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Biomedical subjects

K K Chan

Publications and source records attributed to K K Chan.

At least 91 records · Page 5Linked to original sources
PubMed1996

Prospective randomized comparison of anodal monophasic shocks versus biphasic cathodal shocks on defibrillation energy requirements.

Biphasic shocks are believed to be superior to monophasic shocks. Monophasic anodal shocks, as opposed to cathodal shocks, are associated with improved defibrillation energy requirements (DERs). However, it is unclear how the DER of anodal monophasic shocks compare with conventional biphasic shocks. Therefore the purpose of this study was to prospectively compare the DER of an anodal monophasic shock with that of a cathodal biphasic shock. A transvenous defibrillation lead with distal and proximal shocking electrodes was used. The subjects of this study were 20 consecutive patients with a mean age of 64.2 +/- 10.5 years ( +/- SD) and a mean left ventricular ejection fraction of 0.36 +/- 0.18. Six had had cardiac arrest. The DER, defined as the lowest energy that converted ventricular fibrillation to sinus rhythm, was determined twice with a step-down protocol (25 J, 20 J, 15 J, 10 J, 5 J, 3 J, 1 J). If the DER was > or = 25 J, then a subcutaneous patch was deemed necessary for system implantation. In random order the DER was determined with a monophasic anodal shock (distal electrode positive) and then with a cathodal (first phase, distal electrode negative) biphasic shock. The mean DER with anodal monophasic shocks was 15.1 +/- 8.5 J compared with 13.6 +/- 8.1 J with cathodal biphasic shocks (p = 0.4). A DER > or = 25 J was present in three patients with the monophasic waveform and in three patients with the biphasic waveform (p = NS). In conclusion, the DER and frequency of subcutaneous patch use with an anodal monophasic waveform is comparable to that obtained with cathodal biphasic waveform.

Aged↗
PubMed1996

Atrioventricular node properties in patients with accessory pathways.

A study during the era of surgical ablation suggested that atrioventricular (AV) nodal conduction is faster in patients with accessory pathways than in controls. In the present study, AV nodal characteristics were studied in 30 patients who underwent radiofrequency ablation of an accessory pathway and compared to 23 control patients. Sinus cycle length, AH and HV intervals, AV block cycle length, ventriculoatrial (VA) block cycle length, AV nodal effective refractory period, and VA effective refractory periods were measured in control and postablation accessory pathway patients before and after autonomic blockade with 0.04 mg/kg of atropine and 0.2 mg/kg of propranolol. The mean sinus cycle length in the control and accessory pathway groups did not differ significantly at baseline (798 +/- 211 and 766 +/- 156 msec, respectively) or after autonomic blockade (654 +/- 98 and 649 +/- 108 msec, respectively). The mean AH interval in the accessory pathway group (77 +/- 15 msec) was significantly shorter than in the control group (91 +/- 22 msec; p < 0.05) at baseline; however, there was no difference after autonomic blockade. No other significant differences were observed between the accessory pathway and control groups. These results demonstrate that AV nodal properties of patients with accessory pathways are not significantly different from controls and suggest that previously reported differences may have been due to selection bias.

Adult↗
PubMed1996

Evaluation and extraction of the Accufix atrial J lead.

The Accufix (Telectronics Pacing Systems, Englewood, Colo.) atrial active fixation pacemaker lead has a preformed J stiff retention wire that can fracture and erode through the atrium. We screened 85 patients with digital fluoroscopy and detected 18 (21%) lead fractures. Fourteen (16%) leads were successfully extracted by percutaneous techniques. The mean time for extraction and placement of a new atrial lead was 109 +/- 53 min, and a lead > 1 year old but not in the presence of a fracture was associated with a significantly longer extraction time. There were two extraction complications. One patient had a fever following the extraction, and one patient had a focal sensory deficit 1 week after the extraction probably caused by a paradoxical embolus. Standard percutaneous extraction tools can be used for successful and safe removal of a fractured Accufix lead.

Aged↗
PubMed1996

No subacute thrombosis and femoral bleeding complications under full anticoagulation in 150 consecutive patients receiving non-heparin-coated intracoronary Palmaz-Schatz stents.

