Biomedical subjects

Helen Fletcher

Publications and source records attributed to Helen Fletcher.

10 recordsLinked to original sources

PubMed2006

Recognition of stage-specific mycobacterial antigens differentiates between acute and latent infections with Mycobacterium tuberculosis.

Mycobacterium tuberculosis is estimated to infect 80 to 100 million people annually, the majority of whom do not develop clinical tuberculosis (TB) but instead maintain the infection in a latent state. These individuals generally become positive in response to a tuberculin skin test and may develop clinical TB at a later date, particularly if their immune systems are compromised. Latently infected individuals are interesting for two reasons. First, they are an important reservoir of M. tuberculosis, which needs to be considered for TB control. Second, if detected prior to recrudescence of the disease, they represent a human population that is making a protective immune response to M. tuberculosis, which is very important for defining correlates of protective immunity. In this study, we show that while responsiveness to early secretory antigenic target 6 is a good marker for M. tuberculosis infection, a strong response to the 16-kDa Rv2031c antigen (HspX or alpha-crystallin) is largely restricted to latently infected individuals, offering the possibility of differential immunodiagnosis of, or therapeutic vaccination against, TB.

Acute Disease↗

PubMed2006

Tuberculosis vaccines: current status and future prospects.

There is an urgent need to develop more effective tuberculosis vaccines as chemotherapy and Bacille Calmette-Guérin (BCG) have failed to control the current epidemic. BCG does have some protective effect in childhood, so using a second vaccine to boost BCG would be the most ethical and logistically feasible strategy. The cost of tuberculosis efficacy trials will be high and return on investment into the development of a tuberculosis vaccine will be low. Incentives such as orphan drug status could encourage industrial interest. As more vaccines enter into early clinical trials, there is an urgent need for the identification of correlates of protection to aid decisions about which vaccines should go forward into efficacy testing. Research efforts that focus on reducing the cost and risk of conducting clinical trials will be of direct benefit to tuberculosis vaccine development.

Animals↗

PubMed2005

Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection.

Understanding the regulation of immune responses is central for control of autoimmune and infectious disease. In murine models of autoimmunity and chronic inflammatory disease, potent regulatory T lymphocytes have recently been characterized. Despite an explosion of interest in these cells, their relevance to human disease has been uncertain. In a longitudinal study of malaria sporozoite infection via the natural route, we provide evidence that regulatory T cells have modifying effects on blood-stage infection in vivo in humans. Cells with the characteristics of regulatory T cells are rapidly induced following blood-stage infection and are associated with a burst of TGF-beta production, decreased proinflammatory cytokine production, and decreased antigen-specific immune responses. Both the production of TGF-beta and the presence of CD4+CD25+FOXP3+ regulatory T cells are associated with higher rates of parasite growth in vivo. P. falciparum-mediated induction of regulatory T cells may represent a parasite-specific virulence factor.

Animals↗

PubMed2004

Healthy individuals that control a latent infection with Mycobacterium tuberculosis express high levels of Th1 cytokines and the IL-4 antagonist IL-4delta2.

The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop disease and identifying what constitutes "protective immunity" is one of the holy grails of M. tuberculosis immunology. It is known that IFN-gamma is essential for protection, but it is also apparent that IFN-gamma levels alone do not explain the immunity/susceptibility dichotomy. The controversy regarding correlates of immunity persists because identifying infected but healthy individuals (those who are immune) has been problematic. We have therefore used recognition of the M. tuberculosis virulence factor early secretory antigenic target 6 to identify healthy, but infected individuals from tuberculosis (TB)-endemic and nonendemic regions (Ethiopia and Denmark) and have compared signals for cytokines expressed directly ex vivo with the pattern found in TB patients. We find that TB patients are characterized by decreased levels of Th1 cytokines and increased levels of IL-10 compared with the healthy infected and noninfected community controls. Interestingly, the healthy infected subjects exhibited a selective increase of message for the IL-4 antagonist, IL-4delta2, compared with both TB patients or noninfected individuals. These data suggest that long-term control of M. tuberculosis infection is associated not just with elevated Th1 responses but also with inhibition of the Th2 response.

Adult↗

PubMed2002

Identification of Pneumocystis carinii DNA in oropharyngeal mouth washes from AIDS children dying of respiratory illnesses.

Polymerase chain reaction (PCR) using Pneumocystis carinii-specific primers pAZ 102-H(5'-GTGTACGTTGCAAAGTACTC-3') and pAZ 102-E(5'-GATGGCTGTTTCCAAGCCCA-3') was performed on oropharyngeal washes obtained at autopsy from 22 AIDS children with histologically confirmed P. carinii pneumonia (PCP), and 48 control AIDS children who died from other infections. Fifteen of 22 (68%) PCP samples and none of 48 (0%) control samples had detectable P. carinii DNA (sensitivity 68%; specificity 100%; positive predictive value 100%; negative predictive value 87%). This method requires further validation in clinical practice.

Acquired Immunodeficiency Syndrome↗

PubMed2002

The prospective evaluation of a nested polymerase chain reaction assay for the early detection of Aspergillus infection in patients with leukaemia or undergoing allograft treatment.

Patients with acute leukaemia or undergoing allogenic bone marrow transplantation at University College London Hospital Trust were screened for the presence of aspergillosis by polymerase chain reaction (PCR). Aspergillus DNA, from whole blood samples, was amplified by nested PCR to detect a 135 bp fragment in the mitochondrial region of Aspergillus fumigatus or A. flavus (121 bp). One colony-forming unit (CFU) per 2 ml of blood or 1-10 fg DNA could be detected. Patients at risk of aspergillosis were classified as probable or possible based on the European Organization for Research and Treatment of Cancer definitions. Antifungal drugs given were recorded. In four of 17 patients studied, infection was not suspected and the PCR was negative. Four patients were considered to have possible aspergillosis infection and were PCR positive on at least one occasion. Of the three patients in the probable group, four of the nine samples tested PCR positive from one patient and in another patient only one of nine samples tested positive. The remaining six patients were not suspected of having fungal infection but each had one or two PCR-positive results. In summary, six of seven patients thought to have clinical evidence of infection were PCR positive on at least one occasion and treatment with antifungals may have reduced infection below detectable levels.

