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Biomedical subjects

C Feldman

Publications and source records attributed to C Feldman.

At least 19 recordsLinked to original sources
PubMed2003

Investigation of mycobacterial colonisation and invasion of the respiratory mucosa.

BACKGROUND: The pathogenesis of Mycobacterium avium complex and Mycobacterium tuberculosis in the respiratory tract is poorly understood, as are the reasons for their differing virulence. We have previously shown that their initial adherence to the mucosa is identical. METHODS: The interaction of M avium complex, M tuberculosis, and M smegmatis with human respiratory tissue was investigated in an organ culture model with an air interface. Tissue was infected for intervals up to 14 days and assessed by scanning electron microscopy for adherent bacteria or cultured for recoverable bacteria. RESULTS: The mean number of adherent bacteria/mm(2) (and the viable count of macerated tissue, cfu/ml) at 15 minutes, 3 and 24 hours, 7 and 14 days were: M avium complex 168 (153), 209 (136), 289 (344), 193 (313), 14140 (16544); M tuberculosis 30 (37), 39 (23), 48 (53), 1 (760), 76 (2186); M smegmatis 108 (176), 49 (133), 97 (81), 114 (427), 34 (58), (n=6). There was no significant change in morphology between infected and uninfected tissue or tissue infected with the different species over 14 days. The number of M avium complex on the mucosa and recovered from tissue increased over time (p=0.03). M tuberculosis decreased on the surface, but recoverable bacteria increased (p=0.01). M smegmatis numbers on the mucosa and recovered from tissue decreased. Sectioned tissue showed M avium complex and M tuberculosis in submucosal mucus glands and M tuberculosis penetrating epithelial cells in one experiment. CONCLUSIONS: The initial adherence to the mucosa of the three species was similar, but after 14 days they varied in their interaction with the tissue in a manner compatible with their pathogenicity.

Bacterial Adhesion↗
PubMed2003

Pulmonary echinococcosis.

Echinococcosis or hydatid disease is caused by larvae of the tapeworm Echinococcus. Four species are recognised and the vast majority of infestations in humans are caused by E. granulosus. E. granulosus causes cystic echinococcosis, which has a worldwide distribution. Humans are exposed less frequently to E. multilocularis, which causes alveolar echinococcosis. E. vogeli and E. oligarthrus are rare species and cause polycystic echinococcosis. In cystic echinococcosis, humans are an accidental host and are usually infected by handling an infected dog. The liver and lungs are the most frequently involved organs. Pulmonary disease appears to be more common in younger individuals. Although most patients are asymptomatic, some may occasionally expectorate the contents of the cyst or develop symptoms related to compression of the surrounding structures. Other symptoms of hydatid disease can result from the release of antigenic material and secondary immunological reactions that develop from cyst rupture. The cysts are characteristically seen as solitary or multiple circumscribed or oval masses on imaging. Detection of antibody directed against specific echinococcal antigens is found in only approximately half of patients with pulmonary cysts. Surgical excision of the cyst is the treatment of choice whenever feasible.

Animals↗
PubMed2003

Dual infection with Streptococcus pneumoniae and Mycobacterium tuberculosis in HIV-seropositive patients with community acquired pneumonia.

Pulmonary infections with more than one organism are common in human immunodeficiency virus (HIV) seropositive patients. We describe nine cases of dual infection with Streptococcus pneumoniae and Mycobacterium tuberculosis in HIV-seropositive patients presenting with community acquired pneumonia (CAP). It is important to exclude pulmonary tuberculosis in HIV-seropositive patients with CAP who fail to respond appropriately to initial antibiotic therapy, even if another etiological pathogen has been found.

AIDS-Related Opportunistic Infections↗
PubMed2002

Surveillance of resistance in bacteria causing community-acquired respiratory tract infections.

