Systems biology aims to integrate multiple biological data types such as genomics, transcriptomics and proteomics across different levels of structure and scale; it represents an emerging paradigm in the scientific process which challenges the reductionism that has dominated biomedical research for hundreds of years. Systems biology will nevertheless only be successful if the technologies on which it is based are able to deliver the required type and quality of data. In this review we discuss how well positioned is proteomics to deliver the data necessary to support meaningful systems modelling in parasite biology. We summarise the current state of identification proteomics in parasites, but argue that a new generation of quantitative proteomics data is now needed to underpin effective systems modelling. We discuss the challenges faced to acquire more complete knowledge of protein post-translational modifications, protein turnover and protein-protein interactions in parasites. Finally we highlight the central role of proteome-informatics in ensuring that proteomics data is readily accessible to the user-community and can be translated and integrated with other relevant data types.
Systems-biology; proteomics; transcriptomics; genomics; parasites; host-parasite interactions; Descartes; reductionism
Rheumatoid arthritis (RA) is associated with increased incidence cardiac failure. It is yet unclear how much the increased incidence is secondary to ischaemic damage, or whether inflammatory cytokines might have a direct effect on the myocardium
To establish if patients with active rheumatoid arthritis but no history of cardiac disease have higher serum levels of brain natriuretic peptide (BNP), than patients with less active RA, or disease-free controls.
90 patients with RA and 31 healthy control subjects were recruited. Each was screened to exclude previous history of cardiac disease. RA disease activity was measured using the DAS28 assessment, and other demographic, physical and laboratory tests performed. Serum BNP levels were measured in all subjects.
There was no difference in the age, percentage females or BMI between the RA and control subjects. Median BNP in the RA patients was 80.0 pg/ml (IQR 38.0–132.0) compared with 48.5 (26.0–86.0) in the control subjects (p=0.017). There was a significant correlation between DAS28 and serum BNP in the RA group, r=0.37, p<0.01. RA patients were divided into three groups according to DAS28 scores. Patients with very active disease (DAS28>5.1) had significantly higher BNP levels than patients with moderately active disease (3.2
RA patients with no history of cardiac disease have higher serum BNP levels than healthy control subjects. RA patients with active RA have higher BNP levels than RA patients with moderately active or inactive disease, raising the possibility of a directly depressive effect of inflammatory cytokines on the myocardium
chronic diffuse sclerosing osteomyelitis; ibandronate; osteocalcin
pre-diabetes; acute coronary syndromes; impaired fasting glucose; diabetes
Colorectal cancer (CRC) is the most common cause of non-tobacco-related cancer deaths in Canadian men and women, accounting for 10% of all cancer deaths. An estimated 7800 men and women will be diagnosed with CRC, and 3250 will die from the disease in Ontario in 2007. Given that CRC incidence and mortality rates in Ontario are among the highest in the world, the best opportunity to reduce this burden of disease would be through screening. The present report describes the findings and recommendations of Cancer Care Ontario’s Colonoscopy Standards Expert Panel, which was convened in March 2006 by the Program in Evidence-Based Care. The recommendations will form the basis of the quality assurance program for colonoscopy delivered in support of Ontario’s CRC screening program.
Cancer Care Ontario; Colonoscopy; Colonoscopy standards; Colorectal cancer screening
The present report describes a young woman with no previous gastrointestinal complaints who was initially diagnosed with postinfective irritable bowel syndrome (IBS) after a confirmed case of Campylobacter jejuni enteritis. However, because of persistent diarrhea, new-onset bloating and the development of iron and vitamin deficiencies, serological markers for celiac disease (CD) were evaluated. A positive tissue transglutaminase immunoglobulin A antibody test and repeat endoscopy with duodenal biopsy showing a Marsh IIIa lesion confirmed the diagnosis of CD. Infectious gastroenteritis is a well-established risk factor for the development of IBS, and there is recent evidence that it could play a role in the initiation and exacerbation of inflammatory bowel disease. The present case suggests that the clinical expression of CD can be unmasked by an acute gastrointestinal infection and supports the hypothesis that environmental factors other than gliadin may play a role in the clinical onset of CD in a genetically susceptible host. The increasing availability of serological testing and upper endoscopy has led to increasingly frequent diagnoses of CD and recognition that it may mimic IBS. The present case findings suggest that CD should be considered in the differential diagnosis of persistent IBS-like symptoms after an episode of infectious gastroenteritis.