Intracoronary stenting has been shown to have better immediate and long-term clinical outcomes and less restenosis than standard balloon angioplasty. However, the benefit was achieved at the cost of higher rates of coronary thrombosis, bleeding complications, the need for anticoagulation, and longer hospital stay. For the latter reasons there is a tendency to replace the anticoagulants by antiplatelet agents alone after stenting. However, we prospectively monitored 150 consecutive patients (133 men, 17 women, mean age 58.5 years) from two centers since February 1993. They all had coronary artery disease and underwent percutaneous implantation of non-heparin-coated Palmaz-Schatz coronary stents under a full but lower dose of anticoagulation. The femoral approach was used in all patients except one. In the 150 patients, 200 stents were implanted in 165 target arteries with 172 lesions. Stenting was performed without the guidance of intravascular ultrasonography; high-pressure poststenting inflation was used in only 17.3% of patients with less than optimal angiographic results. Coronary angiography was performed at baseline, immediately after the procedure, and after 6 months (mean 207 +/- 53.6 days SD) of stenting. The mean (+/-SD) coronary minimum luminal diameter increased from 0.52 0.31 mm to 3.13 +/- 0.42 mm immediately after stenting was performed and was 2.12 +/- 0.91 mm at 6 months. There was a 0% subacute thrombosis rate and a 0% femoral bleeding complication rate in the whole series. Only three (2%) major events occurred: one Q-wave myocardial infarction from closure of an angioplasty site distal to the stent on a very long lesion, one cerebrovascular accident, and one noncoronary-related death. The only patient who underwent the brachial approach had hematoma; otherwise no other minor event occurred. The mean hospital stay was 4.5 days in one of the two study centers. The long-term clinical follow-up rate was 97.3%. The mean (+/- SD) clinical follow-up period was 589 +/- 363 days. Clinical symptoms improved; the percentage of patients who had angina according to the Canadian Cardiovascular Society functional class II, III, and IV was 31.3%, 44.7%, and 4%, respectively, before stenting was performed and was reduced to 4.7%, 3.7%, and 0%, respectively at 6-month follow-up after stenting was performed. The 6-month angiographic restudy rate was 90.6%, and the restenosis rate was 18.3%. In contrast to other reported series, these results support the idea that with careful puncture technique and meticulous postoperative wound care, intracoronary stenting can be successfully performed with the patient under full anticoagulation without major risks of bleeding and femoral vascular complications. Furthermore with a full but comparatively lower dose of anticoagulation, subacute thrombotic complications can be reduced to 0% even with non-heparin-coated stents without the use of intravascular ultrasound guidance and without the use of adjunctive high-pressure poststenting inflation in most patients. The restenosis rate and long-term clinical outcomes remained very favorable.

Acute Disease↗
PubMed1996

Use of isoproterenol during programmed ventricular stimulation in patients with coronary artery disease and nonsustained ventricular tachycardia.

Twenty-three consecutive patients (20 men and 3 women) with coronary artery disease and nonsustained ventricular tachycardia (VT) in whom sustained VT was not inducible in a baseline electrophysiology test underwent repeated testing during isoproterenol infusion to determine the inducibility of sustained monomorphic VT. After the baseline study, each patient received a 2 to 4 microgram/min infusion of isoproterenol (mean 2.5 +/- 0.8 microgram/min). The sinus cycle length shortened by a mean of 29% +/- 9% and programmed stimulation was repeated. Nineteen patients had no inducible sustained, monomorphic VT, two patients had only inducible nonsustained VT, and two patients had ventricular fibrillation. Patients were followed up for 10 to 20 months (mean 14.4 +/- 2.9 months) and had no syncope, sustained monomorphic VT, or sudden death. Isoproterenol infusion during programmed stimulation in patients with coronary heart disease and nonsustained VT does not facilitate the induction of sustained monomorphic VT.

Aged↗
PubMed1996

Incidence of lead system malfunction detected during implantable defibrillator generator replacement.

Implantable cardioverter-defibrillator (ICD) generator replacement due to a depleted battery is a frequently performed procedure. The frequency with which sensing and defibrillation system failures are identified during device replacement procedures has not been previously described. Therefore, the purpose of this study was to prospectively determine the frequency of lead system malfunction detected at the time of device replacement in 55 consecutive patients undergoing ICD generator replacement. The mean age of the patients was 63 +/- 10 years and 40 of them were men. Forty-nine patients had an epicardial lead system, and six patients had a nonthoracotomy lead system. Four [7%] of these 55 patients were noted to have previously undetected lead system failure, either sensing (n = 3) or defibrillation (n = 1), necessitating system revision. The lead systems that failed were 40 +/- 6 months old (33-49 months). In summary, during ICD generator replacement, previously undetected problems with sensing or defibrillation may be identified in approximately 10% of patients. Therefore, a comprehensive evaluation of the sensing and the defibrillation functions should be an essential component of the ICD generator replacement procedure.

