Biomedical subjects

C S Chiu

Publications and source records attributed to C S Chiu.

At least 19 recordsLinked to original sources

PubMed2006

Behavioral and biochemical characterization of a mutant mouse strain lacking D-amino acid oxidase activity and its implications for schizophrenia.

D-amino acid oxidase (DAO) degrades D-serine, a co-agonist at the NMDA receptor (NMDAR). Hypofunction of the NMDAR has been suggested to contribute to the pathophysiology of schizophrenia. Intriguingly, DAO has been recently identified as a risk factor for schizophrenia through genetic association studies. A naturally occurring mouse strain (ddY/DAO-) has been identified which lacks DAO activity. We have characterized this strain both behaviorally and biochemically to evaluate DAO as a target for schizophrenia. We have confirmed that this strain lacks DAO activity and shown for the first time it has increased occupancy of the NMDAR glycine site due to elevated extracellular D-serine levels and has enhanced NMDAR function in vivo. Furthermore, the ddY/DAO- strain displays behaviors which suggest that it will be a useful tool for evaluation of the clinical benefit of DAO inhibition in schizophrenia.

Acoustic Stimulation↗

PubMed2002

Outcome of infants with right atrial isomerism: is prognosis better with normal pulmonary venous drainage?

OBJECTIVE: To compare the outcome of infants and children who have right atrial isomerism and normal pulmonary venous drainage with those who have anomalous drainage, and to determine factors associated with poor outcome. DESIGN AND PATIENTS: Retrospective review of management and outcome of 116 infants and children determined to have right atrial isomerism between January 1980 and December 2000. SETTING: Tertiary paediatric cardiac centre. RESULTS: The 116 patients presented at a median of one day (range 1 day to 3.7 years) with cyanosis in the majority (96%). No interventions were planned in 31 (27%) patients, all of whom died. The early surgical mortality for pulmonary venous repair was 25% (2 of 8), Fontan procedure 26% (5 of 19), cavopulmonary shunting 7.7% (1 of 13), and systemic pulmonary arterial shunt insertion 1.9% (1 of 53). Late mortality was related to infection (n = 10), sudden death of unknown aetiology (n = 7, 5 with history of arrhythmia), and documented arrhythmia (n = 1). Patients with obstructed anomalous pulmonary venous drainage had the worst survival (p < 0.001). The mean (SEM) survival estimates for those with normal pulmonary venous drainage at 1, 5, 10, and 15 years was 81 (5.3)%, 67 (6.6)%, 60 (7.8)%, and 43 (12)%, respectively, similar to those for patients with non-obstructed anomalous drainage (p = 0.06). Independent risk factors for mortality included pulmonary venous obstruction (relative risk 3.8, p = 0.001) and a single ventricle (relative risk 2.9, p = 0.016). An analysis of only patients with normal pulmonary venous drainage identified no risk factors for mortality. CONCLUSIONS: The long term outcome of infants and children with right atrial isomerism in association with a normal pulmonary venous drainage remains unfavourable. Sepsis and sudden death that may potentially be related to cardiac arrhythmia are major causes of late mortality.

Algorithms↗

PubMed2001

Analysis of indications for surgical closure of subarterial ventricular septal defect without associated aortic cusp prolapse and aortic regurgitation.

Subarterial ventricular septal defect (VSD) is relatively common in Orientals. We reviewed the outcome of 214 patients (137 males) who were followed for 8.6 +/- 5.2 years (range 0.1 to 24.3) and addressed the issue regarding the necessity and optimum timing of closing subarterial defects before development of aortic valve deformities. Demographic data, transthoracic and transesophageal echocardiographic findings, cardiac catheterization results, and operative findings were reviewed. Kaplan-Meier actuarial analysis was performed to assess the development of aortic valve complications over time. Seventy-five patients with heart failure and pulmonary hypertension underwent surgical closure of VSD at the age of 2.4 +/- 2.9 years. No patient had aortic cusp prolapse before operation and none developed aortic cusp prolapse or aortic regurgitation (AR) on follow-up. In contrast, of the 139 asymptomatic patients managed conservatively, 102 (73%) developed aortic cusp prolapse, 78% of whom (80 of 102) developed AR. The prevalence of aortic cusp prolapse and AR at 1, 5, 10, and 15 years old was 8%, 30%, 64%, and 83%, and 3%, 24%, 45%, and 64%, respectively. Significant prolapse or AR prompted surgical closure of VSD with (n = 22) or without (n = 26) valvoplasty in 48 of 102 patients (47%). The size of the VSD was significantly larger in patients with heart failure (9.6 +/- 3.3 mm) or aortic cusp prolapse (11.7 +/- 4.1 mm) compared with those without heart failure (4.5 +/- 1.4 mm, p <0.001). All patients with aortic cusp prolapse and all but 1 with heart failure had a defect size of > or =5 mm. In conclusion, subarterial VSD of > or =5 mm should be closed as early as possible to prevent development of aortic cusp prolapse and AR. Asymptomatic patients with small defects <5 mm could be managed conservatively.

