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Biomedical subjects

P Chan

Publications and source records attributed to P Chan.

At least 37 records · Page 2Linked to original sources

The left human speech-processing cortex is thinner but longer than the right.

We present histological data from 21 post-mortem, adult human cases that indicate the neocortex on the left planum temporale (secondary auditory cortex) is thinner but longer than that on the right side. The volumes of the left and right regions are approximately equal. Thus, the left planum temporale cortex is long and thin and the right short and thick. The present data fit excellently with previous studies of the volume, surface area, cytoarchitectonics, and neuronal structures of these areas. From these studies we suggest that the hemispheric differences arise from a so-called "balloon model" of cortical development. In this the cortex is extended and stretched by white matter growth. The stretching is greater on the left side, leaving greater distances between neuronal columns and more tangentially (to the pial surface) oriented dendrites on that side. This difference in fine structure can result in more independent activity of individual columns on the left, and could be an anatomical factor in the usual dominance of the left hemisphere for speech perception (Seldon, 1982, 1985).

Journal Article↗

Superovulation using recombinant human FSH and ultrasound-guided transabdominal follicular aspiration in baboon (Papio anubis).

The response of baboon females to a modified human ovarian stimulation protocol incorporating start of pituitary suppression in the luteal phase of the cycle with a GnRH agonist (GnRHa) and recombinant human FSH (rhFSH) was studied. A long-acting GnRHa implant supplying goserelin acetate was administered s.c. to six adult female baboons experiencing regular menstrual cycles (33-34 days) on days 22-24 of the cycle. Follicular development was monitored by transabdominal ultrasonography and serum levels of E2 and progesterone (P4) and rhFSH were determined by ELISA. Menses occurred 9-10 days after GnRHa administration. Daily i.m. administration of 75 IU rhFSH commenced 9-10 days after menses and continued for 9-10 days. When most follicles were > or =5mm diameter and serum E2 had reached its maximum level, 2000 IU hCG was administered i.m. to induce follicle maturation. Transabdominal ultrasound-guided follicular aspiration of follicles > or =2mm diameter was performed 30-34h after hCG administration. One baboon did not show an adequate response to rhFSH stimulation. This animal did not receive further treatment and no data for it are presented. The number of follicles aspirated was 21+/-4 and 17.2+/-3.8 oocytes were recovered per animal with an average recovery rate of 82% (86/105). The number of oocytes collected from five animals were 14, 21, 16, 15, and 20 (n=86). Most of the oocytes recovered were in metaphase II and 3h after recovery 91% (78/86) were considered suitable for in vitro fertilization. It was concluded that recombinant human FSH can successfully induce follicular recruitment and oocyte maturation in baboon females during pituitary suppression with a GnRHa

Animals↗

The effects of exercise training on walking function and perception of health status in elderly patients with peripheral arterial occlusive disease.

OBJECTIVE: To determine the effects of 12-week exercise programme on ambulatory function, free-living daily physical activity and health-related quality of life in disabled older patients with intermittent claudication. DESIGN: Prospective, randomized controlled trial. SETTING: University Medical Center and Veterans Affairs Medical Center, Taipei, Taiwan. SUBJECTS: Thirty-two of 64 patients with Fontaine stage II peripheral arterial occlusive disease (PAOD) were randomized to exercise training and 32 to usual care control. Five patients from the exercise group and six patients from the control group dropped out, leaving 27 and 26 patients, respectively, completing the study in each group. INTERVENTIONS: Twelve weeks of treadmill exercise training. MAIN OUTCOME MEASURES: Treadmill walking time to onset of claudication pain and to maximal claudication pain, 6-min walk distance, self-reported ambulatory ability and perceived health-related quality of life (QOL). RESULTS: Compliance of exercise programme was 83% of the possible sessions. Exercise training increased treadmill walking time to onset of claudication pain by 88% (P < 0.001), time to maximal pain by 70% (P < 0.001), and 6-min walk distance by 21% (P < 0.001). SUBJECTS: Perception of health-related QOL improved from 12% to 178% in the exercise group. These improvements were significantly better than the changes in the control group (P < 0.05). CONCLUSIONS: Significant improvements in claudication following 12-week exercise training in elderly PAOD patients were observed. Increase in treadmill walking time to maximal claudication pain in these patients translated into the improvement of perceived physical health, which enabled the patients to become more functionally independent.

