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Biomedical subjects

C Chiu

Publications and source records attributed to C Chiu.

At least 37 records · Page 2Linked to original sources
PubMed1999

Dopamine receptor genes are associated with age at first sexual intercourse.

The dopaminergic system in the brain seems to play an important role in the regulation of sexual behaviour. The relationship between genes for the D1, D2 and D4 dopamine receptors and age at first sexual intercourse (AFSI) was examined in a sample of 414 non-Hispanic, European-American men and women. A significant association was observed between a DRD2 allele and AFSI and an even stronger association when the DRD2 allele was interacted with a DRD1 allele. A constrained regression model was constructed predicting AFSI using sex and a group of nine psychosocial variables as predictors. Adding the DRD2 and the DRD2-by-DRD1 predictors to this model increased the explained variance by 23 and 55%, respectively. Although these findings suggest a stronger association among males than among females, further research will be necessary to clarify this question, as well as to establish whether the observed association holds in other racial/ethnic groups.

Adolescent↗
PubMed1999

Adenosine-induced atrial pro-arrhythmia in children.

Adenosine has become the preferred acute treatment for common types of supraventricular tachycardia because of its efficacy and safety. There have been a few reports of serious proarrhythmic events associated with its use, including the induction of atrial fibrillation in adult patients. Three instances of adenosine-induced atrial proarrhythmia (two atrial fibrillation and one atrial flutter) have been observed in children with manifest or concealed Wolff-Parkinson-White syndrome at the Hospital for Sick Children, Toronto, Ontario since 1990, which indicates a previously unreported risk of atrial arrhythmia for children as well. Because adenosine may enhance antegrade bypass tract conduction, its use carries a risk of ventricular acceleration, including progression to ventricular fibrillation. Because of such rare and potentially life-threatening adverse effects, appropriate monitoring and precautions are required during the administration of the drug to children and adults.

Adenosine↗
PubMed1997

Blood-retinal barrier (BRB) breakdown in experimental autoimmune uveoretinitis: comparison with vascular endothelial growth factor, tumor necrosis factor alpha, and interleukin-1beta-mediated breakdown.

Experimental autoimmune uveoretinitis (EAU) induced in Lewis rats by immunization with S-antigen is a model of human uveitis. By using immunocytochemical staining for albumin, relatively minor blood-retinal barrier (BRB) breakdown was initially shown in the peripheral retina 8 days after immunization and in the posterior retina by 10 days. Albumin extravasation appeared to occur by opening of the retinal vascular endothelial (RVE) and the retinal pigmented epithelial (RPE) tight junctions, by transendothelial vesicular transport, and by permeating damaged RVE cells. Each of three anti-inflammatory agents reduced or delayed autoimmune-mediated cell destruction but did not eliminate any particular route of extravasation. Vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF alpha), and interleukin-1beta (IL-1beta) are intimately associated with the development of EAU and are capable of causing BRB dysfunction. A high percentage of RVE tight junctions appeared open ultrastructurally after intravitreal injection of VEGF (26.7%), TNF alpha (35.6%), or IL-1beta (22.1%) compared with saline-injected control (11.4%) or normal, untreated rabbits (4.1%). Heat treatment abolished the effect of IL-1beta on the BRB but only partially reduced the effect of VEGF. By 24 hr after injection, the effect of TNF alpha had reversed, but that of IL-1beta had not; VEGF-mediated BRB dysfunction was partially reversible. In addition, albumin-filled vesicle-like structures were seen in the RVE cytoplasm following treatment with each mediator. This study shows that VEGF, TNF alpha, and IL-1beta each cause BRB breakdown by opening tight junctions between RVE cells and possibly by increasing transendothelial vesicular transport. Each of these agents may contribute to BRB breakdown in EAU and in patients with uveitis.

Albumins↗
PubMed1997

Studies of the potential role of the dopamine D1 receptor gene in addictive behaviors.

