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Interventions for the prevention and management of oropharyngeal candidiasis associated with HIV infection in adults and children.

BACKGROUND: Oral candidiasis (OC) associated with human immunodeficiency virus (HIV) infection occurs commonly and recurs frequently, often presenting as an initial manifestation of the disease. Left untreated these lesions contribute considerably to the morbidity associated with HIV infection. Interventions aimed at preventing and treating HIV-associated oral candidal lesions form an integral component of maintaining the quality of life for affected individuals. OBJECTIVES: To determine the effects of any intervention in preventing or treating OC in children and adults with HIV infection. SEARCH STRATEGY: The search strategy was based on that of the HIV/AIDS Cochrane Review Group. The following electronic databases were searched for randomised controlled trials for the years 1982 to 2005: Medline; AIDSearch; EMBASE and CINAHL. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness and the Cochrane Central Register of Controlled Trials (CENTRAL) was also searched through May 2005. The abstracts of relevant conferences, including the International Conferences on AIDS and the Conference on Retroviruses and Opportunistic Infections, as indexed by AIDSLINE, were also reviewed. The strategy was iterative, in that references of included studies were searched for additional references. All languages were included. SELECTION CRITERIA: Randomised controlled trials (RCTs) of palliative, preventative or curative therapy were considered, irrespective of whether the control group received a placebo. Participants were HIV positive adults. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the methodological quality of the trials and extracted data. Study authors were contacted for additional data where necessary. MAIN RESULTS: Four trials were conducted in developing countries with eleven of the trials conducted in the United States of America. Twenty eight trials (n=3225) were included. Nineteen trials investigated treatment and nine trials the prevention of OC. One trial, comparing fluconazole and ketoconazole, investigated the treatment of OC in children. Eighteen of the included studies reported CD4 cell counts. None of the included studies investigated the effects of HAART or any other form of antiretroviral treatment on OC treatment or prevention.TreatmentTreatment was assessed in the majority of trials looking at both clinical and mycological cures. In the majority of comparisons there was only one trial. Compared to nystatin, fluconazole favoured clinical cure in adults(1 RCT; n=167; RR 1.69; 95% CI 1.27 to 2.23). There was no difference with regard to clinical cure between fluconazole compared to ketoconazole (2 RCTs; n=83; RR 1.27; 95% CI 0.97 to 1.66), itraconazole (2 RCTs; n=434; RR 1.05; 95% CI 0.94 to 1.16) or clotrimazole (2 RCTs; n=358; RR 1.14; 95% CI 0.92 to 1.42). When compared with clotrimazole, both fluconazole (2 RCTs; n=358; RR 1.47; 95% CI 1.16 to 1.87) and itraconazole (1 RCT; n=123; RR 2.20; 95% CI 1.43 to3.39) proved to be better for mycological cure. Both gentian violet (1 RCT; n=96; RR 5.28; 95% CI 1.23 to 22.55) and ketoconazole (1 RCT; n=92; RR 5.22; 95% CI 1.21 to 22.53) were superior to nystatin in bringing about clinical cure. PreventionSuccessful prevention was defined as the prevention of a relapse while receiving prophylaxis. Fluconazole was compared with placebo in one trial (5 RCTs; n=599; RR 0.61; 95% CI 0.5 to 0.74) and with no treatment in another (1 RCT; n=65; RR 0.16; 95% CI 0.08 to 0.34). In both instances the prevention of clinical episodes was favoured by fluconazole. Comparing continuous fluconazole treatment with intermittent treatment (1 RCT; n=62; RR 0.37; 95% CI 0.15 to 0.92), prevention is favoured by the continuous treatment. AUTHORS' CONCLUSIONS: Implications for practiceDue to only one study in children it is not possible to make recommendations for treatment or prevention of OC in children. Amongst adults, there were few studies per comparison. Due to insufficient evidence no conclusion could be made about the effectiveness of clotrimazole, nystatin, amphotericin B, itraconazole or ketoconazole with regard to OC prophylaxis. In comparison to placebo, fluconazole is an effective preventative intervention. However, the potential for resistant Candida organisms to develop, as well as the cost of prophylaxis, might impact the feasibility of implementation. No studies were found comparing fluconazole with other interventions. Direction of findings suggests that ketoconazole, fluconazole, itraconazole and clotrimazole improved the treatment outcomes. Implications for researchThere is an urgent need for gentian violet and other less expensive anti-fungal drugs for OC treatment to be evaluated in larger studies. More well designed treatment trials with larger sample size are needed to allow for sufficient power to detect differences in not only clinical, but also mycological response and relapse rates. There is also a strong need for more research to be done on the treatment and prevention of OC in children as it is reported that OC is the most frequent fungal infection in children and adolescents who are HIV positive. More research on the effectiveness of less expensive interventions also needs to be done in resource-poor settings. Currently few trials report outcomes related to quality of life, nutrition, or survival. Future researchers should consider measuring these when planning trials. Development of resistance remains under-studied and more work must be done in this area. It is recommended that trials be more standardised and conform more closely to CONSORT as this will improve research and also clinical practice.

