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Biomedical subjects

K Y Chan

Publications and source records attributed to K Y Chan.

At least 73 records · Page 4Linked to original sources

Transcatheter occlusion of atrial septal defects: an initial experience with the Amplatzer septal occluder.

OBJECTIVE: To discuss the initial experience with the use of a new double disc occluding device, the Amplatzer septal occluder in transcatheter occlusion of secundum atrial septal defects (ASD). METHODS: Transvenous sizing of secundum ASD was performed in five children under general anaesthesia using transoesophageal echocardiographic and fluoroscopic guidance. An Amplatzer septal occluder equal to or minimally larger than the stretched diameter of the ASD was used for transcatheter occlusion of the defect in three suitable patients. Pulmonary balloon valvuloplasty with a 18 mm x 3 cm Mansfield balloon catheter was carried out in one patient with associated pulmonary valvar stenosis in the same procedure setting. RESULTS: Stretched diameters of the defects in the three patients ranged from 14 to 17 mm. Devices of sizes 14, 17 and 17 were deployed through 7F and 8F sheaths, respectively. The upper and lower rims of interatrial septum were more than 8 mm in all patients. All patients had successful occlusion with complete obliteration of the atrial left to right shunting. Simultaneous pulmonary balloon valvuloplasty for the valvar stenosis reduced pressure gradient from 53 mmHg to 22 mmHg across the valve prior to septal occlusion in one patient. No intraprocedural or short-term complication was encountered. CONCLUSIONS: The design of the Amplatzer septal occluder permits ease in loading, delivery, deployment and stable seating of the device. This initial experience shows that Amplatzer device occlusion is feasible, relatively safe and effective and appears to be a viable alternative to surgical closure of secundum atrial septal defects in properly selected patients.

Cardiac Catheterization↗

The benefit and risk of postmastectomy radiation therapy in patients with high-risk breast cancer.

To evaluate the efficacy of postmastectomy radiation therapy (PMRT) for prophylaxis against locoregional recurrence in high-risk breast cancer patients, and the rate of complication associated with such treatment, we retrospectively reviewed 79 breast cancers in 78 patients, who were given therapy (PMRT) between April 1990 and March 1995. Radiation doses were 46-50 Gy in 2-Gy fractions. High-risk factors included primary tumor (> or = 5 cm) in 19 (24.1%) patients, positive axillary lymph nodes (> or = 4) in 56 (70.9%) patients, positive or close (< or = 2 mm) surgical margins in 14 (17.7%) patients, and central or inner quadrant tumor with positive axillary nodes and lymphovascular invasion in seven (8.9%) patients. Adjuvant chemotherapy was also given to 69 of 78 (88.5%), patients and hormonal therapy to 41 of 78 (53.7%) patients. The median follow-up time was 25 months (range, 7-66 months) after mastectomy. Our study revealed that locoregional failure as the first site of failure occurred in only one of 78 (1.3%) patients. Relapse-free survival at 3 years was 67.7% [95% confidence interval (CI), 52.0-81.3], and overall survival was 76.9% (95% CI, 63.3-90.6). The incidence of radiological evidence of lung fibrosis increased significantly in patients whose internal mammary chain was included in the radiation field. The occurrence of lung fibrosis can be reduced by changing radiation treatment technique and keeping central lung distance (CLD) of tangential field to < or = 2.8 cm in tangential field technique or < or = 1.4 cm in tangential with a separate internal mammary field technique. We concluded that the risk of locoregional recurrence in high-risk breast cancer patients can be much reduced by PMRT. With careful selection of radiation treatment fields, radiotherapy technique, and limitation of CLD to < or = 2.8 cm in tangential technique or < or = 1.4 cm in separate technique, the risk of symptomatic radiation pneumonitis is minimal. PMRT should be recommended for breast cancer patients who are at high risk for locoregional recurrence.

Adult↗

Simultaneous transcatheter valvuloplasty and Amplatzer septal occlusion for pulmonary valvar stenosis and secundum atrial septal defect.