Abnormalities in the dopaminergic reward pathways have frequently been implicated in substance abuse and addictive behaviors. Recent studies by Self and coworkers have suggested an important interaction between the dopamine D1 and D2 receptors in cocaine abuse. To test the hypothesis that the DRD1 gene might play a role in addictive behaviors we examined the alleles of the Dde I polymorphism in three independent groups of subjects with varying types of compulsive, addictive behaviors-Tourette syndrome probands, smokers and pathological gamblers. In all three groups there was a significant in the frequency of homozygosity for the DRD1 Dde I 1 or 2 alleles in subjects with addictive behaviors. The DRD1 11 or 22 genotype was present in 41.3% of 63 controls and 57.3% of 227 TS probands (P = 0.024). When 23 quantitative traits were examined by ANOVA those carrying the 11 genotype consistently had the highest scores. Based on these results, we examined the prevalence of the 11 genotype in controls, TS probands without a specific behavior, and TS probands with a specific behavior. There was a progressive, linear increase, significant at alpha < or = 0.005 for scores for gambling, alcohol use and compulsive shopping. Problems with three additional behaviors, drug use, compulsive eating and smoking were significant at alpha < or = 0.05. All six variables were related to addictive behaviors. In a totally separate group of controls and individuals attending a smoking cessation clinic, and smoking at least one pack per day, 39.3% of the controls versus 66.1% of the smokers carried the 11 or 22 genotype (P = 0.0002). In a third independent group of pathological gamblers, 55.8% carried the 11 or 22 genotype (P = 0.009 vs the combined controls). In the TS group and smokers there was a significant additive effect of the DRD1 and DRD2 genes. The results for both the DRD1 and DRD2 genes, which have opposing effects on cyclic AMP, were consistent with negative and positive heterosis, respectively. These results support a role for genetic variants of the DRD1 gene in some addictive behaviors, and an interaction of genetic variants at the DRD1 and DRD2 genes.

Adult↗
PubMed1997

A comparison of two stab-on unipolar epicardial pacing leads in children.

The Oscor MP52V and Medtronic 4951 leads have similar construction and intended application. To determine if one of these designs was more suited to pediatric pacing, we reviewed implant, 3 month, and 12 months follow-up thresholds for all 18 MP52V implants at our institution from December 1989 to April 1991 and compared them to the 4951 implants from January 1982 to October 1989. Lead survival for the MP52V implants was compared to the most recent 36 4951 implants. Patients ranged in ages from 2 days-16 years (median = 4 years) and required antibradycardia pacing for congenital or acquired heart disease. Patients were compared for weight and proportion of atrial leads in each group by t-test and Fisher exact tests respectively. Energy thresholds were assessed in microJ and compared by t-test. Lead survival was defined by abandonment or replacement for any reason. Kaplan & Meier survival curves were plotted and compared by Gehan's Wilcoxan Test. There were no significant differences between the MP52V and 4951 groups for age at implant (53 months vs 80 months) or proportion of atrial implants (5/18 vs 11/36). Lead survival was poor but did not differ significantly (70% vs 78% cumulative survival at 3 years), usually failing by exit block. Implant and follow-up thresholds did not differ significantly between leads. The MP52V did not provide significant improvement in performance over the 4951. New epicardial lead designs are needed to improve lead survival and thresholds in children.

Adolescent↗
PubMed1996

Studies of the c-Harvey-Ras gene in psychiatric disorders.

Hérault et al. (1993) previously reported a significant association between autism and the larger fragments of the c-Harvey-Ras (HRAS) Bam H1 polymorphism. We have sought to verify this finding and determine if there was any evidence for an association with other psychiatric disorders. Because of its greater sensitivity, we have examined the HRAS Msp 1 polymorphism. We found a just significant increase in the prevalence of the > 2.1 kb alleles in 48 subjects with autism versus 50 control subjects. There was no increase in the prevalence of the > 2.1 kb alleles in 164 probands with Tourette's syndrome. Examination of 16 preselected symptom clusters, however, showed a significant trend toward higher scores for obsessive-compulsive and phobic symptoms in > 2.1 kb homozygotes. While this locus requires further study, in conjunction with the results of Hérault et al., the present findings suggest that genetic defects in HRAS, and possibly other components of the G protein secondary messenger system, may play a role in some psychiatric disorders.

Adolescent↗
PubMed1996

Fetal globin expression in New World monkeys.