Adult↗

Recurrence and survival after mesorectal excision for rectal cancer.

BACKGROUND: Mesorectal excision for rectal cancer has resulted in local recurrence rates of 3-11 per cent compared with up to 38 per cent after conventional methods. The results of a prospective Danish study with a historical control group are presented. METHODS: Three hundred and eleven patients with a mobile rectal cancer had mesorectal excision with curative intent performed by certified surgeons and were followed for 3 years. Demographic, perioperative and follow-up data were recorded prospectively. A series of patients who had conventional operations for rectal cancer served as a control group. RESULTS: The cumulative 3-year local recurrence rate was 11 per cent after mesorectal excision compared with 30 per cent after conventional surgery (hazard ratio (HR) 0.33 (95 per cent confidence interval (c.i.) 0.21 to 0.52); P < 0.001). Multivariate regression analysis showed that only advanced age (HR 0.97 (95 per cent c.i. 0.94 to 1.00); P = 0.048) and tumour in the lower third of the rectum (HR 0.21 (95 per cent c.i. 0.04 to 1.97); P = 0.075) were marginal independent predictors of local recurrence after mesorectal excision. The cumulative crude 3-year survival rate was 77 per cent after mesorectal excision and 62 per cent after conventional surgery (HR 0.58 (95 per cent c.i. 0.43 to 0.77); P < 0.001). Age was the only independent predictor of death after mesorectal excision (HR 1.04 (95 per cent c.i. 1.02 to 1.07); P = 0.001). CONCLUSION: Mesorectal excision is associated with a considerably lower risk of local recurrence and a better survival rate than conventional surgery, and is the optimum method for rectal cancer resection.

Adenocarcinoma↗

Retroperitoneal soft tissue sarcomas: patterns of recurrence in 167 patients treated at a single institution.

BACKGROUND: The objective of this study was to assess long-term prognosis and patterns of failure in patients with retroperitoneal soft tissue sarcoma who underwent surgery with curative intent at a single institution. Several series of patients with retroperitoneal sarcoma were reported, providing widely variable data regarding local and distant failure. METHODS: Overall, 167 consecutive patients who underwent surgery for retroperitoneal soft tissue sarcoma over a 20 year span at a single referral center were reviewed retrospectively. Eighty-two patients presented with primary disease, whereas 85 patients had recurrent locoregional tumors. Surgical resection was considered macroscopically complete in 147 of 167 patients (88%). RESULTS: Overall survival at 10 years after definitive surgery was approximately 27%, and the disease-free survival was approximately 16%. Only a minority of patients developed distant metastases. The risk of recurrence was correlated with whether patients underwent surgery for primary disease or for recurrent disease; the 10 year disease-free survival rate was 27% in the former group and 4.6% in the latter group. Histotype and malignancy grade were other prognostic factors, with the former found to be predictive of the pattern of failure and the latter predictive of overall survival. CONCLUSIONS: Local recurrence after primary surgery and high-grade malignancy were associated with the worst survival. Histologic subtype appeared to influence the pattern of recurrence, which mainly was local for patients with liposarcoma but was both local and distant for patients with the other histotypes.

Adolescent↗

Cancer recurrence after total laryngectomy: treatment options, survival, and complications.