Defibrillators, Implantable↗
PubMed1996

Paravertebral muscles in disease of the cervical spine.

OBJECTIVES: Cervical spine disorders are common in the older population. The paravertebral muscles are essential to the support and stabilisation of the cervical spine but have been little studied. The aim was to determine whether pathological changes develop in these muscles in patients with severe cervical spine disease, which, if present, might contribute to the pathogenesis and symptomatology of their disorder. METHODS: Open biopsies of superficial and deep paravertebral muscles were obtained during the course of surgical procedures to alleviate cervical myelopathy. Most of these patients had cervical spondylosis or rheumatoid arthritis involving the cervical spine. The biopsies were compared with muscle obtained at necropsy from patients without a history of cervical spine or neuromuscular disorder. RESULTS: Muscle from both the study and control groups showed a similar range and severity of abnormalities. In several patients, grouped fibre atrophy suggested chronic partial denervation. Most biopsies showed type 1 fibre predominance and selective type 2 fibre atrophy. Ragged red fibres were a frequent finding and electron microscopy disclosed accumulations of mitochondria, a small proportion of which contained rounded, or longitudinally oriented, single osmiophilic inclusions. Fibres containing core-like areas were also frequent. These pathological features were seen with increasing severity and frequency with increasing age. CONCLUSIONS: The paravertebral cervical muscles develop pathological abnormalities with increasing age with both neurogenic and myopathic features, the pathogenesis of which is probably multifactorial. Such a muscle disorder would be expected to be accompanied by functional impairment which may contribute to the development and symptomatology of cervical spine disease with increasing age.

Aged↗
PubMed1996

Drainage catheters: in vitro comparison of internal retention mechanisms.

In five drainage catheters, internal retention mechanisms (locking pigtail [14 and 8 F], inflatable balloon [14 F], or wings [14 and 24 F]) were evaluated for resistance to and distortion from dislodgment. Catheters were inserted into simulated tissue, and weight was added until dislodgment occurred. Resistance to dislodgment increased when the mechanisms were locked; the locking pigtail supported the most weight. Distortion caused by dislodgment was minimal.

Catheters, Indwelling↗
PubMed1996

Phase I and pharmacokinetic study of oral UFT, a combination of the 5-fluorouracil prodrug tegafur and uracil.

UFT is an oral preparation combining the 5-fluorouracil (FU) prodrug tegafur (FT) and uracil (U) in a 1:4 ratio, which is commercially available in Japan for the treatment of breast and gastrointestinal cancers. We sought to determine the tolerance of daily oral UFT and to relate this tolerance to the pharmacokinetics of FT and/or the derived FU, while exploring the possibility of circadian FU kinetics contributing to the results. A 28-day schedule followed by 2 weeks rest was began at the initial level of 300 mg/m2/day administered either at 8 a.m. or at 6 p.m. At the following level, 400 mg/m2/day patients were randomly assigned to a split-dose administration or to the above single, timed dose administration. Intolerance to single dosing was clearly demonstrated, and only the split dosing was advanced to 500 mg/m2/day. When this level proved too toxic, 400 mg/m2 was studied further on a 7 a.m., 3 p.m., and 11 p.m. (every 8 h) schedule. Pharmacology was determined on selected patients. In the single dose administration, areas under the curves of FU were higher following p.m. dosing, although substantial interpatient variation was present. Toxicities (diarrhea and neutropenia) were more severe in patients receiving the drug in single daily doses. We conclude that the kinetics of FT are saturable, with disproportionate increases in area under the curve (and toxicities) as dose levels are increased. With divided dosing, tolerance improves. UFT at a dose of 400 mg/m2/day administered as three divided doses (every 8 h) is suitable for Phase II studies, although toxicity requiring cessation of drug administration prior to completion of 28-day cycles will occur in some patients.

Administration, Oral↗
PubMed1995

Analysis of ifosfamide, 4-hydroxyifosfamide, N2-dechloroethylifosfamide, N3-dechloroethylifosfamide and iphosphoramide mustard in plasma by gas chromatography-mass spectrometry.

