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Biomedical subjects

W Chan

Publications and source records attributed to W Chan.

At least 19 recordsLinked to original sources
PubMed2006

Influence of premorbid IQ and education on progression of Alzheimer's disease.

BACKGROUND: Lower education is associated with a higher risk of developing Alzheimer's disease (AD). Years of education and measures of general intellectual function (IQ) are highly correlated. It is important to determine whether there is a relationship between education and AD outcomes that is independent of IQ. OBJECTIVE: To test the hypothesis that premorbid IQ is a stronger predictor of cognitive decline, global progression, and overall survival, than education in patients with AD. METHODS: The study included 478 probable AD patients (322 women and 156 men, mean age 74.5 years) followed in a large AD referral center for a mean of 3.2 years. Eligible participants had a baseline estimate of premorbid IQ using the American version of the Nelson Adult Reading Test (AMNART) and at least one follow-up visit with complete neuropsychological assessment. We used random effects linear regression analysis, and Cox proportional hazards analysis to determine whether or not education and/or premorbid IQ were independently associated with cognitive decline, global progression of AD, and survival. RESULTS: When the baseline AMNART score was included in regression models along with education and other demographic variables, AMNART score, but not education, was associated with a higher baseline score and slower rate of decline in MMSE and ADAS-Cog scores, and the Clinical Dementia Rating sum of boxes score. Neither higher premorbid IQ nor higher education was associated with longer survival. CONCLUSIONS: We conclude that a baseline AMNART score is a better predictor of cognitive change in AD than education, but neither variable is associated with survival after diagnosis.

Aged↗
PubMed2005

A study of the prevalence of significant increases in serum creatinine following angiotension-converting enzyme inhibitor administration.

Angiontension-converting enzyme inhibitors (ACEIs) are beneficial in the treatment of diabetic and nondiabetic kidney disease, coronary artery disease and congestive heart failure. One adverse effect of ACEIs use is a rise in serum creatinine and potential renal failure. This paper attempts to quantify this risk and assess the need for pre- and post-ACEI serum creatinine measurements. A computerized search of Kaiser Permanente Northwest's electronic medical record was conducted to find patients over the age of 40 years taking lisinopril between July 1, 2000 and June 30, 2002. Patient demographic information and presence in diabetes and coronary artery disease registries was collected. A subsequent search for pre- and postlisinopril serum creatinine levels within 6 months of initial lisinopril prescription was conducted. Patients with prelisinopril creatinine < or = 1.2 mg/dl and postlisinopril creatinine > 2.5 mg/dl underwent chart review to discern adverse events associated with the rise in serum creatinine. A total of 18,977 patients were prescribed lisinopril between July 1, 2000 and June 30, 2002. In all 13 166 patients had a pre- and postlisinopril creatinine checked. In all, 31 patients had a rise in creatinine from < or = 1.2 mg/dl to > 2.5 mg/dl (0.2%). Possible contributors to rise in creatinine included congestive heart failure, dehydration and infection. No patients developed end-stage renal disease, although three died. In conclusion, end-stage renal disease is an unlikely outcome among patients prescribed lisinopril and is most likely associated with other events.

Adult↗
PubMed2005

Functional analysis of genetic variants in the human concentrative nucleoside transporter 3 (CNT3; SLC28A3).

The human concentrative nucleoside transporter, CNT3 (SLC28A3), plays an important role in mediating the cellular entry of a broad array of physiological nucleosides and synthetic anticancer nucleoside analog drugs. As a first step toward understanding the genetic basis for interindividual differences in the disposition and response to antileukemic nucleoside analogs, we examined the genetic and functional diversity of CNT3. In all, 56 variable sites in the exons and flanking intronic region of SLC28A3 were identified in a collection of 270 DNA samples from US populations (80 African-Americans, 80 European-Americans, 60 Asian-Americans, and 50 Mexican-Americans). Of the 16 coding region variants, 12 had not been previously reported. Also, 10 resulted in amino-acid changes and three of these had total allele frequencies of >/=1%. Nucleotide diversity (pi) at nonsynonymous and synonymous sites was estimated to be 1.81 x 10(4) and 18.13 x 10(4), respectively, suggesting that SLC28A3 is under negative selection. All nonsynonymous variants, constructed by site-directed mutagenesis and expressed in Xenopus laevis oocytes, transported purine and pyrimidine model substrates, except for c. 1099G>A (p. Gly367Arg). This rare variant alters an evolutionarily conserved site in the putative substrate recognition domain of CNT3. The presence of three additional evolutionarily conserved glycine residues in the vicinity of p. Gly367Arg that are also conserved in human paralogs suggest that these glycine residues are critical in the function of the concentrative nucleoside transporter family. The genetic analysis and functional characterization of CNT3 variants suggest that this transporter does not tolerate nonsynonymous changes and is important for human fitness.