Bacterial resistance to antibiotics in community-acquired respiratory tract infections is a serious problem and is increasing in prevalence world-wide at an alarming rate. Streptococcus pneumoniae, one of the main organisms implicated in respiratory tract infections, has developed multiple resistance mechanisms to combat the effects of most commonly used classes of antibiotics, particularly the beta-lactams (penicillin, aminopenicillins and cephalosporins) and macrolides. Furthermore, multidrug-resistant strains of S. pneumoniae have spread to all regions of the world, often via resistant genetic clones. A similar spread of resistance has been reported for other major respiratory tract pathogens, including Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. To develop and support resistance control strategies it is imperative to obtain accurate data on the prevalence, geographic distribution and antibiotic susceptibility of respiratory tract pathogens and how this relates to antibiotic prescribing patterns. In recent years, significant progress has been made in developing longitudinal national and international surveillance programs to monitor antibiotic resistance, such that the prevalence of resistance and underlying trends over time are now well documented for most parts of Europe, and many parts of Asia and the Americas. However, resistance surveillance data from parts of the developing world (regions of Central America, Africa, Asia and Central/Eastern Europe) remain poor. The quantity and quality of surveillance data is very heterogeneous; thus there is a clear need to standardize or validate the data collection, analysis and interpretative criteria used across studies. If disseminated effectively these data can be used to guide empiric antibiotic therapy, and to support-and monitor the impact of-interventions on antibiotic resistance.

Africa↗
PubMed2002

The effects of pneumolysin and hydrogen peroxide, alone and in combination, on human ciliated epithelium in vitro.

We have investigated the effects of pneumolysin and H2O2, putative virulence factors of Streptococcus pneumoniae, on the ciliary beat frequency and structural integrity of human ciliated epithelium in vitro. Human ciliated epithelium was obtained by brushing the inferior nasal turbinate of healthy human volunteers. Ciliary slowing (CS) was measured using a photo-transistor technique and epithelial damage (ED) was documented using a visual scoring index. Effects of recombinant pneumolysin (100 ng/ml), a mutant pneumolysin preparation with markedly reduced haemolytic activity (100 ng/ml) and reagent H2O2 (100 microM) were measured alone and in combination, in the absence and presence of catalase (1000 units/ml). When used individually, both recombinant pneumolysin and H2O2 caused significant (P < 0.05) CS and ED. The effects of H2O2 but not those of pneumolysin were almost completely attenuated by catalase, while the mutant pneumolysin preparation did not cause significant CS or ED. When used in combination, the effects of pneumolysin and H2O2 on CS and ED were additive as opposed to synergistic. These actions of pneumolysin and H2O2 may contribute to the pathogenesis of respiratory tract infections caused by the pneumococcus.

Bacterial Proteins↗
PubMed2001

Proinflammatory interactions of pneumolysin with human neutrophils.

The effects of pneumolysin on the proinflammatory activity of human neutrophils, as well as on cation fluxes in these cells, have been investigated. Superoxide production, release of elastase, CR3 expression, phospholipase A2 activity, and alterations in membrane potential were measured by use of lucigenin-enhanced chemiluminescence and colorimetric, flow cytometric, radiometric, and spectrofluorimetric procedures, respectively; and cation fluxes were measured by use of 45Ca2+ and 86Rb+ and by fura-2 spectrofluorometry. Pneumolysin at concentrations >1.67 ng/mL caused influx of Ca2+ and increased phospholipase A2 activity and CR3 expression, which were associated with enhanced superoxide production and release of elastase after activation of the cells with the chemotactic tripeptide FMLP. At the same concentrations, pneumolysin caused efflux of K+ and membrane depolarization. The effects of pneumolysin on cation fluxes were not attributable to inhibition of Ca2+-adenosine triphosphatase (ATPase) or Na+, K+-ATPase. Pneumolysin potentiates the proinflammatory activities of neutrophils by a pore-forming mechanism resulting in Ca2+ influx.

Adenosine Triphosphate↗
PubMed2001

Pneumonia in the elderly.

Pneumonia, including community-acquired, LTCF-acquired, and nosocomial infections, is a major cause of morbidity and mortality among the elderly. The aged with pneumonia often present with atypical features, including confusion, lethargy, and general deterioration of condition (silent infection). Further investigations, such as a chest radiograph frequently are required for diagnosis. The chest radiograph may be normal early on in the course of infection, particularly in dehydrated patients. The elderly are hospitalized more frequently for pneumonia, have a greater need for intravenous therapy, have a longer hospital stay, have a more prolonged course, have greater morbidity, and ultimately have a poorer outcome. Nevertheless, it may not be chronologic age per se that has a negative impact on the manifestations and outcome of pneumonia in the elderly, but rather the presence of underlying comorbid illness. The mainstay of therapy for pneumonia is antibiotics, and studies in the community and hospital have confirmed the important positive impact of early appropriate empiric therapy on outcome. Many relatively simple procedures, including attention to nutrition, influenza and pneumococcal vaccination, and avoidance of intubation, may help limit the occurrence of such infections.