Transcatheter balloon valvuloplasty had been established as the treatment of choice in patients with pulmonary valvar stenosis. Non surgical closure of secundum atrial defects by various occlusive devices is currently being evaluated. We report the first successful simultaneous transvenous Mansfield balloon dilation and Amplatzer septal occlusion in a 7-year-old girl with moderately severe pulmonary valvar stenosis and secundum atrial defect in April 1997. Satisfactory reduction of pressure gradient across pulmonary valve and complete obliteration of left to right atrial shunt were achieved.

Cardiac Catheterization↗

Signal-averaged electrocardiography in healthy children: relationship with age, sex, and anthropometry.

Signal-averaged electrocardiograms (SAECGs) have been found to be influenced by sex and anthropometry in adults. The purpose of this study was to evaluate this relationship in children. Total filtered QRS duration (TQRS), duration of high-frequency, low-amplitude signals in the terminal portion of the QRS complex that were less than 40 microV (HFLA) root-mean-square voltage in the last 40 ms of the filtered QRS (RMS40) were determined by high-resolution electrocardiographic (ECG) recording (MAC 15 ECG System, Marquette Electronics, Milwaukee, WI). These parameters were correlated with age, sex, body weight, height, relative weight, body mass index, and body surface area. As HFLA and RMS40 were not normally distributed, they were logarithmically transformed for regression analysis. The best subset multiple regression procedure was used to evaluate the variables that would optimally influence SAECG measurements and to obtain regression equations for the prediction of each SAECG parameter. Although univariate analysis shows that almost all the body characteristics and age are significantly correlated with SAECGs, multiple regression analysis reveals that TQRS is significantly influenced by height (P < .0001), relative weight (P = .012), and body mass index (P = .041); HFLA is influenced by weight (P = .001), height (P = .004), and body mass index (P = .001); and RMS40 is influenced by height (P < .0001) and relative weight (P = .001). Sex is noted to significantly influence both TQRS and RMS40 (P < .0001, P = .002, respectively), while HFLA is found to be significantly related to age (P = .001). In summary, SAECGs in Chinese children are shown to be influenced by height, weight, and relative weight or body mass index, but not body surface area, while age and sex also significantly contribute to the variation of some SAECG parameters.

Adolescent↗

Traumatic brainstem deafness with normal brainstem auditory evoked potentials.

A 48-year-old woman became totally deaf after a head injury. Magnetic resonance imaging showed bilateral contusions around the inferior colliculi and the brainstem auditory evoked potentials (BAEP) failed to show any abnormality. This case demonstrates that small, symmetrical, bilateral lesions around the inferior colliculi may cause deafness and may still be associated with a normal BAEP.

Auditory Pathways↗

AF12198, a novel low molecular weight antagonist, selectively binds the human type I interleukin (IL)-1 receptor and blocks in vivo responses to IL-1.

Interleukin-1 (IL-1) -alpha and -beta are potent regulators of inflammatory responses. The naturally occurring interleukin-1 receptor antagonist (IL-1ra) is effective in vitro and in vivo in modulating biological responses to IL-1. We have previously reported the discovery of IL-1 antagonist peptides from the search of phage display libraries. Further characterization of this group of peptides has led to a 15-mer, AF12198, Ac-FEWTPGWYQJYALPL-NH2 (J represents the unnatural amino acid, 2-azetidine-1-carboxylic acid), with both in vitro and in vivo IL-1 antagonist activity. AF12198 selectively binds the human type I IL-1 receptor but not the human type II receptor or the murine type I receptor. In vitro, AF12198 inhibits IL-1-induced IL-8 production by human dermal fibroblasts with a half-maximal inhibition concentration or IC50 of 25 nM and IL-1-induced intercellular adhesion molecule-1 (ICAM-1) expression by endothelial cells with an IC50 of 9 nM. When given as an intravenous infusion to cynomolgus monkeys, AF12198 blocks ex vivo IL-1 induction of IL-6 and down modulates in vivo induction of IL-6. This is the first small molecule to show IL-1 receptor antagonist activity in vivo.

Amino Acid Sequence↗

The Singapore naltrexone community-based project for heroin addicts compared with drugfree community-based program: the first cohort.

