Replication study of SNP associations for colorectal cancer in Hong Kong Chinese.

BACKGROUND: Recent genome-wide association studies of colorectal cancer (CRC) have identified common single-nucleotide polymorphisms (SNPs) mapping to 10 independent loci that confer modest increased risk. These studies have been conducted in European populations and it is unclear whether these observations generalise to populations with different ethnicities and rates of CRC. METHODS: An association study was performed on 892 CRC cases and 890 controls recruited from the Hong Kong Chinese population, genotyping 32 SNPs, which were either associated with CRC in previous studies or are in close proximity to previously reported risk SNPs. RESULTS: Twelve of the SNPs showed evidence of an association. The strongest associations were provided by rs10795668 on 10p14, rs4779584 on 15q14 and rs12953717 on 18q21.2. There was significant linear association between CRC risk and the number of independent risk variants possessed by an individual (P=2.29 × 10(-5)). CONCLUSION: These results indicate that some previously reported SNP associations also impact on CRC risk in the Chinese population. Possible reasons for failure of replication for some loci include inadequate study power, differences in allele frequency, linkage disequilibrium structure or effect size between populations. Our results suggest that many associations for CRC are likely to generalise across populations.

The first 5 years since trauma center designation in the Hong Kong Special Administrative Region, People's Republic of China.

BACKGROUND: In 1994, the Hong Kong Special Administrative Region (HKSAR) introduced plans to implement a trauma system based on the recommendations outlined by Professor Donald Trunkey in his report to the local Hospital Authority. Five government-subsidized public hospitals were subsequently designated as trauma centers in 2003. This article reviews the initial experience in these five centers. METHODS: Prospective trauma registries from January 2004 to December 2008 were reviewed. Primary clinical outcome measures were hospital mortality. The Trauma and Injury Severity Score methodology was used for benchmarking with the Major Trauma Outcome Study (MTOS) database. RESULTS: The majority (83.3%) of the 10,462 patients suffered from blunt trauma. Severe injury, defined as Injury Severity Score>15, occurred in 29.7% of patients. The leading causes of trauma were motor vehicle collisions and falls, with crude hospital mortality rates of 6.9% and 10.7%, respectively. The M-statistic was 0.95, indicating comparable case-mix with the MTOS. The worst outcome occurred in the first year. Significant improvement was seen in patients with penetrating injuries. By 2008, these patients had significantly higher survival rates than expected (Z-statistic=0.85). Although the overall mortality rates for blunt trauma were higher than expected, the difference was no longer statistically significant from the second year onward. CONCLUSIONS: The case-mix of trauma patients in the HKSAR is comparable with that of the MTOS. A young trauma system relatively unburdened by dissimilar reimbursement and patient access issues may achieve significant improvement and satisfactory patient outcomes. Our findings may serve as a useful benchmark for HK and other Southeast Asian cities and trauma systems to establish local coefficients for future evaluations.

The evaluation of a radioimmunoassay for phenothiazines and thioxanthenes using an iodinated tracer.

Antisera have been raised in rabbits to the immogen 2-trifluoromethylphenothiazine-10-beta-propionate bovine serum albumin. An [125I]-labelled tyrosine methyl ester derivative of the immunogen precursor has been synthesised and used with the antisera to develop a simple, precise and sensitive radioimmunoassay for phenothiazines and thioxanthenes bearing 2-trifluoromethyl substituents. The assay can detect 0.4 ng/ml of fluphenazine, trifluorperazine or (Z)-flupenthixol in 100 microliter of human serum without interference from their sulphoxide or 7-hydroxylated metabolites. An acceptable correlation between this assay and an established fluphenazine radioimmunoassay using commercial [3H]fluphenazine has been obtained for plasma samples.

Anatomic extent of colitis and disease severity are not predictors of pouchitis after restorative proctocolectomy for mucosal ulcerative colitis.

BACKGROUND: Pouchitis is a common complication following restorative proctocolectomy with ileal pouch anal anastomosis (RPC-IPAA) for mucosal ulcerative colitis (MUC). The aim of this study was to determine if perioperative anatomic extent and severity of disease are predictors of pouchitis. METHODS: All consecutive patients who underwent RPC-IPAA for MUC between 1988 and 2002 were retrospectively studied. Pouchitis was classified as acute, recurrent or refractory. Colectomy specimen slides were histopathologically evaluated by a single blinded pathologist (MB), who assessed extent and severity of disease. RESULTS: Of 112 patients assessed, 70 (62.5%) had some form of pouchitis at a median follow-up of 38 months (range, 1-204 months). No association was found between the extent or severity of disease and subsequent development of acute or chronic pouchitis. A positive correlation was found between the histopathologic score and the occurrence of clinical pouchitis (p=0.014). The presence of colonic metaplasia in the pouch biopsy was significantly correlated with a histopathologic diagnosis of pouchitis (p<0.0001, r=-0.449). CONCLUSIONS: Following RPC for MUC, the extent and severity of disease do not predict the subsequent development of pouchitis.