Aged↗

In whose best interests? An examination of the ethics of the UK government's White Paper 'Reforming the Mental Health Act'.

Throughout history the legislative framework for the treatment of the mentally ill has reflected societies' attitudes, and the proposals in the United Kingdom (UK) government's White Paper 'Reforming the Mental Health Act' are no exception. This paper examines some of the fundamental ethical issues invoked by the proposals, particularly the concept of paternalism and use of risk assessment in determining 'best interests'. The issue of power in relation to the mentally ill is also examined, alongside the impact of the change on nurses' ethical decision making. As will be seen, the proposed Act will require high standards of professional practice to ensure the ethical application of care, particularly in the case of individuals diagnosed as suffering from 'dangerous and severe personality disorders'. Nurses need to ensure that the interventions used are of the highest quality and are indeed in the patient's 'best interests'. If they are not, then again nurses need to be very clear as to why the profession should be involved at all. Nurses should demonstrate vigilance and high professional standards to ensure they are maintaining rigorous safeguards to promote the public interest. Although relating specifically to UK legislation the underlying ethical dilemmas posed by this proposed legislation are relevant to all mental health nurses, as they challenge fundamental assumptions regarding the role of nurses in supporting mental health legislation that may have a social, rather than therapeutic, function.

Ethics, Clinical↗

Early introduction of clinical skills teaching in a medical curriculum--factors affecting students' learning.

OBJECTIVE: To evaluate the effects of the early introduction of clinical skills teaching on students' learning following an overhaul of the curriculum of a traditional Asian medical school. METHODS: Randomly selected medical students in Year I and II were invited to participate in 30 focus group interviews while all students were asked to assist with the questionnaire survey. Most students were contacted personally to help them understand the objectives of the study. Confidentiality was emphasised and a non-faculty interviewer was recruited for the interviews. RESULTS: Two hundred and eight of Year I/Year II students attended the lunchtime focus group interviews (response rate=86.7%) while 252 (73.5%) students returned the questionnaire. The majority of them (87%) agreed or strongly agreed that it was good to introduce clinical skills in the early years of the curriculum. They reflected that the course enhanced their learning interest and made them feel like doctors. They also made many constructive suggestions on how the course could be improved during the interactive focus group interviews so that the negative effects could be minimised. CONCLUSION: It is useful to introduce clinical skills in the early years of a medical curriculum. A comprehensive course evaluation, using both quantitative and qualitative methods, helps to collect useful information on how the course can be improved.

Clinical Competence↗

Latissimus dorsi mini-flap: a technique for extending breast conservation.

The latissimus dorsi (LD) flap was first used in patients for breast reconstruction in 1896. More recently it has been used to fill defects after quadrantectomy or very wide excision. We have developed a two stage procedure for excision of large breast cancers which would otherwise require mastectomy. The first stage is a wide excision of the cancer without removal of the overlying skin. Thirty patients with large localized operable breast cancer underwent wide local excision followed 5 to 10 days later in 25 patients who had clear histological margins by an axillary dissection with transfer of the LD muscle and overlying fat into the defect in the breast (mini-flap). The cosmetic outcome of these 25 patients who underwent mini-flap were compared with age matched patients having a standard wide local excision and axillary node clearance or mastectomy and immediate breast reconstruction. The volume of tissue excised in patients having their defects filled by LD mini-flap was significantly greater than those women undergoing standard wide excision, p<0.001. Compared with patients who had a mastectomy and immediate breast reconstruction, patients who had mini-flaps reported a better treated breast shape, p=0.04, a greater resemblance to the opposite breast, less self consciousness and less change in attitude of their spouse, p=0.03 and they were more likely to choose the same operation in future compared with patients having immediate whole breast reconstruction, p=0.02. Results as rated by patients in the mini-flap group were similar to those women treated by standard wide local excision. Only one patient in the mini-flap group felt sexually inhibited. When wide local excision and LD mini-flap is performed as a two stage procedure, it is an oncologically safe technique and extends breast conservation to women with larger tumours. The cosmetic outcomes appear better than those following the alternative of mastectomy and immediate breast reconstruction.

