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Introduction: Most differentiated thyroid carcinomas (DTC) are treated by total thyroidectomy in Hong Kong. This study investigates the outcome of tumour control in selected patients treated by hemithyroidectomy, which is beneficial in terms of having a lower operative morbidity., Methods: This is a retrospective study of prospectively collected data from our cancer registry. Patients with pathologically proven differentiated thyroid carcinoma were stratified into risk groups according to the patients' age, tumour size, extrathyroid spread and distant metastasis. Low-risk patients were managed with hemithyroidectomy without postoperative radioactive iodine. Central compartment lymph node dissection was also carried out if the diagnosis was confirmed preoperatively. The oncological outcome and surgical morbidity were evaluated., Results: A total of 236 patients with the diagnosis of DTC underwent a thyroidectomy at our institution during a 24-year period. 93 patients were initially treated by hemithyroidectomy. Subsequent evaluation was focused on this subgroup. The mean follow-up period was 63.3 +/- 55.1 months. The mean tumour diameter was 22.1 +/- 20.8 mm. The histopathologic diagnoses were papillary carcinoma (69 cases; 74.2 percent), follicular carcinoma (20 cases; 21.5 percent) and Hurthle cell carcinoma (four cases; 4.3 percent). 23 (24.7 percent) patients underwent hemithyroidectomy coupled with central compartment dissection. Pathologically proven lymph node metastasis was diagnosed in 12 (12.9 percent) patients. Transient vocal cord palsy occurred in six (6.5 percent) patients, while permanent vocal cord palsy occurred in two (2.2 percent). Local tumour recurrence arose in only one (1.1 percent) patient. No patient succumbed to the thyroid cancer., Conclusion: Hemithyroidectomy coupled with central compartment dissection in selected cases of DTC can achieve excellent tumour control with minimal surgical morbidity.

Background: Mercury is a prominent environmental contaminant that causes detrimental effects to human health. Although the liver has been known to be a main target organ, there is limited information on in vivo molecular mechanism of mercury-induced toxicity in the liver. By using transcriptome analysis, phenotypic anchoring and validation of targeted gene expression in zebrafish, mercury-induced hepatotoxicity was investigated and a number of perturbed cellular processes were identified and compared with those captured in the in vitro human cell line studies., Results: Hepato-transcriptome analysis of mercury-exposed zebrafish revealed that the earliest deregulated genes were associated with electron transport chain, mitochondrial fatty acid beta-oxidation, nuclear receptor signaling and apoptotic pathway, followed by complement system and proteasome pathway, and thereafter DNA damage, hypoxia, Wnt signaling, fatty acid synthesis, gluconeogenesis, cell cycle and motility. Comparative meta-analysis of microarray data between zebrafish liver and human HepG2 cells exposed to mercury identified some common toxicological effects of mercury-induced hepatotoxicity in both models. Histological analyses of liver from mercury-exposed fish revealed morphological changes of liver parenchyma, decreased nucleated cell count, increased lipid vesicles, glycogen and apoptotic bodies, thus providing phenotypic evidence for anchoring of the transcriptome analysis. Validation of targeted gene expression confirmed deregulated gene-pathways from enrichment analysis. Some of these genes responding to low concentrations of mercury may serve as toxicogenomic-based markers for detection and health risk assessment of environmental mercury contaminations., Conclusion: Mercury-induced hepatotoxicity was triggered by oxidative stresses, intrinsic apoptotic pathway, deregulation of nuclear receptor and kinase activities including Gsk3 that deregulates Wnt signaling pathway, gluconeogenesis, and adipogenesis, leading to mitochondrial dysfunction, endocrine disruption and metabolic disorders. This study provides important mechanistic insights into mercury-induced liver toxicity in a whole-animal physiology context, which will help in understanding the syndromes caused by mercury poisoning. The molecular conservation of mercury-induced hepatotoxicity between zebrafish and human cell line reveals the feasibility of using zebrafish to model molecular toxicity in human for toxicant risk assessments.

The toxicity mechanism of bisphenol A (BPA) to zebrafish (Danio rerio) was studied in the molecular level,by the method of zebrafish microarray and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Zebrafish embryos were exposed to 0.5, 1.5 and 4.5 mg/L BPA for 8 days since fertilization. The results from microarray and validated by qRT-PCR showed that, 50 specific genes were up-or down-regulated, and dose-responses for them were significant (p < 0.05). This study demonstrates the genotoxicity of BPA. Moreover,according to their function and pathway analysis,it could support the mechanisms for the morphological toxicity and metabolize turbulence observed in prophase study.

In this communication, we describe the general aspects of omics approaches for analyses of transcriptome, proteome, and metabolome, and how they can be strategically incorporated into chemical screening and perturbation studies using the zebrafish system. Pharmacological efficacy and selectivity of chemicals can be evaluated based on chemical-induced phenotypic effects; however, phenotypic observation has limitations in identifying mechanistic action of chemicals. We suggest adapting gene-expression-based high-throughput screening as a complementary strategy to zebrafish-phenotype-based screening for mechanistic insights about the mode of action and toxicity of a chemical, large-scale predictive applications and comparative analysis of chemical-induced omics signatures, which are useful to identify conserved biological responses, signaling pathways, and biomarkers. The potential mechanistic, predictive, and comparative applications of omics approaches can be implemented in the zebrafish system. Examples of these using the omics approaches in zebrafish, including data of ours and others, are presented and discussed. Omics also facilitates the translatability of zebrafish studies across species through comparison of conserved chemical-induced responses. This review is intended to update interested readers with the current omics approaches that have been applied in chemical studies on zebrafish and their potential in enhancing discovery in chemical biology.

Background, Aim, and Scope: Photochemical smog, characterized by high concentrations of O(3) and fine particles, is of great concern in the urban areas, in particular megacities and city clusters like the Pearl River Delta., Materials, Methods, and Results: Ambient ozone (O(3)) and its precursors were simultaneously measured at two sites in the Pearl River Delta, namely, Wan Qing Sha (WQS) in Guangzhou and Tung Chung (TC) in Hong Kong, from 23 October to 01 December 2007 in order to explore their potential relationship. Eight high O(3) episode days were identified at WQS and two at TC during the sampling campaign, indicating a more serious O(3) pollution in Guangzhou than in Hong Kong. An observation-based model was employed to determine the ozone-precursor relationship. At both sites, O(3) production was found to be volatile organic compound (VOC)-limited, which is consistent with previous observations. Anthropogenic hydrocarbons played a key role in O(3) production, while reducing nitric oxide emissions aided the buildup of O(3) concentrations. Among VOC species, the summed relative incremental reactivity (RIR) of the top 12 compounds accounted for 89% and 85% of the total RIR at WQS and TC, respectively, indicating that local photochemical O(3) formation can be mainly attributed to a small number of VOC species., Discussion and Conclusions: A large increment in both simulated HO(2) and O(3) concentrations was achieved with additional input of hourly carbonyl data. This suggested that apart from hydrocarbons, carbonyls might significantly contribute to the O(3) production in the Pearl River Delta.

