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A Cheng

Publications and source records attributed to A Cheng.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cardiovascular drug therapy in patients with hepatic diseases and patients with congestive heart failure.

Hepatic impairment can alter the pharmacokinetic profiles of cardiovascular drugs, which can lead to unwanted toxicity. In the presence of cirrhosis, portosystemic shunting occurs and cytochrome P450 activity is reduced. Impaired oxygen uptake caused by changes in the liver's sinusoids, as proposed by the oxygen limitation theory, may also explain the alteration of drug metabolism seen in cirrhosis. With congestive heart failure, sinusoidal congestion and hypoperfusion of the liver are seen. Similar to cirrhosis, the common pathway for hepatic damage in congestive heart failure seems to be liver hypoxia, which may explain the disease's effect on drug metabolism. Since routine hepatic function tests do not always relate to the liver's ability to eliminate drugs, existing guidelines for dosing cardiovascular drugs in patients with hepatic impairment are limited. This article provides guidance for dosing cardiovascular drugs in cirrhotic and heart failure patients based on available research data. Altered drug metabolism, especially in congestive heart failure, tends to be overlooked or not realized in clinical practice. Therefore, further research is needed in congestive heart failure to better elucidate safe prescribing patterns.

Cardiovascular Agents↗
PubMed2000

Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome.

Androgen insensitivity syndrome (AIS) is the most common single entity that results in male under-masculinization, but large cohort studies of AIS have rarely been performed. Over the last decade, nationwide cooperation between pediatric endocrinologists in the United Kingdom has allowed the creation of a database of cases of intersex and ambiguous genitalia where detailed clinical information on every notified case has been collected via a questionnaire. Among the 816 entries recorded by January 1999, there were 105 clinically diagnosed cases of complete AIS (CAIS) and 173 cases of partial AIS (PAIS). A masculinization score was devised by scoring the external phenotype, and a score of 12 represented normal masculinization. Androgen receptor (AR) binding was determined by studying binding capacity (Bmax) and receptor affinity (K(d)), and cases were classified as either zero, abnormal, or normal binding. Mutation screening of all eight exons of the AR gene was performed by single-strand conformational polymorphism analysis, followed by direct DNA sequencing. All cases of PAIS presented within the first month of birth. The median age at presentation of children with CAIS was 1 yr (P10,P90: 0.1,10.4). The testes were palpable in the labioscrotal folds or the inguinal region in 77% and 41% of cases of CAIS and PAIS, respectively. There was marked overlap between the masculinization score of those children with PAIS reared as girls [2.5(P10,P90:1, 6)] and those reared as boys [3(P10,P90:2, 7.5)]. Gonadectomy was performed prepubertally in 66% and postpubertally in 29% of the cases of CAIS. The median age of the latter group was older at 14 yr (P10,P90:0.1,18). No cases of malignancy or carcinoma in situ were reported in the 121 cases of AIS where histology results were available. Biochemical endocrine investigations were reported to have been performed in a greater number of cases of PAIS than CAIS (98% vs. 48%). AR binding was abnormal in 44 of 51 (86%) and 40 of 113 (35%) cases of CAIS and PAIS, respectively. Zero binding was encountered in 29 of 43 (67%) and 1 of 55 (2%) cases of CAIS and PAIS, respectively. Mutational analysis of the AR gene, performed in 102 index cases was positive in 57 of 69 (83%) cases of CAIS and 12 of 43 (28%) cases of PAIS. In 24 of these cases, the mutation identified was novel. The mutations in PAIS cases were all missense, whereas in CAIS the mutations were more diverse. AR binding was only normal in 3 of 69 mutation-positive cases. In the PAIS group, mutation-positive cases had a significantly higher Kd and Bmax compared to the mutation negative cases. The clinical diagnosis of AIS can be confirmed in a significant number of cases by a combination of androgen-binding studies and mutational analysis. There is some correlation between the phenotypic features and the abnormalities discovered on mutational analysis of the AR gene, but there is a need to improve this further by developing optimal bioassays of AR function. The phenotypic heterogeneity among clinically diagnosed cases of AIS emphasizes the need for appropriate comprehensive evaluation of male under-masculinization.

