The use of high-flow nasal oxygen during airway management in a child with epidermolysis bullosa dystrophica and a difficult airway.

The role of high-flow nasal oxygen in paediatric anaesthesia has been emerging in recent years. However, literature regarding its benefits in paediatric difficult airway management is limited. In this case report, we describe the use of high-flow nasal oxygen during airway management of a child with a difficult airway due to epidermolysis bullosa dystrophica in whom the use of a facemask would have been potentially harmful. Deep sedation was achieved with propofol and remifentanil while maintaining spontaneous breathing before flexible bronchoscopic tracheal intubation was attempted. However, on attempted tracheal intubation difficulty was encountered due to poor visualisation and contact bleeding. Tracheal intubation was eventually successful after converting to videolaryngoscopy. Oxygenation was maintained throughout the process despite deep sedation and a long procedure time. Moreover, no skin abrasions or mucosal injury resulted from the use of high-flow nasal oxygen. We conclude that high-flow nasal oxygen has a valuable role during airway management for a child with a predicted difficult airway when the use of a facemask would have been potentially harmful.

An unusual cause of oesophageal variceal bleeding in a Chinese human immunodeficiency virus-infected patient.

Non-cirrhotic portal hypertension is an unusual but potentially serious liver disorder in human immunodeficiency virus-infected patients with prolonged exposure to didanosine. Due to its rarity, the diagnosis is often delayed. It is postulated that didanosine contributes to obliterative portal venopathy and causes portal hypertension. Affected patients may present with abnormal liver function or signs of portal hypertension, while the diagnosis usually depends on liver biopsy. We report a case of non-cirrhotic portal hypertension in a human immunodeficiency virus-infected patient. The reported histological features include nodular regenerative hyperplasia and hepatoportal sclerosis. Early recognition is important as timely management of severe portal hypertension may prevent potentially fatal gastro-intestinal bleeding.

An efficient alignment algorithm for searching simple pseudoknots over long genomic sequence.

Structural alignment has been shown to be an effective computational method to identify structural noncoding RNA(ncRNA) candidates as ncRNAs are known to be conserved in secondary structures. However, the complexity of the structural alignment algorithms becomes higher when the structure has pseudoknots. Even for the simplest type of pseudoknots (simple pseudoknots), the fastest algorithm runs in O(mn3) time, where m, n are the length of the query ncRNA (with known structure) and the length of the target sequence (with unknown structure), respectively. In practice, we are usually given a long DNA sequence and we try to locate regions in the sequence for possible candidates of a particular ncRNA. Thus, we need to run the structural alignment algorithm on every possible region in the long sequence. For example, finding candidates for a known ncRNA of length 100 on a sequence of length 50,000, it takes more than one day. In this paper, we provide an efficient algorithm to solve the problem for simple pseudoknots and it is shown to be 10 times faster. The speedup stems from an effective pruning strategy consisting of the computation of a lower bound score for the optimal alignment and an estimation of the maximum score that a candidate can achieve to decide whether to prune the current candidate or not.

Memory efficient algorithms for structural alignment of RNAs with pseudoknots.

In this paper, we consider the problem of structural alignment of a target RNA sequence of length n and a query RNA sequence of length m with known secondary structure that may contain simple pseudoknots or embedded simple pseudoknots. The best known algorithm for solving this problem runs in O(mn3) time for simple pseudoknot or O(mn4) time for embedded simple pseudoknot with space complexity of O(mn3) for both structures, which require too much memory making it infeasible for comparing noncoding RNAs (ncRNAs) with length several hundreds or more. We propose memory efficient algorithms to solve the same problem. We reduce the space complexity to O(n3) for simple pseudoknot and O(mn2 + n3) for embedded simple pseudoknot while maintaining the same time complexity. We also show how to modify our algorithm to handle a restricted class of recursive simple pseudoknot which is found abundant in real data with space complexity of O(mn2 + n3) and time complexity of O(mn4). Experimental results show that our algorithms are feasible for comparing ncRNAs of length more than 500.

Structural alignment of RNA with complex pseudoknot structure.

The secondary structure of an ncRNA molecule is known to play an important role in its biological functions. Aligning a known ncRNA to a target candidate to determine the sequence and structural similarity helps in identifying de novo ncRNA molecules that are in the same family of the known ncRNA. However, existing algorithms cannot handle complex pseudoknot structures which are found in nature. In this article, we propose algorithms to handle two types of complex pseudoknots: simple non-standard pseudoknots and recursive pseudoknots. Although our methods are not designed for general pseudoknots, it already covers all known ncRNAs in both Rfam and PseudoBase databases. An evaluation of our algorithms shows that it is useful to identify ncRNA molecules in other species which are in the same family of a known ncRNA.