Adolescent↗

PubMed2001

Activation-dependent changes in receptor distribution and dendritic morphology in hippocampal neurons expressing P2X2-green fluorescent protein receptors.

ATP-gated P2X(2) receptors are widely expressed in neurons, but the cellular effects of receptor activation are unclear. We engineered functional green fluorescent protein (GFP)-tagged P2X(2) receptors and expressed them in embryonic hippocampal neurons, and report an approach to determining functional and total receptor pool sizes in living cells. ATP application to dendrites caused receptor redistribution and the formation of varicose hot spots of higher P2X(2)-GFP receptor density. Redistribution in dendrites was accompanied by an activation-dependent enhancement of the ATP-evoked current. Substate-specific mutant T18A P2X(2)-GFP receptors showed no redistribution or activation-dependent enhancement of the ATP-evoked current. Thus fluorescent P2X(2)-GFP receptors function normally, can be quantified, and reveal the dynamics of P2X(2) receptor distribution on the seconds time scale.

Adenosine Triphosphate↗

PubMed2001

Single-molecule measurements calibrate green fluorescent protein surface densities on transparent beads for use with 'knock-in' animals and other expression systems.

Quantitative aspects of synaptic transmission can be studied by inserting green fluorescent protein (GFP) moieties into the genes encoding membrane proteins. To provide calibrations for measurements on synapses expressing such proteins, we developed methods to quantify histidine-tagged GFP molecules (His6-GFP) bound to Ni-NTA moieties on transparent beads (80-120 microm diameter) over a density range comprising nearly four orders of magnitude (to 30000 GFP/microm2). The procedures employ commonly available Hg lamps, fluorescent microscopes, and CCD cameras. Two independent routes are employed: (1) single-molecule fluorescence measurements are made at the lowest GFP densities, providing an absolute calibration for macroscopic signals at higher GFP densities; (2) known numbers of His6-GFP molecules are coupled quantitatively to the beads. Each of the two independent routes provides linear data over the measured density range, and the two independent methods agree with root mean square (rms) deviation of 11-21% over this range. These satisfactory results are obtained on two separate microscope systems. The data can be corrected for bleaching rates, which are linear with light intensity and become appreciable at intensities > approximately 1 W/cm2. If a suitable GFP-tagged protein can be chosen and incorporated into a 'knock-in' animal, the density of the protein can be measured with an absolute accuracy on the order of 20%.

Animals↗

PubMed2001

Coronary artery fistulas: long-term results of surgical correction.

BACKGROUND: Opinions vary as to whether operation should be offered patients with coronary artery fistula, particularly to those who are asymptomatic. Published studies lacked long-term follow-up data. METHODS: We studied 41 patients with coronary artery fistula operated in our unit in the past 30 years with restudies including coronary angiograms in those who agreed to the investigation. RESULTS: There was no operative mortality and operative morbidity was low. The mean duration of follow-up was 9.1 years and 96.9% of the patients were asymptomatic. Twenty-one patients had a coronary angiogram. The native coronary artery either remained dilated and tortuous, or more frequently had thromboses with a short proximal stump. (None of these patients had evidence of myocardial ischemia.) Four patients had demonstrable recurrence fistula but without hemodynamic disturbance. CONCLUSIONS: We advocate operation for all patients with coronary artery fistulas and demonstrable shunting in view of minimal operative risks. Small asymptomatic fistulas without demonstrable shunting should be left alone. The relatively high incidence of residual or recurrent fistula makes long-term follow-up mandatory.

Adolescent↗

PubMed2000

Effects of biatrial pacing in prevention of postoperative atrial fibrillation after coronary artery bypass surgery.

