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Biomedical subjects

H Gaya

Publications and source records attributed to H Gaya.

At least 37 records · Page 2Linked to original sources

Factors associated with bacteraemia in febrile, granulocytopenic cancer patients. The International Antimicrobial Therapy Cooperative Group (IATCG) of the European Organization for Research and Treatment of Cancer (EORTC).

The objective of this investigation was to determine factors predictive of bacteraemia at presentation in febrile, granulocytopenic cancer patients in order to estimate the probability of bacteraemia in each patient, and to compare factors associated with a diagnosis of gram-positive or gram-negative bacteraemia. Retrospective analysis of two sets of data (derivation and validation sets) randomly obtained from a large prospective study was conducted in a multicentre study of febrile, granulocytopenic cancer patients admitted for empiric antibacterial therapy. Within the derivation set, prognostic factors (clinical and laboratory data) likely to be associated with a generic diagnosis of bacteraemia and with a specific diagnosis of gram-positive or gram-negative bacteraemia were analysed by means of three backward, stepwise, logistic regression analyses. The predictive probability of bacteraemia was calculated using the logistic equation. The discriminating ability of the model in predicting bacteraemia was evaluated in the derivation and validation sets using receiver-operating characteristic curves. The predictive probability of gram-positive or gram-negative bacteraemia was not calculated. In the derivation set, 157 of 558 episodes (28%) were microbiologically documented bacteraemias. Predicting factors were antifungal prophylaxis, duration of granulocytopenia before fever, platelet count, highest fever, shock and presence and location of initial signs of infection. The variables institution, antibacterial prophylaxis and underlying disease showed borderline associations with bacteraemia. Shock was associated with gram-negative bacteraemia, while signs of infection at catheter site were predictive of gram-positive bacteraemia. Quinolone prophylaxis was negatively associated with gram-negative bacteraemia. When tested in the validation set, the model was poorly predictive, although a small subgroup of episodes (representing only 16% of the total sample size) with low risk of bacteraemia was identified. Factors predictive of bacteraemia can be identified, with discrimination between gram-positive and gram-negative aetiology. Further studies are warranted in order to improve the discriminant ability of the model.

Adolescent↗

Characteristics of patients with drug resistant and drug sensitive tuberculosis in East London between 1984 and 1992.

BACKGROUND: The aim of this study was to investigate retrospectively factors associated with drug resistant tuberculosis at the London Chest Hospital. METHODS: The microbiology results for patients with tuberculosis at the hospital for the period 1984-92 were reviewed, together with case notes and chest radiographs of all patients with drug resistant tuberculosis and of 101 patients with drug sensitive tuberculosis notified during the same period as a control group. RESULTS: Culture positive pulmonary tuberculosis occurred in 292 patients. Drug resistant strains were isolated from 20 patients (6.8%). Ten of the 292 (3.4%) had strains resistant to a single drug and nine (3.1%) had resistance to more than one first line drug. One patient had strains resistant to isoniazid and capreomycin. Strains resistant to more than one drug were all resistant to isoniazid and rifampicin. In five patients these strains were also resistant to pyrazinamide and in two they were resistant to streptomycin. Single drug resistant strains were resistant to isoniazid (nine patients) or streptomycin (one patient). Among the risk factors studied previous treatment for tuberculosis was the most significant association with drug resistant tuberculosis (7/9) for patients with resistance to more than one drug; 5/11 for single drug resistance compared with 6/101 patients in the drug sensitive group (odds ratio 22.8). Other risk factors were bilateral disease at presentation (odds ratio 8.5), and disease at a young age (odds ratio 1.03). CONCLUSIONS: Previous treatment for tuberculosis and bilateral disease at presentation were found to be more commonly associated with cases of drug resistant than with drug sensitive tuberculosis.

Adolescent↗

Nasal application of the cationic liposome DC-Chol:DOPE does not alter ion transport, lung function or bacterial growth.

Liposome-mediated gene transfer is commonly used for in vitro transfection of deoxyribonucleic acid (DNA) into mammalian cells. We and others have recently demonstrated that this can be an effective method for in vivo delivery of plasmid DNA containing the human cystic fibrosis transmembrane conductance regulator (CFTR) gene to mouse models of cystic fibrosis (CF). This suggests that cationic liposomes may be useful for transferring CFTR complementary DNA (cDNA) into the airways of CF subjects. In such trials, measurement of nasal potential difference (PD) will be used to monitor the efficacy of correction of the CF bioelectric defect and to provide a sensitive assay of epithelial integrity [corrected]. We therefore assessed whether the cationic liposome DC-Chol: DOPE altered nasal ion transport parameters, in six normal and three CF subjects. Lung function was also measured as a further marker of safety. Finally, as CF airways are chronically infected, we studied whether DC-Chol:DOPE or DC-Chol:DOPE-DNA complexes altered the bacterial growth and sensitivities of CF sputum. No significant effect was seen on any of these parameters, suggesting that DC-Chol:DOPE may be appropriate for use in human trials of liposome-mediated gene therapy for CF.