Age Distribution↗
PubMed2001

An open, randomised, multi-centre study comparing the safety and efficacy of sitafloxacin and imipenem/cilastatin in the intravenous treatment of hospitalised patients with pneumonia.

This was a phase II, randomised, open-label, multi-centre study to assess the safety, tolerability, and efficacy of sitafloxacin (DU-6859a, 400 mg once daily) compared with imipenem (imipenem/cilastatin, 500 mg three times daily) in the treatment of hospitalised patients with pneumonia. Patients (n=69) were entered into the study in the intent-to-treat group, 35 in the sitafloxacin and 34 in the imipenem group. Patients (n=65) were included in the clinically evaluable population and 42 in the bacteriologically evaluable population. Baseline demographic data and clinical characteristics were similar for both treatment groups and across all patient populations. The incidence, severity and type of adverse events were similar in both treatment groups. The frequency of adverse events, which were considered to be related to the study of drugs was low and generally similar between the two groups. Mild transient increases in alanine aminotransferase and alkaline phosphatase occurred in the sitafloxacin treatment group, but there were no apparent trends in the other serum enzyme levels. The clinical response at the first and second follow-up assessments indicated that 94-97% of patients in the clinically evaluable population and 91% of patients in the intent-to-treat population were classified as cured in both treatment groups. The bacteriological response was classified as satisfactory for all patients (100%) in the bacteriologically evaluable population in the imipenem treatment group and satisfactory for 90 and 95% of cases at the first and second follow-up assessments in the bacteriologically evaluable population in the sitafloxacin treatment group, respectively. In conclusion, for the treatment of pneumonia, sitafloxacin was considered as safe and as tolerable as imipenem and preliminary data from this study suggest that it may have similar efficacy.

Adolescent↗
PubMed2001

Prognostic factors in severe community-acquired pneumonia in patients without co-morbid illness.

OBJECTIVES: We wished to determine the prognostic factors and the impact of initial empirical antibiotic therapy on the outcome of severe community-acquired pneumonia in patients without underlying co-morbid illness. METHODOLOGY: This is a retrospective record review of consecutive patients with severe community-acquired pneumonia who were divided into those with and without underlying co-morbid illness. RESULTS: There were 182 patients including 112 primary (no co-morbid illness) and 70 secondary (underlying co-morbid illness) pneumonias. The overall mortality was 41.8% and there were no differences in APACHE II score or mortality when comparing cases with primary (37.5%) and secondary infections (48.6%). The mortality was significantly higher in patients with negative microbiology. Univariate analysis identified a number of parameters and various antibiotic regimens, which appeared to be associated with a significantly poorer outcome. On multivariate analysis multilobar pulmonary consolidation, need for mechanical ventilation, inotropes and dialysis were documented to be independent predictors of mortality. Only in their absence could different antibiotic regimens be shown to have an apparent impact on outcome and further analysis suggested that the reason for these differences related predominantly to differences in the severity of the infection. CONCLUSIONS: Markers of disease severity appear to be the most important predictors of outcome in patients with severe community-acquired pneumonia.

APACHE↗
PubMed2001

Streptococcus pneumoniae respiratory tract infections.

This review describes recent contributions to our understanding of pneumococcal pneumonia. Two genes have been described that encode enzymes involved with the biosynthesis of muropeptides. These enzymes may be novel antibiotic targets. The clinical impact of increasing antibiotic resistance on the treatment of pneumonia is the particular focus of the review. As resistant strains are more commonly associated with severe infections in patients with underlying disease, the interpretation of an association of resistance with poor clinical outcome is complicated.

Aged↗
PubMed2001

Vitamin E attenuates the injurious effects of bioactive phospholipids on human ciliated epithelium in vitro.