Reverse phase chromatography of the globin chains of adult, newborn, and fetal erythrocytes from three species of New World monkeys (Cebus apella, Aotus azarae, and Callithrix jacchus) representing three of the seven platyrrhine clades showed that gamma-globin expression was fetal in these animals. The globins were identified by a combination of chemical sequencing and mass spectrometric analysis. Since gamma-globin expression is fetal in the other major simian branch, the catarrhines, but embryonic in prosimian primates and nonprimate placental mammals, the evolution of fetal recruitment can now be assigned to the period between the simian-prosimian divergence (55 million years ago) and the platyrrhine-catarrhine divergence (35 million years ago). The gamma-globin gene underwent tandem duplication during the same evolutionary epoch, in accord with a model that suggests that the downstream duplicated gamma-gene (gamma2) was free to acquire the mutations necessary for fetal recruitment. Mass spectrometric analysis of tryptic digests of the gamma-globins verified the amino acid sequences deduced from genomic sequencing. Detailed analysis of high performance liquid chromatography and matrix-assisted laser desorption/ionization mass spectrometry data showed that gamma2-globin in Cebus was expressed to a far greater extent than gamma1-globin, supporting inferences drawn from a study of the promoter sequences. A "pre-gamma"-globin was observed in C. apella and shown to be primarily the glutathionyl adduct. The other species, A. azarae and C. jacchus, also express only one gamma-globin polypeptide. This work provides biochemical evidence of an evolutionary trend in the platyrrhines to alter the duplicated gamma-globin gene locus so that only one gamma-globin polypeptide is expressed.

Abortion, Veterinary↗
PubMed1996

Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: the additive and subtractive effect of the three dopaminergic genes--DRD2, D beta H, and DAT1.

Polymorphisms of three different dopaminergic genes, dopamine D2 receptor (DRD2), dopamine beta-hydroxylase (D beta H), and dopamine transporter (DAT1), were examined in Tourette syndrome (TS) probands, their relatives, and controls. Each gene individually showed a significant correlation with various behavioral variables in these subjects. The additive and substractive effects of the three genes were examined by genotyping all three genes in the same set of subjects. For 9 of 20 TS associated comorbid behaviors there was a significant linear association between the degree of loading for markers of three genes and the mean behavior scores. The behavior variables showing the significant associations were, in order attention deficit hyperactivity disorder (ADHD), stuttering oppositional defiant, tics, conduct, obsessive-compulsive, mania, alcohol abuse and general anxiety-behaviors that constitute the most overt clinical aspects of TS. For 16 of the 20 behavior scores there was a linear progressive decrease in the mean score with progressively lesser loading for the three gene markers. These results suggest that TS, ADHD, stuttering oppositional defiant and conduct disorder, and other behaviors associated with TS, are polygenic, due in part to these three dopaminergic genes, and that the genetics of other polygenic psychiatric disorders may be deciphered using this technique.

Adolescent↗
PubMed1996

Intraoperative TEE assessment of ventricular septal defect with aortic regurgitation.

BACKGROUND: It is desirable to repair but not replace the aortic valve in patients with ventricular septal defect and acquired aortic regurgitation. Precise definition of the valvar pathology with monitoring of its repair perioperatively would enhance the surgical management of this condition. METHODS: Fourteen consecutive patients (age, 10.6 +/- 6 years; weight 29.7 +/- 5.7 kg) who underwent repair of ventricular septal defect with aortic regurgitation were studied by intraoperative transesophageal echocardiography. The severity of prolapse of each of the individual aortic cusps and its adjacent sinus was assessed and the valvar regurgitation quantified by Doppler-derived regurgitant indices. The echocardiographic and surgical findings were correlated and the preoperative and postoperative echocardiographic data were compared to assess the effectiveness of operation. RESULTS: Eight subarterial and six perimembranous defects were located accurately and their sizes (11.8 +/- 3.0 mm) correlated well (r = 0.80) with the surgical measurements. Transesophageal echocardiography detected prolapse of the aortic valve and its sinus in all 14 patients. The severity of the prolapse was severe in 10, moderate in 4, and mild in 5 leaflets. One the basis of these findings, together with the Doppler-derived mean regurgitant indices, exploration of the valve and valvuloplasty were executed appropriately in 12 of 14 patients. In all 14 patients, transesophageal echocardiography after bypass revealed no further cuspal prolapse and significant reduction of the mean regurgitant index (0.55 +/- 0.23 to 0.17 +/- 0.15, p < 0.0001). Residual ventricular septal defect was detected in 5 patients and the only patient with significant shunting who required reexploration was identified correctly. CONCLUSIONS: Intraoperative transesophageal echocardiography can assess effectively the surgical repair of ventricular septal defect with aortic regurgitation and provide information that directs and alters surgical plans to the benefit of patients.