BACKGROUND: Atrial fibrillation (AF) is common after coronary artery bypass surgery (CABG) and results in prolonged hospitalization. The purpose of this study was to evaluate the efficacy of biatrial pacing in preventing post-CABG AF compared with single-site atrial pacing. METHODS AND RESULTS: A total of 132 patients who had no history of AF and who underwent CABG were randomized to 1 of the following 4 groups: biatrial pacing (BiA), left atrial pacing (LA), right atrial pacing (RA), or no pacing (control) in postoperative period. Overdrive atrial pacing was performed for 5 days. The incidence of AF was significantly reduced in the BiA group (12.5%) compared with the other 3 groups (LA, 36.4%; RA, 33.3%; control, 41. 9%; P<0.05). The mean length of hospital stay was significantly reduced in the BiA group. At baseline, the mean P-wave duration (P(dur)) and dispersion (P(dis)) were not prolonged. BiA pacing resulted in the most significant percentage of reduction in P(dis) when compared with the LA or RA groups (BiA, 42+/-8%; LA, 13+/-6%; RA, 10+/-9%; P<0.05 for BiA versus LA or RA). No significant differences existed in mean P(dur) and P(dis) between patients who developed AF and those who remained in sinus rhythm at baseline. However, only those patients who remained in sinus rhythm had a significant reduction in mean P(dur) and P(dis) after pacing therapy. CONCLUSIONS: Biatrial overdrive pacing is more effective in preventing post-CABG AF than single-site atrial pacing; this therapy also results in a shortened hospital stay. The overall reduction in atrial activation time with BiA pacing was reflected in the reduction in P(dis).

Aged↗

PubMed1999

Single-molecule fluorescence observed with mercury lamp illumination.

We demonstrate that it is possible to observe single fluorescent molecules using a standard fluorescence microscope with mercury lamp excitation and an inexpensive cooled charge-coupled device (CCD) camera. With this equipment, we have been able to observe single molecules of tetramethyl-rhodamine, rhodamine 6G, fluorescein isothiocyanate and green fluorescent protein. Immobilized molecules were observed both in air and in aqueous solution.

Green Fluorescent Proteins↗

PubMed1999

Left ventricular rupture after mitral valve replacement.

BACKGROUND: What are the immediate and long term outcomes of patients who had rupture of the left ventricle after mitral valve replacement? METHODS EXPERIMENTAL DESIGN: A retrospective study with a 20-year follow-up. SETTING: Experience in a single tertiary referral cardiothoracic surgery hospital. PARTICIPANTS: 20 out of 3105 patients that received mitral valve replacement. INTERVENTION: All these 20 patients received re-exploration for a trial of repair of left ventricular rupture either by an internal or an external or a combined repair. MEASURES: Operative mortality and long term outcome of the survivals. RESULTS: Most patients (16.80%) were female and had rheumatic mitral valve disease. The mean age of the patients was 58.1 years. All patients underwent attempted repair, usually by removal of the prosthesis and reconstitution of the ventricle from within the left atrium (75%). Thirteen (65%) patients died. Two late deaths were of unrelated cause. One surviving patient developed a late ventricular false aneurysm but did not undergo repeat surgery. One patient developed severe mitral regurgitation due to tissue failure of the bioprosthesis 12 years after surgery and she underwent a successful reoperation. CONCLUSIONS: We believe that all patients should be placed back on cardiopulmonary bypass for an internal repair. The long term outcome of the survivals is satisfactory.

Female↗

PubMed1998

Surgical resection of pulmonary metastases.

BACKGROUND: To review the results of complete surgical resection of pulmonary metastasis -- a ten-year experience. SETTING: Retrospective analysis of all patients with lung secondaries who received complete surgical resection of pulmonary metastases (from 1984 to 1995) in Grantham Hospital, Hong Kong. Sixty patients over a 10-year period were studied. METHODS: Eighty thoracotomies were performed with 88 tumour nodules excised. The follow-up period ranged from 5 months to 111 months. RESULTS: Thirteen (14.8%) specimens were found to have tumour size greater than 5.0 cm. This may reflect late detection of metastatic tumour and probably accounts for the higher percentage of our patients receiving more major lung resections (63.3%) than just wedge resections (36.6%). The mean survival period for the subgroup with hepatocellular carcinoma was 28.2 months and for the nasopharyngeal carcinoma group was 25 months. The mean survival of the whole group was 26.4 months. CONCLUSIONS: The favourable outcome for hepatocellular carcinoma and nasopharyngeal carcinoma could be due to the result of selection of patients with more favourable prognosis for surgery. The latent period, using 12 months as a break-off point, did not affect patient survival in our study.

