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Biomedical subjects

W S Chan

Publications and source records attributed to W S Chan.

At least 37 records · Page 2Linked to original sources

Efficacy and mechanism of aluminium phthalocyanine and its sulphonated derivatives mediated photodynamic therapy on murine tumours.

The efficacy of photodynamic therapy (PDT) mediated by aluminium phthalocyanine (AlPc) and its mono- and disulphonated derivatives (AlPcS1 and AlPcS2, respectively) on murine EMT-6 tumour were compared in vivo. AlPc (0.25 mumol/kg) PDT resulted in no tumour recurrence in all treated mice. In contrast, PDT with AlPcS1 (2 mumol/kg) and AlPcS2 (1 mumol/kg) only produced tumour cure in 75% and 86% of mice, respectively. Immediately after AlPc-PDT, tumour cells were found to be viable as determined by in vitro clonogenicity, but progressive cell death occurred thereafter. In contrast, AlPcS1 and AlPcS2 PDT produced substantial cell death (approximately 35% and 70%, respectively, of entire tumour) immediately after phototherapy, and yet further loss of tumour cell viability continued after PDT. In all cases, few vascular effects were observed at 0 h post-PDT, as indicated by the retention of 99mTc-MIBI in the tumour. However, the reduction of blood flow in tumours progressed with time, such that blood flow in tumours fell to approximately 25% of the control level by 24 h after both AlPc and AlPcS1 PDT. With AlPcS2, there was only an approximate 50% fall in tumour blood flow by 24 h. These results demonstrate a greater PDT efficiency with AlPc on tumour destruction, which is an indirect mechanism involving damage of tumour vasculature, whereas AlPcS2 has a greater effect on direct tumour cytotoxicity and AlPcS1 exerts both direct and indirect modes of action against tumours.

Animals↗

Prevention of hypotension during spinal anaesthesia for caesarean section: ephedrine infusion versus fluid preload.

We compared the efficacy of prophylactic ephedrine infusion over fluid preloading in prevention of maternal hypotension during spinal anaesthesia for Caesarean section. Forty-six women undergoing elective Caesarean section at term were allocated randomly to receive either intravenous fluid preloading with Hartmann's solution 20 ml.kg-1 (fluid group) or prophylactic intravenous ephedrine 0.25 mg.kg-1 (ephedrine group). Moderate hypotension was defined as > or = 20% reduction in systolic blood pressure and severe hypotension as > or = 30% reduction in systolic blood pressure. Maternal uterine circulation was measured using Doppler ultrasound in 11 parturients before and after spinal anaesthesia. There was a lower incidence of severe hypotension in the ephedrine group compared with the fluid group (35% vs. 65%, p = 0.04), although the incidence of moderate hypotension was similar. Mean umbilical venous pH was higher in the ephedrine group than in the fluid group (7.33 vs. 7.29, p = 0.02) and the number of patients shivering was lower in the ephedrine group (2 vs. 9, p = 0.02). No difference was found between pre- and postspinal uterine artery pulsatility indices in either group. We conclude that prophylactic ephedrine infusion alone is at least as good as fluid preload alone in combating the hypotension associated with spinal anaesthesia for Caesarean section.

Anesthesia, Obstetrical↗

An audit of the safety of an acute pain service.