Amino Acid Sequence↗
PubMed2000

Diagnosis of pacemaker lead infection using transoesophageal echocardiography: a case report.

INTRODUCTION: Vegetative lead infection is an uncommon complication of permanent pacemaker implantation. The diagnosis is difficult using conventional imaging methods. CLINICAL PICTURE: An elderly Indian woman with a history of diabetes mellitus developed Staphylococcus aureus infection after implementation of a permanent pacemaker. Following a non-diagnostic transthoracic echocardiogram, transoesophageal echocardiography was performed and showed a large vegetative mass attached to the pacemaker lead within the right atrium. TREATMENT: The pacemaker was removed and intravenous vancomycin administered for six weeks. OUTCOME: She was discharged well but demised two months later from a second episode of septicaemia. CONCLUSIONS: Pacemaker lead infection remains a challenging management problem. Transoesophageal echocardiography can facilitate its diagnosis.

Aged↗
PubMed2000

Hybrid cardiac revascularisation surgery.

Currently, 3 methods of myocardial revascularisation are available for the treatment of coronary artery disease: i) coronary artery bypass grafting (CABG); ii) percutaneous transluminal coronary angiography (PTCA), and iii) transmyocardial laser revascularisation (TMR). Until recently, these procedures were performed exclusive to one another. We report 2 cases of minimally invasive direct coronary artery bypass grafting with subsequent PTCA, and 1 case of staged PTCA followed by TMR performed at our institution. We discuss the role of hybrid procedures in the current era of treatment of ischaemic heart disease.

Aged↗
PubMed2000

Initial experience of radiofrequency catheter ablation of supraventricular tachycardia in paediatric patients.

INTRODUCTION: The management of supraventricular tachycardia (SVT) in paediatric patients until recently has frequently been pharmacologic therapy, but this approach suffers from the drawbacks of treatment failure, development of drug intolerance and/or side-effects. AIM: In keeping with recent advances in paediatric cardiology, we share our experience with radiofrequency catheter ablation as an alternative and definitive modality of therapy. MATERIALS AND METHOD: 4 young patients with recurrent SVT underwent electrophysiologic study followed by radiofrequency ablation of the accessory pathways. RESULTS: Resolution of symptoms was achieved in all patients and no major complication was encountered. CONCLUSIONS: The ability to ablate permanently the reentrant circuit responsible for SVT has now permitted cure by non-surgical means, and is an important alternative to drug therapy in the management of SVT in children.

Adolescent↗
PubMed2000

Biophysics and synchrotron radiation where the marriage fails. X-ray damage of lipid membranes and mesophases.

The call for brighter synchrotron X-radiation sources for use in structural biology research is barely audible as we enter the new millennium. Our brightest sources are already creating havoc when used at design specifications because of radiation damage. The time is long overdue to take stock of where we are and where we wish to go with regards to using existing sources and to designing new ones. The problem of radiation damage is particularly severe in studies involving kinetics and mechanism where cryotechniques are not always viable. Accordingly, we need to understand the very nature of radiation damage and to devise means for minimizing it. This is the thrust of the current study as applied to lipid membranes and mesophases. Here, we report on two very different types of radiation damage. One involves a dramatic phase transformation and the other a disordering of lamellar stacking. How beam energy and dose/rate affect damage is also discussed. The work highlights the nature of the damage process and the need for additional studies if we are to make most efficient use of an important resource, synchrotron radiation.

Biophysical Phenomena↗
PubMed2000

The use of abciximab in coronary angioplasty--an Asian centre's experience.

