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Biomedical subjects

C Feldman

Publications and source records attributed to C Feldman.

At least 55 records · Page 3Linked to original sources
PubMed1999

Bacteremic pneumococcal pneumonia in HIV-seropositive and HIV-seronegative adults.

STUDY OBJECTIVES: To compare the demographic, clinical, laboratory, and microbiological data, and the hospital course and outcome of HIV-seropositive and HIV-seronegative adults with bacteremic pneumococcal pneumonia. DESIGN: Retrospective observation study conducted over a 2-year period. SETTING: Academic teaching hospital attached to the University of the Witwatersrand, Johannesburg, South Africa. PATIENTS: Consecutive patients with bacteremic pneumococcal pneumonia were identified on the basis of positive blood culture results. INTERVENTIONS: All available demographic, clinical, routine laboratory, radiographic, and microbiological data were recorded retrospectively for each of the patients, and the combined data for the HIV-seropositive patients were compared with those of the HIV-seronegative patients. MEASUREMENT AND RESULTS: A total of 112 patients (31 HIV-seropositive and 81 HIV-seronegative patients) were entered into the study. The HIV-seropositive patients were significantly younger than the HIV-seronegative patients (32.8 vs 39.6 years old) and had lower admission hemoglobin (11.8 vs 13.4 g/dL), WBC count (10.3 vs 14.3 x 10(9)/L), serum albumin (31 vs 36 g/L), sodium (129 vs 132 mmol/L), and potassium (3.0 vs 3.5 mmol/L), respectively. Although the HIV-seropositive patients appeared to have more multilobar pulmonary consolidation on the chest radiograph than the HIV-seronegative patients (60% vs 34%), this did not quite reach statistical significance. In addition, the HIV-seropositive patients had significantly more infections (48.4% vs 20.8%) with pneumococcal serogroups/serotypes (serogroups 6, 19, 23, and serotype 14) that are found more commonly in children, and they also had more penicillin-resistant isolates (13% vs 2.5%) than the HIV-seronegative patients, respectively. Similarly, it was noted that when these data were analyzed according to gender (irrespective of HIV status), women had significantly more infections than men (47% vs 21%) with serogroups/serotypes that are usually found in children, more penicillin-resistant isolates (15% vs 1%), and more co-trimoxazole-resistant isolates (21% vs 5%), respectively. There were no differences noted in any of the other parameters, including initial APACHE (acute physiology and chronic health evaluation) II score, PaO2/fraction of inspired oxygen ratio, duration of temperature, duration of IV therapy, duration of hospitalization, complications, and outcome, when comparing HIV-seropositive and HIV-seronegative patients. Two patients in each group died. CONCLUSIONS: The clinical features of bacteremic pneumococcal pneumonia are similar in HIV-seropositive and HIV-seronegative patients. Although differences are noted in various laboratory and microbiological parameters, they do not appear to have an impact on outcome.

APACHE↗
PubMed1999

Penicillin- and cephalosporin-resistant Streptococcus pneumoniae. Emerging treatment for an emerging problem.

The global emergence of pneumococci resistant to antimicrobial therapy has led to dilemmas in the management of pneumococcal infections. The principles of pharmacodynamics predict that penicillin and cephalosporin therapy of pneumonia will be successful against pneumococci with minimum inhibitory concentrations of penicillin up to 4 micrograms/ml. These predictions are supported by the observations of a number of recent clinical studies. Otitis media therapy is influenced by penicillin-resistance and current recommendations are that amoxicillin is the drug of choice for this infection, given at a double dose of 80 to 90 mg/kg/day. For the therapy of meningitis, cefotaxime or ceftriaxone in maximal doses is recommended and vancomycin may be added if cephalosporin-resistant strains are encountered with reasonable frequency in the population. The new fluoroquinolones with excellent antipneumococcal activity may be considered for use in the setting of pneumonia caused by highly resistant pneumococci and are under evaluation for the management of meningitis.

Cephalosporin Resistance↗
PubMed1999

Pneumocystis carinii pneumonia in HIV infected patients from South Africa.