A sensitive and specific method for the simultaneous quantitation of ifosfamide (IF), 4-hydroxylifosfamide (4-OHIF), N2-dechloroethylifosfamide (N2D), N3-dechloroethylifosfamide (N3D) and iphosphoramide mustard (IPM) has been developed using gas chromatography-mass spectrometry (GC-MS) with an ion-trap mass spectrometer. Deuterium labeled analogues for each of these analytes were synthesized as the internal standards. The labile 4-OHIF in plasma was first converted to the more stable cyanohydrin adducts before dichloromethane extraction. IPM was extracted by C18 reversed-phase resin. All analytes were converted to their silyl derivatives before GC-MS analysis. The sensitivity limits ranged from 0.1 to 0.5 microgram/ml when 100 microliters of plasma was used. This method was validated with within-run coefficients of variation less than 5% (n = 8) and between-run coefficients of variation less than 12% (n = 6). The method was applied to the determination of plasma levels of IF and metabolites in the rat.

Animals↗
PubMed1995

Apolipoprotein E type epsilon 4 allele frequency is not increased in patients with sporadic inclusion-body myositis.

The apolipoprotein E genotype was determined for 11 patients with sporadic inclusion-body myositis. Seven cases had the genotype epsilon 3/epsilon 3, the other four cases, epsilon 3/epsilon 4. The frequency of the epsilon 4 allele in this group of patients (0.182) was not significantly increased compared with elderly controls (0.147; n = 58), in contrast to Alzheimer's disease in which there was a significant increase (0.328; n = 67). The epsilon 2 allele was not found in any of the 11 sporadic inclusion-body myositis patients and its frequency was decreased in Alzheimer's disease. Despite certain pathological similarities that exist between inclusion body myositis and Alzheimer's disease, their association with particular apolipoprotein E genotypes is distinct.

Aged↗
PubMed1995

A novel multivariate approach for estimating the degree of similarity in bioavailability between two pharmaceutical products.

Statistical assessment of bioavailability and bioequivalence of drug products is generally carried out with a univariate analysis by independently comparing each relevant parameter [such as, area under the drug concentration curve (AUC) and peak drug concentration (Cmax)] of the test and reference products. The assumption is made that AUC and Cmax are independent of each other. In reality, AUC, Cmax, and other pharmacokinetic parameters are dependent on each other. Therefore, a multivariate approach is theoretically superior. In this report, a novel multivariate approach to determine the bioavailability and bioequivalence of pharmaceutical products is described. The method determines the bivariate confidence ellipse (CE) between Cmax and AUC and the trivariate confidence ellipsoid (CED) among Cmax, AUC, and either Tmax or MRT for test and reference products. The similarity between the test and reference products can be assessed by the fraction of overlapping areas of CE and volumes of CED. The method and its comparison with conventional univariate analysis are demonstrated with data obtained from a bioequivalence study of ketoconazole tablets.

Analysis of Variance↗
PubMed1995

Intraperitoneal 5-fluoro-2'-deoxyuridine (FUDR) and (S)-leucovorin for disease predominantly confined to the peritoneal cavity: a pharmacokinetic and toxicity study.

Intraperitoneal (IP) administration of fluorinated pyrimidines has been evaluated for ovarian and gastrointestinal malignancies in phase I, II, and III trials. The tolerance and pharmacokinetic profile of IP 5-fluoro-2'-deoxyuridine(FUDR) alone and with (R,S)-leucovorin ((R,S)-LV) have each been evaluated in previous phase I studies. FUDR doses of 3 g per day with and without (R,S)-LV doses up to 640 mg per day given IP are well tolerated. The current phase I study was designed to determine the pharmacokinetic profiles and clinical tolerance of escalating doses of the pure biologically active S-isomer of leucovorin ((S)-LV) given IP with the same dosing schedule of FUDR. A group of 16 patients with disease confined to the abdominal cavity were treated in this study. Pharmacokinetic studies of blood and peritoneal fluid, toxicity profiles, and clinical response for the first three cycles are reported here. The toxicity profile did not significantly differ from the prior two studies. All non-hematologic toxicities, such as fatigue, nausea, vomiting, diarrhea, and abdominal discomfort were less than grade 4, and most were less than grade 3. Neutropenia and thrombocytopenia were uncommon and observed only in patients with compromised bone marrow reserve. The pharmacokinetic profiles were also congruent with the previous studies and indicate a three-log advantage for FUDR. The (S)-LV profiles in the peritoneal cavity paralleled those of FUDR. Antitumor effects or absence of progression until after cessation of therapy were documented in 11 patients. At a median follow-up of 18 months 44% of patients were alive. IP administration of 3-g of FUDR and up to 640 mg (S)-LV daily for three days was well tolerated. The tolerance and antitumor effects observed during IP FUDR and LV in these studies encourage further exploration of this regimen against ovarian and gastrointestinal malignancies. The actual role and optimal dose of LV as an enhancer of the antitumor actions of FUDR administered by this route remain unknown.