BACKGROUND: A follow-up schedule to detect asymptomatic cancer recurrence is offered to all patients with laryngeal cancer. In this study, the therapeutic options, prognosis, and morbidity of patients with total laryngectomy, who were found to have cancer recurrence during this follow-up schedule were determined. METHODS: Patients who had undergone a total laryngectomy between January 1, 1990, and January 1, 2000, and had cancer recurrence were included. Data from this group were analyzed retrospectively. RESULTS: The prognosis was poor after the development of cancer recurrence. Curative therapy could only be offered to 27.5% of these patients. Only 5% of the patients were disease free at the end of the study period. Many patients with cancer recurrence needed interventions. A large proportion of them had complications. CONCLUSIONS: The follow-up schedule offered to patients after total laryngectomy should put greater emphasis on care than on early detection of cancer recurrence.

Adult↗

Lymphangitis carcinomatosis of the lesser omentum: a prognostic factor in gastric cancer.

A series of 126 patients with gastric cancer who underwent radical gastrectomy with systemic lymph node dissection revealed 9 patients who survived for a median time of only 3 months. Of these 9 patients, 4 were classified by the UICC system as stage II and 5 as stage III, all of whom had lymphangitis carcinomatosis of the lesser omentum. These data suggest that although lymphangitis carcinomatosis of the lesser omentum is an uncommon finding, if it is present, curative surgery is impossible and an operation should therefore be limited to tumor palliation.

Adult↗

Colonoscopy in ostomy patients. Results at the first postoperative examination.

Patients with a personal history of rectal cancer are considered at high risk for metachronous large-bowel primaries. Since a malignant growth was the main reason for performing a colostomy in patients followed at the centers of the authors' association (AISTOM), a correct follow-up approach for these patients is very important. A multicentric clinical trial was thus carried out to evaluate the efficacy of transstomal endoscopic exploration (TEE) of the residual colon, and data collection began on May 31, 1984. Nine hundred fifty-seven patients were submitted to TEE after curative abdominoperineal resection (Miles) for rectal cancer. The male-female ratio was 1.3; 89.6 percent of the patients were over 50 years of age. A family history of large-bowel cancer was present in 18 percent, and in 23 percent of the patients the cancer was associated with synchronous adenomas. Only 31 percent of the patients had colonoscopy or double-contrast barium enema x-ray beyond the neoplastic area before surgery. TEE was done in 96.8 percent of the patients; in 3.3 percent the examination was not possible, mainly for stenosis of the stoma (in 2.3 percent). In 82 percent of the patients a complete large-bowel exploration was possible: a new large, bowel cancer was found in 22 patients (2.2 percent) and an adenoma in 183 patients (19.1 percent). These results show that, because it is safe, practical, and effective, endoscopy plays an important role in the follow-up of ostomates.

Adenocarcinoma↗

Colorectal cancer staging: reappraisal of N/PN classification.

PURPOSE: Current American Joint Committee on Cancer and the Union Internationale Contre le Cancer TNM classification disregards location of positive nodes, discontinuing N3 category, which constitutes a major modification to 1987 version. This study was designed to assess the impact of the recategorization of former N3 cases and the reliability of the current N1-N2 subcategorization of Stage III patients. METHODS: Prospectively collected data from 1,391 patients (55.8 percent males; median age, 64 (range, 21-97) years), operated on with curative intent between 1980 and 1999, were analyzed. The median follow-up was 60 (interquartile range, 27-97) months with 129 cases lost to follow-up. RESULTS: Of positive node cases, 25.3 percent were former N3. Among them, 30.5 percent migrated to the N1 group and 69.5 percent to the N2 group. The proportions of former N3 cases in N1 and N2 groups were 12.5 percent and 46.1 percent, respectively (P<0.001). Node-positive patients had an actuarial five-year survival rate of 56.7 percent (95 percent confidence interval, 53-59), with a significant difference between N1/N2 categories (63.6 vs. 44.1 percent, respectively; P<0.001). Although apical node involvement and more than three positive nodes were associated with poorer outcomes in univariate analysis, only the number of positive nodes had independent association (hazard ratio, 1.6 (range, 1.2-2.2); P<0.001). Integration of former N3 cases did not modify outcomes. CONCLUSIONS: The recategorization of former N3 involved a high proportion of positive node cases. Current N1/N2 categories clearly defined different outcomes and were not modified by the integration of former N3.

Adult↗

Carcinoembryonic antigen (CEA) measurement during follow-up for rectal carcinoma is useful even if normal levels exist before surgery. A retrospective study of CEA values in the TME trial.