Bioactive phospholipids (PL), particularly lysophosphatidylcholine (LPC), are being increasingly implicated in the pathogenesis of various acute and chronic inflammatory disorders, particularly those of the airways, while there is emerging evidence that vitamin E may function as a natural antagonist of these lipid mediators of inflammation. The aims of this study were to document the effects of vitamin E on the inhibition of ciliary beating and damage to structural integrity of human ciliated epithelium induced by the PL, platelet-activating factor (PAF), lyso-PAF and LPC in vitro in relation to the anti-oxidative and membrane-stabilizing properties of the vitamin. Ciliary beat frequency was measured by a phototransistor technique, and damage to structural integrity assessed by a visual-scoring index, while superoxide production by polymorphonuclear leukocytes and membrane-stabilizing potential were measured using lucigenin-enhanced chemiluminescence and haemolytic procedures, respectively. All three PL caused inhibition of ciliary beating and structural damage to human ciliated epithelium by membrane-directed cytotoxic mechanisms, which were potentiated by human polymorphonuclear leukocytes due to induction of oxidant-mediated injury. Both direct and phagocyte-inflicted epithelial injury was attenuated by vitamin E. In haemolytic and chemiluminescence assays, vitamin E neutralized both the membrane-destabilizing and pro-oxidative actions of all three PL, while spectrophotometric analysis of mixtures of vitamin E with PAF, lyso-PAF and LPC revealed alterations in peak intensity, as well as peak shifts, indicative of physicochemical interactions between the vitamin and the PL. Vitamin E status may be a determinant of susceptibility to phospholipid-mediated airway inflammation and damage.

Cells, Cultured↗
PubMed2000

CGS 21680, dibutyryl cyclic AMP and rolipram attenuate the pro-inflammatory interactions of the Pseudomonas aeruginosa -derived pigment, 1-hydroxyphenazine, with human neutrophils.

The effects of the intracellular adenosine 3':5' cyclic monophosphate (cAMP)-elevating agents, CGS 21680 (0.01- 1 microM) and rolipram (0.01-1 microM), as well as those of dibutyryl cAMP (0. 05-4 mM) on the pro-inflammatory interactions of the P. aeruginosa -derived pigment, 1-hydroxyphenazine (1-hp, 3.1 and 12.5 microM), with human neutrophils have been investigated in vitro. Ca(2+)fluxes in FMLP-activated neutrophils were measured using a fura-2/AM spectrofluorimetric procedure, while a colourimetric method was used to measure release of the primary granule enzyme, elastase, from the cells. Treatment with 1-hp resulted in delayed clearance of Ca(2+)from the cytosol of N -formyl- L -methionyl- L -leucyl- L -phenylalanine (FMLP, 1 microM)-activated neutrophils and increased release of elastase. All 3 test agents caused dose-related antagonism of 1-hp-mediated potentiation of elastase release from activated neutrophils, which was associated with restoration of Ca(2+)homeostasis. These observations demonstrate the potential of cAMP-elevating agents, acting on Ca(2+)clearance mechanisms in activated neutrophils, to attenuate the potentially harmful pro-inflammatory effects of 1-hp.

Adenosine↗
PubMed2000

Investigation of the anti-inflammatory and membrane-stabilizing potential of spiramycin in vitro.

The effects of the 16-member macrolide spiramycin (2.5-80 mg/L) and the 14-member agent clarithromycin on the production of superoxide by activated human neutrophils were compared in vitro and related to membrane-stabilizing activity. Superoxide production was measured by lucigenin-enhanced chemiluminescence with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (1 microM) as the stimulus, and membrane-stabilizing activity was measured by a haemolytic procedure. Clarithromycin, but not spiramycin, caused dose-related inhibition of superoxide production by activated neutrophils and also protected erythrocytes against haemolysis, while spiramycin possessed only weak membrane-stabilizing activity. These observations underscore the apparent association between the anti-inflammatory and membrane-stabilizing properties of macrolides.

Adult↗
PubMed2000

Detection of coronary artery disease based on the calcification index obtained by helical computed tomography.

OBJECTIVE: To assess the relation between coronary artery disease and the calcification index on helical computed tomography. METHOD: We studied 22 patients (ages ranging from 40 to 70 years) who underwent coronary angiography because of chest pain suggestive of angina pectoris. Findings on coronary angiography were classified as follows: significant obstructive disease (stenosis > or = 50 %), nonobstructive disease (stenosis <50 %), and no disease. With no previous knowledge of the results of the coronary angiography and within 7 days, helical computed tomography of the chest was performed. Then, data of the coronary angiography were correlated with the calcification index obtained by helical computed tomography. RESULTS: The sensitivity of helical computed tomography to the presence of significant obstructive lesions on coronary angiography was 87.5 %, specificity was 100 %, and negative and positive predictive values were 75 % and 100 %, respectively. The mean calcification index was greater in patients with severe coronary lesions, mainly when involvement of 2 or 3 vessels occurred, than that in patients with no coronary artery disease or with nonobstructive coronary artery lesions (p<0.05). CONCLUSION: Helical computed tomography is an effective method for detecting and quantifying coronary artery calcification, and it has proved to be sensitive to and specific for the noninvasive diagnosis of coronary artery stenosis.