BACKGROUND: Abciximab, a monoclonal antibody to platelet glycoprotein IIb/IIIa receptor, has been shown to be effective in reducing ischemic complications after coronary angioplasty in recent trials. However, little is known about its efficacy and safety when used in Asian patients. METHODOLOGY: Based on our abciximab registry, we performed a retrospective analysis of 115 Asian patients who received the antiplatelet agent while undergoing percutaneous coronary intervention in our centre. They constituted 18.4% of the total number of patients undergoing percutaneous revascularisation during the corresponding period. The majority of the patients were males (84%). The mean age of the cohort was 54 and the mean weight was 70 kg. The ethnic composition of the study population was: Chinese 54%, Indians 21%, Malays 19% and Others 6%. All patients received aspirin 100 mg and weight-adjusted heparin before the procedure. Abciximab may be administered on a preplanned basis prior to the procedure or be given as a 'bailout' strategy. RESULTS: There was a high clinical success rate of 95.8% and low incidence of ischemic complications when abciximab was given during coronary angioplasty. There were 0% Q myocardial infarction, 3.3% non-Q myocardial infarction and 0.8% death in our series. Bleeding complications were uncommon at 7.6%, predominantly involving the groin and gingiva. Thrombocytopenia occurred in 5.8% of patients. Abciximab was noted to increase the procedural activated clotting time (ACT) by 38 seconds when given concomitantly with heparin. The mean maximal procedural ACT achieved was 323 +/- 51 seconds. CONCLUSIONS: Abciximab may be used safely and efficaciously in Asian patients undergoing coronary angioplasty. The drug confers protection against ischemic complications during the procedure whether it is administered electively or as a 'bailout'. There is however, a need to redefine the heparin regime for our patients, given the high ACT obtained when abciximab is administered.

Abciximab↗
PubMed2000

Development of an affordable diaphragmatic pump for cardiopulmonary bypass: an in vivo evaluation.

A new diaphragmatic pump (L-Y pump) and its drive unit were developed in our institute. The pump has a priming volume of 80 ml. The pump housing is 72 mm in diameter and 42 mm in height. Its total weight is 139 g. To assess and confirm the function and controllability of this pump, comparative studies of cardiopulmonary bypass (CPB) with L-Y pump (group A) and conventional roller pump (Group B) were performed using dogs. Both pumps provided pump flow of 90 to 100 ml/kg/min. The hemodynamics of both groups were stable and within the normal range. No leakage or thrombus formation was observed in the L-Y pump. All biochemistry data showed no significant differences between the 2 groups. This data demonstrated low plasma-free hemoglobin levels in the L-Y pump group; after 120 min of CPB, mean plasma free hemoglobin levels were 48.7 +/- 8.6 mg/dl in the roller pump group and 21.4 +/- 7.1 mg/dl in the L-Y pump group, and minimal hemolysis was indicated. In conclusion, this L-Y pump and its controller system might be useful for CPB in terms of its low hemolysis and good pump quality. This pump demonstrated easy manipulation, good controllability, and provided a sufficient pulsatile flow. This pump is suitable not only for CPB, but also as a long-term circulatory support system.

Animals↗
PubMed1999

Menopausal symptoms and symptom clustering in Chinese women.

OBJECTIVES: this paper aims to report the prevalence of symptoms in the Hong Kong Chinese perimenopausal women; to construct reported symptoms into symptom groupings; and to clarify whether the symptom groups are associated with menopausal status. METHODS: a random telephone survey of perimenopausal women aged 44-55 years was conducted in 1996. Eligible subjects were identified through telephone dialing of a random sample of the numbers listed in the residents' telephone directory. Standardized questionnaire, including a 22-item symptom check list, was administered over the telephone. The principal component analysis method followed by varimax rotation was used to examine the relations among the symptoms. RESULTS: differences in the prevalence of menstrual problems across the menopausal status were noted with perimenopausal women having the most complaints. Musculoskeletal conditions were the top complaints reported by the respondents, followed by headaches and psychological symptoms. About 10% of the women complained of hot flushes, and less than 5% of cold sweats. Five symptom clusters, namely psychological, musculoskeletal/gastrointestinal, non-specific somatic, respiratory, and vasomotor, have been identified. After adjustment for age, the analysis of variance showed that psychological, non-specific somatic and vasomotor symptoms were significantly associated with menopausal status, while musculoskeletal and respiratory were of borderline statistical significance. CONCLUSIONS: compared with pre- and post-menopausal women, perimenopausal women had the highest reports of symptom complaints. Musculoskeletal complaints were the most prevalent complaints, followed by psychological symptoms. While vasomotor symptoms were significantly associated with menopausal status, their prevalence was comparatively lower than that reported in Caucasian populations.

Adult↗
PubMed1999

Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases.