Adolescent↗

PubMed1997

Mediastinal irradiation for graft-versus-host disease in a heart-lung transplant recipient.

Graft-versus-host disease in solid organ transplantation is very rare, but the prognosis is poor when the condition causes pancytopenia. We report a case of graft-versus-host disease in a heart-lung transplant recipient who at 2 weeks after transplantation had development of features of graft-versus-host disease, including bone marrow aplasia, that could not be attributed to drugs or viral infections. The diagnosis was confirmed by skin biopsy and demonstration of chimerism of peripheral lymphocytes. Augmentation of immunosuppression with intravenous methylprednisolone resulted in improvement in liver function but had no effect on the pancytopenia. Mediastinal irradiation was given with increase in both white blood cell and platelet counts. Unfortunately the patient eventually died of gastrointestinal bleeding and fungemia.

Adult↗

PubMed1996

Surgical resection of pulmonary metastases from nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC), unlike other head and neck cancers,is known for its propensity for distant metastases. Chemotherapy remains the mainstay of treatment because of this and the chemosensitivity of the tumour, but long-term control is rare. The surgical management of pulmonary metastases of other extrathoracic malignancies prompted this review of surgical management of patients with NPC. METHODS: Thirteen thoracotomies were performed in 12 patients with pulmonary metastases as the first and only site of relapse of nasopharyngeal carcinoma. Postoperative chemotherapy was given in four patients, radiotherapy to the mediastinum in one patient and both chemotherapy and radiotherapy in two patients. The survival pattern of this group of 12 patients was compared with a historical control group consisting of 65 patients without surgical resection. RESULTS: Lymph node involvement was documented in four patients during operation. Four patients relapsed after surgical resection, two of them were from the group of three patients with lymph node involvement. The site of subsequent relapse was the lung for three patients and the skeletal system for the fourth. The 2 year actuarial survival of the surgically resected group compared favourably with the historical control group (80% and 24.1%, respectively; P=0.0002 by Mantel-Cox text). CONCLUSIONS: Surgical resection of pulmonary metastases from NPC seems to be a promising approach thought the effect of case selection cannot be excluded and further studies are indicated. The importance of exploration and dissection of mediastinal nodes in the surgical management of pulmonary metastases from NPC was demonstrated.

Actuarial Analysis↗

PubMed1993

Chemical transformation/derivatization of O6-methyl- and O6-(hydroxyethyl)guanine for detection by GC-EC/MS.

In this project we set out to make an important class of DNA adducts, comprising O6-alkyl and O6-(hydroxyalkyl)guanines, susceptible to sensitive detection by GC-EC/MS. While existing literature indicated that pentafluorobenzylation would be useful for the ring NH site on these compounds, how to best overcome the polarity of the exocyclic NH2 and OH groups, without losing the O6-alkyl moiety, was less clear. Working with O6-methylguanine and O6-(2'-hydroxyethyl)guanine as representative analytes, we found that the NH2 group could be converted into fluoro without loss of the O6 substituent. For the OH group, a comparison of several derivatives (OR') led to R' = tert-butyl as the best choice at this stage. The latter work, especially via NMR, also allowed exact structural assignments to be made for the N7 and N9 pentafluorobenzyl isomeric derivatives that formed. Of these R' derivatives, the N7 isomers migrated slower on silica-TLC, had higher GC retention times, had lower responses by GC-EC/MS, and were preferentially destroyed as the GC column aged. However, the N9 isomer was slower on TLC when the OH was not derivatized. This behavior was rationalized using a concept of "polar footprint" for the derivatives. The concept also seemed to explain the puzzling GC-EC/MS behavior of some related compounds in our laboratory. Apparently the polar footprint should be minimized in designing derivatives for trace detection by GC-EC/MS.

Chromatography, Thin Layer↗

PubMed1992

The facial soft tissue profile of the southern Chinese: prosthodontic considerations.