In an effort of validating the zebrafish model for studies of human tumors, our previous transcriptome analyses revealed striking molecular similarities between zebrafish and human liver neoplasia. However, as biological processes function at modular levels such as pathways and cascades, it is also important to capture conservation at the modular levels and in regulatory program(s) controlling these modules. In this study, we performed comparative transcriptome analyses with two modules, biological modules and transcription factor target modules, using gene set enrichment analysis against carcinogen-induced liver tumors in zebrafish with four tissue types of human tumors. We observed conservation of enriched modules that are associated to tumorigenesis such as cell cycle, metastasis, and hypoxia in these tumors. More importantly, we identified conserved regulatory programs linking these cancer-related modules with transcription factors and oncogenes such as Myc, E2F, STAT, and YY1. Taken together, our analyses revealed that carcinogen-induced liver tumors in zebrafish capture cancerous hallmarks observed in human tumors not only for cancer-related biological modules but also at transcriptional program, further implicating conserved tumorigenesis mechanism in both zebrafish and human.

We report a case of primary hepatic peripheral T-cell lymphoma in a patient with hepatitis B virus-related cirrhosis. This patient presented with a solitary hepatic lesion with computed tomography and magnetic resonance imaging features that did not resemble hepatocellular carcinoma. Subsequent biopsy of the lesion revealed that it was a peripheral T-cell lymphoma. The patient was successfully treated with multi-agent chemotherapy followed by radiofrequency ablation. Although hepatocellular carcinoma is the most frequently encountered primary hepatic tumour in patients with hepatitis B virus-related cirrhosis, primary hepatic lymphoma should also be borne in mind. Nevertheless, primary hepatic lymphoma is a rare entity, and has no proven association with chronic hepatitis B infection.

The availability of microarray technology for zebrafish research has enabled the expression of tens of thousands of genes to be studied simultaneously in one experiment. The experiment usually involves measuring and comparing the relative abundance of tens of thousands of mRNA species in experimental samples obtained from mutant versus wild-type embryos, disease versus normal tissues, embryos/fish of different developmental stages, physiologic states, or from multiple treatments and/or time-points. A microarray experiment comprised of several stages can be divided into two distinct parts (i.e., the "wet-lab" and the "dry-lab"). The success of a microarray experiment hinges on the "wet-lab" procedures, which include technology that allows for generation of arrays with very high-density DNA where tens of thousands of genes are represented in an area smaller than a standard glass microscope slide, and procedures that enable extraction of high-quality RNA, efficient fluorescent labeling of nucleic acids, as well as specific hybridization of fluorescent labeled-samples with arrayed probes. This chapter describes these "wet-lab" procedures. "Dry-lab" procedures are described in the next chapter.

In expression microarray experiments, post-hybridization procedures involving data acquisition and analysis are mainly computational and hence are described as "dry-lab procedures." The aim of these procedures is to acquire the fluorescent signals representing the relative abundance of tens of thousands of RNA species in samples with biological interest, and transform them into meaningful data with biological significance. These procedures begin with image and data acquisition followed by data normalization and processing, and thereafter primary and secondary data analyses. Although the actual data analysis is carried out after the wet-lab procedures, the strategy for data analysis should be planned prior to wet lab procedures when designing the experiment, to ensure effective downstream data handling and interpretation. Principal steps and advisory notes for acquiring, processing, and analyzing data that are commonly associated with various zebrafish expression profiling experiments are described in this chapter.

The ability to perform large-scale, expression-based chemogenomics on whole adult organisms, as in invertebrate models (worm and fly), is highly desirable for a vertebrate model but its feasibility and potential has not been demonstrated. We performed expression-based chemogenomics on the whole adult organism of a vertebrate model, the zebrafish, and demonstrated its potential for large-scale predictive and discovery chemical biology. Focusing on two classes of compounds with wide implications to human health, polycyclic (halogenated) aromatic hydrocarbons [P(H)AHs] and estrogenic compounds (ECs), we generated robust prediction models that can discriminate compounds of the same class from those of different classes in two large independent experiments. The robust expression signatures led to the identification of biomarkers for potent aryl hydrocarbon receptor (AHR) and estrogen receptor (ER) agonists, respectively, and were validated in multiple targeted tissues. Knowledge-based data mining of human homologs of zebrafish genes revealed highly conserved chemical-induced biological responses/effects, health risks, and novel biological insights associated with AHR and ER that could be inferred to humans. Thus, our study presents an effective, high-throughput strategy of capturing molecular snapshots of chemical-induced biological states of a whole adult vertebrate that provides information on biomarkers of effects, deregulated signaling pathways, and possible affected biological functions, perturbed physiological systems, and increased health risks. These findings place zebrafish in a strategic position to bridge the wide gap between cell-based and rodent models in chemogenomics research and applications, especially in preclinical drug discovery and toxicology., Competing Interests: The authors have declared that no competing interests exist.

Objective: To assess the feasibility and advantages of submandibular sialoadenectomy under local anesthesia., Study Design: Retrospective clinical study., Subjects and Methods: Twenty patients with benign submandibular masses underwent submandibular sialoadenectomy. The procedure was carried out under local anesthesia (LA) in 12 patients and general anesthesia (GA) in 8 patients. The patient and tumor characteristics, as well as treatment outcome or complications, were compared between the two groups., Results: There was no conversion from LA to GA. Nine patients in the LA group could be discharged as day-case surgery versus none in the GA group, P = 0.001. The postoperative hospital stay was also much shorter in the LA group: 0.4 day vs 2.0 days, P < 0.001. Postoperative vomiting occurred in only two of the eight patients of the GA group. Complication rate was similar., Conclusion: Submandibular sialoadenectomy under local anesthesia is feasible. It can shorten the hospital stay and facilitate day-case surgery.