Administration, Intranasal↗

A multidisciplinary investigation of a cluster of deaths on a paediatric intensive care unit.

During late December 1989 and early January 1990, a cluster of six unexplained deaths occurred on a paediatric intensive care unit (PICU) among children with congenital heart disease who had undergone cardiac surgical procedures. The children were all aged three years or less. In each case death was preceded by an unexpected increase in ventilatory pressure requirement followed by the development of a similar pulmonary shadowing on chest radiography. The radiological abnormality was felt to be consistent with a pneumonitis associated with some small airway disease. The clustering of these deaths, occurring in a similar unusual manner, was felt to constitute an outbreak warranting investigation. An Incident Committee was established to plan and manage a large multidisciplinary investigation during which the unit was temporarily closed. Following extensive investigation no bacterium, virus, fungus or other pathogen, toxic agent, or any other explanation for the cluster of deaths could be found. The possibility that the cluster occurred by chance remains although this was felt to be unlikely.

Cause of Death↗

Pseudomonas cepacia: pulmonary infection in patients with cystic fibrosis.

This retrospective study reviews the patterns of P. cepacia pulmonary infection in 75 of a total of 872 mainly adults with cystic fibrosis, registered here during the 4 years 1987-1990; 35 (47%) were female. During this period, 55 patients acquired P. cepacia and the annual incidence and prevalence rates have remained between 1.6 and 3.1%, and 4.1 and 5.9%, respectively. The mean age at the time of the first isolation of P. cepacia was 23 years, ranging 11-45 years. Sixty-eight percent of the initial isolates were multi-resistant (sensitive to fewer than three of 15 anti-pseudomonal agents). Prior to acquisition of P. cepacia, 28 (50.9%) patients already had severe lung disease and only three had normal lung function. Infection was transient in 39.1% of patients. Initial multi-resistance of P. cepacia to anti-pseudomonal agents was significantly associated with persistent infection. Clinical outcome was unaffected by age, sex and early intravenous antibiotic therapy but was significantly adversely affected by increasing severity of lung disease at the onset of P. cepacia infection and by initial multi-resistance, and persistence of the organism. Thus, all patients with normal or mild lung disease at the outset of infection have remained clinically stable, whereas, only six of 28 patients with severe disease remained stable, three of whom were transiently infected with P. cepacia. The prevalence of P. cepacia at the time of death fluctuated between 12.5% and 26.9% during the study period.

Adolescent↗

A study of glutaraldehyde disinfection of fibreoptic bronchoscopes experimentally contaminated with Mycobacterium tuberculosis.

Mycobacteria are difficult to inactivate, and concern about the spread of tuberculosis at bronchoscopy has a major influence on infection control practices. Recommendations from the UK Department of Health are based largely on in-vitro mycobactericidal assays which do not take into account the particular conditions encountered in endoscopy units. In this applied study cleaning and disinfection methods were examined using five bronchoscopes that were heavily contaminated with a recent isolate of Mycobacterium tuberculosis in sputum. Cleaning reduced contamination by a mean 3.5 log(10) colony forming units (cfu) per ml; all bronchoscopes were free of detectable mycobacteria after 10 min in 2% alkaline glutaraldehyde (AG). It is recommended that all bronchoscopes be thoroughly pre-cleaned and disinfected in 2% AG for 20 min as part of a uniform policy of infection control.

Bronchoscopes↗

Temocillin and cystic fibrosis: outcome of intravenous administration in patients infected with Pseudomonas cepacia.

Twelve courses of intravenous temocillin were given in combination with an intravenous aminoglycoside to five patients with cystic fibrosis (CF) for pulmonary exacerbations associated with Pseudomonas cepacia. All patients were infected concurrently with Pseudomonas aeruginosa in addition to P. cepacia. Improvement occurred after six of seven courses given to three patients in which temocillin was used as first-line therapy and following three of five courses given to two patients after failure of other antipseudomonal agents. All ten pre-treatment isolates of P. cepacia were resistant to aminoglycosides and eight were sensitive to temocillin. Clinical improvement was seen on both occasions in which the pre-treatment isolates were resistant to temocillin.

Adolescent↗

Complement activation during bypass in acquired C1 esterase inhibitor deficiency.

