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Biomedical subjects

T C Sorrell

Publications and source records attributed to T C Sorrell.

At least 55 records · Page 3Linked to original sources
PubMed1994

Subtyping of Mycobacterium avium complex (MAC) isolates by thin-layer chromatography--distribution of subtypes from patients with AIDS compared with clinically non-significant isolates.

Thin-layer chromatography (TLC) was compared with seroagglutination for subtyping of Mycobacterium avium complex (MAC) bacteria. Seventy-five significant MAC isolates from patients with AIDS were typed by both methods and 36 isolates, judged to be clinically non-significant, were examined by TLC only. Overall, 75% of isolates tested were typable by seroagglutination and 91% by TLC; the results correlated between the two except for minor discrepancies. Serovars 1, 8 and 21 and mixed serovars 1-21 and 1-8-21 were common among isolates from AIDS patients and together represented 83% of isolates compared with only 36% in the non-significant group (odds ratio 8.4; 95% confidence interval 3.4-23.3). This difference remained significant after exclusion of serovar 41 (M. scrofulaceum), which was the commonest isolate (28%) in the non-significant group but was not isolated from patients with AIDS. TLC is useful to supplement seroagglutination for subtyping of MAC. Further study is required to determine whether apparent differences between isolates from patients with AIDS and from other sources reflect differences in virulence or in environmental prevalence of MAC subtypes.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Amebic abscess of the spleen complicated by metronidazole-induced neurotoxicity: case report.

We describe a patient with a liver abscess due to Entamoeba histolytica, in whom metronidazole therapy (total dose, 21 g over 14 days) was complicated by reversible deafness, tinnitus, and ataxia and who relapsed 5 months later with a splenic abscess. Two courses of tinidazole (the second in combination with percutaneous aspiration of the abscess) were required to achieve cure.

Adult↗
PubMed1994

Circulating polymorphonuclear leukocytes from patients with gram-negative bacteremia are not primed for enhanced production of leukotriene B4 or 5-hydroxyeicosatetraenoic acid.

The hypothesis was tested that polymorphonuclear leukocytes (PMNL) from patients with gram-negative bacteremia are primed to produce leukotriene B4 (LTB4) or 5-hydroxyeicosatetraenoic acid (5-HETE), in response to concentrations of calcium ionophore A23187, which are substimulatory for control PMNL. PMNL from 11 bacteremic patients and 8 healthy subjects (11 samples) produced similar quantities of LTB4, omega-oxidation products of LTB4, and 5-HETE after incubation with 0.3 and 0.5 microM A23187 for 5 min. At the detection threshold of 0.3 microM A23187, LTB4 was present in PMNL preparations from 9 of 11 patients and 7 of 11 control samples and 5-HETE from the same 9 patients and from 6 controls. There was no correlation between LTB4 or 5-HETE and plasma levels of endotoxin. In this group of patients, priming of PMNL by gram-negative bacteremia did not lead to enhanced production of LTB4, its omega-oxidation products, or 5-HETE when PMNL were challenged with low concentrations of A23187.

Adult↗
PubMed1994

Eicosapentaenoic acid modulates neutrophil leukotriene B4 receptor expression in cystic fibrosis.

In patients with cystic fibrosis (CF), high intrapulmonary concentrations of the neutrophil chemotaxin leukotriene B4 (LTB4) are associated with specific reduction of LTB4-induced chemotaxis of circulating neutrophils. The chemotactic abnormality is partially corrected by dietary supplementation with eicosapentaenoic acid (EPA). LTB4-induced neutrophil chemotaxis is mediated by specific, high-affinity, cell surface LTB4 receptors. The hypotheses that neutrophil LTB4 receptors are down-regulated in CF, and that EPA normalizes receptor expression, were tested by measuring the number (Rmax) and affinity (Kd) of LTB4 receptors on neutrophils from eight CF patients before and after EPA (6 weeks of 2.7 g/day), and from nine normal individuals. High-affinity receptor Rmax was depressed in CF patients (0.6 +/- 0.2 x 10(4)/cell (mean +/- s.d.) versus 1.8 +/- 0.7 x 10(4)/cell in normals), but corrected to normal (2.0 +/- 1.9 x 10(4)/cell) after EPA. High-affinity receptor Kd was depressed in CF patients (0.4 +/- 0.3 nM versus 1.4 +/- 0.5 nM in normals), and also corrected to normal with EPA (1.4 +/- 1.2 nM). Low-affinity receptors were depressed, but did not change significantly with EPA. These results indicate that neutrophil responses in chronic inflammatory lung disease can be influenced directly by LTB4 receptor modulation, and that this effect of EPA predominates over alterations in neutrophil signal transduction in situations of chronic exposure to LTB4.

Adolescent↗
PubMed1993

Pseudomonas aeruginosa bacteraemia. Is pancreatobiliary disease a risk factor?