Improving the accuracy of signal transduction pathway construction using Level-2 neighbours.

In this paper, we consider the problem of reconstructing a pathway for a given set of proteins based on available genomics and proteomics information such as gene expression data. In all previous approaches, the scoring function for a candidate pathway usually only depends on adjacent proteins in the pathway. We propose to also consider proteins that are of distance two in the pathway (we call them Level-2 neighbours). We derive a scoring function based on both adjacent proteins and Level-2 neighbours in the pathway and show that our scoring function can increase the accuracy of the predicted pathways through a set of experiments. The problem of computing the pathway with optimal score, in general, is NP-hard. We thus extend a randomised algorithm to make it work on our scoring function to compute the optimal pathway with high probability.

Correcting short reads with high error rates for improved sequencing result.

In the sequencing process, reads of the sequence are generated, then assembled to form contigs. New technologies can produce reads faster with lower cost and higher coverage. However, these reads are shorter. With errors, short reads make the assembly step more difficult. Chaisson et al. (2004) proposed an algorithm to correct the reads prior to the assembly step. The result is not satisfactory when the error rate is high (e.g., >or=3%). We improve their approach to handle reads of higher error rates. Experimental results show that our approach is much more effective in correcting errors, producing contigs of higher quality.

Compressed indexing and local alignment of DNA.

MOTIVATION: Recent experimental studies on compressed indexes (BWT, CSA, FM-index) have confirmed their practicality for indexing very long strings such as the human genome in the main memory. For example, a BWT index for the human genome (with about 3 billion characters) occupies just around 1 G bytes. However, these indexes are designed for exact pattern matching, which is too stringent for biological applications. The demand is often on finding local alignments (pairs of similar substrings with gaps allowed). Without indexing, one can use dynamic programming to find all the local alignments between a text T and a pattern P in O(|T||P|) time, but this would be too slow when the text is of genome scale (e.g. aligning a gene with the human genome would take tens to hundreds of hours). In practice, biologists use heuristic-based software such as BLAST, which is very efficient but does not guarantee to find all local alignments. RESULTS: In this article, we show how to build a software called BWT-SW that exploits a BWT index of a text T to speed up the dynamic programming for finding all local alignments. Experiments reveal that BWT-SW is very efficient (e.g. aligning a pattern of length 3 000 with the human genome takes less than a minute). We have also analyzed BWT-SW mathematically for a simpler similarity model (with gaps disallowed), and we show that the expected running time is O(/T/(0.628)/P/) for random strings. As far as we know, BWT-SW is the first practical tool that can find all local alignments. Yet BWT-SW is not meant to be a replacement of BLAST, as BLAST is still several times faster than BWT-SW for long patterns and BLAST is indeed accurate enough in most cases (we have used BWT-SW to check against the accuracy of BLAST and found that only rarely BLAST would miss some significant alignments). AVAILABILITY: www.cs.hku.hk/~ckwong3/bwtsw CONTACT: twlam@cs.hku.hk.

The mutated subsequence problem and locating conserved genes.

MOTIVATION: For the purpose of locating conserved genes in a whole genome scale, this paper proposes a new structural optimization problem called the Mutated Subsequence Problem, which gives consideration to possible mutations between two species (in the form of reversals and transpositions) when comparing the genomes. RESULTS: A practical algorithm called mutated subsequence algorithm (MSS) is devised to solve this optimization problem, and it has been evaluated using different pairs of human and mouse chromosomes, and different pairs of virus genomes of Baculoviridae. MSS is found to be effective and efficient; in particular, MSS can reveal >90% of the conserved genes of human and mouse that have been reported in the literature. When compared with existing softwares MUMmer and MaxMinCluster, MSS uncovers 14 and 7% more genes on average, respectively. Furthermore, this paper shows a hybrid approach to integrate MUMmer or MaxMinCluster with MSS, which has better performance and reliability.

Efficient constrained multiple sequence alignment with performance guarantee.

The constrained multiple sequence alignment problem is to align a set of sequences of maximum length n subject to a given constrained sequence, which arises from some knowledge of the structure of the sequences. This paper presents new algorithms for this problem, which are more efficient in terms of time and space (memory) than the previous algorithms, and with a worst-case guarantee on the quality of the alignment. Saving the space requirement by a quadratic factor is particularly significant as the previous O(n4)-space algorithm has limited application due to its huge memory requirement. Experiments on real data sets confirm that our new algorithms show improvements in both alignment quality and resource requirements.