We audited and analysed the adverse effects and safety of postoperative pain management on 2509 consecutive patients under care of the Acute Pain Service at a tertiary referral teaching hospital over a 32-month period. Our standard respiratory monitoring consisted of continuous pulse oximetry, hourly respiratory rate counting, sedation scoring and intermittent arterial blood gas sampling. This protocol was reliable and detected six episodes of bradypnoea, 13 of hypercapnia and 23 of oxygen desaturation occurring in 39 patients (1.8% of all spontaneously breathing patients). Two patients required naloxone injection and none had long-term sequelae. Hypotension due to epidural bupivacaine 0.0625% and fentanyl 3.3 micrograms.ml-1 infusion occurred in four patients (1.2%), all with a sensory block higher than T5. They readily responded to fluid infusion and ephedrine (two patients). Postoperative nausea or vomiting occurred in 723 (28.8%) and 380 (15.1%) patients, respectively. Odds ratio analysis showed that the risk factors for postoperative nausea and vomiting were: female gender, gynaecological operations, nongeriatric patients and systemic analgesia. Postoperative nausea and vomiting decreased analgesic efficacy by discouraging the use of patient-controlled analgesia and was regarded as equally distressing as pain. Other side-effects included: pruritus in 182 patients; dizziness in 333 and lower limb weakness in 73 (21.2% of patients receiving epidural local anaesthetics). It is concluded that a standard monitoring and management protocol, an experienced nursing team and reliable Acute Pain Service coverage is mandatory for the safe use of modern analgesic techniques.

Aged↗

Epidural infusion of bupivacaine 0.0625% plus fentanyl 3.3 micrograms/ml provides better postoperative analgesia than patient-controlled analgesia with intravenous morphine after gynaecological laparotomy.

One hundred and twenty women undergoing gynaecological abdominal operations were randomized to receive either epidural bupivacaine 0.0625% + fentanyl 3.3 micrograms/ml infusion (Group EPI, n = 57), or patient-controlled intravenous morphine analgesia (Group PCA, n = 54) for postoperative pain relief. The groups were comparable in demographic data, types and duration of operation. Group EPI achieved significantly lower verbal rating scale of pain (VRS) at rest at 0, 4, 12, 16, 20, 28 and 40th postoperative hours. The VRS during cough were also significantly lower in Group EPI at 0, 4, 8, 12, 28 and 36th postoperative hours. None of the patients had respiratory depression or hypotension. Nausea/vomiting occurred in 52.6%/33.3% of patients in Group EPI and 52.7%/37.0% in Group PCA. Most patients (84.2% in Group EPI and 72.2% in Group PCA) rated their pain management as "good". We conclude that epidural infusion of bupivacaine 0.0625% and fentanyl 3.3 micrograms/ml provide better analgesia than patient-controlled intravenous morphine after gynaecological laparotomy.

Analgesia, Epidural↗

The efficacy, applicability and side-effects of postoperative intravenous patient-controlled morphine analgesia: an audit of 1233 Chinese patients.

We analyzed data from 1233 Chinese patients of a wide age range who received patient-controlled analgesia (PCA) intravenous morphine for postoperative pain relief, during the period of January 1992 to May 1995. The analgesic regimen was standardized as follows: PCA bolus 1 to 1.5 mg; lock-out interval 5 minutes; one-hour maximum dose 0.075 to 0.1 mg.kg-1 and background infusion 0 or 0.5 mg.h-1. Most patients underwent major surgery that was broadly subclassified according to the anatomical area involved. The median verbal numerical rating scales of pain (0 to 10) at rest and while coughing for the first, second and third 24 hours were 3.0/5.0, 1.5/4.0 and 0/3.0 respectively and the corresponding demand to delivery ratios were 2.8 +/- 2.9, 2.6 +/- 2.4 and 2.4 +/- 2.6. The overall morphine consumptions in 1004 of these Chinese patients were 27.5 +/- 16.8, 17.8 +/- 16.1 and 18.1 +/- 21.0 micrograms.kg-1.h-1 during the first 16, 17 to 41 and 42 to 66 postoperative hours respectively. These figures were the same as for Caucasian patients managed in the same institution. Morphine consumption was significant higher following thoracic, upper abdominal and spinal surgery. Also it was higher in patients younger than 65 years, males, cigarette smokers and those with ASA physical status I or II. The commonest side-effects were nausea (34.5%) and vomiting (18.2%). Bradypnoea and oxygen desaturation occurred in 0.5% and 1.6% respectively. All cases were promptly detected and managed with no adverse outcomes. Most patients were satisfied (76.7% ranked "good") with their postoperative analgesia. The commonest reasons for dissatisfaction were inadequate pain relief, nausea and reluctance to self-control analgesic administration. It is concluded that PCA with intravenous morphine is effective and safe as a routine postoperative technique for Chinese surgical patients.