3H and 125I radioimmunoassays of haloperidol compared with fluoroimmunoassay involving antibody coupled to magnetizable solid phase.

Radioimmunoassays for haloperidol are described, involving use of tritium- or 125I-labeled drug or tritium-labeled spiroperidol, and a rabbit antiserum to a drug/bovine serum albumin conjugate. The 125I-labeled drug was prepared by the Chloramine T iodination technique. A fluoroimmunoassay for haloperidol is also described in which the antiserum is coupled to magnetizable solid-phase medium, and fluorescein-labeled haloperidol is used. The assays have acceptable accuracy, precision, and reproducibility, and are specific for haloperidol and similar butyrophenones, with no significant interference from known metabolites and other drugs. Only the radioimmunoassays have sufficient sensitivity to cover the whole range of haloperidol concentrations in serum. The fluoroimmunoassay can be used to monitor high concentrations of haloperidol in 150-microL samples or the complete concentration range of 1-mL serum samples that are extracted and concentrated before assay.

Total and free serum haloperidol levels in schizophrenic patients and the effect of age thioridazine and fatty acid on haloperidol-serum protein binding in vitro.

1 Using radioimmunoassays, steady-state levels of total and free haloperidol (obtained by ultrafiltration and dialysis) have been determined in twenty-two patients on long term treatment receiving doses from 3 to 45 mg per day. 2 For the group, both total serum concentration and free drug concentration showed significant correlations (P less than 0.001) with daily dose. 3 No significant correlation was observed between age of the patient and percentage free haloperidol in serum. 4 In vitro experiments using sera from twenty-three healthy volunteers showed significant negative correlations (P less than 0.01) between age and percentage free haloperidol. 5 Thioridazine and oleic acid significantly enhanced the percentage of free haloperidol in normal human sera in vitro.

Serum concentration of depot neuroleptics in tardive dyskinesia.

Using radioimmunoassay techniques, serum levels of depot neuroleptics, fluphenazine and flupenthixol, were estimated in two groups of chronic schizophrenic patients with, and without, tardive dyskinesia. There were high significant difference in dose-related serum levels of either drug between the groups. The hypothesis that patients with tardive dyskinesia develop the syndrome because they do not metabolise neuroleptics as efficiently as those without the syndrome was not supported by the data.

Analysis of randomly amplified flow-sorted chromosomes using the polymerase chain reaction.

Bivariate fluorescence-activated sorting is a method for obtaining relatively pure fractions of chromosomal DNA. Unfortunately, the yields (< 0.25 microgram/day) frequently limit the types of molecular analysis that can be performed. The polymerase chain reaction (PCR) is capable of amplifying unique sequences from scant amounts of template DNA. The purpose of this study was to determine whether the sensitivity of the PCR could be used to detect sequences specific to chromosomes discriminated and purified by flow cytometry. Flow-sorted chromosomal DNA was prepared by collecting approximately 10(5) chromosomes onto a nitrocellulose filter and eluting the DNA by boiling. Amplification products were not detected when different amounts of chromosomal DNA were used in a single 30 to 40-cycle PCR assay. However, when the eluted DNA was primed with degenerate 15-bp oligonucleotides and randomly amplified prior to performing the PCR assay, sequence-tagged sites (STSs) were detected after gel electrophoresis and ethidium bromide staining. This random amplification step eliminated the need for both reamplification with nested primers and detection by DNA hybridization. Furthermore, the random amplification scheme provided enough template DNA from a single sort (10(5) chromosomes) to perform > 1000 PCR assays. Representational analysis of one chromosome type revealed that > 74% of 70 STSs were detected. Moreover, the technology could be used to identify and delineate the breakpoint region of a marker chromosome. This amplification scheme should simplify greatly the molecular analysis of normal and aberrant chromosomes.

A serine proteinase inhibitor locus at 18q21.3 contains a tandem duplication of the human squamous cell carcinoma antigen gene.

The squamous cell carcinoma antigen (SCCA) is a member of the ovalbumin family of serine proteinase inhibitors (serpins). A neutral form of the protein is found in normal and some malignant squamous cells, whereas an acidic form is detected exclusively in tumor cells and in the circulation of patients with squamous cell tumors. In this report, we describe the cloning of the SCCA gene from normal genomic DNA. Surprisingly, two genes were found. They were tandemly arrayed and flanked by two other closely related serpins, plasminogen activator inhibitor type 2 (PAI2) and maspin at 18q21.3. The genomic structure of the two genes, SCCA1 and SCCA2, was highly conserved. The predicted amino acid sequences were 92% identical and suggested that the neutral form of the protein was encoded by SCCA1 and the acidic form was encoded by SCCA2. Further characterization of the region should determine whether the differential expression of the SCCA genes plays a causal role in development of more aggressive squamous cell carcinomas.