Adenosine↗
PubMed2002

Ophthalmopathy in childhood Graves' disease.

AIMS: To study the ocular manifestations and their severity in children with Graves' disease. METHODS: All patients with Graves' disease having regular follow up in a paediatric endocrine clinic were recruited for the study. A comprehensive ophthalmic assessment including ocular motility, exophthalmometry, intraocular pressure (IOP), slit lamp, and fundus examinations was performed. RESULTS: 83 patients (72 female, 11 male) aged 16 years or below were examined. All are Chinese. Ocular symptoms occurred in 12 patients. Ocular signs of ophthalmopathy were documented in 52 patients (62.7%). Most of them presented with eyelid abnormalities such as lid oedema, lid lag, and lagophthalmos, whereas lower lid retraction was the commonest clinical sign noted (38.6%). Diffuse conjunctival injection was found in four patients (4.8%). 10 patients (12.0%) had mild proptosis of less than 3 mm. Only one patient (1.2%) had limited extraocular motility in extreme gaze. Punctate epithelial corneal erosions were reported in 11 patients (13.3%). CONCLUSIONS: This is the largest series on the ocular complications of childhood Graves' disease in the literature. Although 52 patients (62.7%) were identified with positive ocular changes, none of them had visual threatening complications or debilitating myopathy.

Adolescent↗
PubMed2001

Acute stroke care in non-urban emergency departments.

OBJECTIVE: To evaluate the practice patterns for stroke care in rural emergency departments (ED). METHODS: The authors prospectively evaluated clinical practice decisions for all ED patients in two non-urban East Texas communities using active and passive surveillance methods. Data collected included demographics, risk factors, symptoms, and treatment. Data analysis consisted of descriptive statistics and logistic regression analysis. RESULTS: During the study period, 429 patients presented with validated strokes. Risk factors included hypertension (65%), previous stroke (41%), coronary artery disease (33%), diabetes (25%), current smoking (17%), and atrial fibrillation (11%). In the ED, neurology consultation occurred in 32%, head CT in 88%, and ECG in 85%. Heparin was used in 9%, and 5% received aspirin. Blood pressure was lowered in 19% from a mean high of 189(+/-38)/97(+/-26), average reduction 34 points (18%) systolic. Motor symptoms were more likely to prompt a neurology consultation (OR = 2.47). Heparin was used more commonly for patients with atrial fibrillation (OR = 2.93). Socioeconomic factors did not alter care. IV recombinant tissue plasminogen activator was used in 1.4% of ischemic stroke cases. CONCLUSIONS: Acute stroke care in this representative non-urban community frequently does not follow published guidelines or clinical trial results. Whereas a high percentage of patients receive CT, aggressive blood pressure treatment occurs commonly and at pressures below current recommendations. The use of heparin is common, more so than aspirin treatment. These facts argue for educational interventions aimed at non-urban physicians to improve evidence-based medical practice.

Acute Disease↗
PubMed2001

Community-wide coronary heart disease mortality in Mexican Americans equals or exceeds that in non-Hispanic whites: the Corpus Christi Heart Project.

PURPOSE: Previous comparisons of coronary heart disease mortality between Mexican Americans and non-Hispanic whites have given paradoxic results: despite their adverse cardiovascular risk profiles, especially a greater prevalence of diabetes, Mexican Americans are reported to have lower rates of mortality from coronary heart disease. SUBJECTS AND METHODS: We performed a community-based surveillance among all residents of Nueces County, Texas, aged 25 to 74 years, from 1990 to 1994. All death certificates were obtained and coded, and deaths potentially related to coronary heart disease were selected and validated by standardized methods blinded to ethnicity. Validated in-hospital and out-of-hospital coronary heart disease mortality was compared between 785 Mexican Americans and 862 non-Hispanic white women and men. RESULTS: Validated coronary heart disease mortality in Mexican Americans exceeded that for non-Hispanic whites in the same community. Among women, definite coronary heart disease mortality was 40% greater among Mexican Americans (rate ratio [RR] 1.43, 95% confidence interval [CI]: 1.12 to 1.82), as was all coronary heart disease mortality (RR, 1.32, 95% CI: 1.08 to 1.63). Among men, Mexican Americans had greater rates of all (RR, 1.11; 95% CI: 0.96 to 1.28) and definite coronary heart disease mortality (RR, 1.16; 95% CI: 0.91 to 1.47), but the associations were not statistically significant. CONCLUSIONS: When community-wide mortality rates from coronary heart disease are properly validated, Mexican Americans have rates equal to or higher than those of non-Hispanic whites. Community-based surveillance with validation of coronary heart disease as the cause of death is necessary to avoid the errors that occur with the use of death certificates alone.