Filtering of ineffective siRNAs and improved siRNA design tool.

MOTIVATION: Short interfering RNAs (siRNAs) can be used to suppress gene expression and possess many potential applications in therapy, but how to design an effective siRNA is still not clear. Based on the MPI (Max-Planck-Institute) basic principles, a number of siRNA design tools have been developed recently. The set of candidates reported by these tools is usually large and often contains ineffective siRNAs. In view of this, we initiate the study of filtering ineffective siRNAs. RESULTS: The contribution of this paper is 2-fold. First, we propose a fair scheme to compare existing design tools based on real data in the literature. Second, we attempt to improve the MPI principles and existing tools by an algorithm that can filter ineffective siRNAs. The algorithm is based on some new observations on the secondary structure, which we have verified by AI techniques (decision trees and support vector machines). We have tested our algorithm together with the MPI principles and the existing tools. The results show that our filtering algorithm is effective. AVAILABILITY: The siRNA design software tool can be found in the website http://www.cs.hku.hk/~sirna/ CONTACT: smyiu@cs.hku.hk

An efficient algorithm for optimizing whole genome alignment with noise.

MOTIVATION: This paper is concerned with algorithms for aligning two whole genomes so as to identify regions that possibly contain conserved genes. Motivated by existing heuristic-based software tools, we initiate the study of an optimization problem that attempts to uncover conserved genes with a global concern. Another interesting feature in our formulation is the tolerance of noise, which also complicates the optimization problem. A brute-force approach takes time exponential in the noise level. RESULTS: We show how an insight into the optimization structure can lead to a drastic improvement in the time and space requirement [precisely, to O(k2n2) and O(k2n), respectively, where n is the size of the input and k is the noise level]. The reduced space requirement allows us to implement the new algorithm, called MaxMinCluster, on a PC. It is exciting to see that when tested with different real data sets, MaxMinCluster consistently uncovers a high percentage of conserved genes that have been published by GenBank. Its performance is indeed favorably compared to MUMmer (perhaps the most popular software tool for uncovering conserved genes in a whole-genome scale). AVAILABILITY: The source code is available from the website http://www.csis.hku.hk/~colly/maxmincluster/ detailed proof of the propositions can also be found there.

Selective functional deficit in dendritic cell--T cell interaction is a crucial mechanism in chronic hepatitis B virus infection.

A defect in specific T cell immunity has long been assumed to be the central mechanism of persistent Hepatitis B virus (HBV) infection. Recent studies on HBV transgenic mice have suggested, however, that functional deficit of dendritic cells (DC) was an underlying cause for the T cell dysfunction. The functions of monocyte-derived DC were determined by studying 75 subjects that included chronic hepatitis B patients with low or high HBV load; antibody to hepatitis B surface antigen (anti-HBs) positive individuals who had recovered completely from previous acute HBV infection; healthy donors who had received hepatitis B vaccination and were anti-HBs positive; and immunologically naïve to HBV or the vaccine individual. Impaired interactions between monocyte-derived DC and T cells were shown in chronic HBV infection patients, especially in those with active virus replication. The dysfunctions included: (i) failure of DC to increase human leukocyte antigen (HLA-II), B7 expression and interleukin-12 secretion in responses to hepatitis B surface antigen (HBsAg), (ii) defective induction of T cell proliferative response to HBsAg, (iii) failure to activate T cells to produce cytokines and (iv) deficit in the induction of antigen specific cytotoxic T lymphocytes (CTLs). In vitro treatment of DC with tumour necrosis factor-alpha improved HLA-II and B7 expression, as well as Th cell and CTL responses. It is concluded that defective DC-T cell interactions may account for the specific T cell immune defects in chronic HBV infection. Immunotherapy that aims at restoring DC functions could offer a new opportunity for effectively managing persistent HBV infections.

Rare pulmonary complications after transarterial chemoembolisation for hepatocellular carcinoma: two case reports.

We report two rare cases of acute pulmonary complication after transarterial chemoembolisation for inoperable hepatocellular carcinoma. Both cases involved a large tumour and hepatic vein invasion. The first patient, a 27-year-old man, died of pulmonary tumour embolism 4 days after transarterial chemoembolisation. Acute dyspnoea developed in the second patient, a 63-year-old man, following the procedure due to pulmonary oil embolisation and chemical pneumonitis. The chest condition of this patient improved, but he subsequently died of liver failure 3 weeks later. Our cases illustrate the point that if locoregional treatment is offered as a palliative treatment, patients with hepatic vein invasion should be warned of the possible complications of massive tumour embolism, pulmonary oil embolisation, and subsequent death.