Celiac disease; Postinfective irritable bowel syndrome
Objective. To examine the role of adenosine receptor 2a gene (ADORA2a) polymorphisms on outcome of MTX treatment in RA.
Methods. Subjects included 309 RA patients with a defined response to MTX. Patients were included if they were (i) good responders (n = 147) (ESR <20 for >6/12 on stable dose of MTX) (ii) inefficacy failures (n = 101) (physician statement and failure to reduce ESR/CRP by 20%) or (iii) adverse event (AE) failures (n = 61) (verified by medical record review). AEs were sub-divided into gastrointestinal (GI) (n = 24), abnormal LFTs (n = 20) or other (n = 17). 8 single nucleotide polymorphisms (SNPs) within ADORA2a were genotyped using the Sequenom MALDI-TOF platform.
Results. Five SNPs within ADORA2a were associated with stopping MTX for AEs (OR 2.1–3.07, P < 0.05 for all). Analysis by AE type showed that the association was specific for GI toxicity. No association was observed between ADORA2a and inefficacy outcomes.
Conclusion. Genetic variation within ADORA2a is significantly associated with AEs on MTX, specifically GI AEs. Knowledge of the ADORA2a genotype may help to improve identification of patients at high risk of GI toxicity with MTX.
Rheumatoid arthritis; Methotrexate; Adenosine; Polymorphism
Study objective: Occupational structure represents the unequal geographical distribution of more desirable jobs among communities (for example, white collar jobs). This study examines joint effects of social class, race, and county occupational structure on coronary mortality rates for men, ages 35–64 years, 1988–92, in upstate New York.
Design: Upstate New York's 57 counties were classified into three occupational structure categories; counties with the lowest percentages of the labour force in managerial, professional, and technical occupations were classified in category I, counties with the highest percentages were in category III. Age adjusted coronary heart disease (CHD) mortality rates, 35–64 years, (from vital statistics and census data) were calculated for each occupational structure category.
Main results: An inverse association between CHD mortality and occupational structure was observed among blue collar and white collar workers, among black men and white men, with the lowest CHD mortality observed among white collar, white men in category III (135/100 000). About two times higher mortality was observed among blue collar than white collar workers. Among blue collar workers, mortality was 1.3–1.8 times higher among black compared with white workers, and the highest rates were observed among black, blue collar workers (689/100 000). Also, high residential race segregation was shown in all areas.
Conclusions: Results suggest the importance of community conditions in coronary health of local populations; however, differential impact on subpopulations was shown. Blue collar and black workers may especially lack economic and other resources to use available community services and/or may experience worse working and living conditions compared with white collar and white workers in the same communities.
Study objective: Examine the association between county occupational structure, services availability, prevalence of risk factors, and coronary mortality rates by sex, for 1980–96, in New York state.
Design: New York's 62 counties were classified into three occupational structure categories; counties with the lowest percentages of the labour force in managerial, professional, and technical occupations were classified in category I, counties with the highest percentages were in category III. Directly age adjusted coronary heart disease (CHD) mortality rates, aged 35–64 years, (from vital statistics and census data), per capita services (Census County Business Patterns), and the prevalence of CHD risk factors (BRFSS data) were calculated for each occupational structure category.
Results: CHD mortality rates and the prevalence of risk factors were inversely associated with occupational structure for men and women. Income from manufacturing jobs declined most in category I and per capita numbers of producer services for banking, business credit, overall business services, and personnel/employment services were 9–15 times greater in category III compared with I counties. Consumer services such as grocery stores, fitness facilities, doctors offices, and social services were 1.5–4 times greater in category III compared with I counties.