Journal Article↗

Effects of rapid atrial pacing on the arrhythmogenic activity of single cardiomyocytes from pulmonary veins: implication in initiation of atrial fibrillation.

BACKGROUND: Pulmonary veins (PVs) are important sources of paroxysmal atrial fibrillation. Long-term rapid atrial pacing (RAP) changes atrial electrophysiology and facilitates the maintenance of atrial fibrillation. It is not clear whether RAP alters the arrhythmogenic activity of PVs. The purpose of this study was to isolate single PV cardiomyocytes from control and RAP dogs and evaluate their electrophysiological characteristics. METHODS AND RESULTS: The action potential and ionic currents were investigated in PV cardiomyocytes from control and long-term (6 to 8 weeks) RAP (780 bpm) dogs by use of the whole-cell clamp technique. Dissociation of PVs yielded rod-shaped single cardiomyocytes without (n=91, 60%) or with (n=60, 40%) pacemaker activity. Compared with the control group, the RAP dog PV cardiomyocytes had faster beating rates (0.86+/-0.28 versus 0.45+/-0.07 Hz, P<0.05) and shorter action potential duration. The RAP dog PV cardiomyocytes with pacemaker activity have a higher incidence of delayed (59% versus 7%, P<0.001) or early (24% versus 0%, P<0.005) after depolarization. The RAP dog PV cardiomyocytes with pacemaker activity had smaller slow inward and transient outward but larger transient inward (0.017+/-0.004 versus 0.009+/-0.002 pA/pF, P<0.05) and pacemaker (0.111+/-0.019 versus 0.028+/-0.008 pA/pF, P<0.001) currents. The RAP dog PV cardiomyocytes without pacemaker activity had only smaller slow inward and transient outward and larger pacemaker currents. CONCLUSIONS: PVs contain multiple cardiomyocytes with distinct electrophysiological characteristics. RAP changes the electrophysiological characteristics and arrhythmogenic activity of PVs.

Action Potentials↗

[Association between DLST gene polymorphism and Alzheimer's disease].

OBJECTIVE: To investigate the association between the polymorphic alleles of dihydrolipoamide succinyltransferase (DLST) gene cDNA at position A19117G in intron 13 and C19183T in exon 14 and the risk for sporandic Alzheimer's disease (SAD). METHODS: The polymorphism of DLST gene was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques in 105 patients with sporadic Alzheimer disease and 109 normal controls. RESULTS: The frequency of AT/AC genotype was found to be significantly higher in SAD patients (21%) than in controls (10%) with an odds ratio of 2.36 (P < 0.05). The frequencies of AC/AC, AT/AT genotypes and AC allele were slightly decreased in cases with SAD as compared with controls. While the frequencies of the GC/GC genotype and GC allele were slightly higher in SAD patients than in controls. However, these differences were not statistically significant (P > 0.05). CONCLUSION: The AT/AC genotype of DLST gene is associated with an increased risk for SAD.

Acyltransferases↗

Enhancement of the anti-herpetic effect of trichosanthin by acyclovir and interferon.

Trichosanthin (TCS) is a type I ribosome-inactivating protein that has a wide range of pharmacological activities. The present study investigated the effectiveness of TCS on herpes simplex virus (HSV-1). The anti-viral activity and toxicity of TCS on Vero cells were measured. Results showed that the ED(50), TD(50) and the therapeutic indices were 38.5, 416.5 and 10.9 microg/ml, respectively. Anti-viral activity of TCS was substantially potentiated when it was used in conjunction with other anti-viral agents. The ED(50) of TCS was reduced 125-fold by acyclovir at a concentration of 0.001 microg/ml, which was practically devoid of significant anti-viral activity. Similarly, the ED(50) of TCS was reduced 100-fold by interferon-alpha2a at a concentration of 100 IU/ml. In conclusion, TCS is effective against HSV-1 and other anti-viral agents such as acyclovir or interferon can potentiate its action substantially.