Acute Disease↗

PubMed2002

Identification of Pneumocystis carinii DNA by polymerase chain reaction in necropsy lung samples from children dying of respiratory tract illnesses.

Polymerase chain reaction for Pneumocystis carinii DNA was performed on necropsy lung samples from children by means of P carinii -specific primers.P carinii DNA was identified in 22 of 22 (100%) samples with histologically proven P carinii pneumonia and 13 of 75 (17%) with non-P carinii pneumonia respiratory illness (sensitivity, 100%; specificity, 83%). The low specificity precludes the use of polymerase chain reaction as an alternative to histopathologic diagnosis.

Autopsy↗

PubMed2002

Remifentanil, fentanyl, and cardiac surgery: a double-blinded, randomized, controlled trial of costs and outcomes.

UNLABELLED: Remifentanil may be beneficial in patients undergoing coronary artery bypass graft surgery, by promoting hemodynamic stability, reducing drug requirements, and attenuating the neurohumoral "stress response." We enrolled 77 cardiac surgical patients in a double-blinded, randomized trial and randomly allocated them to one of three groups: remifentanil infusion at 0.83 micro g. kg(-1). min(-1) (Group R); fentanyl bolus, small dose, at 12 micro g/kg (Group FLD); and fentanyl bolus, moderate dose, at 24 micro g/kg (Group FMD). We found a significant difference in the median time to tracheal extubation: Group FLD, 6.5 h; Group R, 7.3 h; and Group FMD, 9.7 h (P = 0.025). Group R patients had similar times to those of Groups FLD (P = 0.14) and FMD (P = 0.30). Group FLD patients had a longer length of hospital stay (P = 0.030). Patients in Group R had a significantly infrequent rate of hypertension but a frequent rate of hypotension (P < 0.01). The urinary cortisol excretion was larger in Group FLD patients (P < 0.0005), and urine flow was smaller (P < 0.0005). Remifentanil was associated with a propofol dose reduction (P = 0.0005) and a concomitant higher bispectral index (P = 0.032). Three Group FLD patients, but none in groups FMD and R, had postoperative myocardial infarctions (P = 0.032). Remifentanil has larger drug acquisition costs but does not increase the total hospital costs associated with cardiac surgery. IMPLICATIONS: Remifentanil did not significantly reduce the duration of tracheal intubation after cardiac surgery. Remifentanil, when compared with fentanyl (total doses of approximately 15 and 28 micro g/kg), blunts the hypertensive responses associated with cardiac surgery but is associated with more hypotension; when compared with fentanyl 15 micro g/kg, remifentanil reduces cortisol excretion. Larger-dose opioids (remifentanil 0.85 micro g. kg(-1). min(-1) or fentanyl 28 micro g/kg) were associated with a decreased rate of myocardial infarction after cardiac surgery.

Aged↗

PubMed2002

Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers.

BACKGROUND: Smoking is considered to be a risk factor for patients undergoing surgery and anesthesia, but it is unclear whether this is applicable to patients undergoing ambulatory surgery. The aim of this study was to determine the risk of respiratory complications and wound infection among smokers. METHODS: The authors studied a random selection of 489 adult patients undergoing ambulatory surgery. Smoking status was determined by self-report and confirmed with end-expired carbon monoxide analysis. The risk of respiratory complications (i.e., desaturation, cough, laryngospasm, bronchospasm, breath-holding, or apnea) and wound infection (i.e., wound redness or discharge +/- positive microbial culture, requiring antibiotic therapy) in smokers nonsmokers was ascertained. Odds ratios were estimated from multivariable logistic regression and adjusted for age, gender, body mass index, partner's smoking status, domiciliary smoking exposure, and extent and duration of surgery. RESULTS: Most smokers continued to smoke up until the day of surgery. Smokers had a higher rate of respiratory complications (32.8% vs. 25.9%; adjusted odds ratio, 1.71; 95% confidence interval, 1.03-2.84; = 0.038) and wound infection (3.6% vs. 0.6%; odds ratio, 16.3; 95% confidence interval, 1.58-175; = 0.019). Odds ratios comparing current plus ex-smokers with nonsmokers were of similar magnitude for most of these complications. CONCLUSIONS: Smoking was associated with an increased risk of respiratory complications and postoperative wound infection in ambulatory surgery patients. These findings warrant increased efforts at promoting smoking avoidance and cessation.

Adult↗

PubMed2002

Phonological awareness in children with Down syndrome.

Research in the area of phonological awareness has mainly focused on the nature of the relationship between reading ability and awareness of phonemes. However, a recent study of phonological awareness in children with Down syndrome questioned the existence of any necessary relationship (Cossu, Rossini & Marshall, 1993). This paper describes a study of phonological awareness in children with Down syndrome with varying levels of reading ability. The sample consisted of 10 male and 7 female children with Down syndrome (aged 9 years 2 months to 14 years 5 months). All children received a battery of tests which consisted of assessments of: 1) phonological awareness, 2) reading and spelling competence, 3) non-word reading and spelling ability, and 4) non-verbal measures. Children with Down syndrome demonstrated measurable levels of phonological awareness. Significant positive correlations were found between phonological awareness and: reading and spelling competence, ability to spell non-words and non-verbal measures.

Adolescent↗