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Biomedical subjects

V Gant

Publications and source records attributed to V Gant.

At least 19 recordsLinked to original sources
PubMed2001

The effects of leucodepletion in patients who develop the systemic inflammatory response syndrome following cardiopulmonary bypass.

The development of the systemic inflammatory response syndrome (SIRS) is associated with increased morbidity and mortality. Numerous anticytokine trials have failed to demonstrate any outcome benefit and there has been little evidence of improvement in the prognosis of this condition over the past 20 years. This study examines the effect of using a white cell filter designed to remove polymorphonuclear cells (PMNs) in patients who developed SIRS 36 h after cardiopulmonary bypass (CPB). Twenty-four patients were randomized to receive either leucofiltration (LF) or control therapy (CT). The two groups were well matched at study entry in terms of age, severity of illness and length of time on CPB. LF patients received 60 min filtration periods using a venovenous extracorporeal circuit at a flow rate of 200 ml/min with the cycle repeated every 12 h while SIRS and other entry criteria were met. CT patients received standard therapy. LF patients received an average of 4.2 cycles (range 1-8) and, after 15 min filtration, the total leucocyte count had fallen from 16.2 +/- 5.3 to 10.4 +/- 3.3 x 10(9)/l and PMN from 14.4 +/- 5.2 to 8.3 +/- 4.2 x 10(9)/l. The mean platelet count changed from 127 +/- 87 to 117 +/- 82 x 10(9)/l. No adverse effects related to leucodepletion were observed. There was no difference between the groups in either mortality or length of stay at the intensive care unit or at hospital discharge. Organ function was assessed regularly during the study period and significant changes occurred only in respiratory and renal function. In the LF patients, respiratory function assessed by change in hypoxaemia index from baseline and renal function assessed by serum creatinine showed significant treatment effects compared to CT patients (p < 0.01, < 0.01 respectively); three CT patients, but no LF patients, received haemofiltration during the study period. Leucofiltration safely and effectively removes circulating PMNs from patients with SIRS following CPB. This may result in improved pulmonary and renal function in these patients. Further studies are required of the kinetics and phenotypic characteristics of PMN removal by leucofiltration and a larger multicentre study will be necessary to determine whether this novel therapy has a significant outcome benefit in critically ill patients with SIRS.

Aged↗
PubMed2000

Community-acquired pneumonia.

Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality worldwide and has significant financial implications for health-care systems. The epidemiology and fundamental biology of the disease has evolved, reflecting the human immunodeficiency virus pandemic, increasing world travel, and, as always, poverty. The promise held out by molecular diagnostic technology has yet to deliver in this arena, and antibiotic resistance continues to drive the quest for new antimicrobial agents. The emergence of multidrug-resistant Streptococcus pneumoniae, the microorganism most often implicated as a cause of CAP, continues to threaten treatment options. The evolution of this organism, the persistently high mortality rate associated with CAP, and increasing health-care costs have prompted the publication of guidelines by various authorities that can be used to assist in the initial assessment of the patient and then guide empirical antimicrobial therapy. It is unclear whether these guidelines will have significant impact on cost and mortality, although the trend toward a rational and evidence-based approach to antimicrobial therapy must be a goal to aspire to.

Anti-Bacterial Agents↗
PubMed1999

Quality specifications for ordinal scale measurements with multiproperty (multiple) urine test strips.

Analytical quality specifications for ordinal scale measurements have not been presented so far. Criteria are suggested for multiproperty (multiple) urine test strips based on upper limits of healthy reference intervals, analytical performance and statistical tests applicable to ordinal scales. Trueness (accuracy) can be evaluated against an acceptable comparison method by applying sensitivity and specificity concepts, and defining a grey zone with a lower detection limit and an upper confirmation limit. Concordance (agreement) of two or more ordinal scale categories should be evaluated by subtracting random agreement, using Kappa statistics. Repeatability (precision) can be calculated for categorized results using binomial statistics.

Clinical Laboratory Techniques↗
PubMed1998

Persistence of Pseudomonas aeruginosa strains in respiratory infection in AIDS patients.

OBJECTIVES: To establish the clinical pattern of Pseudomonas aeruginosa respiratory infections in HIV-seropositive patients and to determine whether repeated isolation of the organism represents reinfection or recurrence and to assess whether common source, nosocomial infection occurred. DESIGN AND METHODS: Evaluation of the clinical pattern of P. aeruginosa respiratory infections by case note review and epidemiological characterization of P. aeruginosa by serotype determination and Xbal DNA macrorestriction analysis. Serum sensitivity testing of strains was performed to further define phenotypic characteristics of the isolated organisms. RESULTS: Seventy-three per cent (29 out of 40) of individuals had P. aeruginosa isolated on two or more occasions in the setting of clinical respiratory infection. Overall, 85% had evidence of P. aeruginosa to within 2 months of study completion or death. Epidemiological characterization revealed persistence of unique single strains in 93% of individuals where multiple isolates were available for testing, whereas only two patients harboured a common strain. The serotype distribution of strains was similar to that reported from non-HIV-positive patients. CONCLUSIONS: Once established, eradication of P. aeruginosa from the respiratory tract of HIV-seropositive individuals with advanced immunosuppression is problematic and a chronic infective state appears common. There was no evidence of nosocomial transmission. Serotype loss and development of sensitivity to normal human serum were both observed and were highly correlated. This represents truncation of O-antigenic lipopolysaccharide on the cell surface of P. aeruginosa and may reflect progression to phenotypes commonly associated with chronic infection in other clinical settings such as cystic fibrosis.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Structure-function relationship of antibacterial synthetic peptides homologous to a helical surface region on human lactoferrin against Escherichia coli serotype O111.