Fallen television sets can cause significant injuries in toddlers. We report the case of a child with a focal brainstem injury who presented with subtle physical examination findings, which eventually led to aspiration and airway compromise. This case illustrates the importance of maintaining a high index of suspicion and performing a careful physical examination in traumatized, preverbal children who sustain an apparently minor head injury. The limitation of computed tomography studies in detecting brainstem injury is also discussed.

To explore the in vivo significance of ShcA during mammary tumorigenesis, we used mice expressing several phosphotyrosine-deficient ShcA alleles under the control of their endogenous promoter. We show that all three ShcA tyrosine phosphorylation sites are involved in the early stages of mammary tumour progression, including loss of the myoepithelial cell layer surrounding hyperplasias and during progression to carcinoma. We have determined that signals emanating from Y313 are important for tumour cell survival, whereas Y239/240 transduce signals promoting tumour vascularization. We further demonstrate that loss of ShcA expression in mammary epithelial cells abrogates tumour development. This study is the first to directly demonstrate that signalling downstream from the ShcA adaptor protein is critical for breast cancer development.

Bioassay-guided fractionation against alpha-glucosidase resulted in isolation and characterization of eight active compounds from the EtOH extract of the seeds of Syagrus romanzoffiana. Of these, seven are stilbenoids, and two of them, 13-hydroxykompasinol A (1) and scirpusin C (4), possess potent inhibitory activity against alpha-glucosidase type IV from Bacillus stearothermophilus with the IC50 value of 6.5 and 4.9 microM, respectively. The in vivo assay on normal Wistar rats using oral sucrose challenge also demonstrated that kompasinol A (2) and 3,3',4,5,5'-pentahydroxy-trans-stilbene (5) possess significant effect in reducing the postprandial blood glucose level (10.2% and 12.1% at 10mg/kg, respectively). These results suggest that stilbenoids might be explored for their therapeutic potential as hypoglycemic agents.

Objective: To study clinical perspectives pertaining to chronic sclerosing sialadenitis, which is also known as Kuttner's tumour., Design: Retrospective medical chart review., Setting: Regional hospital, Hong Kong., Patients: From February 2005 to February 2007, nine cases with Kuttner's tumour were identified from our hospital electronic database., Interventions: They underwent submandibular sialadenectomy under either local (n=6) or general (n=3) anaesthesia., Main Outcome Measures: The results of preoperative ultrasonography, fine-needle aspiration cytology, and intra-operative frozen section examination were correlated with the final diagnosis. Operative morbidity was also evaluated., Results: The mean age of the patients at diagnosis was 61 years; three were females. Three had bilateral submandibular swellings. Following preoperative ultrasonography in six of the patients, tumours were suspected in two, an enlarged lymph node in one, and diffuse enlargement was visualised in the other three. Six patients had preoperative fine-needle aspiration cytology; five yielded scanty acini with normal-looking ductal cells, variable degrees of infiltration by chronic inflammatory cells without granuloma admixing fibrosis. In the sixth patient, only bland-looking epithelial cells, indicative of ductal differentiation suspicious of neoplasm were noted. Intra-operative frozen section examination was conducted in three patients: chronic inflammation without evidence of carcinoma was visualised in each. Operations performed under local anaesthesia were well tolerated; only one patient endured a transient, marginal facial nerve palsy., Conclusions: Kuttner's tumour is by no means rare. When supported by ultrasonography and fine-needle aspiration cytology, an accurate diagnosis can be made preoperatively and surgery can be reserved for symptomatic cases. Submandibular sialadenectomy is a safe and effective means of treating Kuttner's tumour, and can be accomplished under local anaesthesia.

The conventional treatment of ranula is surgical procedure. We report an innovative method for ranula by using botulinum toxin type A on 3 patients. All 3 cases of ranula resolved after this minimally invasive therapy. The treatment complication was minimal.

Background: Information about diagnostic features of tuberculosis (TB) peritonitis among patients with end-stage renal failure (ESRF), compared with those without ESRF, is limited. Here, we review our experience with TB peritonitis in patients with and without ESRF over a period of 11 years, with special reference to the clinical features of and diagnostic tools for TB peritonitis., Methods: The records of all patients with TB peritonitis who were seen at United Christian Hospital (Hong Kong) from 1996 through 2006 were reviewed. The diagnosis of TB peritonitis was based on (1) detection of mycobacteria on smear and/or Mycobacterium tuberculosis on culture of ascitic fluid and/or peritoneal biopsy specimens and/or (2) demonstration of caseating granulomata on histological assessment of peritoneal biopsy specimens., Results: During the study period, 52 patients (19 without ESRF and 33 with ESRF) had TB peritonitis. Patients with ESRF tended to have more-acute onset of symptoms and neutrophil-predominant peritoneal fluid, which mimicked bacterial peritonitis. Diagnosis was made earlier among patients without ESRF than among those with ESRF. Laparotomy or laparoscopy was the initial diagnostic tool for 12 patients (63%) without ESRF, whereas mycobacterial culture was the diagnostic method for 18 patients (55%) with ESRF., Conclusions: TB peritonitis has nonspecific and protean manifestations. It should be considered in the context of culture-negative peritonitis and in the context of culture-positive peritonitis that fails to respond to appropriate antibiotics. Laparoscopy with biopsy should be considered at an early stage when TB peritonitis is suspected.

ErbB-2 overexpression and amplification occurs in 15% to 30% of human invasive breast carcinomas associated with poor clinical prognosis. Previously, we have shown that four ErbB-2/Neu tyrosine-autophosphorylation sites within the cytoplasmic tail of the receptor recruit distinct adaptor proteins and are sufficient to mediate transforming signals in vitro. Two of these sites, representing the growth factor receptor binding protein 2 (Grb2; Neu-YB) and the Src homology and collagen (Shc; Neu-YD) binding sites, can induce mammary tumorigenesis and metastasis. Here, we show that transgenic mice bearing the two other ErbB-2 autophosphorylation sites (Neu-YC and Neu-YE) develop metastatic mammary tumors. A detailed comparison of biological profiles among all Neu mutant mouse models revealed that Neu-YC, Neu-YD, and Neu-YE mammary tumors shared similar pathologic and transcriptional features. By contrast, the Neu-YB mouse model displayed a unique pathology with a high metastatic potential that correlates with a distinct transcriptional profile, including genes that promote malignant tumor progression such as metalloproteinases and chemokines. Furthermore, Neu-YB tumor epithelial cells showed abundant intracellular protein level of the chemokine CXCL12/SDF-1alpha, which may reflect the aggressive nature of this Neu mutant mouse model. Taken together, these findings indicate that activation of distinct Neu-coupled signaling pathways has an important impact on the biological behavior of Neu-induced tumors.