Efficient constrained multiple sequence alignment with performance guarantee.

The Constrained Multiple Sequence Alignment problem is to align a set of sequences subject to a given constrained sequence, which arises from some knowledge of the structure of the sequences. This paper presents new algorithms for this problem, which are more efficient in terms of time and space (memory) than the previous algorithms [14], and with a worst-case guarantee on the quality of the alignment. Saving the space requirement by a quadratic factor is particularly significant as the previous O(n(4))-space algorithm has limited application due to its huge memory requirement. Experiments on real data sets confirm that our new algorithms show improvements in both alignment quality and resource requirements.

A randomized clinical trial comparing autologous blood clot and gelfoam in transarterial chemoembolization for inoperable hepatocellular carcinoma.

BACKGROUND/AIM: Inoperable hepatocellular carcinoma is common in Asia and is usually treated with repeated transarterial chemoembolization. Gunji et al. showed better survival and fewer complications with autologous blood clot as compared with gelfoam used for embolization. Our aim was to compare the effect of blood clot versus gelfoam. METHODS: We conducted a prospective randomized trial in 100 patients with inoperable hepatocellular carcinoma, and compared the side effects and cumulative survival in the two groups. Cox's proportional hazard model was used to study the prognostic factors. RESULTS: The diameter of the main tumor was 7.9+/-4.6 cm. Our study did not show additional beneficial effects of blood clot. The proportion of side effects was similar and the common ones included fever, pain and vomiting. Though the hepatic artery remained patent for a longer period with blood clot (p=0.061), there was no difference in survival (p=0.129 for Okuda I disease and p=0.388 for Okuda II disease). Subgroup analysis showed longer survival in patients with vascular occlusion (p=0.034 for Okuda I and p=0.029 for Okuda II disease). The independent factors of survival were sex, Child's class, Okuda stage, tumor type and presence of metastases. CONCLUSION: This study showed no additional benefits of blood clot in patients with inoperable hepatocellular carcinoma, in Okuda I and II disease. The longer survival in patients with vascular occlusion suggested that the damage to normal liver tissue by planned periodic transarterial chemoembolization may outweigh its benefit in later sessions of repeated TACE in certain patients.

Percutaneous ethanol injection as a possible curative treatment for malignant portal vein thrombosis in hepatocellular carcinoma.

Postoperative residual hepatocellular carcinoma (HCC) with malignant portal vein thrombosis in a 48-year-old man was cured with transarterial chemoembolization (TACE) for the parenchymal portion and percutaneous ethanol injection (PEI) for the malignant portal vein thrombosis. No evidence of tumor recurrence was noted after 18 months of follow-up. The only severe complication in our patient was biliary stricture which was treated with an internal stent via endoscopic retrograde pancreatico-cholangiography (ERCP).

Profile of opportunistic infections among HIV-1 infected people in Hong Kong.

BACKGROUND: To determine the spectrum of opportunistic infections in patients with human immunodeficiency virus (HIV-1) infection in Hong Kong. METHODS: A retrospective study of 214 HIV-1-infected patients, seen between December 1984 and December 1993 in a specialist clinic for HIV/AIDS: RESULTS: A majority (94%) of the patients in the cohort were male; 84% had acquired HIV via sexual contacts. Two-thirds were ethnic Chinese. Ninety-two (43%) had developed AIDS, and 54(25%) had presented with other non AIDS-defining opportunistic infections during the study period. The primary AIDS defining illnesses of 80 patients were infections: Pneumocystis carinii pneumonia (50%), extrapulmonary tuberculosis (10%) and cytomegalovirus (CMV) disease (8%). Opportunistic infections among Chinese and non-Chinese were similar in spectrum, though higher frequencies of infection with CMV, Mycobacterium avium intracellulare and tuberculosis were seen among Chinese, whereas the opposite was true for Pneumocystis carinii pneumonia, toxoplasmosis and cryptosporidiosis. Disseminated Penicillium marneffei infection was another significant disease for HIV-positive patients. Common non AIDS-defining opportunistic infections included herpes zoster, oral candidiasis, herpes simplex infection and genital/anal wart. The median CD4 count at HIV diagnosis for AIDS patients was much lower than non-AIDS patients (147 vs 546/ul). Survival of deceased AIDS patients was poor, with a median of only five months. Survival has however, apparently, improved over the recent years. CONCLUSIONS: In Hong Kong, Pneumocystis carinii pneumonia remained the most common primary AIDS event, while Penicillium marneffei was emerging as another significant cause of major infection. Herpes zoster and oral candidiasis were the two most frequently encountered minor opportunistic infections.