OBJECTIVE: To compare the spectrum of pulmonary disease in human immunodeficiency virus positive patients of African and European origin, with particular reference to Pneumocystis carinii pneumonia. DESIGN: Descriptive study with retrospective record review. SETTING: Tertiary care, university teaching hospitals in Johannesburg, South Africa. SUBJECTS: Sixty seven HIV-infected patients and 36 HIV-negative renal transplant patients (who served as controls) whose sputa were negative for tuberculosis and Pneumocystis carinii, and who had fibreoptic bronchoscopic evaluation for pulmonary disease between January 1985 and August 1992. MEASUREMENTS: Histological and cytological evaluation of pulmonary diseases. RESULTS: In the HIV infected group Pneumocystis carinii pneumonia was the most frequent disease in patients of both African and European origin but occurred less commonly in Africans than in Europeans (27.3% and 58.8%, respectively; p = 0.01). There was no statistically significant difference between patients of African and European origin in the frequency of any other diagnosis. In the renal transplant group the most frequent diagnosis was non-specific interstitial pneumonitis (Africans 33.3%, Europeans 37.0%), followed by Pneumocystis carinii pneumonia (Africans 22.2%, European 14.8%). There was no difference between HIV-infected and renal transplant patients in the frequency of any diagnosis. CONCLUSION: Pneumocystis carinii pneumonia should be considered in the diagnosis of HIV-infected African patients with pulmonary disease whose sputum smears for tuberculosis are negative.

AIDS-Related Opportunistic Infections↗
PubMed1998

Anti-oxidative effects of theophylline on human neutrophils involve cyclic nucleotides and protein kinase A.

The effects were studied of the non-specific phosphodiesterase inhibitor, theophylline (37.5-300 microM), on intracellular levels of cyclic adenosine monophosphate (cAMP) and superoxide generation following exposure of human neutrophils to four different stimuli of neutrophil membrane-associated oxidative metabolism, each of which utilizes a different transductional mechanism to activate NADPH-oxidase, in vitro. Exposure of neutrophils to FMLP (1 microM), the calcium ionophore A23187 (1 microM), and opsonized zymosan (OZ, 0.5 mg/ml) was accompanied by activation of superoxide production and increased concentrations of intracellular cAMP. Inclusion of theophylline resulted in augmentation of cAMP and inhibition of superoxide production by these stimuli. These negative effects of theophylline on neutrophil superoxide generation were mimicked by dibutyryl cAMP and 8-bromo-cGMP, while the inhibitory activity of all 3 agents was antagonized by the protein kinase A inhibitor KT 5720, but not by the G-kinase inhibitor KT 5823. Unlike FMLP, OZ and A23187, intracellular cAMP levels did not increase in cells activated with phorbol-12-myristate-13-acetate (PMA, 25 ng/ml), while oxidant production activated by this stimulus was insensitive to the inhibitory effects of theophylline. These observations suggest that the beneficial, anti-inflammatory interactions of theophylline with human neutrophils are related to the phosphodiesterase inhibitory properties of this agent, and are selective for those pro-inflammatory stimuli which elevate cAMP, resulting in enhanced activity of protein kinase A and inhibition of the production of potentially harmful reactive oxidants by these cells.

Alkaloids↗
PubMed1998

Effect of rolipram and dibutyryl cyclic AMP on resequestration of cytosolic calcium in FMLP-activated human neutrophils.

1. We have investigated the effects of the selective phosphodiesterase (PDE) type 4 inhibitor, rolipram (0.01-1 microM) on cytosolic Ca2+ fluxes in FMLP-activated human neutrophils, as well as on superoxide production by, and release of elastase from, these cells. 2. Cytosolic Ca2+ fluxes were measured by use of fura-2 spectrofluorimetry in combination with a radiometric procedure that enables distinction between net efflux and influx of the cation. Superoxide production and elastase release were measured by lucigenin-enhanced chemiluminescence and a colorimetric procedure, respectively. 3. Pretreatment of neutrophils with rolipram did not affect the FMLP-activated release of Ca2+ from intracellular stores, but was associated with dose-related acceleration of the rate of decline in fura-2 fluorescence and with decreased efflux, as well as store-operated influx of 45Ca2+, indicative of enhancement of resequestration of the cation by the endo-membrane Ca2+-ATPase. 4. Inhibition of superoxide production and elastase release was observed at concentrations of rolipram which accelerated the clearance of Ca2+ from the cytosol of FMLP-activated neutrophils. 5. These effects of rolipram on FMLP-activated Ca2+ fluxes, superoxide generation and elastase release were mimicked by pretreatment of neutrophils with dibutyryl cyclic AMP (0.5-4 mM), while theophylline (10-150 microM), a non-specific PDE inhibitor, as well as the beta2-agonist, salbutamol, were less effective. 6. We conclude that rolipram deactivates FMLP-stimulated human neutrophils by enhancement of cyclic AMP-dependent resequestration of cytosolic Ca2+.

Adrenergic beta-Agonists↗
PubMed1998

Effect of dirithromycin on Haemophilus influenzae infection of the respiratory mucosa.