The cornerstone of heroin rehabilitation in Singapore from 1991 to 1993 was the Three Phase Program (3PP). This was a multimodal approach embracing job placement, individual and family counselling, home placement and restriction of movement by electronic monitoring. Opioid addicts in Singapore are detained by executive order. Inmates volunteer to be on the community program. The completion rate (i.e. the number of inmates presumptively drug-free after 1 year) was 24%. In August 1993, naltrexone, an opiate antagonist without euphorigenic properties was added to the 3PP creating the Naltrexone Pilot Project (NPP). Sufficient similarity existed between the 3PP and NPP for some comparison between the two. The missing link was the chemical blockade offered by naltrexone to provide a deconditioning experience for the decay of learned responses to heroin. The subject can confidently be exposed to drug cues without fear of relapse. Subjects on naltrexone for the first year had a completion rate of 76.3%. In the second year without naltrexone, electronic tagging and counselling, 32.2% were still drug-free. The subject type who was successful was married, older and better educated with late onset in heroin abuse.

Journal Article↗

A case report of a large thymic carcinoid.

Thymic carcinoid is a rare tumour. A case of giant thymic carcinoid with extensive necrosis is reported in a 44-year-old Chinese male. Diagnosis was difficult to make before the operation and even intraoperatively. Subtotal excision was performed followed by adjuvant radiation therapy. The patient remained disease-free at the last follow-up 12 months after surgery. Complete excision remains the mainstay of treatment for this disease.

Carcinoid Tumor↗

Diagnosis of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes in a Chinese family by PCR/restriction enzyme analysis.

The clinical presentation and the biochemical and molecular genetic findings are described in a 13 year old Chinese boy with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). The diagnosis was initially suspected because of the characteristic clinical features and the strong family history of convulsions. Using polymerase chain reaction-restriction enzyme analysis, the heteroplasmic nt3243 A-->G mutation in mtDNA of peripheral blood leucocytes and a muscle sample was demonstrated. The oligosymptomatic relatives were then screened by this method and the degree of heteroplasmy was analysed. This appears to be the first report of a MELAS family in Hong Kong with this described mutation. Molecular genetic techniques are advantageous in the diagnosis of MELAS.

Journal Article↗

Cluster analysis of Helicobacter pylori genomic DNA fingerprints suggests gastroduodenal disease-specific associations.

BACKGROUND: Helicobacter pylori infection is now accepted as the most common cause of chronic active gastritis and peptic ulcer disease. The etiologies of many infectious diseases have been attributed to specific or clonal strains of bacterial pathogens. Polymerase chain reaction (PCR) amplification of DNA between repetitive DNA sequences, REP elements (REP-PCR), has been utilized to generate DNA fingerprints to examine similarity among strains within a bacterial species. METHODS: Genomic DNA from H. pylori isolates obtained from 70 individuals (39 duodenal ulcers and 31 simple gastritis) was PCR-amplified using consensus probes to repetitive DNA elements. The H. pylori DNA fingerprints were analyzed for similarity and correlated with disease presentation using the NTSYS-pc computer program. RESULTS: Each H. pylori strain had a distinct DNA fingerprint except for two pairs. Single-colony DNA fingerprints of H. pylori from the same patient were identical, suggesting that each patient harbors a single strain. Computer-assisted cluster analysis of the REP-PCR DNA fingerprints showed two large clusters of isolates, one associated with simple gastritis and the other with duodenal ulcer disease. CONCLUSIONS: Cluster analysis of REP-PCR DNA fingerprints of H. pylori strains suggests that duodenal ulcer isolates, as a group, are more similar to one another and different from gastritis isolates. These results suggest that disease-specific strains may exist.

Adult↗

Determination of MDL 74,405, a synthetic analogue of alpha-tocopherol, in dog plasma and heart tissue by high-performance liquid chromatography with electrochemical detection.