Polyarteritis nodosa is a systemic necrotising vasculitis that affects the small- and medium-sized arteries. Multifocal aneurysmal formation in the renal, hepatic, and mesenteric vasculature is a hallmark of this condition, and spontaneous aneurysmal rupture may occur, resulting in life-threatening haemorrhage. We describe a 42-year-old man who initially presented with fever of unknown origin. A diagnosis could not be reached at that time despite extensive investigations. The fever subsided spontaneously after 8 weeks, and the patient remained well for 6 years until he was admitted again for evaluation of fever. During his hospital stay, he developed a spontaneous massive intra-hepatic haemorrhage resulting in hepatic rupture and a haemoperitoneum. The bleeding was controlled at emergency laparotomy. An abdominal angiography demonstrated multiple microaneurysms in the hepatic and mesenteric arterial vasculature. The clinical findings suggested polyarteritis nodosa, and the source of bleeding was probably a ruptured intra-hepatic artery aneurysm.

Background: The submental flap was described for head and neck reconstruction more than a decade ago. Its application is confined mainly to nonmalignant diseases or low-grade malignancies, as the submental flap resides in the level I lymphatic drainage region of the neck. The authors report the use of the submental flap for soft-tissue reconstruction in a selected group of patients with aggressive orofacial cancer., Methods: From March of 2003 to September of 2005, 10 patients (nine with intraoral squamous cell carcinoma and one with facial angiosarcoma) underwent submental flap reconstruction after surgical extirpation of aggressive orofacial malignancies. The indications were severe comorbidity, old age, the presence of another incurable cancer, and/or the patient's skepticism about undergoing a free flap operation., Results: Of the surviving patients, the median follow-up was 21 months (range, 2 to 37 months). There were no cases of total flap failure, but partial necrosis occurred in two cases. Three patients experienced tumor recurrence, but only one case might have been related to use of the submental flap. Postoperative oral function, in terms of swallowing and speech, was well preserved; conventional dentures were fabricated for four patients., Conclusions: In selected patients with aggressive orofacial cancer, the submental flap is an expedient alternative to free tissue transfer for reconstruction. Nonetheless, indiscriminate use might compromise the oncological outcome, so it cannot be regarded as a standard method of treatment.

Hypothesis: Most patients undergoing long-term dialysis are anemic because of underproduction of erythropoietin and its inhibition by high parathyroid hormone levels due to secondary hyperparathyroidism. Renal anemia can be improved by parathyroidectomy., Design: Retrospective cohort study., Setting: Regional hospital., Patients: Twenty-three Chinese patients without a previous functioning renal transplant underwent parathyroidectomy for severe secondary hyperparathyroidism in a 3-year period., Intervention: Total parathyroidectomy with or without parathyroid autograft at the forearm., Main Outcome Measures: The preoperative and 6-month postoperative hematological and biochemical variables were compared for any differences by means of a paired t test., Results: The mean +/- SD follow-up duration was 17.7 +/- 8.1 (range, 6-34) months. Three patients (13%) developed persistent or recurrent hyperparathyroidism and 2 patients (9%) were biochemically hypoparathyroid. The other 18 patients (78%) were euparathyroid. Surgical morbidity was minimal; only 1 patient had complications, consisting of a postoperative fever of unknown origin that resolved with conservative treatment. The mean +/- SD hemoglobin level (8.6 +/- 2.1 vs 9.4 +/- 2.1 g/dL) but not the mean platelet level was significantly (P = .04) increased 6 months postoperatively. Likewise, the following other mean +/- SD biochemical values improved after surgery: parathyroid hormone (2235 +/- 500 vs 151 +/- 312 pg/mL; P<.001), alkaline phosphatase (645 +/- 349 vs 123 +/- 82 U/L; P<.001), calcium (10.8 +/- 4.0 vs 9.3 +/- 1.0 mg/dL; P<.001), phosphate (1.93 +/- 0.73 vs 1.50 +/- 0.51 mmol/L; P = .02), and albumin (3.5 +/- 0.5 vs 3.8 +/- 0.6 g/dL; P = .006)., Conclusions: Parathyroidectomy is highly effective to control secondary hyperparathyroidism with an exceedingly low complication rate. The hemoglobin level was significantly elevated 6 months postoperatively. The long-term effect warrants future trials.

Background: The great auricular nerve (GAN) is frequently sacrificed during parotidectomy and causes sensory disturbance of the auricle. Our study is to investigate whether GAN preservation can improve the sensory recovery., Methods: Patients undergoing superficial or total conservative parotidectomy for benign tumours were recruited consecutively from November 1998 to September 2001. Different sensory methods (light touch, two-point discrimination and sharp pain) of the auricle were evaluated by a designated physiotherapist preoperatively as well as at 1, 3, 6 and 12 months postoperatively. The patients and the physiotherapist were blinded to the integrity of the GAN. Long-term subjective assessment was also carried out beyond 2 years postoperatively., Results: A total of 21 patients were recruited for the study. GAN were preserved in 10 patients. The mean follow up was 16 months (12-42 months). There was no difference in sex distribution, type of operation and pathology of parotid tumour between the two groups. No postoperative mortality occurred and postoperative morbidity did not differ between the two groups. Patients with GAN preserved had significantly better light touch and sharp pain recovery at 1 year postoperatively. Subjective assessment of sensory dysfunction also favoured GAN preservation., Conclusion: Great auricular nerve preservation minimizes the postoperative sensory disturbance and should be considered whenever tumour clearance is not compromised.

Eight compounds, including two flavonoid glycosides, were isolated from the butanol-soluble fraction of the methanolic extract of the leaves of Phyllanthus reticulatus by conventional methods. A polyphenol rich fraction, obtained by Sephadex LH-20 fractionation, was also studied using an HPLC-SPE-NMR technique leading to the characterization of six compounds including three additional flavonoid glycosides. The latter approach used only 1 mg of samples, theoretically equivalent to 0.3 g of dry leaves. This study demonstrates that HPLC-SPE-NMR is very useful for thorough chemical investigation and also offers the advantages of saving time, plant materials and consumables over more conventional methods.