Macrolides have properties other than their antibiotic action which may benefit patients with airway infections. We have investigated the effect of dirithromycin (0.125 to 8.0 microg/ml) on the interaction of Haemophilus influenzae with respiratory mucosa in vitro using human nasal epithelium, adenoid tissue, and bovine trachea. Dirithromycin did not affect the ciliary beat frequency of the nasal epithelium or the transport of mucus on bovine trachea, but dirithromycin (1 microg/ml) did reduce the slowing of the ciliary beat frequency and the damage to the nasal epithelium caused by H. influenzae broth culture filtrate. Amoxicillin (2 microg/ml) did not reduce the effects of the H. influenzae broth culture filtrate. H. influenzae infection of the organ cultures for 24 h caused mucosal damage and the loss of ciliated cells. Bacteria adhered to damaged epithelium and to a lesser extent to mucus and unciliated cells. Incubation of H. influenzae with dirithromycin at sub-MICs (0.125 and 0.5 microg/ml) prior to infection of the organ cultures did not reduce the mucosal damage caused by bacterial infection. By contrast, incubation of adenoid tissue with dirithromycin (0.125 to 1.0 microg/ml) for 4 h prior to assembling the organ culture reduced the mucosal damage caused by subsequent H. influenzae infection by as much as 50%. The number of bacteria adherent to the mucosa was reduced, although the tissue that had been incubated with dirithromycin (0.125 and 0.5 microg/ml) did not inhibit bacterial growth. This was achieved by a reduction in the amount of damaged epithelium to which H. influenzae adhered and a reduction in the density of bacteria adhering to mucus. We conclude that dirithromycin at concentrations achievable in vivo markedly reduces the mucosal damage caused by H. influenzae infection due to a cytoprotective effect.

Amoxicillin↗
PubMed1998

Influence of antimicrobial chemotherapy on spirometric parameters and pro-inflammatory indices in severe pulmonary tuberculosis.

Patients who have completed a treatment for severe pulmonary tuberculosis (TB) are often left with severe respiratory disability. There have been few prospective studies assessing the effect of treatment on lung function in such patients. The influence of antimicrobial chemotherapy on lung function was investigated over a six month period in patients with newly diagnosed pulmonary TB to test the hypothesis that treatment improves lung function, as well as to identify factors that may influence lung function outcome. Seventy-six patients were recruited into the study, of whom 74 completed the treatment programme. Forty-two were current smokers and 13 seropositive for the human immunodeficiency virus. Improvement in lung function occurred in 54% of patients, but residual airflow limitation or a restrictive pattern was evident in 28% and 24% of patients, respectively. The extent of lung infiltration (radiographic score) both at the outset and after chemotherapy was significantly and negatively related to forced expiratory volume in one second (FEV1) (% pred) (r=-0.41, and r=-0.46, respectively). The post-treatment serum C-reactive protein and alpha1-protease inhibitor levels were negatively associated with FEV1 (% pred) (r=-0.30 and r=-0.35, respectively). These findings demonstrate that, while antimicrobial chemotherapy may lead to improved lung function in patients with pulmonary tuberculosis, a large proportion of patients has residual impairment. The most significant factor influencing post-treatment lung function status, as measured by forced expiratory volume in one second (% predicted), is the pretreatment and post-treatment radiographic score, which acts as a marker of the extent of pulmonary parenchymal involvement in tuberculosis.

Adult↗
PubMed1997

Roxithromycin, clarithromycin, and azithromycin attenuate the injurious effects of bioactive phospholipids on human respiratory epithelium in vitro.

The effects of the bioactive phospholipids (PL), platelet-activating factor (PAF), lyso-PAF, and lysophosphatidylcholine (LPC) on the beat frequency and structural integrity of human ciliated respiratory epithelium were studied in vitro, in the presence or absence of polymorphonuclear leukocytes (PMNL), the antimicrobial agents, roxithromycin, clarithromycin, and azithromycin and the antioxidative enzymes catalase and superoxide dismutase (SOD). All three PL caused dose-dependent slowing of ciliary beat frequency (CBF) and epithelial damage (ED) at concentrations > or = 1 microgram/ml, which were unaffected by inclusion of the antimicrobial agents and antioxidative enzymes. When epithelial strips were exposed to the combination of PMNL and PL, there was significant potentiation of ciliary dysfunction and ED, which was ameliorated by pretreatment of the PMNL with the antimicrobial agents or by inclusion of catalase, but not SOD. These results demonstrate that LPC, PAF, and lyso-PAF cause epithelial damage by direct mechanisms which are oxidant-independent, as well as by indirect mechanisms involving phagocyte-derived reactive oxidants. Macrolides and azalide antimicrobial agents may have beneficial effects on airway inflammation in asthma and microbial infections by protecting ciliated epithelium against oxidative damage inflicted by PL-sensitized phagocytes.