Conclusions: An ecological model for conceptualising communities and health and for intervention design is discussed; key community characteristics are occupational and industrial structure, availability and diversity of consumer services, prevalence of health practices, and level of premature CHD.
Aims: To determine the relation between lower airway infection and inflammation, respiratory symptoms, and lung function in infants and young children with cystic fibrosis (CF).
Methods: A prospective study of children with CF aged younger than 3 years, diagnosed by a newborn screening programme. All were clinically stable and had testing as outpatients. Subjects underwent bronchial lavage (BL) and lung function testing by the raised volume rapid thoracoabdominal compression technique under general anaesthesia. BL fluid was cultured and analysed for neutrophil count, interleukin 8, and neutrophil elastase. Lung function was assessed by forced expiratory volume in 0.5, 0.75, and 1 second.
Results: Thirty six children with CF were tested on 54 occasions. Lower airway infection shown by BL was associated with a 10% reduction in FEV0.5 compared with subjects without infection. No relation was identified between airway inflammation and lung function. Daily moist cough within the week before testing was reported on 20/54 occasions, but in only seven (35%) was infection detected. Independent of either infection status or airway inflammation, those with daily cough had lower lung function than those without respiratory symptoms at the time of BL (mean adjusted FEV0.5 195 ml and 236 ml respectively).
Conclusions: In young children with CF, both respiratory symptoms and airway infection have independent, additive effects on lung function, unrelated to airway inflammation. Further studies are needed to understand the mechanisms of airway obstruction in these young patients.
Objectives: To report 18 month outcome of a randomised trial of two courses of dexamethasone to prevent chronic lung disease of prematurity.
Study design: Babies of birth weight 1250 g or less ventilated at 7 days of age were randomised to a 42 day reducing course (long) or a 3 day pulsed (pulse) course of dexamethasone.
Growth, cardiovascular status, and respiratory and neurodevelopmental outcomes were assessed at 18 months.
Results: Seventy six babies were enrolled. Nine died and three were lost to follow up. Babies receiving the long course were weaned off oxygen more quickly than those receiving the pulse course (47% v 69% on oxygen at 28 days; p = 0.01), but there were no differences in 18 month outcomes. However, children averaged -1 SD for growth parameters, half had moderate or severe disability, and 35% and 19% respectively required oxygen at 36 weeks and discharge.
Conclusions: The dexamethasone course used did not influence long term outcome. However, entry criteria for this study selected a group of babies at high risk of poor long term outcome.
Background: Measurements of the subarachnoid space during routine cranial sonography may provide an indirect method of monitoring brain growth in preterm infants.
Methods: The width of the subarachnoid space was measured on coronal views during head sonography. Initial scans (within five days of birth) were compared with follow up scans.
Results: A total of 361 scans were performed on 201 preterm infants. The mean width of the subarachnoid space was < 3.5 mm for 95% of initial scans. It was slightly larger in neonates born closer to term, the equivalent of an increase of 0.02 mm/gestational week (95% confidence interval 0 to 0.10 mm) for initial scans. When the scans of all infants, born at 24–36 gestational weeks who were 36 weeks corrected gestational age were compared, the mean (SD) subarachnoid space was 60% larger for follow up scans than for intial scans: 3.2 (1.38) v 1.95 (1.35) mm (p = 0.002) or the equivalent of a mean increase of 0.20 mm/week (95% confidence interval 0.15 to 0.30 mm) for follow up scans. At 36 weeks corrected gestational age, mean head circumference was not different between those having initial or follow up scans (33.0 (2.0) v 32.2 (1.9) cm; p = 0.31).
Conclusions: The mean subarachnoid space is normally < 3.5 mm in preterm infants. The difference between initial and follow up scans suggests reduced brain growth in extrauterine preterm babies.
This study critically reviews sigmoid colon resection for diverticulitis comparing open and laparoscopic techniques.