Serial complement estimations during cardiopulmonary bypass are reported in a patient with acquired C1 esterase inhibitor deficiency. Although the extent of classic and alternative pathway activation appeared appropriate, exaggerated common pathway activation with massive increase in the C3d:C3 ratio occurred. A fatal hemostatic disorder, pulmonary edema, and circulatory collapse ensued despite prophylaxis and therapy.

Aged↗

Prospective randomized evaluation of ciprofloxacin versus piperacillin plus amikacin for empiric antibiotic therapy of febrile granulocytopenic cancer patients with lymphomas and solid tumors. The European Organization for Research on Treatment of Cancer International Antimicrobial Therapy Cooperative Group.

Empiric therapy for febrile granulocytopenic patients is mandatory, but whether monotherapy is a safe alternative and whether fluoroquinolones are useful agents for this indication are still controversial issues. The use of monotherapy with intravenous ciprofloxacin (200 to 300 mg every 12 h) was evaluated against combined therapy with piperacillin plus amikacin in febrile granulocytopenic patients with solid tumor or lymphoma. The study was discontinued prematurely because patients treated with ciprofloxacin had a significantly lower overall success rate than patients treated with piperacillin plus amikacin (31 of 48 patients [65%] versus 48 of 53 patients [91%], P = 0.002). Patients with gram-positive coccal bacteremia had a particularly poor outcome: therapy failed for six of eight patients (75%) treated with ciprofloxacin, while therapy failed for none of four patients treated with piperacillin plus amikacin. Death from primary infection during initially randomized protocol therapy occurred in 7 of 48 patients (14.5%) treated with ciprofloxacin and in 3 of 53 (6%) treated with piperacillin plus amikacin. This study does not support the use of this dose of intravenous ciprofloxacin as empiric monotherapy for fever in granulocytopenic patients.

Adult↗

Recovery of the human immunodeficiency virus from fibreoptic bronchoscopes.

Ten bronchoscopes that had been used on patients with the acquired immunodeficiency syndrome were sampled to determine the nature and extent of microbial contamination. Samples were taken by irrigating the suction biopsy channel with modified viral transport medium and by swabbing the insertion tube. Sampling was repeated after they had been cleaned in detergent and after two minutes' disinfection in 2% alkaline glutaraldehyde. Before being cleaned the seven bronchoscopes tested by polymerase chain reaction were contaminated with the human immunodeficiency virus, though infectivity and antigen assays gave negative results. Other organisms identified were hepatitis B virus (1), commensal bacteria (9), and Pneumocystis carinii (4). Mean bacterial contamination was 2.27 log colony forming organisms per millilitre. Cleaning the bronchoscope before disinfection removed all detectable contaminants with a reduction in bacterial growth of up to 8 log colony forming units/ml.

Bronchoscopes↗

Reduction of complement activation during bypass by prime manipulation.

Complement activation is believed to be of importance in the development of complications arising after cardiopulmonary bypass. The effect on complement activation of priming the extracorporeal circuit with crystalloid alone, crystalloid plus albumin, or crystalloid plus the plasma expander polygeline was assessed in 36 patients undergoing coronary artery operations with cardiopulmonary bypass using a bubble oxygenator. Activation of the alternative and common complement pathways was monitored before, during, and after the bypass period by measuring concentrations of factor B and its fragment Ba and C3 and its fragment C3d. Complement activation occurred in all three groups of patients, with no difference between the crystalloid and crystalloid-albumin groups. In contrast, Ba fragment concentrations were persistently and significantly lower during and after bypass in the polygeline group, denoting reduced complement activation. C3d levels also showed a tendency to be lower in this group. Our results indicate that addition of polygeline to the priming solution reduces complement activation. Because complement activation is associated with morbidity after cardiopulmonary bypass, addition of polygeline to the priming solution may offer an inexpensive method of reducing morbidity after cardiopulmonary bypass.

Albumins↗

Complement activation before, during and after cardiopulmonary bypass.

Plasma levels of the complement parent molecules C3, C4, and factor B and their split products, C3d, C4d, and Ba were measured in 12 patients undergoing cardiopulmonary bypass for coronary artery surgery. Alternative and common complement pathway activation, demonstrated by statistically significant rising levels of Ba (P less than 0.05), and C3d (P less than 0.05) and by elevated Ba:B (P less than 0.05) and C3d:C3 (P less than 0.05) ratios were found before the institution of cardiopulmonary bypass but following heparin administration suggesting that heparin may itself initiate alternative pathway activation. In addition, significant depletion of parent complement components and elevation of split product concentrations was seen during bypass suggesting classical and alternate pathway activation (P less than 0.01). This study clarifies the pathways of complement activation during bypass and presents evidence that heparin administration may initially activate the complement cascade.

