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Biomedical subjects

P P Wang

Publications and source records attributed to P P Wang.

At least 19 recordsLinked to original sources

The SARS outbreak in a general hospital in Tianjin, China -- the case of super-spreader.

Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease with a high case-fatality rate and devastating socio-economic impact. In this report we summarized the results from an epidemiological investigation of a SARS outbreak in a hospital in Tianjin, between April and May 2003. We collected epidemiological and clinical data on 111 suspect and probable cases of SARS associated with the outbreak. Transmission chain and outbreak clusters were investigated. The outbreak was single sourced and had eight clusters. All SARS cases in the hospital were traced to a single patient who directly infected 33 people. The patients ranged from 16 to 82 years of age (mean age 38.5 years); 38.7% were men. The overall case fatality in the SARS outbreak was 11.7% (13/111). The outbreak lasted around 4 weeks after the index case was identified. SARS is a highly contagious condition associated with substantial case fatality; an outbreak can result from one patient in a relatively short period. However, stringent public health measures seemed to be effective in breaking the disease transmission chain.

Adolescent↗

Improving the accuracy of long-term prognostic estimates in hepatitis C virus infection.

Obtaining unbiased estimates of HCV prognosis is difficult because of potential biases associated with study design and calculation methods. We propose a new method for estimating fibrosis progression rates. A Markov model with fibrosis health states (F0-F4) was created. The maximum likelihood method was used to estimate stage-specific progression rates. We compared the standard method to the new method using two well-known cohort studies. The known stage distribution at the end of follow-up was compared with stage predicted by the Markov model using both methods of calculating transition rates. We also compared rates obtained using both methods to known fibrosis rates in a series of Monte Carlo simulations. For Kenny-Walsh's study (1999), transition rates between F0-F1, F1-F2, F2-F3, and F3-F4 were 0.042, 0.045, 0.097 and 0.070 fibrosis units/year (new method) and 0.045 units/year (standard method). The new method predicted fibrosis stage and known transition rates in Monte Carlo simulations more accurately. The standard method underestimates 30-year cirrhosis rates by up to 40%. The new (Markov maximum likelihood or MML) method allows accurate estimation of stage-specific transition probabilities from the many studies in which only a single biopsy is available. Application of the method supports the hypothesis that rates of fibrosis vary between stages.

Biopsy↗

Twenty-year trends of primary liver cancer incidence rates in an urban Chinese population.

The objective of this study was to describe trends in the incidence rates of primary liver cancer in a geographically defined Chinese population. Primary liver cancer cases (N=13 685) were diagnosed between 1981 and 2000 and identified by the Tianjin Cancer Registry. Age-adjusted and age-specific incidence rates were examined in both males and females. Poisson regression was employed to assess the incidence rate trends. Crude and age-adjusted incidence rates in the study period were: 27.4/100 000 and 16.4/100 000 in males and 11.5/100 000 and 6.4/100 000 in females, respectively. While the results from Poisson regression analyses suggest statistically significant trends of declining incidence rates of primary liver cancer overall, trends were not consistent across age and sex groups. The decline in incidence was observed, for the most part, in the 40-69 age group, with a greater decrease in males. Our findings provide a new evidence of a downward trend in incidence rates of this disease in China for a period of 20 years. As the observed decline is relatively small and inconsistent across sex and age groups, a continued epidemiological observation on this condition is required.

Adult↗

A framework for integrating the songbird brain.

Biological systems by default involve complex components with complex relationships. To decipher how biological systems work, we assume that one needs to integrate information over multiple levels of complexity. The songbird vocal communication system is ideal for such integration due to many years of ethological investigation and a discreet dedicated brain network. Here we announce the beginnings of a songbird brain integrative project that involves high-throughput, molecular, anatomical, electrophysiological and behavioral levels of analysis. We first formed a rationale for inclusion of specific biological levels of analysis, then developed high-throughput molecular technologies on songbird brains, developed technologies for combined analysis of electrophysiological activity and gene regulation in awake behaving animals, and developed bioinformatic tools that predict causal interactions within and between biological levels of organization. This integrative brain project is fitting for the interdisciplinary approaches taken in the current songbird issue of the Journal of Comparative Physiology A and is expected to be conducive to deciphering how brains generate and perceive complex behaviors.

Animals↗

Expressed sequence tags from a NaCl-treated Suaeda salsa cDNA library.