We conducted a retrospective review of all open and laparoscopic cases of diverticulitis between 1992 and 2001. Data analyzed included the following: indications for operation, postoperative complications, and incidence of laparoscopic conversion to laparotomy. Major and minor complications were analyzed in relation to patients' preoperative diagnosis, age, presence or absence of splenic flexure mobilization, length of stay, and laparoscopic sigmoid resection versus open sigmoid resection.
Over a 10-year period, 166 resections for diverticulitis were performed including 126 open cases and 40 laparoscopic cases. No significant differences existed in patient characteristics between the groups. Major complications occurred in 14% of patients, and the laparoscopic conversion rate was 20%. The presence of abscess, fistula, or stricture preoperatively was associated with a higher complication rate only in patients ≥50 years old undergoing open sigmoid resection. The length of stay between patients undergoing laparoscopic resection was significantly less than in patients having open resection.
Advanced laparoscopic sigmoid resection is an alternative to open sigmoid resection in patients with diverticulitis and its complications. Open sigmoid resection in patients >50 years may have a higher complication rate in complicated diverticulitis when compared with laparoscopic sigmoid resection (all patient ages) and open sigmoid resection (patients <50 years old). Regarding complications, no difference existed between the length of stay in patients with open vs. laparoscopic resection.
Laparoscopy; Sigmoid resection; Diverticulitis
A 14-year-old boy with bronchiectasis secondary to chronic aspiration developed multiresistant Pseudomonas aeruginosa lower respiratory disease following several inpatient periods where accommodation and physiotherapy services were shared with cystic fibrosis (CF) patients known to be infected with the genetically identical strain of P. aeruginosa. Cross-infection with P. aeruginosa between CF patients and non-CF patients has not previously been described, and this finding raises significant issues relevant to the treatment of patients with non-CF suppurative lung disease.
BACKGROUND—Endoscopic oesophageal changes are diagnostically helpful and identify patients exposed to the risk of disease chronicity. However, there is a serious lack of agreement about how to describe and classify the appearance of reflux oesophagitis
AIMS—To examine the reliability of criteria that describe the circumferential extent of mucosal breaks and to evaluate the functional and clinical correlates of patients with reflux disease whose oesophagitis was graded according to the Los Angeles system.
METHODS—Forty six endoscopists from different countries used a detailed worksheet to evaluate endoscopic video recordings from 22 patients with the full range of severity of reflux oesophagitis. In separate studies, Los Angeles system gradings were correlated with 24 hour oesophageal pH monitoring (178 patients), and with clinical trials of omeprazole treatment (277 patients).
RESULTS—Evaluation of circumferential extent of oesophagitis by the criterion of whether mucosal breaks extended between the tops of mucosal folds, gave acceptable agreement (mean κ value 0.4) among observers. This approach is used in the Los Angeles system. An alternative approach of grouping the circumferential extent of mucosal breaks as occupying 0-25%, 26-50%, 51-75%, 76-99%, or 100% of the oesophageal circumference, gave unacceptably high interobserver variation (mean κ values 0-0.15) for all but the lowest category of extent (mean κ value 0.4). Severity of oesophageal acid exposure was significantly (p<0.001) related to the severity grade of oesophagitis. Preteatment oesophagitis grades A-C were related to heartburn severity (p<0.01), outcomes of omeprazole (10 mg daily) treatment (p<0.01), and the risk for symptom relapse off therapy over six months (p<0.05).
CONCLUSIONS—Results add further support to previous studies for the clinical utility of the Los Angeles system for endoscopic grading of oesophagitis.