Adult↗
PubMed2000

Guideline for the management of chronic asthma in adults--2000 update. South African Pulmonology Society Adult Asthma Working Group.

OBJECTIVE: To make recommendations for the cost-effective management of asthma incorporating recent advances in the understanding and treatment of asthma since the last guideline statement in 1992. The guideline is applicable to adults and children over 12 years of age. OPTIONS: Asthma should be graded according to standard severity criteria. The principle of 'hit early, hit hard' with corticosteroids to achieve rapid control is encouraged; thereafter treatment should be tailed down to the lowest dose of corticosteroids that maintains the aims of asthma treatment. OUTCOMES: The aims of asthma management should be achieved; these include: (i) avoidance of causative and trigger factors; (ii) abolition of symptoms and ability to lead a normal lifestyle; (iii) restoration of normal (or best possible) lung function; (iv) reduction of the risk of severe attacks; and (v) optimisation of treatment with minimal side-effects. EVIDENCE: Based on a selective review of randomised, controlled studies to support an evidence-based approach to treatment. BENEFITS, HARMS AND COSTS: Appropriate management of asthma should lead to a reduction in morbidity and mortality of asthma and a consequent reduction in cost of asthma care. Side-effects of corticosteroids are placed in perspective together with a strategy to minimise these effects. RECOMMENDATIONS: Asthma should be managed with inhaled corticosteroids as the most important anti-inflammatory treatment, except in the case of mild intermittent asthma which may be treated with beta 2 agonists on a pro re nata (prn) basis. It is preferable to add long-acting beta 2 agonists to low-dose inhaled corticosteroids before increasing corticosteroids. Leukotriene receptor antagonists are currently recommended for use in combination with inhaled corticosteroids pending further data on their long-term benefits. Differentiation of asthma from chronic obstructive pulmonary disease (COPD) is important. Early referral to a pulmonologist in difficult cases is encouraged. VALIDATION: Endorsed by the South African Pulmonology Society, the Allergy Society of South Africa and the South African Medical Association. The guideline is compatible with those of other international societies.

Adrenal Cortex Hormones↗
PubMed1999

The ketolide antimicrobial agent HMR-3004 inhibits neutrophil superoxide production by a membrane-stabilizing mechanism.

We have investigated the membrane-stabilizing potential of the prototype ketolide antimicrobial agent, HMR-3004 (3.75-125 microM), as well as the effects of this agent on the production of superoxide by human neutrophils activated with FMLP, the calcium ionophore A23187, phorbol 12-myristate 13-acetate (PMA) or opsonized zymosan (OZ), each of which uses different transductional mechanisms to activate NADPH-oxidase. Membrane-stabilizing activity was investigated using a hemolytic procedure, while superoxide production was assayed by lucigenin-enhanced chemiluminescence. At concentrations of 3.75 microM and greater, HMR-3004 caused dose-related inhibition of superoxide production by neutrophils activated by all four stimuli of membrane-associated oxidative metabolism, which was not associated with cytotoxicity or superoxide-scavenging activity. At the same concentrations, HMR-3004 antagonized the hemolytic actions of the membrane-disruptive bioactive phospholipids, lysophosphatidylcholine (LPC), platelet-activating factor (PAF) and lyso-PAF. A mechanistic relationship between the membrane-stabilizing and the anti-oxidative properties of HMR-3004 was suggested by the observation that treatment of neutrophils with non-cytolytic concentrations of LPC antagonized the inhibitory effects of the ketolide on superoxide production by these cells. These membrane-stabilizing, anti-oxidative activities of HMR-3004 suggest that in addition to its antimicrobial properties, this agent possesses anti-inflammatory properties which are superior to those of the presently available macrolide and azalide agents.

Adult↗