Anti-Bacterial Agents↗
PubMed1997

Severe community-acquired pneumonia.

Severe community-acquired pneumonia is now considered a separate clinical entity that is important to recognize, particularly because of its high mortality rate. This article reviews several of the studies published in the past year that focus on risk and prognostic factors, etiology, diagnostic evaluation, pathogenesis, and therapy of this important condition.

Community-Acquired Infections↗
PubMed1997

Differences in the prevalence of a TaqI RFLP in the 3' flanking region of the alpha 1-proteinase inhibitor gene between asthmatic and non-asthmatic black and white South Africans.

The prevalence of the Taq I(-) allele in variants of alpha 1-proteinase inhibitor (alpha 1PI) was investigated in a group of 28 black asthmatic patients and 32 black control individuals, and was compared to 43 white asthmatic patients and 32 white control individuals. The plasma concentration of alpha 1PI was determined in eight black and 14 white asthmatics without the Taq I(-) allele, and compared to seven black and three white asthmatics with the Taq I(-) allele. Alpha-1-PI concentration was also determined in 10 black and 29 white control individuals without the Taq I(-) allele and compared to seven black and three white controls with the Taq I(-) allele. There was a highly significant difference in the frequency of the Taq I(-) allele between black South Africans (24.1%) and white South Africans (6%) (p < 0.00001) and a significant difference in the frequency of the Taq I(-) allele between black asthmatics and white asthmatics (p = 0.0004) and between black controls and white controls (p = 0.011). The Taq I(-) allele was significantly associated with the M1 (Val213) variant as compared to the M1 (Ala213) of alpha 1PI (p = 0.0042). There was no difference in the concentration of alpha 1PI between the asthmatics (black and white) lacking the Taq I(-) allele and the asthmatics (black and white) with the allele. However, a significant increase in plasma alpha 1PI concentration was found in the asthmatics compared to the controls (p = 0.011). The Taq I(-) allele did not seem to interfere with the basal expression of alpha 1PI in the groups of asthmatic patients in this study.

Adolescent↗
PubMed1996

Membrane-stabilizing, anti-inflammatory interactions of macrolides with human neutrophils.

The effects of the macrolide antimicrobial agents azithromycin, clarithromycin, erythromycin and roxithromycin on the prooxidative activity of stimulated human neutrophils have been investigated in vitro. Superoxide generation by activated neutrophils was measured by lucigenin-enhanced chemiluminescence. At the concentrations used (2.5-80 micrograms/ml) none of the test agents was cytotoxic, nor did they possess superoxide-scavenging properties. Treatment of neutrophils with all 4 macrolides was accompanied by dose-related inhibition of superoxide production by cells activated with FMLP or the calcium ionophore (A23187), while the responses activated by phorbol myristate acetate (PMA) or opsonized zymosan were minimally affected. The anti-oxidative interactions of roxithromycin with FMLP-activated neutrophils were neutralized by pretreatment of the cells with low, non-cytotoxic concentrations (0.5 microgram/ml) of the prooxidative, proinflammatory bioactive phospholipids, lysophosphatidylcholine (LPC), platelet-activating factor (PAF) and lyso-PAF (LPAF). Using an assay of membrane-stabilizing activity, the macrolides antagonized the membrane-disruptive effects of LPC, PAF and LPAF, without affecting enzymes involved in their synthesis. These membrane-stabilizing interactions of macrolides with neutrophils may counteract the proinflammatory, prooxidative activity of several bioactive lipids which have been implicated in the pathogenesis of bronchial asthma.

Adult↗
PubMed1996

Study of critically ill patients with systemic lupus erythematosus.

OBJECTIVES: To determine the presenting features, prognostic factors, course, and outcome of critically ill patients with systemic lupus erythematosus admitted to the intensive care unit (ICU). DESIGN: Retrospective patient record review. SETTING: Two academic teaching hospitals. PATIENTS: All patients with systemic lupus erythematosus admitted to the ICUs between January 1982 and July 1993. MEASUREMENTS AND MAIN RESULTS: There were 28 female and two male patients. Fifteen patients were white, 11 patients were black, and four patients were Asian. The median age was 29 yrs. The reasons for admission to the ICU were multifactorial. However, most patients were admitted for infective, renal, cardiac, or coagulation complications. Despite aggressive management, 16 (53%) patients died in the ICU or shortly after discharge. The median ICU survival rate (admission to death) was 22 days. The only pretreatment factor that predicted a poor outcome was the presence of renal involvement due to systemic lupus erythematosus. CONCLUSIONS: Our study suggests that patients with systemic lupus erythematosus admitted to an ICU often have florid disease manifestations with multifactorial reasons precipitating the admission. The prognosis for such patients is poor, particularly in the presence of renal involvement.