BACKGROUND: Carcinoembryonic antigen (CEA) as a marker in the follow-up after curative resection of colorectal carcinoma (CRC) is often omitted from follow-up despite guideline recommendations. One reason is the assumption that when a normal CEA value exists before curative resection of CRC, it will neither rise during follow-up. This study investigates this relationship. METHOD: Data were derived from a study initiated to evaluate treatment regimes for rectal carcinoma (Dutch TME trial, n=1861) from which 954 were eligible for analysis. Recurrent disease occurred in 272 of these patients (29.5%). The pre-operative CEA value was compared to CEA values during follow-up, using threshold values of 2.5 and 5.0 ng/ml. RESULTS: Normal pre-operative CEA values were present in 63% (CEA<5.0) and 39% (CEA<2.5) of patients with recurrent disease. Patients with a normal pre-operative CEA and recurrent disease had elevated CEA values during follow-up in 41% (CEA<5.0), 50% (CEA<2.5) and in 60% with both threshold values when the last measurement was done within 3 months before recurrent disease was diagnosed. CONCLUSION: A normal pre-operative CEA is common in patients with rectal carcinoma. CEA does rise due to recurrent disease in at least 50% of patients with normal pre-operative values. Serial post-operative CEA testing cannot be discarded based on a normal pre-operative serum CEA.

Adult↗

What is the relevance of bioinformatics to pharmacology?

Although bioinformatics achieved prominence because of its central role in genome data storage, management and analysis, its focus has shifted as the life sciences exploit these data. In pharmacology, genomic, transcriptomic and proteomic data are being used in the quest for drugs that fulfill unmet medical needs, are disease modifying or curative and are more effective and safer than current drugs. Bioinformatics is used in drug target identification and validation and in the development of biomarkers and toxicogenomic and pharmacogenomic tools to maximize the therapeutic benefit of drugs. Now that the 'parts list' of cellular signalling pathways is available, integrated computational and experimental programmes are being developed, with the goal of enabling in silico pharmacology by linking the genome, transcriptome and proteome to cellular pathophysiology.

Computational Biology↗

Five-year follow-up of saliva in patients treated for lymphomas.

OBJECTIVE: Patients treated for Hodgkin's disease and non-Hodgkin lymphomas were followed for 5 years after start of therapy. The patients received combinations of anticancer drugs for curative intent for 6 months (Hodgkin's disease) or 7 months (non-Hodgkin lymphomas). STUDY DESIGN: Cumulated data of 22 surviving patients (mean age, 49 years) were compared with that of 17 patients (mean age, 52 years) who had died or were terminally ill at the 5-year examination. Saliva samples were taken at baseline, and 4, 6, 12, and 60 months after start of chemotherapy. Salivary flow rate and a variety of biochemical constituents were analyzed. RESULTS: The results showed no long-term effect of anticancer treatment on salivary flow rates. Neither was there any difference between the surviving or deceased patients' baseline values (1.5 +/- 0.7 mL/minute versus 1.5 +/- 0.8 mL/minute) and after chemotherapy. Lysozyme, IgA, IgG, and IgM concentrations decreased after chemotherapy. Significantly lower values were observed at the 5-year examination than at baseline. This was particularly evident in IgA, which is the major immunoglobulin in saliva; mean IgA was 70.5 +/- 52.8 mg/mL at baseline, 35.8 +/- 15.0 mg/mL 5 years later (p < 0.001). Salivary total protein and amylase concentrations were significantly decreased (p < 0.001 and p < 0.05, respectively), whereas albumin concentration was significantly increased at the 5-year examination (p < 0.05). When the salivary biochemical results were compared between the surviving and deceased patients, no statistically significant differences were observed. At baseline, however, the mean immunoglobulin values were lower in patients who later died, in comparison with those who survived. CONCLUSIONS: These results showed that modern anticancer therapy need not cause severe side effects on salivary flow rates and composition. In addition, apart from the long-term immunosuppression, no significant decreases were expressed in salivary defensive factors.

Adult↗

Perioperative allogeneic blood transfusion does not cause adverse sequelae in patients with cancer: a meta-analysis of unconfounded studies.