Activating phosphorylation of cyclin-dependent protein kinases (CDKs) is necessary for their kinase activity and cell cycle progression. This phosphorylation is carried out by the Cdk-activating kinase (CAK); in contrast, little is known about the corresponding protein phosphatase. We show that type 2C protein phosphatases (PP2Cs) are responsible for this dephosphorylation of Cdc28p, the major budding yeast CDK. Two yeast PP2Cs, Ptc2p and Ptc3p, display Cdc28p phosphatase activity in vitro and in vivo, and account for approximately 90% of Cdc28p phosphatase activity in yeast extracts. Overexpression of PTC2 or PTC3 results in synthetic lethality in strains temperature-sensitive for yeast CAK1, and disruptions of PTC2 and PTC3 suppress the growth defect of a cak1 mutant. Furthermore, PP2C-like enzymes are the predominant phosphatases toward human Cdk2 in HeLa cell extracts, indicating that the substrate specificity of PP2Cs toward CDKs is evolutionarily conserved.

CDC28 Protein Kinase, S cerevisiae↗
PubMed1999

Estimating the mass of asteroid 433 eros during the NEAR spacecraft flyby

The Near Earth Asteroid Rendezvous (NEAR) spacecraft flew within 3830 kilometers of asteroid 433 Eros on 23 December 1998. The gravitational perturbation on NEAR was evident in the spacecraft tracking data. Ground-based Doppler and range tracking of the spacecraft as well as spacecraft images of the asteroid's center of figure and surface features were used to determine the mass and rotation pole of Eros. The mass of Eros is (7.2 +/- 1.8) x 10(18) grams and, coupled with a volume estimate provided by the NEAR imaging team, this mass suggests a bulk density of 2.5 +/- 0.8 grams per cubic centimeter. The rotation pole position is 15.6 (+/-3.7) degrees in right ascension and 16.4 (+/-1.8) degrees in declination, which is consistent with ground-based and NEAR imaging team observations.

Journal Article↗
PubMed1999

Imaging of asteroid 433 eros during NEAR's flyby reconnaissance

During the 23 December 1998 flyby of asteroid 433 Eros, the Near-Earth Asteroid Rendezvous (NEAR) spacecraft obtained 222 images of Eros, as well as supporting spectral observations. The images cover slightly more than two-thirds of Eros (best resolution is approximately 400 meters per pixel) and reveal an elongated, cratered body with a linear feature extending for at least 20 kilometers. Our observations show that Eros has dimensions of 33 x 13 x 13 kilometers. The volume, combined with the mass determined by the NEAR radio science experiment, leads to a density of 2.5 +/- 0.8 grams per cubic centimeter. This relatively high density, and the presence of an extensive linear feature, suggest that Eros may be a structurally coherent body.

Journal Article↗
PubMed1999

In vivo human brachial artery elastic mechanics: effects of smooth muscle relaxation.

BACKGROUND: The effects of smooth muscle relaxation on arterial wall mechanics are controversial. We used a new, in vivo, noninvasive technique to measure brachial artery wall mechanics under baseline conditions and following smooth muscle relaxation with nitroglycerin (NTG). METHODS AND RESULTS: Eight healthy, normal subjects (6 male, 2 female; age 30+/-3.1 years) participated in the study. The nondominant brachial artery was imaged through a water-filled blood pressure cuff using an external ultrasound wall-tracking system at baseline and following 0.4 mg sublingual NTG. Simultaneous radial artery pressure waveforms were recorded by tonometry. Transmural pressure (TP) was reduced by increasing water pressure in the cuff. Brachial artery area, unstressed area, compliance, stress, strain, incremental elastic modulus (Einc), and pulse wave velocity (PWV) were measured over a TP range from 0 to 100 mm Hg. Baseline area versus TP curves generated 30 minutes apart were not significantly different. NTG significantly shifted area versus TP (P<0.0001) and compliance versus TP (P<0.001) curves upward, whereas the Einc versus TP (P<0.05) and PWV versus TP (P<0. 01) curves were shifted downward. NTG also significantly shifted stress versus strain (P<0.01) and Einc versus strain (P<0.01) curves to the right. CONCLUSIONS: We conclude that brachial artery elastic mechanics can be reproducibly measured over a wide range of TP and smooth muscle tone using a new noninvasive ultrasound technique. Smooth muscle relaxation with NTG increases isobaric compliance and decreases isobaric Einc and PWV in the human brachial artery.