A high-performance liquid chromatographic (HPLC) procedure with electrochemical detection was developed to analyze MDL 74,405 (I), the (-)-(S)-enantiomer of an alpha-tocopherol analogue, in dog plasma and heart tissue after infusion (0.3 mg/kg/h). The sample preparation involved the addition of an internal standard to either the dog plasma and heart tissue prior to protein precipitation. After centrifugation, the resulting supernatant was directly analyzed by HPLC with a Zorbax Rx C8 column and a mobile phase of acetonitrile-0.04 M potassium phosphate, pH 7.0 (70:30, v/v). The concentration of I found was ca. 100 ng/ml in plasma and ca. 3 micrograms/g in heart tissue. A chiral separation with an Ultron ES-OVM column and a mobile phase of methanol-0.025 M potassium phosphate, pH 6.5 (17:83, v/v) was also used to investigate the enantiomeric conversion of I. Preliminary results of a probe study indicated that I is not inverted to the (+)-(R)-enantiomer in vivo.

Animals↗

Coarctation of the aorta: difficulties in prenatal diagnosis.

OBJECTIVE: To formulate echocardiographic criteria for the prenatal diagnosis of coarctation of the aorta. DESIGN: A retrospective study examining the echocardiograms of fetuses with a verified aortic arch abnormality and those in whom the diagnosis was suspected prenatally but was not subsequently confirmed. SETTING: Tertiary referral centre for fetal echocardiography. PATIENTS: 87 fetuses in whom the diagnosis of coarctation was correctly made in 54, suspected but unproved in 24, and overlooked prenatally in nine. MAIN OUTCOME MEASURES: Measurements of left and right ventricular size, the diameters of the great arteries, the diameters of the left and right atrioventricular valvar orifices, the appearance of the aortic arch, and the direction of the flow of blood across the foramen ovale. RESULTS: Measurements of the ventricular widths, diameters of the great arteries, or the diameters of the atrioventricular valvar orifices, did not allow clear distinction between cases that definitely had a coarctation and those in whom the diagnosis was unproved. The appearance of the aortic arch, particularly in the horizontal projection, was more helpful in distinguishing cases of coarctation, although this also was not always diagnostic. A predominantly left to right shunt across the foramen ovale was detected more often in cases with a substantiated coarctation (58%) than in those with an unproved diagnosis (12%). CONCLUSIONS: The most severe forms of coarctation are associated with relative hypoplasia of the left heart structures compared with the right and a correct diagnosis can be made in early pregnancy. The milder forms of coarctation, however, are consistent with a normal early fetal echocardiogram. In late pregnancy it may be impossible to exclude coarctation categorically as the right heart structures may appear larger than the left in the normal fetus. Thus although a combination of echocardiographic features can correctly identify aortic arch anomalies in the fetus, none either alone or in combination, could clearly distinguish between real and false positive cases, particularly in late gestation.

Aorta, Thoracic↗

Direct enantiomeric separation of terfenadine and its major acid metabolite by high-performance liquid chromatography, and the lack of stereoselective terfenadine enantiomer biotransformation in man.

Direct enantiomeric separation of terfenadine and its major acid metabolite was achieved by using two different chiral stationary phase columns with two different mobile phase systems. Further, the enantiomeric composition of the human urinary acid metabolite has been determined, indicating a non-stereoselective biotransformation in man.

Biotransformation↗

Determination of the metabolites of terfenadine in human urine by thermospray liquid chromatography-mass spectrometry.

Thermospray liquid chromatography-mass spectrometry (TSP LC-MS) was used to determine human urinary metabolites of terfenadine after oral administration of terfenadine tablets. In addition to the two previously identified major metabolites, azacyclonol (MDL 4829) and the 'acid' metabolite (MDL 16,455), three additional metabolites were also detected. One of the additional metabolites was identified as the 'alcohol' metabolite (MDL 17,523) and the other two were proposed to be an 'aldehyde' and a 'ketone-acid' metabolites from their TSP mass spectra. The results of this study demonstrated that TSP LC-MS is a useful technique for the study of terfenadine biotransformation.

Chromatography, Liquid↗

Immunosuppressive therapy in the management of acute myocarditis in children: a clinical trial.