BACKGROUND: There is controversy over whether perioperative allogeneic red blood cell transfusions are associated with an increased risk of cancer recurrence, postoperative infection or death in patients with cancer undergoing surgery. METHODS: A systematic meta-analysis was performed to answer this question. Studies were identified from electronic databases (Medline 1966-1997, Cancerlit 1983-1997, Current Contents, Cinahl 1982-1996, Healthstar 1990-1997, Bioabstracts 1990-1996 and Embase), by hand search of the bibliographies of identified studies and relevant journals, and by contact with experts in the field. All randomized controlled trials or prospective cohort studies with active comparator controls (autologous or leucocyte-depleted allogeneic blood) were eligible for inclusion if they reported on mortality, infection or recurrence rate in patients with cancer undergoing potentially curative surgical resection. The validity of the identified studies was assessed by means of a standardized scale, and data abstraction was carried out by two investigators independently. A random effects model was used for data synthesis. RESULTS: Of the 2172 references identified, only 17 studies fulfilled the inclusion criteria. After exclusion of duplicate publications, six randomized controlled trials and two prospective cohort studies with appropriate concurrent controls were included in the analysis. The summary risk ratios were 0.95 (95 per cent confidence interval (c.i.) 0.79-1.15) for all-cause mortality and 1.06 (95 per cent c.i. 0.88-1.28) for cancer recurrence, the two endpoints that were appropriate to combine statistically. There was significant heterogeneity (explainable by differences in study design and patient characteristics) in the postoperative infection data and the summary risk ratio was 1.00 (95 per cent c.i. 0.76-1.32) for the four studies that were appropriate to subject to meta-analysis. Given the sample sizes of these eight studies, this meta-analysis had insufficient power to detect a relative difference of less than 20 per cent in the frequency of death, cancer recurrence or infection between the allogeneic and control transfusion arms. CONCLUSION: Although more studies are required before a definitive statement can be made, at this time there is no evidence that allogeneic blood transfusion increases the risk of clinically important adverse sequelae in patients with cancer undergoing surgery.

Cohort Studies↗

A systematic overview of chemotherapy effects in gastric cancer.

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This overview of the literature on chemotherapy in the treatment of gastric cancer is based on 153 scientific papers including one meta-analysis, 18 reviews, 60 randomised studies and 57 prospective studies. The trials consist of 12,367 patients. The conclusions reached can be summarized into the following points: A meta-analysis of 21 randomised adjuvant studies revealed a statistically significant survival benefit. The Odds Ratio (OR) is 0.84 (95% confidence interval, 95% CI, 0.74-0.96). However, by analysing Western world and Asian studies separately, a statistically significant difference can be noticed; the Western world studies showed an OR of 0.96 (95% CI 0.83-1.12) and the Asian an OR of 0.58 (95% CI 0.44-0.76). The cause of this difference is not apparent. There is not sufficient evidence to recommend adjuvant chemotherapy as routine treatment in the Western world. Preoperative chemotherapy given to patients with non-resectable tumours or locally advanced potentially resectable tumours has achieved resectability rates of 40-100% and potentially curative resections in 37-80%. One out of two randomised studies showed a significant survival benefit, but reported data are not convincing. Experimental data in favour of preoperative therapy has not yet been confirmed in randomised clinical studies. Therapy is only justified in controlled clinical trials. Published studies on the use of intraperitoneal chemotherapy are few and not conclusive regarding the efficiency and safety. This method of drug administration is, accordingly, justified only in controlled clinical trials. In advanced gastric cancer, phase II studies have indicated better response rates using drug combinations than using single drug regimens, differences that have not, however, been convincingly demonstrated in randomised studies. No firm conclusions can be drawn regarding the superiority for any of the studied drug combinations with respect to response or survival gain. A statistically significant survival benefit has been shown in trials comparing drug combinations with a best supportive care arm in the treatment of advanced gastric cancer. However, the number of included patients is small. The median survival benefit in advanced disease is in the range of three to nine months. The use of chemotherapy in advanced gastric cancer is justified in selected patients, e.g. in younger patients in good performance status, low tumour burden and no other serious medical condition after adequate information of potential gains and risks. The influence of chemotherapy on quality of life in advanced gastric cancer has been reported in only a few studies. It appears that about 50% of the patients have a clinically relevant relief of tumour-related symptoms and thereby improved quality of life. In one study, quality-adjusted survival was estimated to a median of six months in the treated patients compared with two months in the controls. The quality of the literature addressing chemotherapy for gastric cancer is frequently poor with few properly designed randomised trials. In a number of randomised multi-centre adjuvant studies the inclusions rates are remarkably low, which reduces the scientific value of the studies.