Past efforts to improve plant tolerance to osmotic stress have had limited success owing to the genetic complexity of stress responses. The first step towards cataloging and categorizing genetically complex abotic stress responses is the rapid discovery of genes by the large-scale partial sequencing of randomly selected cDNA clones or expressed sequence tags (ESTs). Suaeda salsa, which can survive seawater-level salinity, is a favorite halophytic model for salt tolerant research. We constructed a NaCl-treated cDNA library of Suaeda salsa and sequenced 1048 randomly selected clones, out of which 1016 clones produced readable sequences (773 showed homology to previously identified genes, 227 matched unknown protein coding regions, 16 anomalous sequences or sequences of bacterial origin were excluded from further analysis). By sequence analysis we identified 492 unique clones: 315 showed homology to previously identified genes, 177 matched unknown protein coding regions (101 of which have been found before in other organisms and 76 are completely novel). All our EST data are available on the Internet. We believe that our dbEST and the associated DNA materials will be a useful source to scientists engaging in stress-tolerance study.

Blotting, Northern↗

The neurocognitive phenotype of the 22q11.2 deletion syndrome: selective deficit in visual-spatial memory.

The 22q11.2 deletion syndrome (velocardiofacial/DiGeorge syndrome) is associated with a high frequency of learning disabilities. Although previous work has demonstrated that verbal skills are typically better preserved than non-verbal skills on both IQ and academic achievement testing in children with this syndrome, such measures are not sufficiently specific to determine a selective cognitive deficit. As part of an ongoing prospective study of patients with this syndrome, 29 children aged 5-17 with confirmed 22q11.2 deletions were assessed with a comprehensive neuropsychological test battery, including matched tasks of verbal and visuospatial memory. Results indicate that 22q patients displayed a selective deficit in visual-spatial memory, which was mirrored by deficits in arithmetic and general visual-spatial cognition. Further, a dissociation between visual-spatial and object memory was observed, indicating further selectivity of this pattern of deficit, and providing evidence for the dissociability of these components of visual cognition. These results indicate that children with 22q11.2 deletions display a specific neurocognitive phenotype, and suggest that this region of Chromosome 22q11 may harbor a gene or genes relevant to the etiology of nonverbal learning deficits.

Adolescent↗

The contribution of arthritis and arthritis disability to nonparticipation in the labor force: a Canadian example.

OBJECTIVE: To examine the factors affecting labor force participation and understand how arthritis affects labor force participation in a Canadian working population. METHODS: Data from the 1990 Ontario Health Survey population (n = 35,221) were used. Labor force participation was dichotomized as in the labor force and not in the labor force. Stratified logistic regression analyses by sex were carried out to identify factors associated with not being in the labor force, including arthritis, chronic disorders, and sociodemographic and family composition variables. RESULTS: Overall, 6.7% of men and 23.0% of women were not in the labor force compared with 18.6% and 36.0%, respectively, of men and women with arthritis. After controlling for other covariates, disability caused by arthritis was significantly associated with increased risk of being out of the labor force, with odds ratios of 2.70 for men and 1.91 for women. Low education, pain, and nonarthritis disability were also significantly associated with being out of the labor force. The effects of age and family structure on employment were sex dependent. Women were at higher risk at all age groups. Men with dependent children were more likely to work, as were women who lived alone. For women, having dependent children increased the likelihood of not being in the labor force. CONCLUSION: People with arthritis disability were more likely to be out of the labor force. It was not arthritis per se that limited people in labor force participation, but rather the arthritis disabilities.

Adult↗

Arthritis prevalence and place of birth: findings from the 1994 Canadian National Population Health Survey.

This paper describes the prevalence of arthritis in Canadians by ethnic origin, including Asians, Europeans/Australians, and North American-born Canadians. Data for this study were derived from the 1994 Canadian National Population Health Survey, a cross-sectional survey with a sample of 39,240 persons aged 20 years and older. Arthritis was defined as a long-term health condition of "arthritis or rheumatism" diagnosed by a health professional. Place of birth was determined according to self-reported country of birth. Unconditional multiple logistic regression models were used to adjust for potential confounding effects. The crude prevalence of self-reported arthritis and rheumatism diagnosed by a health professional as a long-term condition for those aged 20 years and older in Canada was 14.2%. The age-sex adjusted prevalence by place of birth was 6.9% in Asians, 14.2% in Europeans/Australians, and 14.5% in North American-born Canadians. In the multivariate analyses using North America-born Canadians as baseline, the risk for arthritis (odds ratio = 0.56) was significantly lower in Asian-born Canadians after adjustment for age, sex, education, income, occupation, and body mass index.

Adult↗

Liquid chromatography--tandem mass spectrometry analysis of cocaine and its metabolites from blood, amniotic fluid, placental and fetal tissues: study of the metabolism and distribution of cocaine in pregnant rats.