Keywords: oesophagitis; endoscopy; stricture; columnar lined mucosa; heartburn; omeprazole; acid reflux
BACKGROUND: The medical profession is often presented with information on the value of treatment in terms of likely risk reduction. If this same information was presented to patients--so enabling them to give proper informed consent--would this affect their decision to be treated? AIM: To examine patients' choice about treatment in response to different forms of risk presentation. DESIGN OF STUDY: Postal questionnaire study. SETTING: The questionnaire was sent to 102 hypertensive patients and 207 matched non-hypertensive patients aged between 35 and 65 years in a UK general practice. METHODS: Patients were asked the likelihood, on a four-point scale, of their accepting treatment for a chronic condition (mild hypertension) on the basis of relative risk reduction, absolute risk reduction, number needed to treat, and personal probability of benefit. RESULTS: An 89% response rate was obtained. Of these, 92% would accept treatment using a relative risk reduction model, 75% would accept treatment using an absolute risk reduction model, 68% would accept treatment using a number needed to treat model, and 44% would accept treatment with a personal probability of benefit model. CONCLUSION: Many patients may prefer not to take treatment for mild hypertension if the risks were fully explained. However, given that the form of the explanation has a strong influence on the patient's decision, it is not clear how decision-making can be fully shared nor what should constitute informed consent to treatment in this situation.
OBJECTIVE—To compare findings of
tests for nut allergy in children.
survey of a clinical practice protocol.
paediatric outpatient clinic.
SUBJECTS—96 children referred by
general practitioners and accident and emergency doctors over 27 months
MAIN OUTCOME MEASURES—Allergic
manifestations (generalised urticarial rash, facial swelling,
bronchospasm, anaphylactic shock, vomiting on three occasions) related
to specific nut IgE concentrations and following touch, skin prick, or
oral ingestion of nuts.
RESULTS—16 children from a sample
of 51 who were tested for nut allergy had no reaction to an oral
challenge. Positive IgE against peanuts was found in nine of these 16children.
CONCLUSIONS—Skin prick testing and
IgE measured by radioallergosorbent testing are inadequate tests for
nut allergy. The definitive diagnostic test for nut allergy in the
hospital setting is direct oral challenge.
The purpose of the present study was to investigate the impact of the use of peripheral blood progenitor cells (PBPCs) on the induction of autologous graft-versus-host disease (GVHD) in patients with advanced breast cancer. 14 women with stage IIIB and 36 women with stage IV breast cancer received cyclosporine (CsA) 2.5 mg kg–1 i.v. daily, d 0–28, and interferon-gamma (IFNg) 0.025 mg/m2 s.c. qod, d7–28, following PBPC-T ± bone marrow transplantation (BMT). Preceding high-dose chemotherapy consisted of cyclophosphamide 6 g/m2 and thiotepa 800 mg/m2. Histologically proven ≥grade II cutaneous GVHD was induced in18/50 (36%) of patients and was independent of the source of haematopoietic support. In vitro studies showed that post-transplant, 76% of patients had developed auto-cytotoxicity against their own pre-transplant PHA-lymphoblasts. A significant correlation between the occurrence of GVHD ≥grade II and cytolysis was observed in the NK cell-line K562 and the T47D breast cancer cell-line. With a median follow-up of 2½ years, the overall survival (OS) is 58%, the disease-free survival (DFS) 26%, both independent of the development of GVHD and similar to what has been observed in other studies on high-dose chemotherapy in advanced breast cancer. It therefore remains unclear whether the induction of autologous GVHD with the occurrence of auto-cytotoxic lymphocytes can result in an anti-tumour effect in this group of patients. © 2000 Cancer Research Campaign http://www.bjcancer.com
breast cancer; autoreactive T-cells; cyclosporine; CLIP; MHC-class II; peripheral stem cells
This paper investigates whether general practitioners (GPs) who do not participate in questionnaire surveys (non-responders) hold different views on participation in primary care reorganisation than their more compliant colleagues. A survey of 72 GPs' involvement in a pilot primary care prescribing group elicited an initial response of 74%. Non-responders were then approached personally and persuaded to complete the questionnaire. Comparison of the responders and the non-responders showed that the latter did differ significantly from the responders in many of their views. This difference needs to be considered whenever the results of surveys are used to guide policy-making in the more corporate model of primary care that is now emerging.