Aged↗

Simultaneous confidence intervals for pairwise multiple comparisons in a two-way unbalanced design.

Turkey's (1953, The Problem of Multiple Comparisons, unpublished report, Princeton University) procedure is widely used for pairwise multiple comparisons in one-way ANOVA. It provides exact simultaneous pairwise confidence intervals (SPCI) for balanced designs and conservative SPCI for unbalanced designs. In this paper, we will extend Turkey's procedure to two-way unbalanced designs. Both the exact and the conservative methods will be introduced. The application of the new procedure is illustrated with sample data from two experiments.

Algorithms↗

Percutaneous Kirschner-wire pinning for severely displaced distal radial fractures in children. A report of 157 cases.

Distal radial fractures are common in children. Recent outcome studies have cast doubt on the success of treatment by closed reduction and application of plaster. The most important risk factor for poor outcome is translation of the fracture. If a distal radial fracture is displaced by more than half the diameter of the bone at the fracture site it should be classified as high risk. We performed percutaneous Kirschner-wire pinning on 157 such high-risk distal radial fractures in children under 16 years of age. The predicted early and late failure rate was reduced from 60% to 14% and only 1.5% of patients had significant limitation of forearm movement of more than 15 degrees in the final assessment at a mean of 31 months after operation. There were no cases of early physeal closure or deep infection.

Adolescent↗

Application of a hierarchical linear model to the study of adolescent deviance in an overlapping cohort design.

Hierarchical linear models provide a conceptual orientation and a flexible set of analytic techniques for studying psychological change in repeated measures studies. The researcher first formulates a model for individual change over time, with each individual's development characterized by a unique set of parameters. These parameters are then viewed as varying randomly over the population of persons. We illustrate this approach with data on attitudes toward deviance during adolescence (Raudenbush & Chan, 1992), indicating how one may assess the psychometric properties of an instrument for studying change, compare the adequacy of linear and curvilinear growth models, control for time invariant and time-varying covariates, and link overlapping cohorts of data. The results suggest that prodeviant attitudes characteristically increase during early adolescence, achieving a peak between 17 and 18 years of age. The typical trajectories for male and female adolescents have the same shape, although female adolescents tend to be less deviant than male adolescents at each age. We briefly consider the statistical power of tests of cohort differences at the points where they overlap.

Adolescent↗

Operative treatment of displaced intra-articular fractures of the calcaneum. Medium-term results.

Since 1986, we have treated displaced intra-articular fractures of the calcaneum by open reduction through a lateral approach, stable internal fixation and bone grafting. We assessed the results at a mean follow-up of 2.92 years in 44 patients, comparing them with those for 19 patients treated non-operatively. Clinical assessment used the scoring system of Crosby and Fitzgibbons (1990) and radiological measurements were made from lateral, axial and internal oblique views. The articular congruity of the subtalar joint and any arthritic changes were also assessed. We found significantly better results in the operated group with respect to pain, activity, range of movement, return to work and swelling of the hind foot. Radiologically, the operated group showed significantly better scores for articular congruity and arthritic changes. We conclude that the operative treatment of displaced intra-articular fractures of the calcaneum gives better medium-term results than conservative management.

Adult↗

Cell and tissue responses of a murine tumour to phthalocyanine-mediated photodynamic therapy.