The ability to simultaneously quantitate cocaine and its 12 metabolites from pregnant rat blood, amniotic fluid, placental and fetal tissue homogenates aids in elucidating the metabolism and distribution of cocaine. An efficient extraction method was developed to simultaneously recover these 13 components using underivatized silica solid-phase extraction (SPE) cartridges. The overall recoveries for cocaine and its metabolites were studied from pregnant rat blood (47-100%), amniotic fluid (61-100%), placental homogenate (31-83%), and fetal homogenate (39-87%). Extraction of the samples using silica is not classical SPE, but rather allows for the concentration of the sample into a small volume prior to injection and the removal of the proteins due to their strong interaction with the active silica surface. A positive ion mode electrospray ionization liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was used and validated to simultaneously quantitate cocaine and 12 metabolites from these four biological matrices. A gradient elution method with a Zorbax XDB C8 reversed-phase column was used to separate the components. Multiple reaction monitoring (MRM) of a product ion arising from the corresponding precursor ion was used in order to enhance the selectivity and sensitivity of the method. Low background noise was observed from the complex biological matrices due to efficient SPE and the selectivity of the MRM mode. Linear calibration curves were generated from 0.01 to 2.50 ppm. The method also showed high intra-day (n =3) and inter-day (n=9) precision (% RSD) and accuracy (% error) for all components. The limits of detection (LODs) for the method ranged from 0.15 to 10 ppb. The LODs of cocaine and its major metabolites were less than 1 ppb from all four biological matrices. This method was applied to the study of the metabolism and distribution of cocaine in pregnant rats following intravenous infusion to a steady state plasma drug concentration. The following results were observed in the pregnant rat study: (1) the observations correlated strongly with the previous literature data on cocaine metabolism and distribution, (2) cocaine and norcocaine accumulated in the placenta, (3) arylhydroxylation of cocaine was a major metabolic pathway, (4) para-arylhydroxylation of cocaine was favored over meta-arylhydroxylation in rats and (5) accumulation of cocaine and its major metabolites was observed in the amniotic fluid.

Amniotic Fluid↗

Morphometry of the head of the caudate nucleus in patients with velocardiofacial syndrome (del 22q11.2).

UNLABELLED: Velocardiofacial syndrome (VCFS) is a chromosomal anomaly syndrome characterized by multiple congenital malformations, including cleft palate and cardiac anomalies. Many patients have attention-deficit (hyperactivity) disorders (AD[H]D) in childhood and schizophrenia in adulthood. We reviewed cranial magnetic resonance imaging (MRI) scans with particular attention to the head of the caudate nucleus and found that in control subjects, the head of the caudate was larger on the left than on the right, whereas VCFS patients showed a reversed right > left pattern or no significant asymmetry. A similar right > left asymmetry or a lack of this asymmetry has been reported in patients with AD(H)D. CONCLUSIONS: These results suggest a common pathophysiological mechanism of behavioural and cognitive problems in patients with AD(H)D and those with VCFS.

Abnormalities, Multiple↗

Pharmacokinetics and hepatic disposition of bis[1-(ethoxycarbonyl)propyl]5-acetylamino-2,4,6-triiodoisophthalate in rats and isolated perfused rat livers.

Bis[1-(Ethoxycarbonyl)propyl]5-acetylamino-2,4,6- triiodoisophthalate+ (NC 68183) was designed as a new computed tomography imaging agent. The purpose of this study was to determine the pharmacokinetics and metabolism of NC 68183 in conscious rats and in the isolated perfused rat liver. Animals were i.v. dosed at 69 and 690 mg of iodine/kg. Blood samples were collected at 5, 15, 30, and 60 min, and 7 days after dosing. Tissue samples (liver, kidney, and spleen) were taken at 60 min and 7 days after dosing. NC 68183 was cleared from blood in first order kinetics following an i.v. administration of 69 mg I/kg. The volume of distribution (Vss) at steady state and elimination half-life (t(1/2)) were estimated as 24 ml and 11 min. The clearance of NC 68183 from blood was changed to zero-order kinetics following administration of 690 mg/kg, and its elimination rate was 16 microg I/ml.min. The liver and spleen were the only tissues to have the nanoparticle residue at day 7 following administration. NC 68183 (75 mg of agent, 35 mg of I) was injected into the isolated perfused rat liver system. Bile flow increased from 1.0 to 1.3 microl/min/g liver following administration. The biliary excretion rate maximum was estimated as 11 microg/min/g liver. The metabolite was identified using liquid chromatography/mass spectrometry as a monocarboxylic acid product, which exclusively excreted into the bile in a soluble iodinated metabolite. Pharmacokinetics data suggested that NC 68183 primarily resides in the blood pool following an i.v. administration with a plasma half-life appropriate for blood pool imaging.

Animals↗

Congenital transmission of Schistosoma japonicum in the rabbit.