OBJECTIVE: To review changes in the epidemiology, course, and outcome of bacteraemia caused by Pseudomonas aeruginosa. DESIGN AND SETTING: A retrospective, descriptive study of consecutive cases of P. aeruginosa bacteraemia occurring at a university teaching hospital. PATIENTS AND METHODS: Between January 1980 and December 1989, 164 patients were admitted to Westmead Hospital with P. aeruginosa bacteraemia. Patients in whom there was no clinical evidence of sepsis were excluded from analysis leaving a cohort of 152 patients. Hospital records were reviewed and details of demography, clinical features, therapy, and outcome were recorded. RESULTS: One hundred and fifty-five episodes of P. aeruginosa bacteraemia were recorded at an average rate of 0.39 per 1000 admissions per year. The respiratory and pancreatobiliary tracts were the most common sources of the bacteraemia. Pancreatobiliary disease, independent of an underlying malignancy or immunosuppression, emerged as a previously undescribed risk factor for pseudomonal bacteraemia (incidence of 3.0 episodes per 1000 hospital admissions for patients with this disease). The crude mortality rate was 52%; 35% was attributable to pseudomonal bacteraemia. Factors identified as being independently associated with an increased mortality included hypotension, age of 60 years or older, and the presence of an underlying malignancy. Combination therapy with an antipseudomonal penicillin and an aminoglycoside confers a significant survival advantage independent of underlying neutropenia. CONCLUSIONS: Bacteraemia caused by P. aeruginosa remains an important cause of morbidity and mortality. Pancreatobiliary disease represents a new risk factor for P. aeruginosa bacteraemia, independent of an underlying malignancy or immunosuppression. It may be prudent to consider P. aeruginosa as a cause of sepsis in these circumstances, especially if there has been instrumentation of the biliary tree. Hypotension, age of 60 years or older, and the presence of an underlying malignancy were independently associated with significantly increased mortality. Appropriate antibiotic therapy consisting of an antipseudomonal beta-lactam in addition to an aminoglycoside resulted in a significant decrease in mortality compared with the use of an aminoglycoside alone, not only in the study population as a whole, but also in patients without neutropenia.

Adolescent↗
PubMed1993

Proton magnetic resonance spectroscopy of polymorphonuclear leukocytes from patients with serious bacterial infections.

Triacylglycerols in human neutrophils exposed to proinflammatory stimuli generate a high-resolution proton magnetic resonance (1H MR) spectrum. Lipid cross-peak F volumes in neutrophils from patients with inflammatory conditions were measured. Values in patients hospitalized with localized infections (14.4 +/- 9.0; mean +/- SD) or bacteremia (19.3 +/- 9.7) were significantly higher than in patients with noninflammatory conditions (6.2 +/- 5.3) and healthy controls (2.0 +/- 3.0; P < .001). The positive predictive value of F volumes > 10 was 93% for all infection; the negative predictive value of volumes < or = 10 was 68% for all infection and 92% for bacteremia. Plasma lipopolysaccharide (LPS) concentrations were highest in bacteremic patients but did not correlate with levels of tumor necrosis factor-alpha (TNF alpha) or interleukin-6. In vitro, LPS increased F volumes of control neutrophils from 2.0 +/- 3.0 to 37.2 +/- 6.7 (P < .001); TNF alpha had no effect. F volumes in 1H MR spectra may be useful clinically to discriminate between serious bacterial infection and other inflammatory conditions. TNF alpha is not the stimulus for generation of lipid spectra in vivo.

Bacterial Infections↗
PubMed1992

A comparison of hospital and community-acquired infective endocarditis.

The epidemiology, clinical features, microbiology and outcome of 30 episodes of nosocomial endocarditis occurring over a 13-year period were reviewed and compared with 148 cases of community-acquired endocarditis. Twenty-eight patients (93%) had been in hospital for > 1 week and 10 patients (33%) for > 1 month when they developed endocarditis. Left-sided infection was most frequent; only 3 cases involved the tricuspid valve. Compared with community-acquired infection, patients tended to be older, had a greater incidence of congestive cardiac failure (p = 0.001) or hypotension (p = 0.0008) at presentation and were more likely to have bacteremia after an invasive procedure (83 vs 31%; p < 0.00001). Intravascular devices were the presumed source of bacteremia in 11 cases (37%); the same organism was isolated from both the blood and the suspected source of infection. Staphylococcus aureus was the most frequent causative organism, accounting for 17 episodes (57%), including 4 (13%) due to methicillin-resistant strains. Nosocomial endocarditis had a significantly higher mortality than did community-acquired infection (40 vs 18%; p = 0.02). Eight patients (27%) needed valve replacement. Proper adherence to protocols for management of intravascular devices and appropriate antimicrobial prophylaxis before procedures may have prevented endocarditis in 15 of 30 patients.

Adult↗
PubMed1992

GMP-140 (P-selectin) inhibits human neutrophil activation by lipopolysaccharide: analysis by proton magnetic resonance spectroscopy.