Adult↗
PubMed2001

Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX1) receptors, with downstream 5-HT2C receptor involvement.

RATIONALE: Orexins A and B have recently been discovered and shown to be derived from preproorexin, primarily expressed in the rat hypothalamus. Orexin-A has been ascribed a number of in vivo functions in the rat after intracerebroventricular (ICV) administration, including hyperphagia, neuroendocrine modulation and, most recently, evidence for a behavioural response characterised by an increase in grooming. OBJECTIVES: Here, we have investigated the orexin-receptor subtypes involved in the grooming response to orexin-A (3 microg, ICV) in the rat. METHODS: Male rats, habituated to clear Perspex behavioural observation boxes, were pretreated with antagonists with mixed selectivity for OX1, OX2, 5-HT2B and 5-HT2C receptor subtypes prior to the administration of orexin-A and the intense grooming response elicited by this peptide assessed. RESULTS: Pretreatment of rats with a mixed OX1/5-HT2B/2C receptor antagonist 1-(4-methylsulfanylphenyl)-3-quinolin-4-ylurea (SB-284422), revealed a significant, but incomplete, blockade of orexin-A-induced grooming. Despite the low potency of orexin-A at 5-HT2B and 5-HT2C receptors in vitro (pKi<5), studies were undertaken to determine whether downstream 5-HT2B or 5-HT2C receptors mediate in the grooming-elicited by orexin-A. Whilst the selective 5-HT2B receptor antagonist, SB-215505 (3 mg/kg, PO, 5-HT2B, pKi=8.58; OX1, pKB < 5.15) failed to effect orexin-A-induced grooming, the selective 5-HT2C receptor antagonist, SB-242084 (1 mg/kg, IP, 5-HT2C, pKi = 8.95; OX1, pKB < 5.1) potently antagonised the grooming response to this peptide. This suggested that the partial blockade of orexin-A-induced grooming obtained with SB-284422 might be attributable to its 5-HT2C and/or OX1 receptor blocking activity. However, complete blockade of orexin-A-induced grooming by the subsequently identified selective OX1 receptor antagonist 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl urea hydrochloride, SB-334867-A (OX1, pKB = 7.4; OX2, pKB = 5.7), devoid of appreciable affinity for either 5-HT2B (pKi < 5.3) or 5-HT2C (pKi < 5.4) receptors, provides the first definitive evidence that a central behavioural effect of orexin-A (grooming) is mediated by OX1 receptors. CONCLUSIONS: This data suggests that orexin-A indirectly activates 5-HT2C receptors downstream from OX1 receptors to elicit grooming in the rat. The use of SB-334867-A in vivo will enable the role of OX,1 receptors within the rat central nervous system to be further characterised.

Animals↗
PubMed2001

Effects of oat and wheat cereals on endothelial responses.

BACKGROUND: This study was undertaken to determine the effects of month-long whole grain oat and wheat cereal supplementation on endothelial function following a fatty meal as measured by brachial artery reactivity studies. METHODS: Fifty healthy adult subjects underwent brachial artery reactivity studies before and after a high-fat meal along with alpha-tocopherol (vitamin E), oats, or a comparable bowl of wheat cereal and were again tested after the high-fat meal following month-long supplementation with oat or wheat cereal in a random crossover with interim washout. RESULTS: In the acute phase, the fatty meal attenuated the hyperemic brachial artery flow response when administered concurrently with wheat cereal (-13.4%; P = 0.02), whereas hyperemic flow was maintained by concurrent administration of either oatmeal or alpha-tocopherol. Following month-long supplementation, postprandial peak flow (wheat +3.88 +/- 5.62%; oat -10.78 +/- 7.15%), and peak diameter (wheat -1.40 +/- 0.96%; oat -0.86 +/- 0.88%) did not differ from preprandial values. Oat and wheat treatments did not differ when directly compared. CONCLUSIONS: Month-long, daily supplementation with either whole-grain oat or wheat cereal may prevent postprandial impairment of vascular reactivity in response to a high-fat meal.

Adult↗
PubMed2001

Progression after release of obstructive nephropathy.