Fourteen pregnant rabbits were each infected with 300 cercariae of Schistosoma japonicum and divided into two groups. Group M (n = 8) was infected during mid-gestation (the organogenetic stage) and group L (n = 6) was infected during late-gestation (the post-organogenetic stage). Mother rabbits and rabbit kittens were killed 45-60 days after infection and perfused in order to obtain worm counts. Furthermore, faecal egg counts and tissue egg counts from livers were obtained from the mother rabbits as well as the rabbit kittens. All mother rabbits became infected harbouring 207.6 +/- 20.2 and 220.0 +/- 27.5 adult worms in group M and L, respectively. In groups M and L, 13.5% and 46.7% of the kittens were infected, respectively. In 12 of 14 litters at least one kitten was infected. The infected kittens harboured between one and three adult S. japonicum. The livers of the kittens infected with a worm pair displaced lesions as a result of egg deposition. The results, therefore, show that congenital transmission of S. japonicumcan occur in rabbits. The close anatomical resemblance between the rabbit and human placenta may be indicative of the presence of congenital transmission of S. japonicum infection in humans.

Animals↗

Cognitive and behavior profile of preschool children with chromosome 22q11.2 deletion.

A microscopic deletion of chromosome 22q11.2 has been identified in most patients with the DiGeorge, velocardiofacial syndrome, conotruncal anomaly face syndrome, and in some patients with isolated conotruncal cardiac anomalies. This study presents the neurodevelopmental outcome, including cognitive development, language development, speech, neuromuscular development, and behavioral characteristics of 40 preschool children (ages 13 to 63 months) who have been diagnosed with the 22q11.2 deletion. The impact of cardiac disease, cardiac surgery, and the palatal anomalies on this population was also studied. In the preschool years, children with a 22q11.2 deletion are most commonly found to be developmentally delayed, have mild hypotonia, and language and speech delays. The more significantly delayed children are at high risk to be subsequently diagnosed with mild or moderate mental retardation. The global delays and the variations in intelligence found are directly associated with the 22q11.2 deletion and are not explained by physical anomalies such as palatal defects or cardiac defects, or therapeutic interventions such as cardiac surgery. Our findings demonstrate that there is a pattern of significant speech disorders within this population. All of the children had late onset of verbal speech. Behavioral outcomes included both inhibition and attention disorders. Early intervention services are strongly recommended beginning in infancy to address the delays in gross motor skills, speech and language, and global developmental delays.

Behavioral Symptoms↗

Structure determination of 4-azido-2-pyrimidinone nucleoside analogs using mass spectrometry.

The nucleoside prodrugs 4-azido-ara-C and 2'-fluoro-2', 3'-dideoxy-4-azido-ara-C and their base-catalyzed reaction products were thoroughly characterized by mass spectrometry. The structures of the base-catalyzed reaction products were determined and confirmed using a combination of high-resolution and tandem mass spectrometry with deuterium exchange. An intra-molecular rearrangement reaction occurred in 4-azido-ara-C at physiological pH leading to the formation of a 2',6-anhydro product. A nucleoside of similar structure, 2'-fluoro-2'3'-dideoxy-4-azido-ara-C was studied to determine if the formation of the 2',6-anhydro ring was due to the presence of the 4-azido group or the arabinose 2'-OH group. The 6-position of 2'-fluoro-2',3'-dideoxy-4-azido-ara-C was found to be unreactive at physiological pH, but could add ammonia under strongly basic conditions (pH 11.0, ammonia solution). Finally, the formation of an intriguing tetrazole ring by the 4-azido moiety was observed.

Antineoplastic Agents↗

Psychoeducational profile of the 22q11.2 microdeletion: A complex pattern.

OBJECTIVES: To examine the psychoeducational profile associated with the chromosome 22q11.2 microdeletion (DiGeorge/velocardiofacial syndrome). STUDY DESIGN: Thirty-three patients (aged 6 to 27 years) with a 22q11.2 microdeletion underwent psychoeducational testing as part of a comprehensive evaluation. Nonparametric statistics were used to compare verbal and performance IQ, academic achievement scores, and receptive versus expressive language scores. Post hoc comparisons were made of IQ subtest scores and of language versus verbal IQ. RESULTS: Full-scale IQ ranged from the normal to the moderately retarded range. Mean verbal IQ was significantly higher than mean performance IQ. In a similar manner, mean reading and spelling scores were superior to the mean mathematics score, although achievement scores typically were in the range of verbal IQ. In addition, many children showed clinically significant language impairments, with mean language scores lower than mean verbal IQ. CONCLUSIONS: The IQ and academic profiles are reminiscent of a "nonverbal learning disability," although achievement was not discrepant from IQ. The coincidence of language impairment with a relative strength in reading belies a unique neuropsychologic profile. Educational programming for these children must address both verbal and nonverbal deficits.

Adolescent↗