APACHE↗
PubMed1996

Anti-inflammatory, membrane-stabilizing interactions of salmeterol with human neutrophils in vitro.

1. We have investigated the effects of salmeterol (0.3-50 microM) on several pro-inflammatory activities of human neutrophils in vitro. 2. Oxidant production by FMLP- and calcium ionophore (A23187)-activated neutrophils was particularly sensitive to inhibition by low concentrations (0.3-3 microM) of salmeterol, while the responses of phorbol myristate acetate- and opsonised zymosan-stimulated cells were affected only by higher concentrations (3-50 microM) of the drug. At these concentrations salmeterol is not cytotoxic, nor does it act as a scavenger of superoxide. 3. These anti-oxidative interactions of salmeterol with neutrophils were insensitive to propranolol but could be eliminated by washing the cells, or by pretreatment with low concentrations (1-2 microM) of the pro-oxidative, membrane-destabilizing phospholipids, lysophosphatidylcholine (LPC), platelet activating factor (PAF) and lysoPAF (LPAF). 4. At concentrations of 6.25-50 microM salmeterol interfered with several other activities of stimulated neutrophils, including intracellular calcium fluxes, phospholipase A2 activity and synthesis of PAF. 5. In an assay of membrane-stabilizing activity, salmeterol (25 and 50 microM) neutralized the haemolytic action of LPC, PAF and LPAF. 6. Of the other commonly used beta 2-adrenoceptor agonists, fenoterol, and formoterol, but not salbutamol, caused moderate inhibition of neutrophil oxidant generation by a superoxide-scavenging mechanism. However, unlike salmeterol, these agents possessed only weak membrane stabilizing properties. 7. We conclude that salmeterol antagonizes the pro-inflammatory, pro-oxidative activity of several bioactive lipids implicated in the pathogenesis of bronchial asthma, by a mechanism related to the membrane-stabilizing, rather than to the beta 2-agonist properties of this agent.

Adenosine Triphosphate↗
PubMed1996

Cryptococcosis: an unusual cause of endobronchial obstruction.

We report the case of a 43 year old male patient, with normal immune function, who presented with right middle and lower lobe collapse. At bronchoscopy, a white lobulated lesion was seen, completely obstructing the origin of bronchus intermedius. Bronchial washings and biopsy of the lesion demonstrated cryptococcal organisms. The patient responded clinically and radiologically to amphotericin B and flucytosine; however, repeat bronchoscopy revealed only partial resolution of the endobronchial lesion.

Adult↗
PubMed1996

IgG subclasses in previously healthy adult patients with acute community-acquired pneumonia.

OBJECTIVE: To measure IgG antibody subclasses in previously healthy adult patients with acute community-acquired pneumonia, and to assess any association between differences of subtype levels and severity of illness or prognosis. DESIGN: Prospective study. SETTING: The intensive care unit (ICU) and general medical wards of Hillbrow Hospital, Johannesburg, an urban general hospital. PATIENTS: Sixty-six previously healthy adult patients with acute community-acquired pneumonia, of whom 47 were considered less severely ill, while 19 were admitted to an ICU. OUTCOME MEASURES: Measurement of IgG subclass levels and determination of any association between differences in subtype levels and various poor prognostic factors in pneumonia, need for ICU admission, complications of illness, and APACHE II score of ICU cases or outcome of patients. RESULTS: A number of statistically significant differences (P < 0.05) were noted between the two groups of patients (critically ill v. others) representing well-known negative prognostic factors in pneumonia. A greater degree of tachycardia and tachypnoea and extremes of white cell count, a higher serum urea concentration and multilobar pulmonary consolidation characterised the patients in the ICU. In addition, the mortality rate in the ICU patients was significantly greater (P < 0.0001). Similar findings were noted when survivors and non-survivors were compared. Few abnormalities of IgG subclass levels were noted in the various patient groups, which did not allow adequate analysis of their clinical significance. CONCLUSION: This study demonstrated a small number of abnormalities in IgG subclass levels in previously healthy adult patients with acute community-acquired pneumonia.

Acute Disease↗