A simple photographic setup was established to produce standardized life-sized black and white prints of Southern Chinese adults. Facial soft tissue profile analysis was performed on 28 men and 31 women aged 19 to 30, dentate Chinese, having class I occlusion and originating from Guangdong province. The facial profile values studied included the profile convexity, the interlabial contour, the nasolabial contour, the columella and upper lip inclination angles to the true horizontal, and the relative positions of upper and lower lips from the Esthetic plane. Data obtained were compared with those from previous Caucasian studies and other accepted empirical values. The lower third of the face presented the greatest ethnic difference: the interlabial contour was more convex and the upper and lower lips were more protrusive among the Southern Chinese. The widely-used standard of a right-angled nasolabial contour proved to be applicable among the Southern Chinese adult males. However, a more obtuse nasolabial angle, almost 100 degrees, occurred among the women.

Adult↗

PubMed1992

Inhibition of mammalian ribonucleotide reductase by cis-diamminedichloroplatinum(II).

Ribonucleotide reductase is a highly regulated, rate-limiting activity in the synthesis of DNA. A previous study has shown that the Escherichia coli enzyme is inhibited by the clinically important antitumor agent cis-diamminedichloroplatinum(II) (DDP), and this has led to the hypothesis that ribonucleotide reductase is an important site of action for this chemotherapeutic agent. This hypothesis has been directly tested in this investigation. We observed that DDP inhibits the mammalian ribonucleotide reductase, with 50% inhibition occurring at 0.3 mM. Unlike the E. coli enzyme where only one of the two protein components is targeted by DDP, we observed that both of the mammalian proteins (R1 and R2) were sites for the inhibitory activity of the drug. Colony-forming experiments, enzyme activity studies, and analyses of R1 and R2 message levels in mutant cell lines containing either high levels of ribonucleotide reductase activity or exhibiting resistance to the cytotoxic effects of DDP were used to further investigate the potential role of ribonucleotide reductase in DDP cytotoxic action and drug resistance. These studies did not support a hypothesis formulated in the earlier investigation that inhibition of ribonucleotide reductase is an important component of DDP cytotoxic activity or that it is a major participant in DDP resistance mechanisms. From a biological point of view, DDP is a very active drug, and in addition to its cytotoxic effects it is capable of inducing a variety of cellular changes. Whether or not the inhibition of mammalian ribonucleotide reductase activity that we have described in this study plays a role in mediating any of these other effects remains to be determined.

Animals↗

PubMed1991

Reproducibility of natural head position.

The orientation of the head, when the natural head position was adopted, was measured relative to the true vertical on standardized black and white profile photographs. Two methods of obtaining the natural head position were compared and their reproducibility tested. No statistically significant difference was found between the two different methods or at different sittings.

Adult↗

PubMed1989

Experience with the management of primary endodermal sinus tumor of the mediastinum.

Ten male patients with extensive primary endodermal sinus tumor of the mediastinum were treated with chemotherapy (with or without surgical excision and radiation therapy) between 1977 and 1985. Three patients, treated with cyclophosphamide-vincristine-based chemotherapy, died 1.5, 2.5, and 6.0 months, respectively, after initial diagnosis. Of the seven patients treated with cisplatin-based chemotherapy, one patient died of septicemia at 2.5 months after diagnosis and was disease-free at autopsy examination. Three other patients died of progressive disease at 7.0, 13.0, and 14.0 months, respectively. The three survivors remain alive at 17.0, 31.0, and 40.0 months from diagnosis; all are without evidence of disease. Of the three patients who underwent excision of the residual mediastinal tumor after cisplatin-based chemotherapy, persistent local disease was found in two patients. One of these two patients died of recurrent disease. All surviving patients had surgical resection of the tumor either before or after cisplatin-based chemotherapy, with or without radiotherapy and the timing of therapeutic interventions was guided by changes in the serum alpha-fetoprotein concentrations after initial therapy and during follow-up. Our experience suggests that the optimal management of patients with primary mediastinal endodermal sinus tumor requires an aggressive multidisciplinary approach guided by the extent of the tumor and the serum tumor marker levels.

Adolescent↗

PubMed1989

Left subclavian arterioesophageal fistula induced by a foreign body.

A left subclavian arterioesophageal fistula was diagnosed in a 35-year-old man at exploratory thoracotomy for suspected aortoesophageal fistula. After successful closure of the arterial fistula the patient developed a mediastinal abscess and esophagopleural fistula. The latter was successfully managed by retrosternal jejunal esophagoplasty followed by excision of the thoracic esophagus. This report documents a case of left subclavian arterioesophageal fistula and illustrates the importance of early diagnosis and surgical intervention of arterial perforation secondary to a foreign body in the esophagus.

Abscess↗