Adolescent↗
PubMed1996

Recurrent bacterial peritonitis caused by Neisseria cinerea in a chronic ambulatory peritoneal dialysis (CAPD) patient.

We present an unusual case of recurrent (chronic ambulatory peritoneal dialysis) CAPD-associated peritonitis caused by Neisseria cinerea. Using DNA restriction fragment length polymorphism (RFLP) analysis, we determined that the recurrent infection was caused by reinfection with a different N. cinerea strain rather than relapse with the index strain and that the probable origin of the reinfecting organism was the patient's upper respiratory tract.

Adult↗
PubMed1996

The dopamine D2 receptor (DRD2) gene: a genetic risk factor in smoking.

Of a group of 312 non-Hispanic Caucasians who smoked at least one pack per day, had unsuccessfully attempted to stop smoking, and were free of alcohol or other drug dependence, 48.7% carried the A1 allele of the DRD2 gene. This was significantly greater than the 25.9% prevalence in the 714 known non-Hispanic Caucasian controls without alcohol or drug abuse, p < 10(-8), and significantly greater than in a smaller set of our study controls. There was a significant, inverse relationship between the prevalence of the D2A1 allele and the age of onset of smoking, p = 0.02, and the maximum duration of time the smokers had been able to quit smoking on their own, p = 0.02. These results suggest the DRD2 gene is one of a multifactorial set of risk factors associated with smoking.

Adult↗
PubMed1996

A study of the dopamine D2 receptor gene in pathological gambling.

Pathological gambling has been termed both the 'pure' and the 'hidden' addiction. 'Pure' because it is not associated with the intake of any addicting substance, and 'hidden' because it is an extension of a common, socially accepted behaviour. The Taq A1 variant of the human DRD2 gene has been associated with drug addiction, some forms of severe alcoholism, and other impulsive, addictive behaviours. We have sought to determine if there is a similar association with pathological gambling. A total of 222 non-Hispanic Caucasian pathological gamblers from multiple sites across the US participated in the study. Of these 171 donated a sample of blood, 127 filled out several questionnaires, and 102 did both. Of the 171 pathological gamblers 50.9% carried the D2A1 allele versus 25.9% of the 714 known non-Hispanic Caucasian controls screened to exclude drug and alcohol abuse, p < 0.00000001, odds ratio (OR) = 2.96. For the 102 gamblers who filled out the questionnaires, 63.8% of those in the upper half of the Pathological Gambling Score (more severe) carried the D2A1 allele (OR versus controls = 5.03), compared to 40.9% in the lower half (less severe). Of those who had no comorbid substance abuse, 44.1% carried the D2A1 allele, compared to 60.5% of those who had comorbid substance abuse. Forty-eight controls and 102 gamblers completed a shorter version of the Pathological Gambling Score. Of the 45 controls with a score of zero, 17.8% carried the D2A1 allele. Of the 99 gamblers with a score of 5 or more, 52.5% carried the D2A1 allele (chi 2 = 15.36, p = 0.00009). These results suggest that genetic variants at the DRD2 gene play a role in pathological gambling, and support the concept that variants of this gene are a risk factor for impulsive and addictive behaviours.

Adult↗
PubMed1996

Exon and intron variants in the human tryptophan 2,3-dioxygenase gene: potential association with Tourette syndrome, substance abuse and other disorders.

Defects in serotonin metabolism, and abnormalities in both blood serotonin and tryptophan levels, have been reported in many psychiatric disorders. Tryptophan 2,3-dioxygenase (TDO2) is the rate limiting enzyme for the breakdown of tryptophan to N-formyl kenurenine. Functional variants of this gene could account for the observed simultaneous increases or decreases of both serotonin and tryptophan in various disorders. We have identified four different polymorphisms of the human TDO2 gene. Association studies show a significant association of one or more of these polymorphisms and Tourette syndrome (TS), attention deficit hyperactivity disorder (ADHD) and drug dependence. The intron 6G-->T variant was significantly associated with platelet serotonin levels. Only the association with TS was significant with a Bonferroni correction (p = 0.005). Our purpose here is not to claim these associations are proven, but rather to report preliminary results and show that easily testable polymorphisms are available. We hope to encourage additional research into the potential role the TDO2 gene in these and other psychiatric disorders.

Electrophoresis, Polyacrylamide Gel↗
PubMed1996

In vitro activity of cefoperazone-sulbactam: Singapore experience.