Mice bearing a subcutaneously growing tumour (Colo 26) were injected intravenously with the photosensitiser chloroaluminum sulphonated phthalocyanine (5 mg/kg) 24 h prior to irradiating the tumour with laser light (675 nm; 50mW, 100 J/tumour). Energy status of the tumour, as assessed by the loss of high energy phosphates in the 31P-nuclear magnetic resonance spectra, was altered dramatically following treatment, such that the ATP fell to undetectable levels within 1 h of light irradiation. However, assessment of the clonogenic capacity of neoplastic cells isolated from dissociated tumours showed that these rapid changes in cellular metabolism were not reflected in similar rapid changes in cell viability. Reductions in clonogenic capacity, which fell to less than 0.1% of control values at 24h postirradiation, closely mirrored those resulting from the cessation of vascular perfusion. Evaluation of tumour blood flow, using the technique of hydrogen washout, showed that the treatment protocol evoked a gradual and selective reduction in flow within the tumour resulting in complete vascular stasis by approximately 5 h after treatment. The results indicate that while chloroaluminum sulphonated phthalocyanine-mediated photodynamic therapy caused early metabolic damage in neoplastic cells, loss of viability paralleled the induction of complete inhibition of vascular flow in the tumour.

Animals↗

Photocytotoxic efficacy of sulphonated species of aluminium phthalocyanine against cell monolayers, multicellular spheroids and in vivo tumours.

The problem of relying solely on in vitro data to predict photosensitiser efficacy was demonstrated by examining the uptake and the ability to mediate photocytotoxicity of mono-, di-, tri- and tetra-sulphonated species of chloroaluminium phthalocyanine (AlS1-4Pc) in monolayer cultures of murine Colo 26 cells and in both monolayer and spheroid cultures of human WiDr cells. Cells treated in vitro, whether in monolayer or as spheroids, with the less sulphonated derivatives, AlS1Pc and AlS2Pc, were more susceptible to photocytotoxicity than those treated with AlS3Pc, cells treated with AlS4Pc were even less susceptibile to the cytotoxic effects of light irradiation. Generally these results mirrored the cellular uptake in vitro. When WiDr spheroids were increased in size from 250 microns to 500 microns there was a reduction in uptake of AlS1Pc and AlS2Pc which was reflected by the decreased sensitivity of the larger spheroids to the effects of light irradiation. AlS1Pc had no effect against Colo 26 cells growing as s.c. tumours in syngeneic BALB/c mice; whereas AlS3Pc, AlS2Pc and AlS4Pc produced significant reductions in tumour weights 5 days post laser light irradiation. Of these, AlS2Pc had the most dramatic effect on the colony forming efficiency of tumour cells recovered 24 h after PDT. While, despite their effects on tumour size, AlS3Pc and AlS4Pc scarcely affected the subsequent viability of cells from dissociated tumours. Thus the in vitro efficacy of the sulphonated species of phthalocyanines is not necessarily predictive of their in vivo effectiveness.

Animals↗

Effect of sulfonation on the cell and tissue distribution of the photosensitizer aluminum phthalocyanine.

Aluminum sulfonated phthalocyanine has potential as a suitable photosensitizer for use in the photodynamic therapy of cancer. In the present study, cellular uptake and retention of the individual mono-, di-, tri-, and tetrasulfonated derivatives (AlS1-4Pc) were examined in tissue culture and in normal and neoplastic tissue of tumor-bearing mice. Uptake and retention of the various derivatives by cells in tissue culture correlated inversely with the degree of sulfonation. Accordingly, Colo 26 cells in monolayer culture, 24 h after addition of 10 microM of appropriate photosensitizer, had accumulated approximately 25-fold more AlS1Pc than AlS3Pc and retained this species longer than more sulfonated derivatives. In contrast to these in vitro results, it was found that Colo 26 growing s.c. in BALB/c mice accumulated photosensitizer to a greater extent when the degree of sulfonation increased, such that A1S4Pc greater than AlS3Pc greater than AlS2Pc greater than AlS1Pc. By 24-48 h after the i.v. injection of 0.1 ml 2.27 mM solution of individual photosensitizer, the relative ratios of tumor:adjacent tissue varied from greater than 10:1 to greater than 2:1, showing that selective tumor uptake may be affected profoundly by the composition of the phthalocyanine compound. The livers and spleens of both normal and tumor-bearing mice, unlike other normal tissue, took up the sulfonated derivatives in an order that provided a mirror image of that observed in neoplastic tissue. These complex in vivo distribution and retention characteristics appear to be a consequence of relative hydrophilicity/hydrophobicity properties of the sulfonated species and indicate the extent to which these characteristics may influence photosensitizer distribution and accumulation.