Progressive glomerular and tubulointerstitial fibrosis develop in 1-year-old rats even after relief (R) of unilateral ureteral obstruction (UUO) at 5 days of age. The present study investigated whether a progressive renal injury model of UUO could be achieved after reversal of UUO (RUUO) in adult instead of neonatal rats. The potential for alpha-tocopherol modulation of mRNA for the fibrogenic cytokine, transforming growth factor-beta1 (TGFbeta1), apoptosis (TUNEL assay), and the presence of the stress protein, heat shock protein-70 (HSP-70), was also studied in this post-obstructive model. Male Sprague-Dawley rats weighing 125-150 g were randomly assigned to groups of 4 animals each for durations of 7 or 14 days of alpha-tocopherol supplementation after RUUO. The groups included: (i) sham, regular chow; (ii) RUUO, regular chow; (iii) RUUO, contralateral nephrectomy (NX); and (iv) RUUO, NX plus alpha-tocopherol supplementation. We found a significant increase in the ratio of kidney weight/body weight in the RUUO+NX group at 14 days compared with the sham and RUUO groups. This rise in the RUUO+NX group was significantly reduced after 14 days of alpha-tocopherol administration. The elevated level of kidney TGFbeta1 mRNA in the RUUO+NX group was only partially reduced at 7 days. But at 14 days this became significantly reduced with the continued alpha-tocopherol treatment. The HSP-70 staining and the apoptosis of the kidney showed results parallel to those of TGFbeta mRNA at 14 days. To separate the effects of hypertrophy after unilateral NX from the RUUO studies, we carried out a second experiment in control animals subjected to NX, with and without alpha-tocopherol supplementation. Fourteen days after NX, the apoptosis and TGFbeta1 mRNA showed no significant differences from the control animals. Our data suggest that a model of progressive renal injury in RUUO can be established in adult rats. After contralateral NX, the progressive injury is evidenced by the increase in the ratio of kidney weight/total body weight, the apoptotic counts, as well as fibrogenic cytokine TGFbeta1 mRNA in the post-obstructed kidney. Finally, our data also support the concept that alpha-tocopherol is renal protective, as judged by TGFbeta1 mRNA, apoptosis, and HSP-70 staining, even in the progressive disease process of the post-obstructed model.

Animals↗
PubMed2001

Does cryotherapy affect refractive error? Results from treated versus control eyes in the cryotherapy for retinopathy of prematurity trial.

PURPOSE: To evaluate the effect of cryotherapy on refractive error status between ages 3 months and 10 years in children with birth weights of less than 1251 g in whom severe retinopathy of prematurity (ROP) developed in one or both eyes during the neonatal period. DESIGN: Randomized clinical trial. PARTICIPANTS: Two hundred ninety-one children in whom severe ROP developed during the neonatal period. INTERVENTION: Cryotherapy for ROP. MAIN OUTCOME MEASURES: Cycloplegic Refraction METHODS: The children underwent repeated follow-up eye examinations, including cycloplegic retinoscopy, between 3 months and 10 years after term due date. Refractive error data from all eyes that were randomized to cryotherapy were compared with data from all eyes that were randomized to serve as controls. Refractive error data were also compared for a subset of children who had both a treated and a control eye that could be refracted. RESULTS: At all ages, the proportion of treated eyes that were unable to be refracted because of retinal detachment, media opacity, or pupillary miosis was approximately half the proportion of the control eyes that were unable to be refracted. When data from all eyes that could be refracted were considered, the distribution of refractive errors between fewer than 8 diopters (D) of myopia and more than 8 D of hyperopia was similar for treated and control eyes at all ages. The proportion of eyes with 8 D or more of myopia was much higher in treated than in control eyes at all ages after 3 months. In the subset of children who had a treated eye and a control eye that could be refracted, distributions of refractive errors in treated versus control eyes were similar at most ages. CONCLUSIONS: In both treated and control eyes, there was an increase in the prevalence of high myopia between 3 and 12 months of age. Between 12 months and 10 years of age, there was little change in distribution of refractive error in treated or control eyes. The higher prevalence of myopia of 8 D or more in treated eyes, as compared with control eyes, may be the result of cryotherapy's preservation of retinal structure in eyes that, in the absence of cryotherapy, would have progressed to retinal detachment.

Astigmatism↗
PubMed2001

mRNA expression for insulin-like growth factor 1, receptors of growth hormone and IGF-1 and transforming growth factor-beta in the kidney and liver of Zucker rats.

Kidney dysfunction and mesangial enlargement are consequences of obesity found in Zucker rats. This study examines some of the early mechanisms by which the kidneys of Zucker rats undergo these changes. Our study shows that the glomerular planar area in the genetically obese Zucker rat undergo enlargement as early as 12 weeks of life, compared to the lean controls. This suggests mesangial proliferation is already occurring at this time, earlier than previously shown. The mRNA expression for IGF-I, and GHR in the kidney and liver of the obese Zucker rats were significantly reduced compared to the lean controls. However, the mRNA of the IGF-IR was significantly elevated in the kidney of the obese Zucker rats. The increase in kidney IGF-1R mRNA in the obese Zucker rat may suggest an increase in IGF-1 binding leading to the kidney hypertrophy observed in these rats.