We present a simple analysis of the global warming problem caused by the emissions of CO2 (a major greenhouse gas) into the atmosphere resulting from the burning of fossil fuels. We provide quantitative tools which enable policymakers and interested citizens to explore the following issues central to the global warming problem. (i) At what rate are we permitted to continue to emit CO2 after the global average atmospheric concentration has 'stabilized' at some chosen target level? The answer here provides the magnitude of the effort, measured by the necessary total reduction of today's global (annual) emissions rate to achieve stabilization. We shall see that stabilized emissions rates for all interesting stabilized concentration levels are much lower than the current emissions rate, but these small finite values are very important. (ii) Across how many years can we spread the total effort to reduce the annual CO2 emissions rate from its current high value to the above-mentioned low and stabilized target value? The answer here provides the time-scale of the total mitigation effort for any chosen atmospheric concentration target level. We confirm the common understanding that targets below a doubling of the pre-industrial concentration create great pressure to produce action immediately, while targets above double the pre-industrial level can tolerate longer periods of inaction. (iii) How much harder is the future mitigation effort, if we do not do our share of the job now? Is it a good idea to overshoot a stabilization target? The quantitative answers here provide the penalty of procrastination. For example, the mitigation task to avoid doubling the pre-industrial level is a problem that can be addressed gradually, over a period extending more than a century, if started immediately, but procrastination can turn the effort into a much more urgent task that extends over only a few decades. We also find that overshooting target levels is a bad idea. The quality of public discourse on this subject could be much enhanced if ball-park quantitative answers to these questions were more widely known.

5,6-Secolycorines possessing a 5,6-dihydrophenanthridine skeleton were facilely prepared from lycorine through chemical transformations, mainly including N-alkylation, Hofmann degradation type reaction, reductive cleavage of trichloroethylcarbonyl moiety, and hydrogenation. Several secolycorine derivatives showed potent inhibitory activity against acetylcholinesterase with the IC(50) value at micromolar range and are more potent than galanthamine.

Arsenic is a prominent environmental toxicant and carcinogen; however, its molecular mechanism of toxicity and carcinogenicity remains poorly understood. In this study, we performed microarray-based expression profiling on liver of zebrafish exposed to 15 parts/million (ppm) arsenic [As(V)] for 8-96 h to identify global transcriptional changes and biological networks involved in arsenic-induced adaptive responses in vivo. We found that there was an increase of transcriptional activity associated with metabolism, especially for biosyntheses, membrane transporter activities, cytoplasm, and endoplasmic reticulum in the 96 h of arsenic treatment, while transcriptional programs for proteins in catabolism, energy derivation, and stress response remained active throughout the arsenic treatment. Many differentially expressed genes encoding proteins involved in heat shock proteins, DNA damage/repair, antioxidant activity, hypoxia induction, iron homeostasis, arsenic metabolism, and ubiquitin-dependent protein degradation were identified, suggesting strongly that DNA and protein damage as a result of arsenic metabolism and oxidative stress caused major cellular injury. These findings were comparable with those reported in mammalian systems, suggesting that the zebrafish liver coupled with the available microarray technology present an excellent in vivo toxicogenomic model for investigating arsenic toxicity. We proposed an in vivo, acute arsenic-induced adaptive response model of the zebrafish liver illustrating the relevance of many transcriptional activities that provide both global and specific information of a coordinated adaptive response to arsenic in the liver.

Objective: To study the clinical and pathological characteristics of patients with intestinal tuberculosis., Design: Retrospective study., Setting: United Christian Hospital, Hong Kong., Patients: Patients with intestinal tuberculosis diagnosed between January 1995 and December 2004 inclusive., Results: The median age of the 13 male and 9 female patients was 53 years (range, 12-81 years). Nineteen (86%) had a definitive diagnosis of intestinal tuberculosis confirmed by the presence of caseating granulomas and/or acid-fast bacilli in histological specimens. In three (14%) the diagnosis was based on histology revealing non-caseating granulomas and a positive response to anti-tuberculous treatment. Common symptoms included abdominal pain (82%), diarrhoea (55%), weight loss (55%), and fever (45%). Three (14%) of the patients were complicated by intestinal obstruction, and another two (9%) had intestinal perforation. Four (18%) had concomitant active pulmonary tuberculosis. The most frequently involved site was the ileocaecal region, which was affected in 19 (86%) patients. Other sites included the jejunum, ascending and sigmoid colon. The diagnosis of intestinal tuberculosis was facilitated by examination of colonoscopic biopsy specimens (11 patients), and by examination of resected surgical specimens in the remainder. Two patients died from terminal malignancy. The remainder completed anti-tuberculous therapy and responded satisfactorily., Conclusions: The diagnosis of intestinal tuberculosis is difficult due to the lack of specific signs or symptoms. Colonoscopy with ileoscopy are useful tools in the search for colonic and terminal ileal tuberculosis. Surgical exploration is reserved for equivocal cases and for those who present as emergencies.

Intestinal perforation is an uncommon but potentially fatal complication of intestinal tuberculosis. We report on a 63-year-old HIV-negative man who developed terminal ileal perforation approximately 3.5 months following initiation of anti-tuberculous treatment for pulmonary tuberculosis and a concomitant tuberculous perianal abscess. Clinical and radiological improvements were initially evident following commencement of anti-tuberculous treatment, and the paradoxical response phenomenon was suspected. The patient subsequently underwent surgical resection of the affected bowel segment with primary anastomosis, and made an uneventful recovery. Anti-tuberculous medication was continued for another 12 months, and after a further 12 months there was no evidence of recurrent tuberculosis. This case illustrates that tuberculous intestinal perforation can develop during chemotherapy for tuberculosis. Prompt diagnosis and appropriate surgical treatment are essential to avoid morbidity and mortality.