Animals↗

Safrole, eugenol and methyleugenol induce intrachromosomal recombination in yeast.

Deletion of an integrated plasmid, a specific type of intrachromosomal recombination, was evaluated for inducibility with the phenylpropenes safrole, eugenol and methyleugenol in the yeast Saccharomyces cerevisiae. These phenylpropenes are found in food products, spices, pharmaceuticals and clove cigarettes. Safrole and eugenol are known carcinogens in animals and methyleugenol is a suspected carcinogen. These phenylpropenes are not detectable by the Ames assay and most other short-term tests used currently in predictive carcinogenesis. Like safrole, which has been shown to be nonmutagenic with the Ames assay, eugenol and methyleugenol were found to be nonmutagenic with the Ames assay. In contrast, with the yeast assays which screen for intra- and inter-chromosomal recombination in logarithmic phase cultures, all 3 compounds gave a positive dose-related response. These results demonstrate further that the yeast system can be modified easily to detect various genetic endpoints and that it deserves serious consideration as a test system for predictive carcinogenesis.

Adenine↗

Effect of tumour location on selective uptake and retention of phthalocyanines.

The effect of anatomical site of tumour growth on selective uptake and retention of chloro-aluminium sulphonated phthalocyanine (ClAlSPc) was determined using the murine colorectal carcinoma (Colo 26). Tumours were established in the liver, spleen, kidney, lung, thoracic cavity and s.c. flank region of syngeneic BALB/c mice and animals received 10 mg/kg ClAlSPc by i.v. injection. Colo 26 growths at s.c., intra-pulmonary, intra-thoracic or intra-renal sites took up and retained greater amounts of ClAlSPc than did adjacent normal tissues. Such selective retention of ClAlSPc by neoplastic tissue was not observed when Colo 26 was grown in the spleen, where tumour and normal tissue took up about the same amounts, or the liver, where normal tissue took up more ClAlSPc than either directly implanted or metastatic tumours. ClAlSPc ratios found in tumour/adjacent tissue may vary for a single tumour growing at different anatomical sites and such variability could have a distinct effect on the efficacy of photodynamic therapy of cancer.

Animals↗

Operative treatment of intraarticular fractures of the os calcis--the role of rigid internal fixation and primary bone grafting: preliminary results.

The treatment of intraarticular fractures of the os calcis remains controversial. Yet it seems illogical that the subtalar joints should be treated differently from other weight-bearing joints. In this paper, we report the results of treating 64 intraarticular fractures of the os calcis by open reduction, rigid internal fixation with primary bone graft, and early mobilization. Of the 64 fractures, 23.43% were tongue-type fractures, 48.43% were joint depression, and 28.12% were comminuted. All the fractures were operated on with lateral incisions. The average period of follow-up was 10.6 months. The results showed that all the patients had minimal pain, swelling, and deformity. Subtalar joint movement was retained (67.8% of active and 80.7% of passive). Eighty percent of normal Bohler angles and 93.5% of normal crucial angles were regained. Over 80% of patients resumed working within 6 months after the injuries. We therefore concluded that the present method of treating intraarticular fractures of os calcis gives very good results.

Activities of Daily Living↗

Use of charge coupled device camera for imaging of intracellular phthalocyanines.

A highly sensitive charge-coupled device (CCD) camera, linked to a computerized image processor, has been used to obtain fluorescence images of chloro-aluminum sulfonated phthalocyanine (ClAlSPc), and its mono- to tetra-sulfonated constituents, in cells recovered from the peritoneal cavity of dye-treated mice. Immunofluorescence and cytochemistry showed that cells which preferentially took up ClAlSPc and its sulfonated species were predominantly of the monocyte-macrophage series. While this technique may be of use in determining the nature of those cells capable of taking up light sensitive dyes and, perhaps, the intracellular location of such agents, the possibility that photoinactivation by dye aggregation could reduce the sensitivity of this procedure is discussed.

Animals↗