 and 163 (92.3-238) min, respectively. The 95% confidence interval for the umbilical venous to maternal venous ratio of propofol at delivery was 0.62-0.86. Plasma protein binding studies showed there was less unbound propofol in maternal plasma (1.28-2.29%) compared with umbilical plasma (2.08-3.88%) (P less than 0.01). Neonatal concentrations of propofol were greater than maternal concentrations at 2 h and were in the range 0.05-0.11 micrograms ml-1 at 4 h.
Anesthesia, Obstetrical↗
An overview of the use of anti-tuberculous drugs in Uganda and Hong Kong.
Anti-tuberculous (Anti-TB) chemotherapy in Uganda is outlined. Its pattern of use and the subsequent shortcomings have prompted the need for the present review. A collateral comparison to that of Hong Kong was run to emphasize the correlation of anti-TB chemotherapy with economic development and regional variation in the population of the two areas. Tuberculosis of the central nervous system (CNS) has a high fatality rate. In the search for a more comprehensive anti-TB dosage regimen, the difficulty in treating tuberculosis of the CNS has attracted special attention with emphasis on the fate of anti-TB drugs across the meninges. The choice of a method for drug analysis in routine therapeutic drug monitoring for a country is likewise determined by factors similar to those for the anti-TB regimen. Uganda needs an inexpensive, precise and selective method for TB treatment tailored to its financial and manpower resources.
Child↗
Dehiscent temporomandibular joint.
The appearance of an acute effusion in a well-pneumatized temporal bone directs attention to the nasopharynx and skull base. Two patients are described in whom dehiscence of the temporomandibular joint allowed herniation of the contents of the joint posteromedically, where they obstructed the middle ear entrance of the eustachian tube, the protympanum. This is, to the authors' knowledge, a previously unreported cause of an acute middle ear and mastoid effusion.
Adolescent↗
Gas-liquid chromatographic determination and pharmacological studies of six clinically-used local anesthetics.
A gas-liquid chromatographic method was developed for the simultaneous assay of six local anesthetics, including amethocaine, bupivacaine, etidocaine, lignocaine, mepivacaine and prilocaine, in biological samples. These drugs and internal standard (clomipramine) in basified samples were extracted into 5 ml n-hexane, and the extract was analyzed by a temperature programming method (the column temperature was kept at 210 degrees C for 5 min, then raised to 280 degrees C at the rate of 10 degrees C/min) using a 3% W/W SP 2250 glass column (2 m x 2 mm i.d.) connected to a nitrogen sensitive detector. The injector and detector temperature were maintained at 300 degrees C. The pKa values, partition coefficients (K) and buccal absorptions of six local anesthetics were determined. The results showed that the onset of action and duration could be shown to be dependent on the pKa values and partition coefficients, respectively. A relatively good positive correlation (r = 0.991) was observed between the percentage of buccal absorption at pH 7.4 and the logarithms of K in n-hexane-Sørensen buffer system, and hence the more lipid soluble the local anesthetic, the greater the buccal absorption. The buccal absorption test supplemented by the n-hexane-buffer partition coefficient could be used as indicators for the ability of the anesthetics to penetrate biological barriers. The lipid penetration of the drugs, and thus their pharmacological action, is also influenced by the pKa values of the anesthetics.
Administration, Buccal↗
Effects of sympathomimetic agents on opiate analgesia, tolerance and dependence in mice.
The effects of chronic pretreatment with ephedrine and phenylpropanolamine (PPA) on the antinociceptive activities of morphine and codeine, as well as their effects on the induction and expression of tolerance to, and dependence on morphine and codeine in mice are reported. Chronic pretreatment with ephedrine or PPA attenuated the antinociceptive effects of subsequently administered morphine or codeine. When administered during the induction phase, sympathomimetics enhanced opiate tolerance with little or no effect on the development of physical dependence. Given in the expression phase, ephedrine and PPA did not significantly affect tolerance, whereas there was significant suppression of withdrawal signs. The possible implications of these results are discussed.
Analgesia↗
Protein binding characterization of pethidine and norpethidine and lack of interethnic variability.
Using dialysis, incubation experiments and gas liquid chromatographic method, we studied the binding of pethidine (P) and norpethidine (N) to various protein components and plasma of both healthy volunteers and patients. The displacement interactions and interethnic variations of P and N were also examined. The (mean +/- S.D.) plasma protein binding ranged from 72 +/- 2.8 to 43 +/- 2.7% and from 57 +/- 3.0 to 27 +/- 3.9%, respectively, at various concentrations of P and N. Protein concentration-dependent binding was observed in P and N with albumin and alpha 1-acid glycoprotein. Albumin was found to be the major protein component in the binding, whereas gamma-globulin contributed smaller binding activity than other protein fractions at therapeutic concentration of the drugs. The binding affinities of P were comparatively higher than N in all circumstances. The % P bound was almost constant with respect to various concentrations of N and vice-versa, indicating these two compounds exhibited no displacement action on the binding site to one another. The (mean +/- S.D.) % P bound for Caucasian, Chinese and Nepalese patients were 59 +/- 15%, 55 +/- 10% and 58 +/- 12%, respectively, at near 0.1 micrograms/ml of P, implying the absence of interethnic variation in P protein binding.