Journal Article↗
PubMed2001

Acute effects of oats and vitamin E on endothelial responses to ingested fat.

OBJECTIVE: To assess the effects of oats and vitamin E on endothelial function following a high-fat meal in healthy adults as measured by brachial artery reactivity studies (BARS). METHODS: A total of 25 men and 25 women (N=50) were recruited from a community population to participate in this randomized, crossover study. All subjects were free of known vascular disease, and female subjects were postmenopausal. Subjects underwent BARS before and after a high-fat meal (50 gm fat) on three occasions 1 week apart, one each with vitamin E 800 IU, oatmeal containing 3 gm beta-glucan, or a comparable bowl of wheat cereal serving as a placebo, in random sequence. The ultrasonographer was blinded to treatment status. RESULTS: Endothelial function, as measured by brachial artery peak flow during one minute of post-occlusive hyperemia, declined significantly from baseline when the high-fat meal was consumed with the wheat cereal (-13.4%; p=0.02). There was no difference in brachial artery flow change before and after a high-fat meal with oats (+0.37%; p=0.77) or a high-fat meal with vitamin E (+1.87%; p=0.42). No significant differences in flow-mediated vasodilation before and after the high-fat meal were detected among the three supplements. CONCLUSIONS: Endothelial dysfunction induced by acute fat ingestion in healthy adults is apparently prevented by concomitant ingestion of oats or vitamin E, but not wheat. Nutrient distribution and meal composition may have important implications for cardiovascular health.

Adult↗
PubMed2001

Self-reported weight and height: implications for obesity research.

BACKGROUND: Self-reported weight and height are under- and over-reported, respectively, in epidemiologic studies. This tendency, which may adversely affect study operations, has not been evaluated among subjects being enrolled into a weight-loss program. METHODS: Self-reported weight, height, and body mass index (BMI) were compared to measured values in 97 overweight or obese (BMI>27.3) women being enrolled into a randomized, controlled trial of two behavioral interventions for weight loss. The effects of demographic factors, baseline weight, baseline height, and baseline BMI on weight and height reporting were assessed. RESULTS: There was a significant difference between measured and reported weight (mean difference=-3.75 lb, p=0.0001) and height (mean difference=+0.35 in., p=0.0007). The mean difference between measured and reported BMI was -1.14 kg/m(2) (p=0.0001). Unemployed, retired, or disabled women were more likely to under-report their BMI than employed women (p=0.001). Six percent of subjects who were initially considered eligible for the study on the basis of the self-report were eventually excluded from the study because they did not meet the inclusion criterion for BMI. CONCLUSIONS: Obese women who seek weight-loss assistance tend to under-report their weight and over-report their height, suggesting that self-reported data are likely to be inaccurate. Misreporting is apparently influenced by employment and disability and has the potential to complicate recruitment of subjects for research studies.

Adult↗
PubMed2001

Progenitor and lymphoma cells in blood stem cell harvests: impact on survival following transplantation.

This study evaluated whether cytokine-induced blood stem cell mobilization also mobilized lymphoma cells and whether lymphoma cell mobilization affected outcome post autologous blood stem cell transplant. Blood stem cell collections from 26 non-Hodgkin's lymphoma (NHL) patients harvested during steady-state (non-mobilized) and from 35 NHL patients harvested after cytokine administration (mobilized) were studied. The harvests were cultured and molecularly evaluated for clonal markers of the primary lymphoma. All patients underwent high-dose chemotherapy and autologous transplantation. Graft products from mobilized patients were more likely to contain lymphoma than graft products from non-mobilized patients (37% vs 19%) but this difference was not significant (P = 0.16). In a multivariate analysis, lymphoma contamination was not associated with patient age, gender, tumor grade, prior radiotherapy, duration of prior chemotherapy, mononuclear cell count, or the number of aphereses performed to obtain the product. Heavily pre-treated patients were less likely to have lymphoma-contaminated harvests (P = 0.064). Lymphoma contamination was positively associated with the number of progenitor cells collected (P = 0.047). In multivariate analyses, the only significant independent predictor of lymphoma contamination was the number of mononuclear cells collected (P = 0.031). Lymphoma contamination of transplanted apheresis products had no apparent impact on event-free and overall survival.

Adult↗