Cardiopulmonary Bypass↗

Double-blind randomized study of prolonged higher-dose oral amoxycillin in purulent bronchiectasis.

Thirty-eight patients with bronchiectasis and daily expectoration of purulent sputum despite conventional antibiotic courses were randomly allocated to receive a sachet of amoxycillin (3 g) or matched placebo twice daily for 32 weeks in a double-blind study. Nine patients (four amoxycillin, five placebo) were withdrawn from the study treatment; the response of the two patients (both on amoxycillin) withdrawn within the first six weeks was not assessed. The pretreatment characteristics of the two groups were similar. Independent assessment of overall response based on patients' diary cards showed that a higher proportion improved in the amoxycillin group (11 of 17) than in the placebo group (four of 19; p = 0.02). Patients in the amoxycillin group spent significantly less time confined to bed and away from work during treatment. The frequency of exacerbations during the study treatment phase was similar in the two groups but they were less severe than before study treatment in the amoxycillin group. There was a greater reduction in purulent sputum volume between exacerbations during the study treatment in the amoxycillin group to 20 per cent of pretreatment volume than in the placebo group (88 per cent of pretreatment volume, p = 0.008), although the concentrations of Haemophilus spp. in sputum between exacerbations was similar in the two groups. Adverse effects experienced were minor except in one patient (amoxycillin) withdrawn after developing a rash and in six patients (three amoxycillin, three placebo) who had diarrhoea lasting more than one week necessitating withdrawal of two patients (one amoxycillin, one placebo) from study treatment. Sputum and stool cultures collected regularly during the study showed no important changes in the bacterial flora in either group. Prolonged higher-dose antibiotic therapy in these patients with severe purulent bronchiectasis significantly reduced the host (patient) inflammatory response to colonizing microorganisms and reduced morbidity.

Adult↗

Contamination of endoscopes used in AIDS patients.

Contamination of twenty endoscopes used in patients with AIDS was assessed. The suction-biopsy, air, and water channels and the insertion tube were sampled after use, after washing in detergent, and after disinfection for 2 min in 2% alkaline glutaraldehyde. The polymerase chain reaction with Southern blotting, cell cultures, and antigen immunoassay were used to detect human immunodeficiency virus (HIV). Samples were also examined for cytomegalovirus, adenoviruses, enteroviruses, herpes simplex virus, myxoviruses, hepatitis B surface antigen, fungi, and bacteria. Seven of twenty unwashed endoscopes were contaminated by HIV. Commensal bacteria were found in all endoscopes, Candida albicans in six, Staphylococcus aureus in five, and Pseudomonas aeruginosa in five. Washing alone removed all detectable organisms from 66 of 68 contaminated sites; Neisseria spp were recovered from two air channels after washing but not after disinfection. Washing achieved a mean reduction of 4.93 (95% confidence interval 3.69-6.17) colony forming units per ml.

Acquired Immunodeficiency Syndrome↗

Empiric antimicrobial therapy for febrile granulocytopenic cancer patients: lessons from four EORTC trials.

The results of the four EORTC trials conducted over the past 15 years suggest: (1) early empiric therapy with broad spectrum antibiotics directed against gram-negative bacterial bacteremia (GNBB) is a reasonable approach in febrile granulocytopenic patients (GCP); (2) the level and dynamics of the granulocyte count are extremely important in determining the outcome of bacteremia; severely and/or persistently neutropenic patients are the true tests of antibiotic efficacy and they benefit from antimicrobial synergism; (3) mortality from GNBB in GCP is not related directly to a given empiric antimicrobial regimen which may 'buy time' and allow appropriate therapeutic alterations; (4) only microbiologically documented infections and especially bacteremias are useful to compare responses to antimicrobial regimens; (5) the response rate of GNBB is clearly influenced by the susceptibility of the causative pathogen to the beta-lactam component of the empiric regimen and emergence of resistance to some antibiotics (cephalothin, carbenicillin, ticarcillin, azlocillin) has rendered some combinations less effective. The combination of an anti-Pseudomonas beta-lactam plus an aminoglycoside is recommended as the 'standard' for empiric therapy in febrile GCP; (6) gram-positive pathogens have become a common cause of bacteremia in GCP and although the response rate to empiric regimens may be marginal, the associated mortality is low. A general conclusion from these trials is that studies of the management of infection in GCP should include sufficient numbers of eligible patients to allow for evaluation of bacteremic patients at highest risk of death. The need for large collaborative studies stems directly from these considerations.

Agranulocytosis↗