Adult↗
PubMed1999

MAP5 expression in proliferating neuroblasts.

MAP5, a microtubule-associated protein present in immature neurons, was found to be expressed in the embryonic mouse telencephalic ventricular zone (VZ). Since the VZ contains proliferating neuroblasts, the source of most of the neurons of the cerebral cortex, this observation raised the possibility that MAP5 is expressed by proliferating neuronal progenitors. MAP5-positive mitotic cells were observed at the ventricular surface, a finding consistent with progenitors expressing MAP5 prior to their last division. This possibility was investigated using dissociated, cortical cells in vitro by measuring the expression of MAP5 and the neuroepithelial marker nestin, together with the incorporation of bromodeoxyuridine (BrdU), a thymidine analogue that labels the DNA of proliferating cells in the S-phase of the cell cycle. All of the proliferating cells expressed nestin. A population of MAP5-positive cells was also found to incorporate BrdU; some cells expressed MAP5 within 30 min of BrdU labeling. The results suggest that uncommitted neuroblasts express only nestin, with expression of MAP5 occurring near the time the cell commits to become a postmitotic neuron after the next cell division. Subsequently, cells expressing both MAP5 and nestin leave the cell cycle and exit the VZ, lose nestin, and differentiate into neurons. Since some cells expressed MAP5 during or shortly after S-phase but before mitosis, MAP5 may be the earliest marker to identify neuronal progenitors that will become post-mitotic neurons following their next mitosis.

Animals↗
PubMed1999

Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene.

Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity.

Animals↗
PubMed1999

Secondary prevention of myocardial infarction: role of beta-adrenergic blockers and angiotensin-converting enzyme inhibitors.

beta-Blockers reduce cardiovascular death and reinfarction in patients with a history of myocardial infarction (MI), and angiotensin-converting enzyme (ACE) inhibitors provide an overall survival benefit in patients with signs or symptoms of left ventricular (LV) dysfunction and a history of acute MI. Despite this, these agents remain underused in clinical practice. Appropriate patient selection in standard clinical practice should be encouraged in order to achieve a mortality rate reduction comparable to that seen in clinical trials. It appears from the findings of recent studies that the greatest benefit from beta-blocker therapy is achieved in patients who are more than 60 years of age and in patients at moderate or high risk for reinfarction and death (eg, patients with LV dysfunction or arrhythmias or both). Patients with class I-IV heart failure treated with ACE inhibitors have fewer recurrent infarctions, a lower incidence of severe congestive heart failure, and a reduced incidence of total cardiovascular death and sudden cardiac death. In addition to the studies completed in patients with MI, there are ongoing studies evaluating whether or not ACE inhibitors can reduce myocardial ischemic events in patients without a prior infarction who have coronary artery disease or hypertension and preserved LV function. There is also growing evidence that concomitant therapy with a beta-blocker and an ACE inhibitor may reduce mortality rates beyond that observed with ACE inhibitors alone in survivors of MI who have LV dysfunction.

Adrenergic beta-Antagonists↗
PubMed1999

Janus kinases and their role in growth and disease.

Janus kinases (JAK) play a crucial role in the initial steps of cytokine signaling. Each of the four members (JAK1, JAK2, JAK3, TYK2) of this non-receptor tyrosine kinase family is indispensable for the effects of distinct cytokines. Moreover, recent reports have added to our knowledge on their highly specific functions: JAK3 knockout mice and JAK3 deficient patients cannot signal through the interleukin-2,4,7,9, or 15 receptors and suffer from severe combined immunodeficiency (SCID). JAK1 and JAK2 knockout mice do not survive, their cells again showing distinct patterns of cytokine signaling deficits. At the other end of the spectrum, JAK fusion proteins have been shown to play a role in leukemias. In addition, a new class of JAK-specific inhibitors was described by several groups, the CIS/SOCS/Jab family. This review on the rapidly growing field focuses on JAK function and regulation, and on their emerging role in development and human disease.

Animals↗