Lactoferricin includes an 11-amino-acid amphipathic alpha-helical region which is exhibited on the outer surface of the amino-terminal lobe of lactoferrin. Synthetic peptides homologous to this region exhibited potent antibacterial activity against a selected range of both gram-negative and gram-positive bacteria. An analog synthesized with methionine substituted for proline at position 26, which is predicted to disrupt the helical region, abolished antibacterial activity against Escherichia coli and considerably reduced antibacterial activity against Staphylococcus aureus and an Acinetobacter strain. The mode of action of human lactoferrin peptide (HLP) 2 against E. coli serotype O111 (NCTC 8007) was established by using flow cytometry, surface plasmon resonance, and transmission electron microscopy. Flow cytometry was used to monitor membrane potential, membrane integrity, and metabolic processes by using the fluorescent probes bis-1,3-(dibutylbarbituric acid)-trimethine oxonol, propidium iodide, and carbonyl cyanide m-chlorophenylhydrazone, respectively. HLP 2 was found to act at the cell membrane, causing complete loss of membrane potential after 10 min and of membrane integrity within 30 min, with irreversible damage to the cell as shown by rapid loss of viability. The number of particles, measured by light scatter on the flow cytometer, dropped significantly, showing that bacterial lysis resulted. The peptide was shown to bind to E. coli O111 lipopolysaccharide by using surface plasmon resonance. Transmission electron microscopy revealed bacterial distortion, with the outer membrane becoming detached from the inner cytoplasmic membrane. We conclude that HLP 2 causes membrane disruption of the outer membrane, resulting in lysis, and that structural considerations are important for antibacterial activity.

Amino Acid Sequence↗
PubMed1998

A helical region on human lactoferrin. Its role in antibacterial pathogenesis.

Human lactoferrin contains a 47 amino acid peptide, named lactoferricin H, which is thought to be responsible for its antimicrobial activity. Lactoferricin includes a loop region, which resides on the outer surface of the N-lobe of lactoferrin, adopting an alpha helix with a hydrophobic tail. Peptides have been synthesised corresponding to the highly charged alpha helix (HLP 2) and hydrophobic tail region (HLP 5). HLP 2 has potent antibacterial activity whereas HLP 5 had no activity. To investigate the relationship between structure and function of HLP 2, HLP 6 was synthesised with a proline replacing methionine. This substitution was predicted to disrupt the helical region of the peptide and the orientation of the positively charged residues. Antibacterial activity was significantly reduced when tested against Escherichia coli serotype 0111, NCTC 8007. The mode of action of HLP 2 against the bacterial membrane was investigated by flow cytometric analysis, using Escherichia coli, NCTC 8007. Membrane potential and integrity were monitored using the fluorescent probes, bis 1,3-(dibutylbarbituric acid) trimethine oxonol and propidium iodide respectively. HLP 2 caused complete loss of membrane potential and integrity, with irreversible damage to the cell as shown by rapid loss of viability. We conclude that HLP 2 causes membrane disruption and that helicity is an important factor for antibacterial activity.

Amino Acid Substitution↗
PubMed1996

Prediction of outcome in critically ill patients using artificial neural network synthesised by genetic algorithm.

BACKGROUND: Decisions about which patients to admit to intensive care and how long to keep them there are difficult. A flexible computer-based mathematical model which is sensitive to the complexity of intensive care medicine, and which accurately models prognosis, seems highly desirable. METHODS: We have created, optimised by genetic algorithms, trained, and evaluated the performance of an artificial neural network (ANN) in the clinical setting of systemic inflammatory response syndrome and haemodynamic shock. 258 patients were selected from an intensive care database of 4484 patients at a London teaching hospital and randomised to a network training set (168) and a test set (90). The outcome evaluated was death during that hospital admission and the performance of the neural net was compared (by receiver operating characteristic [ROC] curves and by Brier scores) with that of a logistic regression model. FINDINGS: Artificial neural network performance increased with successive generations; the best-performing ANN was created after 7 generations and predicted outcome more accurately than the logistic regression model (ROC curve area 0.863 vs 0.753). INTERPRETATION: In this study, ANNs have lent themselves particularly well to modelling a complex clinical situation; we suggest that this relates to their inherently flexible nature which accommodates interactions between the clinical input fields. In addition, we have demonstrated the value of a second computational technique (genetic algorithms) in "tuning" ANN performance. These techniques can potentially be implemented in individual intensive care units; the outcome models which they will generate will be sensitive to local practice. Analysis of such accurate clinical outcome models may empower clinicians with a hitherto unappreciated degree of insight into those elements of their clinical practice which are most relevant to their patients' outcome.

Adult↗
PubMed1995

Should patients positive for HIV infection receive pneumococcal vaccine?

Pneumococcal vaccination effectively reduces the incidence of invasive pneumococcal disease in normal subjects. Such invasive pneumococcal disease is 100 times more common in patients with HIV infection than in healthy people, so it seems logical to target this group of patients for vaccination. Few clinics routinely vaccinate patients positive for HIV, despite Department of Health guidelines. This is because of uncertainty about the vaccine's efficacy in HIV disease. There are many reasons to suspect that the vaccine will fail to protect these patients, including the fact that antibodies alone may not be sufficient protection against all serogroups of Pneumococcus and the vaccine works in healthy people but not immunocompromised subjects. Vaccination of HIV positive patients may not be indicated, at least for the time being. The cost of vaccinating such patients in the absence of data showing efficacy may well be less than the cost of a necessarily large and lengthy trial. But the truth must be sought to end current indecision.

AIDS-Related Opportunistic Infections↗