Background and Study Aims: In a previous study we demonstrated the efficacy of second-look endoscopy with therapy within 16 - 24 hours after index endoscopy in reducing major recurrent peptic ulcer bleeding. In this study, we sought to identify factors that might predict further rebleeding after this scheduled second-look endoscopy., Patients and Methods: We studied 249 patients (181 men, 68 women) with acute bleeding peptic ulcers who were treated at the United Christian Hospital, Hong Kong from 1999 to 2002 and who underwent a scheduled second endoscopy. Those patients who developed rebleeding after the second endoscopy were evaluated, and possible predictive factors for rebleeding were analyzed using a logistic regression model., Results: Of the 249 patients who underwent scheduled second-look endoscopy, 17 patients (6.8 %) developed rebleeding: seven of these patients were treated by another endoscopic therapy; ten patients required surgery. The overall mortality rate was 3.1 %. A logistic regression analysis performed on the possible predictive factors for rebleeding found that the following factors were associated with a significant risk of further rebleeding after scheduled second endoscopy: American Society of Anesthesiologists (ASA) grade III or grade IV status (odds ratio 3.81, 95 % CI 1.27 - 11.44), ulcer size greater than 1.0 cm (odds ratio 4.69, 95 % CI 1.60 - 13.80), and a finding of persistent stigmata of recent hemorrhage at the scheduled second endoscopy (odds ratio 6.65, 95 % CI 2.11 - 20.98)., Conclusions: Endoscopic factors, including large ulcer size and the persistence of endoscopic stigmata of recent hemorrhage are important predictors for recurrent bleeding after scheduled second endoscopy.

Although the zebrafish has many attributes of a promising cancer model, one outstanding question is how similar zebrafish and human tumors are at the molecular level. To date, supporting data from histology and 'gene-to-gene' comparisons with human data offer limited insights. Using comparative microarray analyses, we found striking molecular similarities between zebrafish and human liver neoplasia. Our data indicate that zebrafish liver tumors possess the general molecular hallmarks of human liver cancer and some of the molecular similarities extend to the progression of liver tumors. The molecular conservation between fish and human liver tumors underscored the strong association and fundamental importance of these genes in liver neoplasia as well as their clinical potentials as diagnostic markers and/or therapeutic targets. In addition, our comparative oncogenomic work provides a general framework for comparing and validating microarray data of zebrafish model with human cancer, thus adding confidence of using the zebrafish to model human cancers.

The zebrafish (Danio rerio) has been long advocated as a model for cancer research, but little is known about the real molecular similarities between zebrafish and human tumors. Comparative analysis of microarray data from zebrafish liver tumors with those from four human tumor types revealed molecular conservation at various levels between fish and human tumors. This approach provides a useful strategy for identifying an expression signature that is strongly associated with a disease phenotype.

To develop a transgenic fish system to monitor environmental pollution, we generated a mvtg1:gfp transgenic medaka line, in which the gfp reporter gene was under the control of medaka vitellogenin1 (mvtg1) gene promoter. In this transgenic line, GFP was exclusively expressed in the liver of the mature adult female. Male and juvenile transgenic fish did not express GFP but could be induced to express GFP in the liver after exposure to 17-beta-estradiol (E2). Concurrent accumulation of mvtg1 and gfp mRNAs was observed during both development and estrogen treatment, indicating that the gfp transgene was faithfully expressed under the mvtg1 promoter. Dose- and time-dependent induction of GFP expression by E2 was investigated in male transgenic fish. The lowest-observed-effect concentration (LOEC) of E2 to induce GFP expression was 0.5 microg/L by observation of live fish and 0.05-0.1 microg/L by observation of dissection-exposed liver in a 30 day exposure experiment. GFP expression was observed within 36 h after treatment in high concentrations of E2 (5 microg/L), and it took longer to detect GFP expression under lower concentrations of E2. By removal and readdition of E2, we demonstrated that GFP expression was repeatedly induced. Finally, we also demonstrated that GFP expression could be induced by other estrogenic compounds, including 17-alpha-ethynylestradiol (EE2, 0.05 microg/L), diethylstibestrol (DES, 5 microg/L), estriol (10 microg/ L), and bisphenol A (BPA, 1 mg/L), but not by weak estrogenic chemicals such as nonylphenol (NP, up to 1 mg/ L) and methoxychlor (MXC, up to 20 microg/L). Our experiments indicated the broad application of the transgenic line to monitor a wide range of estrogenic chemicals.

Objectives: To examine the presentation, workup, and surgical complications of substernal goitre., Design: Retrospective study., Setting: Regional hospital, Hong Kong., Patients: Twenty-four mostly elderly patients (mean age, 60.1 years) who underwent thyroidectomy for substernal goitres between 2000 and 2003 (substernal goitres were defined as those having either a caudal mass transgressing the fourth thoracic vertebra or having more than 50% of their overall mass residing within the thorax)., Main Outcome Measures: Symptoms, histopathological diagnoses, morbidities, and complications., Results: Dyspnoea was the most common symptom (n=8, 33%). Three (12.5%) patients presented with acute airway obstruction; however, 13 (54.2%) were asymptomatic apart from the presence of cervical masses. Computed tomographic scans were performed on all but two patients. Malignancy was present in 12.6% of patients, or 16.8% if occult papillary carcinoma is included. Partial or full sternotomies were performed in two (8.3%) patients. Complications included recurrent laryngeal nerve injury (n=1, 2.7% of nerves at risk), transient hypoparathyroidism (n=2, 13.3% of patients at risk), haematoma (n=1, 2.7%), pneumonia (n=1, 2.7%), and wound infection (n=1, 2.7%). There was no operative mortality or permanent hypoparathyroidism. The complication rate was significantly lower in the asymptomatic patients (P=0.033 by Fisher's exact test); clinicopathological parameters were otherwise statistically comparable between the two groups., Conclusions: There is rarely any mortality in thyroidectomy for substernal goitre, and the morbidity is also very low, especially in asymptomatic patients. In the absence of contra-indications, substernal goitre should be treated with early surgery rather than having it run the risk of acute airway distress or cancer.