Acyclovir↗

Stimulatory effect of D-ephedrine on beta3-adrenoceptors in adipose tissue of rats.

The effect of ephedrine on beta3-adrenoceptos (beta3-AR) was studied in the isolated adipose tissue of Wistar rat. Incubation with D-ephedrine (0.1-10 microM) induced a concentration-dependent decrease of uptake of [14C]-deoxy-D-glucose into white adipose tissues (WAT). The inhibitory effect of D-ephedrine was potentiated by BRL 37344, the agonist of beta3-AR and concentration-dependently inhibited by SR 59230A, the selective antagonist of beta3-AR. The action of D-ephedrine on beta3-AR was further blocked by the antibodies for beta3-AR, but not the immunoglobulin. in a concentration-dependent manner. Moreover, D-ephedrine increased glycerol release from the isolated brown adipose tissues (BAT) and this action was also abolished by SR 59230A at concentration sufficient to block beta3-AR. Thus, these results suggest that D-ephedrine has the ability to activate beta3-AR both in WAT and BAT of Wistar rats in vitro.

Adipose Tissue↗

Association of moderate polyglutamine tract expansions in the slow calcium-activated potassium channel type 3 with ataxia.

BACKGROUND: The small-conductance calcium-activated potassium channel gene (hSKCa3) contains 2 CAG repeats, 1 of which is highly polymorphic. Although this repeat is not pathologically expanded in patients with schizophrenia, some studies have suggested an allelic association with schizophrenia. CAG expansions in other genes such as the alpha1 subunit of a brain-specific P/Q-type calcium channel gene cause spinocerebellar ataxia type 6, whereas the length of the CAG repeat in the RAI1 gene modifies the age of onset of spinocerebellar ataxia type 2. OBJECTIVES: To evaluate expansions in the hSKCa3 polyglutamine domain as causative for ataxia, and to study the association between the length of the polyglutamine repeat and the presence of ataxia. METHODS: We analyzed this repeat in 122 patients with autosomal dominant cerebellar ataxia, or sporadic ataxia, and compared allele distribution with 750 alleles seen in 2 healthy control groups and 172 alleles in patients with Parkinson disease. RESULTS: The distribution of alleles in ataxia patients and controls was significantly different by Wilcoxon rank test (P <.001). Twenty-two or more polyglutamine tracts were more common in ataxia patients compared with controls by chi2 analysis (P<.001). CONCLUSION: Longer stretches of polyglutamines in a human potassium channel are not causative for ataxia, but they are associated with the presence of ataxia. There is no association with the presence of Parkinson disease.

Age of Onset↗

Lewy bodies and parkinsonism in families with parkin mutations.

Previous work has established that compound mutations and homozygous loss of function of the parkin gene cause early-onset, autosomal recessive parkinsonism. Classically, this disease has been associated with loss of dopaminergic neurons in the substantia nigra pars compacta and locus ceruleus, without Lewy body pathology. We have sequenced the parkin gene of 38 patients with early-onset Parkinson's disease (<41 years). Two probands with mutations were followed up. Clinical evaluation of their families was performed, blinded to both genetic and pathological findings. Chromosome 6q25.2-27 haplotype analysis was carried out independently of the trait; parkin gene expression was examined at both the RNA and protein levels. Haplotype analysis of these families revealed a common chromosome 6, with a novel 40 bp exon 3 deletion that cosegregated with disease. In the proband of the smaller kindred, an exon 7 R275W substitution was identified in addition to the exon 3 deletion; RNA analysis demonstrated that the mutations were on alternate transcripts. However, Lewy body pathology typical of idiopathic Parkinson's disease was found at autopsy in the proband from the smaller kindred. These data suggest that compound heterozygous parkin mutations and loss of parkin protein may lead to early-onset parkinsonism with Lewy body pathology, while a hemizygous mutation may confer increased susceptibility to typical Parkinson's disease.

Adult↗

The addition of fentanyl does not alter the extent of spread of intrathecal isobaric bupivacaine in clinical practice.