Antineoplastic Combined Chemotherapy Protocols↗

Extracting human protein interactions from MEDLINE using a full-sentence parser.

MOTIVATION: The living cell is a complex machine that depends on the proper functioning of its numerous parts, including proteins. Understanding protein functions and how they modify and regulate each other is the next great challenge for life-sciences researchers. The collective knowledge about protein functions and pathways is scattered throughout numerous publications in scientific journals. Bringing the relevant information together becomes a bottleneck in a research and discovery process. The volume of such information grows exponentially, which renders manual curation impractical. As a viable alternative, automated literature processing tools could be employed to extract and organize biological data into a knowledge base, making it amenable to computational analysis and data mining. RESULTS: We present MedScan, a completely automated natural language processing-based information extraction system. We have used MedScan to extract 2976 interactions between human proteins from MEDLINE abstracts dated after 1988. The precision of the extracted information was found to be 91%. Comparison with the existing protein interaction databases BIND and DIP revealed that 96% of extracted information is novel. The recall rate of MedScan was found to be 21%. Additional experiments with MedScan suggest that MEDLINE is a unique source of diverse protein function information, which can be extracted in a completely automated way with a reasonably high precision. Further directions of the MedScan technology improvement are discussed. AVAILABILITY: MedScan is available for commercial licensing from Ariadne Genomics, Inc.

Abstracting and Indexing↗

The MIPS mammalian protein-protein interaction database.

SUMMARY: The MIPS mammalian protein-protein interaction database (MPPI) is a new resource of high-quality experimental protein interaction data in mammals. The content is based on published experimental evidence that has been processed by human expert curators. We provide the full dataset for download and a flexible and powerful web interface for users with various requirements.

Animals↗

InBase: the Intein Database.

Inteins are self-catalytic protein splicing elements. InBase (http://www.neb.com/neb/inteins.html), the Intein Database and Registry, is a curated compilation of published and unpublished information about protein splicing. It presents general information as well as detailed data for each intein, including tabulated comparisons and a comprehensive bibliography. An intein-specific BLAST server is now available to assist in identifying new inteins.

Alleles↗

IPD--the Immuno Polymorphism Database.

The Immuno Polymorphism Database (IPD) (http://www.ebi.ac.uk/ipd/) is a set of specialist databases related to the study of polymorphic genes in the immune system. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of Killer-cell Immunoglobulin-like Receptors; IPD-MHC, a database of sequences of the Major Histocompatibility Complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. Those sections with similar data, such as IPD-KIR and IPD-MHC share the same database structure. The sharing of a common database structure makes it easier to implement common tools for data submission and retrieval. The data are currently available online from the website and ftp directory; files will also be made available in different formats to download from the website and ftp server. The data will also be included in SRS, BLAST and FASTA search engines at the European Bioinformatics Institute.

Animals↗

BioModels Database: a free, centralized database of curated, published, quantitative kinetic models of biochemical and cellular systems.

BioModels Database (http://www.ebi.ac.uk/biomodels/), part of the international initiative BioModels.net, provides access to published, peer-reviewed, quantitative models of biochemical and cellular systems. Each model is carefully curated to verify that it corresponds to the reference publication and gives the proper numerical results. Curators also annotate the components of the models with terms from controlled vocabularies and links to other relevant data resources. This allows the users to search accurately for the models they need. The models can currently be retrieved in the SBML format, and import/export facilities are being developed to extend the spectrum of formats supported by the resource.

Biochemical Phenomena↗

Human protein reference database--2006 update.

Human Protein Reference Database (HPRD) (http://www.hprd.org) was developed to serve as a comprehensive collection of protein features, post-translational modifications (PTMs) and protein-protein interactions. Since the original report, this database has increased to >20 000 proteins entries and has become the largest database for literature-derived protein-protein interactions (>30 000) and PTMs (>8000) for human proteins. We have also introduced several new features in HPRD including: (i) protein isoforms, (ii) enhanced search options, (iii) linking of pathway annotations and (iv) integration of a novel browser, GenProt Viewer (http://www.genprot.org), developed by us that allows integration of genomic and proteomic information. With the continued support and active participation by the biomedical community, we expect HPRD to become a unique source of curated information for the human proteome and spur biomedical discoveries based on integration of genomic, transcriptomic and proteomic data.

Databases, Protein↗