Zebrafish (Danio rerio) is a well-recognized model for the study of vertebrate developmental genetics, yet at the same time little is known about the transcriptional events that underlie zebrafish embryogenesis. Here we have employed microarray analysis to study the temporal activity of developmentally regulated genes during zebrafish embryogenesis. Transcriptome analysis at 12 different embryonic time points covering five different developmental stages (maternal, blastula, gastrula, segmentation, and pharyngula) revealed a highly dynamic transcriptional profile. Hierarchical clustering, stage-specific clustering, and algorithms to detect onset and peak of gene expression revealed clearly demarcated transcript clusters with maximum gene activity at distinct developmental stages as well as co-regulated expression of gene groups involved in dedicated functions such as organogenesis. Our study also revealed a previously unidentified cohort of genes that are transcribed prior to the mid-blastula transition, a time point earlier than when the zygotic genome was traditionally thought to become active. Here we provide, for the first time to our knowledge, a comprehensive list of developmentally regulated zebrafish genes and their expression profiles during embryogenesis, including novel information on the temporal expression of several thousand previously uncharacterized genes. The expression data generated from this study are accessible to all interested scientists from our institute resource database (http://giscompute.gis.a-star.edu.sg/~govind/zebrafish/data&#95;download.html)., Competing Interests: Competing interests. The authors have declared that no competing interests exist.

Congenital hepatic fibrosis is an uncommon fibrocystic disorder affecting the intrahepatic bile ducts. It has autosomal recessive inheritance. The main consequence of this condition is portal hypertension and it is often misdiagnosed as cirrhosis. Patients with congenital hepatic fibrosis usually present during childhood or early adolescence with oesophageal variceal bleeding. Portosystemic shunt surgery is the treatment of choice for these patients as the risk of postoperative hepatic encephalopathy is low. We report a patient with congenital hepatic fibrosis who presented with oesophageal variceal bleeding at the age of 16 years, initially misdiagnosed as having cryptogenic liver cirrhosis. The patient experienced two further episodes of oesophageal variceal bleeding in subsequent years. She eventually underwent portosystemic shunt surgery. One year after the operation, the shunt remained patent on Doppler ultrasonography, and there had been no further episodes of variceal bleeding post-surgery.

Effects of thyroxine (T4) and methimazole (MMI) on the development of the zebrafish immune system were investigated using continuous immersion treatment experiments. The effects of the treatments on thymus development were determined using computer-aided thymus morphometric analyses on in situ hybridization serial sections of the thymus while the effects on immune-related gene expression levels were monitored using quantitative real-time PCR. The findings indicate that thymus development and thymopoiesis, as indicated by thymus size, thymus Rag-1-positive region, and TCRAC expression level, were affected by T4 and MMI-treatments. With the exception of Ikaros, MMI-treated fish has lower immune-related gene expression levels, although it is not certain whether the effect resulted indirectly from the concomitant growth-retardation and/or directly from an effect on lymphopoiesis itself. The findings were comparable with those in mammalian system, thus providing the first evidence that the thyroid relationship with thymus development and lymphopoiesis is likely to be conserved from fish to higher vertebrates. It suggests the possibility of using zebrafish as a model system to investigate the molecular mechanisms involved in thyroid hormone-dependent disorders in the immune system.

Purpose: Contralateral neck failure after therapy for squamous cell carcinoma of the oral cavity and oropharynx has rarely been studied in detail. We aimed to examine the pattern and outcome of contralateral neck relapse and possible predictive clinicopathologic factors., Patients and Methods: Seventy-three patients undergoing surgery for cancer of oral cavity/oropharynx with curative intent were recruited from the hospital head and neck cancer registry. The age, gender, tumor site, primary tumor laterality, TNM status, clinical N status, pathologic T status, ipsilateral pathologic N status, tumor stage, status of residual disease, histopathologic differentiation, postoperative radiotherapy, local relapse, distant relapse, extracapsular spread of lymph node metastasis and neck dissection were evaluated for association with contralateral neck relapse., Results: Seven patients developed ipsilateral, 5 patients developed contralateral, and 3 patients developed bilateral neck recurrence after therapy. Only 1 patient with contralateral or bilateral neck relapse survived after salvage therapy. Ipsilateral positive nodal status was the only significant clinicopathologic parameter associated with contralateral neck relapse, which occurred rather commonly in well-lateralized tumors., Conclusion: Contralateral and ipsilateral neck relapses are similar in occurrence. Pathologic positive nodal status is associated with a higher incidence of contralateral neck relapse. Aggressive and comprehensive adjuvant radiotherapy to the neck plus close surveillance in the first 2 years postoperatively might curtail the frequency and mortality due to contralateral neck failure.

In the past, numerous reports have advocated primary surgical resection as a treatment of choice for bleeding gastric stromal tumors (GIST). There were scarce reports on primary hemostasis with endoscopic therapy. We encountered two patients who presented to our unit with acute bleeding from gastric fundal stromal tumor, in whom we were able to achieved successful endoscopic hemostasis with hemoclip therapy. We describe the management of these cases and reviewed the current management strategies in bleeding gastric stromal tumor.

In the present study, both zebrafish and medaka vitellogenin genes have been isolated and used as a biomarker to compare the two small aquarium fish in response to estrogen treatment and thus to evaluate the two fish models in development of a biomonitoring system for environmental estrogens. The isolated zebrafish vitellogenin gene, zvtg1, is the most abundantly expressed vitellogenin gene in zebrafish and its complete protein sequence of 1360 amino acids was deduced from a genomic and a cDNA clone. The isolated medaka vitellogenin (mvtg1) genomic clone covers 1053 amino acids in the N-terminal. Both zebrafish zvtg1 and medaka mvtg1 are specifically expressed in female liver and their expression can be induced by 17beta-estradiol (E2) in male fish both by intramuscular injection and immersion treatment. A real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was developed for quantification of vitellogenin mRNA level in both control fish and E2-treated fish. The lowest-observed-effect concentrations of E2 for the induction of vitellogenin mRNAs were observed at 1 microg/l for zebrafish and 0.1 microg/l for medaka in a 2-day exposure experiment. Further kinetics studies of the two fish models indicated that medaka was able to respond much faster to E2 treatment than zebrafish, while the zebrafish can attain a much higher level of vitellogenin mRNAs than medaka after a long-term E2 treatment. The implication of these observations may be that the medaka system is better in monitoring acute treatment while the zebrafish system is better in monitoring chronic exposure.

The coronavirus which causes severe acute respiratory syndrome (SARS) is a virulent and highly contagious organism. Of the 1755 SARS patients in Hong Kong, over 400 were healthcare workers. Meticulous attention to infection control and teamwork are essential to minimize cross-contamination and prevent staff from contracting the illness. These points are especially pertinent when anaesthetizing SARS patients for high-risk procedures such as tracheostomy. We describe the management of such a case.