PURPOSE: Fentanyl is commonly added to intrathecal local anesthetic solutions. In vitro data has shown fentanyl to render isobaric local anesthetics hypobaric, and alter the spread in artificial cerebrospinal fluid. This study examined whether the addition of fentanyl to isobaric bupivacaine with morphine leads to a clinically important alteration in the extent of spread of anesthesia. METHODS: Forty-four ASA I-III patients undergoing lower limb orthopedic procedures completed this double-blind, placebo-controlled trial. Patients were randomized into one of two groups, receiving intrathecal bupivacaine 15 mg and preservative-free morphine 200 microg without (Control group), or with the addition of fentanyl 0.02 mg (Fentanyl group). Patients were maintained at a slight head-up tilt. Variables studied over three hours included sensory level to cold and pinprick, motor blockade (Bromage scale), and circulatory data. RESULTS: No differences existed between the Fentanyl and Control groups with respect to highest level of block for cold: T4 (T2-T5) vs T3.5 (T3-T8) respectively (median, 95% confidence interval) or pinprick: T4 (T3-T6) vs T4.5 (T3-T8). Similarly, there was no difference in the time taken to reach maximum block height to cold (20 +/- 9 vs 23 +/- 13 min, mean +/- SD) or pinprick (20 +/- 9 vs 24 +/- 13 min). CONCLUSION: The addition of fentanyl 0.02 mg to 0.5% bupivacaine with morphine does not affect the maximal block height or time to maximal block in clinical practice.

Adult↗

Efficacy study of video-assisted thoracoscopic surgery pleurodesis for spontaneous pneumothorax.

BACKGROUND: This study aims to assess the efficacy of video-assisted thoracoscopic surgery pleurodesis in the treatment of spontaneous pneumothorax with particular reference to the rate of recurrence after abrasion pleurodesis and postoperative neuralgia. METHODS: One hundred one patients who underwent 109 video-assisted thoracoscopic surgery pleurodesis procedures in the Austin & Repatriation Medical Centre between January 1992 and June 1998 were identified from a computerized database. The follow-up period was from 8 months to 7 years and 1 month (mean, 44.4 months). Patients were telephoned and asked as to whether recurrence occurred, and if so, when it occurred and how it was treated. They were asked to grade their current pain level from 0 to 6. RESULTS: Eighty-two patients were contacted, corresponding to 88 video-assisted thoracoscopic surgery pleurodesis procedures that were followed up (80.7%). There were five recurrences (5.7%). The pain level was rated as 0 in 64 cases (72.7%), 1 in 27 cases (23.9%), 2 in 1 case (1.1%), and 3 in 2 cases (2.3%). CONCLUSIONS: These data suggest that video-assisted thoracoscopic surgery pleurodesis is a valid alternative to thoracotomy with pleurectomy for treatment of spontaneous pneumothorax with an acceptable recurrence rate and minimal amount of postoperative neuralgia.

Adolescent↗

Development of a (32)P-postlabeling/HPLC method for detection of dehydroretronecine-derived DNA adducts in vivo and in vitro.

Pyrrolizidine alkaloids are naturally occurring genotoxic chemicals produced by a large number of plants. Metabolism of pyrrolizidine alkaloids in vivo and in vitro generates dehydroretronecine (DHR) as a common reactive metabolite. In this study, we report the development of a (32)P-postlabeling/HPLC method for detection of (i) two DHR-3'-dGMP and four DHR-3'-dAMP adducts and (ii) a set of eight DHR-derived DNA adducts in vitro and in vivo. The approach involves (1) synthesis of DHR-3'-dGMP, DHR-3'-dAMP, and DHR-3',5'-dG-bisphosphate standards and characterization of their structures by mass and (1)H NMR spectral analyses, (2) development of optimal conditions for enzymatic DNA digestion, adduct enrichment, and (32)P-postlabeling, and (3) development of optimal HPLC conditions. Using this methodology, we have detected eight DHR-derived DNA adducts, including the two epimeric DHR-3',5'-dG-bisphosphate adducts both in vitro and in vivo.

Animals↗