Adult↗
PubMed1995

Analysis of diclofenac and four of its metabolites in human urine by HPLC.

An HPLC method for the determination of diclofenac (DCF) and four of its metabolites (3'-hydroxydiclofenac, 4'-hydroxydiclofenac, 5-hydroxydiclofenac, and 3'-hydroxy-4'-methoxydiclofenac) in human urine is described. Following base hydrolysis, the samples were neutralized and extracted. Evaporated extracts were reconstituted in mobile phase containing ascorbic acid, and chromatographed, using flow-rate programming, on a reversed-phase column. Absolute recovery (average), was at least 78% for diclofenac and ranged from 75 to 85% for the four metabolites. Standard curves showed linearity over the range of concentrations of 0.2 to 40 ug/mL, using 0.25 mL of urine. Specificity was demonstrated by examining chromatograms of extracts of blank urine from 8 volunteers and 24 study subjects. Good accuracy was observed for all compounds over the concentration range of 0.2 to 40 ug/mL using 0.25 mL of urine. Based on accuracy and precision criteria, the limit of quantitation for all 5 analytes was 0.4 ug/mL, using 0.25 mL of urine. Analysis of urine from subjects with normal and reduced renal function who received diclofenac orally demonstrated that total diclofenac and metabolites excreted in the urine represented approximately 31% and 4% of an oral dose of diclofenac, respectively.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Long-term follow-up of patients with advanced ovarian cancer treated in randomised clinical trials.

The data from two prospective randomised phase III trials that were initiated by the West Midlands Ovarian Cancer Study Group (WMOCSG) in 1981 and 1986, recruiting 167 and 195 patients respectively, have been pooled and the survival patterns of the 362 patients treated for advanced epithelial ovarian cancer within clinical trials in the West Midlands over the 10 year period (1981-91) have been explored. All patients had histologically proven epithelial ovarian cancer and all had residual disease after primary surgery, with the majority having stage III/IV disease. The primary treatment for all patients was debulking surgery followed by platinum-based chemotherapy. Eligible patients were further randomised to undergo a second debulking operation. The main end point, survival, was assessed using Kaplan-Meier curves and the log-rank test. A Cox proportional hazards model identified performance status (P = 0.002), residual disease (P = 0.005) and albumin level (P = 0.04) as independent prognostic factors. A multivariate model to predict survival curves for patients with the best and worst prognoses was developed with predicted 5 year survival of 30% and 3% for those in the best and worst prognostic groups respectively. The identification of clinical interventions to improve outcome is an urgent matter since the prognosis for patients with advanced ovarian cancer remains poor.

Animals↗
PubMed1995

The application of flow cytometric DNA analysis in detecting the presence of malignant cells in ovarian carcinoma peritoneal fluids.

OBJECTIVE: To compare flow cytometric detection of malignant cells with standard cytological evaluation in patients with ovarian carcinoma. SETTING: The City Hospital Trust, The Women's Hospital and CRC Trials Unit, Birmingham. SUBJECTS: Forty-three patients with histologically proven ovarian carcinoma and positive cytology, and a control population of 20 patients undergoing surgery for benign gynaecological conditions. METHODS: Prospective, blinded study examining ascitic fluid or peritoneal washings obtained at primary surgery by flow cytometric DNA analysis and cytological examination. RESULTS: Flow cytometry detected aneuploid cells in 27/43 (63%) of malignant and 7/20 (35%) of benign fluid specimens. In malignant samples the mean aneuploid count was 38.5% (range 1-98%) with a mean S-phase fraction of 5.2% (range 0-33.9%). In benign specimens the mean aneuploid count was 30.4% (range 14.5-66.4%). Based on these results, the overall sensitivity of cytometric detection of malignant cells was 71.4%, specificity 65%, with a positive predictive value of 85.1%. False positivity was found mainly in patients with benign ovarian cysts. Further examination revealed four false negative and four false positive results, where the peritoneal fluid and ovarian tissue DNA ploidy status concurred. Assuming such results to be correct increased the sensitivity of the test to 88.5% and specificity to 85%. CONCLUSIONS: Although flow cytometry can glean information beyond the capabilities of cytological assessment, using the premise that aneuploid cells alone indicate malignancy, it remains secondary to cytology in the detection of malignant cells in peritoneal fluids.

Adult↗