Analgesia↗
Anticardiolipin antibodies and lupus anticoagulant in Chinese patients with systemic lupus erythematosus.
Ninety-one consecutive patients with systemic lupus erythematosus (SLE) were studied. Forty-two patients had positive anticardiolipin antibodies (aCl) 40 aCl-IgG (44.4%); 4 aCl-IgA (4.4%); 1 aCl-IgM (1.1%). One patient had both aCl-IgG and aCl-IgA and 1 patient had aCl-IgG, aCl-IgA and aCl-IgM. Ten patients (11.1%) had lupus anticoagulant (LA). Both aCl isotypes and LA had no statistical association with thrombosis or thrombocytopenia.
Adolescent↗
The disposition of antituberculous drugs in plasma of elderly patients. I. Isoniazid and hydrazine metabolite.
The plasma profiles of isoniazid (INH) and hydrazine (HYD) metabolite were compared in 18 elderly patients (67-89 years of age) and 19 young adult patients (19-59 years of age) on the first day and at one month after treatment for tuberculosis with INH, rifampicin (RIF) and pyrazinamide (PZA). There was no difference in the pharmacokinetics of INH between the two age groups. The clearance for INH at steady-state was significantly lower than after the first dose. After the first dose the maximum concentration (Cmax) for HYD was significantly higher (p less than 0.05) in the elderly (0.4 +/- 0.07 microgram/ml) than in the young (0.24 +/- 0.08 microgram/ml). HYD is produced in significant amounts during INH metabolism and this should not be neglected when evaluating INH related toxicity.
Acetylation↗
The disposition of antituberculous drugs in plasma of elderly patients. II. Isoniazid, rifampicin and pyrazinamide.
The pharmacokinetics of isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) were studied in 18 elderly patients (67-89 years of age) and 19 young adult patients (19-59 years of age) on the first day and at one month of treatment for pulmonary tuberculosis. Elderly patients exhibited more side effects but there were no age-related changes in the pharmacokinetics of any of the three drugs when used in this combination. The clearance for INH and RIF at steady-state were significantly lower than after first-dose, while that of PZA remained unchanged. At steady-state the clearances for INH and RIF were not characteristic of polymorphic metabolism and auto-enzyme induction, respectively. Elderly patients are more sensitive to antituberculous (anti-TB) drugs; therefore, a modification in the dosage for this patient group should be considered.
Adult↗
Therapy of refractory/relapsed acute leukemia with cytosine arabinoside plus tetrahydrouridine (an inhibitor of cytidine deaminase)--a pilot study.
Thirty two patients with refractory or recurrent acute leukemia or blast crisis of chronic myelocytic leukemia were treated with 1-beta-D-arabinofuranosylcytosine (Ara-C), 100 mg/m2 [group I (n = 15)] or 200 mg/m2 [group II (n = 18)], and tetrahydrouridine (THU) 350 mg/m2, given concurrently as a 3 h continuous intravenous infusion at 12 h interval for eight doses. Two of 13 (15.3%) evaluable patients in group I achieved a complete response, both of whom had acute myelocytic leukemia. In group II, seven of 14 evaluable patients (50%) obtained objective responses--six with complete responses (42.8%) and one with partial response (7%). Myelosuppression was seen in all patients with a median duration of 32.5 days (group I) and 36.3 days (group II), respectively. Non-hematologic toxicity consisted of nausea, vomiting, diarrhea, conjunctivitis, skin rash, hepatocellular toxicity, hemorrhage, and renal toxicity. Pharmacokinetic studies revealed, for group I, mean peak plasma Ara-C levels at 3 h (Cp3h) of 1254 ng/ml, area under the curve (AUC) 4651 ng x h/ml, total body clearance (TBC) 32.65 l/h/m2, renal clearance (RC) 7.04 l/h/m2 with a mean of 12.36% of the injected amount of Ara-C excreted unchanged in urine over the first 24 h. The corresponding mean values for group II are Cp3h 3305 ng/ml, AUC 15080 ng x h/ml, TBC 20.48 l/h/m2, RC 7.02 l/h/m2 and 26.23%. Ara-C 200 mg/m2 combined with THU gave serum Ara-C levels and response rates comparable to those achieved with high dose Ara-C (HiDAC) (greater than or equal to 1 g/m2). Central nervous system toxicity associated with HiDAC was not seen. Pharmacokinetics for uracil arabinoside (Ara-U) in patients treated with Ara-C 200 mg/m2 plus THU, were comparable to values seen with Ara-C for Cp3h, AUC and 24 h urine, amounting to 3160 ng/ml, 21717 ng x h/ml and 23.62% whereas TBC was significantly lower (p less than 0.001) for Ara-U than for Ara-C (3.02 versus 20.48 l/h/m2).
Adult↗
Synthetic MR images produced by subspace methods: a comparison.
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Brain Neoplasms↗