To assess whether steroid therapy influenced the clinical course of myocarditis in a pediatric population, findings in 13 consecutive infants and children (8 female, 5 male) with biopsy-proved myocarditis were reviewed. The mean age was 5.7 +/- 4.8 years (range 1.1 to 14.8). Congestive heart failure was present in all as were ST-T wave changes, cardiomegaly and pulmonary edema on chest roentgenogram. Echocardiography demonstrated pericardial effusion in five patients and mitral regurgitation in eight. Mean left ventricular ejection fraction was 34 +/- 12%. Prednisone was administered to all patients; one patient also received azathioprine. There was one death. All survivors showed clinical improvement with normalization of ECG changes, heart size and systolic function. No significant side effects occurred. Repeat myocardial biopsy in eight patients demonstrated improvement in all eight and elimination of the inflammatory infiltrate in six. Immunosuppressive therapy in this pediatric population appeared useful in improving the clinical course and cardiac function in acute myocarditis with no adverse side effects.

Azathioprine↗

Cardiac function after surgery for subaortic stenosis: non-invasive assessment of left ventricular performance.

OBJECTIVE: To examine left ventricular function after surgical resection of subaortic stenosis during childhood. DESIGN: Left ventricular performance was measured non-invasively in all patients who responded to an invitation for formal assessment. SETTING: Outpatient study, tertiary referral centre. PATIENTS: Twenty three (12 male and 11 female) patients (age range 3 to 31 years) of 43 consecutive patients with fixed subaortic stenosis undergoing surgical resection between 1975 and 1989 reattended for formal assessment 16 months to 15 years (median 4 years 4 months) after operation. MAIN OUTCOME MEASURES: Left ventricular dimension, left ventricular wall thickness, left ventricular Doppler inflow velocities, and left ventricular diastolic pressure (measured from apexcardiograms). Results were compared with those in controls individually matched for age and sex. RESULTS: All patients were symptom free. Left ventricular cavity dimensions were normal, as was the mean fractional shortening. Posterior wall thickness tended to be greater in the patients and there was a significant increase in septal thickness. Normalised peak rate of posterior wall thinning was significantly lower in the patients and the isovolumic relaxation time was significantly shorter. Doppler inflow velocity measurements showed that early diastolic mitral flow acceleration time was normal but deceleration time was significantly shorter in the patients. The ratio of mitral flow in early diastole (E) to E plus mitral flow in late diastole (A) was significantly higher in the patients and in two patients there was complete absence of A wave flow despite large A waves on the apexcardiogram. CONCLUSIONS: Systolic function was well preserved in patients after operation for subaortic stenosis. A restrictive pattern of left ventricular filling was common, however, and presumably reflected a response to the chronic pressure load and to surgery in the paediatric heart.

Adolescent↗

Pharmacokinetic study of recombinant human epidermal growth factor in the anterior eye.

This study investigated the pharmacokinetics of recombinant human epidermal growth factor (EGF) in the eyes of live rabbits and enucleated human eyes. After intracameral injection of 1.2 muCi (1.1 micrograms) of 125I-EGF into rabbit eyes, tissues in the anterior segment were analyzed for uptake of 125I-EGF after 1, 2, 4, and 24 hr. The half-life of EGF during the initial 4 hr was 1.3 +/- 0.6 hr (+/- the confidence limit at P = 0.05) in the cornea, 0.7 +/- 0.4 hr in the iris, 1.9 +/- 0.9 hr in the lens, and 0.6 +/- 0.5 hr in the aqueous humor (n = 18 for each tissue). Between 4-24 hr, the percent retention of EGF in the tissues (relative to the initial amount in respective tissue) is in the order of lens greater than cornea greater than iris greater than aqueous humor. The kinetics of EGF uptake by excised human corneas was determined by incubating the endothelial surface with 1.2 muCi/ml (100 ng/ml) of 125I-EGF for 4 hr at 37 degrees C or 4 degrees C. After 4 hr, the total amount of EGF accumulated in the corneas was 2.3 +/- 0.2 ng (+/- standard deviation; n = 6) at 37 degrees C, and 1.4 +/- 0.1 ng at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