In vitro activity of commonly used antimicrobial agents against consecutively isolated 521 strains of Gram negative bacilli causing serious infections in the National University Hospital, Singapore were tested in parallel with cefoperazone-sulbactam combination. With the combination complete resistance of 2% and intermediate resistance of 5% were noted among the 521 strains tested. Resistance to imipenem was low (5%) but resistance against other antimicrobial agents varied from 12% (amikacin) to 80% (ampicillin). In vitro data demonstrated a possible future role for cefoperazone-sulbactam in the treatment of sepsis caused by Gram negative bacilli in our hospital.

Anti-Bacterial Agents↗
PubMed1995

Surgical repair of coarctation of the aorta in neonates: factors affecting early mortality and re-coarctation.

Between October 1979 and January 1993, 85 Chinese neonates in Hong Kong underwent surgical repair for coarctation of the aorta. Their mean (s.e.) age and body weight at operation was 15.6(8.5) days and 3.06(0.56) kg, respectively. Simple coarctation was present in 17 babies, while 36 had additional ventricular septal defect and 31 had associated major complex intracardiac lesions. Subclavian flap aortoplasty was performed in 56 babies, resection with end-to-end anastomosis in 18 and aortoplasty with the use of a GORETEX patch in 11. The overall early mortality rate was 16.5%. To identify risk factors for early operative mortality, various clinical variables, surgical options, associated heart lesions and dimensions of the aortic arch at different sites for each patient were reviewed. Univariate analysis identified statistically significant differences between the survivors and non-survivors for the following factors: preoperative body-weight, arterial pH and base excess, serum urea and creatinine levels. Stepwise logistic regression further distinguished serum creatinine levels and the period of operation as two significant risk factors. Contrary to previous reports, the dimensions of the aortic arch and type of surgery did not affect early operative mortality. Among the 71 hospital survivors followed for 38.2(38) months, residual or recurrent coarctation of the aorta was detected in 12(17%). The different surgical operations were not related to the incidence of late complication. The size of the distal transverse arch, however, was different (P=0.05) in those who did and did not develop aortic sequela. Successful balloon angioplasty was subsequently performed in 11 patients. In an era of echocardiography with prenatal diagnosis and therapeutic catheterization, early recognition of the disease with prompt prostaglandin infusion should prevent collapse of the baby, thus avoiding renal impairment and sever metabolic acidosis. Balloon angioplasty would offer a simple effective treatment of patients who developed aortic re-coarctation.

Aortic Coarctation↗
PubMed1995

Isoforms of platelet-derived growth factor and its receptors in epiretinal membranes: immunolocalization to retinal pigmented epithelial cells.

Epiretinal membranes (ERMs) form on the inner surface of the retina in conjunction with various ocular disease processes, but the factors controlling their development are not understood. The predominant cell types involved are retinal pigmented epithelial (RPE) cells and retinal glia. Cultured RPE cells secrete platelet-derived growth factor (PDGF), which is chemotactic and mitogenic for both RPE cells and retinal glia and, therefore, could be involved in the development of ERMs. In the present study, we performed immunohistochemical staining for PDGF A chain (PDGF-A), PDGF B chain (PDGF-B), and both types of PDGF receptors (PDGFr alpha and PDGFr beta) on ERMs associated with various disease processes. PDGF-A is detected in most ERMs, regardless of the associated disease process, and it appears to be localized predominantly in RPE cells, recognized by the presence of pigment and the immunohistochemical demonstration of some or all of the following RPE-associated epitopes: class III beta-tubulin, keratin, the 65-kDa microsomal protein recognized by the RPE9 antibody, and cellular retinaldehyde-binding protein. PDGF-B is found only in minor subpopulations of cells in about half of the ERMs evaluated and, with only occasional exceptions, appears to be localized almost entirely in blood-borne cells found in and around vessels in vascularized ERMs. Both PDGFr alpha and PDGFr beta are demonstrated in most ERMs with neither isotype consistently predominating: they are found predominantly on RPE cells with many cells expressing both receptor types. ERMs with little or no RPE cell component contain little or no PDGF and PDGF receptor, whereas those in which the RPE cell represents the major cell type, have widespread PDGF and PDGF receptor positivity. These findings show that RPE cells in ERMs produce PDGF-A and PDGF alpha and PDGF beta receptors and suggest that autocrine and paracrine stimulation with PDGF may be involved in ERM pathogenesis.

Eye Diseases↗