The development and maturation of the immune system in zebrafish was investigated using immune-related gene expression profiling by quantitative real-time polymerase chain reaction, in situ hybridization (ISH), immunoglobulin (Ig) detection by immuno-affinity purification and Western blotting as well as immersion immunization experiments. Ikaros expression was first detected at 1 day post-fertilization (dpf) and thereafter increased gradually to more than two-fold between 28 and 42dpf before decreasing to less than the initial 1dpf expression level in adult fish (aged 105dpf). Recombination activating gene-1 (Rag-1) expression levels increased rapidly (by 10-fold) between 3 and 17dpf, reaching a maximum between 21 and 28dpf before decreasing gradually. However, in adult fish aged 105dpf, the expression level of Rag-1 had dropped markedly, and was equivalent to the expression level at 3dpf. T-cell receptor alpha constant region and immunoglobulin light chain constant region (IgLC) isotype-1, 2 and 3 mRNAs were detected at low levels by 3dpf and their expression levels increased steadily to the adult range between 4 and 6 weeks post-fertilization (wpf). Using tissue-section ISH, Rag-1 expression was detected in head kidney by 2wpf while IgLC-1, 2 and 3 were detected in the head kidney and the thymus by 3wpf onwards. Secreted Ig was only detectable using immuno-affinity purification and Western blotting by 4wpf. Humoral response to T-independent antigen (formalin-killed Aeromonas hydrophila) and T-dependent antigen (human gamma globulin) was observed in zebrafish immunized at 4 and 6wpf, respectively, indicating that immunocompetence was achieved. The findings reveal that the zebrafish immune system is morphologically and functionally mature by 4-6wpf.

The morphologic transformation of the developing zebrafish thymus from 1 week postfertilization (wpf) to 15 wpf is described. The thymus overall morphology changed from a small pouch-like shape at 1 wpf to a conical shape between 2 and 3 wpf before acquiring a more complex shape from 4 wpf onward. Rapid growth rate along the lateral axis at the region near the pharyngeal epithelium occurred between 1 and 2 wpf, whereas rapid growth rate along the dorsal-ventral axis occurred between 3 and 6 wpf. Expansion of thymocyte population beginning from 1 wpf became more evident by 2 to 3 wpf, as indicated by the apparent increase of different sizes of lymphocytes, recombination activating gene-1 (rag-1), and T-cell antigen receptor alpha chain constant region (TCRAC) -positive cells. Tissue section in situ hybridization (ISH) analysis with rag-1 probe reveals that cortex-medullary regionalization has begun between 1 and 2 wpf as rag-1 expression clearly demarcated the cortex, whereas the medulla was rag-1 negative. The presence of TCRAC-positive cells in the medulla by 2-3 wpf, suggests that the thymic selection processes had begun. The zebrafish thymus is morphologically mature by 3 wpf. Early signs of thymic involution were observed in zebrafish aged 15 wpf., (Copyright 2002 Wiley-Liss, Inc.)

Purpose: Controversies abound regarding the optimal surgical management in noncomplicated diverticulitis of the right colon, ranging from a conservative approach to diverticulectomy to right hemicolectomy. One of the arguments for resection is to exclude carcinoma. However, there is significant morbidity associated with resection. We aim to introduce on-table cecoscopy as a tool to improve the diagnosis of acute diverticulitis of the right colon, exclude carcinoma, and reduce the rate of resection., Methods: From October 1999 to June 2000, five patients presented to our unit with suspected acute appendicitis. Intraoperatively, we found a colonic inflammatory mass at either the cecum or the ascending colon. The cecum and ascending colon were mobilized, and bowel clamps were applied to the ascending colon and ileum. A bronchoscope (Olympus(R) BF-P200) was introduced through the appendix stump. To achieve a good endoscopic view, a limited volume of air was introduced through the working channel., Results: After on-table cecoscopy, all the patients were diagnosed as having acute nonperforated diverticulitis of the right colon. They received appendicectomy, and the diverticulitis was managed conservatively. They were treated with a course of cephalosporin and metronidazole. We performed colonoscopy four weeks later and confirmed that none of them had carcinoma of the colon., Conclusions: On-table cecoscopy is a new, safe, and effective means of diagnosing acute diverticulitis of the right colon. We can confidently exclude carcinoma and reduce the amount of colonic resection in patients with noncomplicated diverticulitis of the right colon.

LOINC is emerging as the standard for laboratory result names, and there is great interest in mapping legacy terms from laboratory systems to it. However, the mapping task is non-trivial, requiring significant resource commitment and a good understanding of the LOINC identifying attributes for the laboratory result names. Because the number of results in a laboratory system may range from around 500 to 2000 or more, manual, one-by-one matching, even with the aid of the RELMA matching tool provided by LOINC, is time consuming and laborious. Moreover, human variation may introduce mapping inconsistencies or errors. Through our experience mapping the results from a variety of laboratory systems to LOINC, an automated mapping method has been developed and is described in this paper. This method allows for data from the laboratory information system to be provided in a manner familiar to the submitting technician, and makes use of parsing and logic rules, combined with synonyms, attribute relationships and mapping frequency data, to perform automated matching to LOINC.

Medication history has always been an integral part of the patient's medical record. With the advent of the computerized medical record and the longitudinal clinical data repository, having the medication history has enabled the development of clinical decision support system that alerts for drug to drug interactions and drug allergies. Furthermore, medication data is increasingly being analyzed from a utilization and clinical outcomes standpoint. For these activities to occur, a controlled pharmacy vocabulary akin to a controlled medical vocabulary is essential. Drug information databases are well-established sources of information for pharmacy-related data and products. However, do they measure up as a controlled vocabulary? Recent experience reviewing drug information databases and integrating pharmacy-related information into a data dictionary in real-time clinical use at multiple health care institutions have revealed several challenges and issues. These are discussed according to Cimino's desiderata for controlled medical vocabularies.

Practice guidelines for the management of deep vein thrombosis were implemented in a Problem-Oriented Patient Management System on the HELP Hospital Information System at the LDS Hospital. A hierarchical knowledge representation was used. The Problem-Oriented Patient Management System was designed to generate patient-specific guideline suggestions according to the clinical situation at the time of generation. A retrospective evaluation was used to compare the appropriateness of the generated guideline suggestions to the appropriateness of the attending physician's management decisions. A significantly higher proportion of guideline suggestions was evaluated to be appropriate, compared to the proportion of attending physician's management decisions found to be appropriate.