Proton magnetic resonance spectroscopy has been used to monitor the effect of GMP-140 on the stimulation of human peripheral blood neutrophils. Stimulation of neutrophils by lipopolysaccharide gives rise to a high resolution lipid spectrum from the intact cells. Fluid phase GMP-140, which prevents adhesion and development of inflammatory responses of neutrophils, was found to inhibit these changes in the lipid spectrum by up to 40%. Anti-GMP-140 Fab fragments reversed this effect while non-immune Fab fragments did not affect the observed inhibition by GMP-140.

Cell Adhesion Molecules↗
PubMed1992

Recombinant interleukin 4 stimulates human immunodeficiency virus production by infected monocytes and macrophages.

Recombinant interleukin 4 (IL-4) stimulated extracellular (EC) and intracellular (IC) production of human immunodeficiency virus (HIV) from infected human blood-derived monocytes and macrophages when incubated with the cells after but not before virus inoculation. Significant stimulation was observed in 20 of 27 experiments with monocytes (inoculated with HIV immediately after adherence) and 10 of 13 experiments with macrophages (inoculated after 5 days adherence) using a total of 30 normal donors of monocytes and macrophages, and 11 recent isolates of monocytotropic HIV strains (after one passage in mononuclear cells). Marked increases in EC and IC HIV antigen were observed in some experiments, which were comparable with the maximal stimulatory effects of other cytokines such as IL-2. IL-4 also had similar effects on infectious HIV concentration as measured by reverse transcriptase and TCID50 assays. Antibody to IL-4 prevented the stimulatory effect of the cytokine. The proportion of monocytes and macrophages infected by HIV, as determined by in situ hybridization, also increased after incubation with IL-4 for 7 days. The most marked effects were observed with HIV-infected macrophages, for which the proportion of unstimulated infected cells was lower (35 to 45% increasing to 66 to 70% with IL-4 treatment). There was also an increased proportion of cells with high granule concentrations, suggesting that IL-4 increases the intracellular concentration of viral nucleic acids. This was supported by semi-quantitative hybridization experiments showing that total HIV RNA increased in IL-4-stimulated monocytes 48 to 96 h after HIV inoculation. A marked increase in aggregates was observed on day 7 in HIV-infected monocytes treated with IL-4, compared to that in HIV-infected cells alone or IL-4-treated uninfected monocytes. These findings suggest that IL-4 stimulates HIV replication in the early phases of infection and may also facilitate virus transmission by aggregate formation.

Base Sequence↗
PubMed1992

Bacterial metabolism of human polymorphonuclear leukocyte-derived arachidonic acid.

Evidence for transcellular bacterial metabolism of phagocyte-derived arachidonic acid was sought by exposing human blood polymorphonuclear leukocytes, prelabelled with [3H]arachidonic acid, to opsonized, stationary-phase Pseudomonas aeruginosa (bacteria-to-phagocyte ratio of 50:1) for 90 min at 37 degrees C. Control leukocytes were stimulated with the calcium ionophore A23187 (5 microM) for 5 min. Radiochromatograms of arachidonic acid metabolites, extracted from A23187-stimulated cultures and then separated by reverse-phase high-performance liquid chromatography, revealed leukotriene B4, its omega-oxidation products, and 5-hydroxy-eicosatetraenoic acid. In contrast, two major metabolite peaks, distinct from known polymorphonuclear leukocyte arachidonic acid products by high-performance liquid chromatography or by thin-layer chromatography, were identified in cultures of P. aeruginosa with [3H]arachidonic acid-labelled polymorphonuclear leukocytes. Respective chromatographic characteristics of these novel products were identical to those of two major metabolite peaks produced by incubation of stationary-phase P. aeruginosa with [3H]arachidonic acid. Production of the metabolites was dependent upon pseudomonal viability. UV spectral data were consistent with a conjugated diene structure. Metabolism of arachidonic acid by P. aeruginosa was not influenced by the presence of catalase, superoxide dismutase, nordihydroguaiaretic acid, ethanol, dimethyl sulfoxide, or ferrous ions but was inhibited by carbon monoxide, ketoconazole, and 1,2-epoxy-3,3,3-trichloropropane. Our data suggest that pseudomonal metabolism of polymorphonuclear leukocyte-derived arachidonic acid occurs during phagocytosis, probably by enzymatic epoxidation and hydroxylation via an oxygenase. By this means, potential proinflammatory effects of arachidonic acid or its metabolites may be modulated by P. aeruginosa at sites of infection in vivo.

Arachidonic Acid↗
PubMed1992

Leukotriene B4 omega-oxidation by human polymorphonuclear leukocytes is inhibited by pyocyanin, a phenazine derivative produced by Pseudomonas aeruginosa.

Human polymorphonuclear leukocytes (PMNL) metabolize the potent chemotaxin leukotriene B4 (LTB4) by omega-oxidation to 20-hydroxyl-LTB4 and 20-carboxy-LTB4. The ability of unstimulated human PMNL to metabolize exogenous LTB4 was found to be inhibited by pyocyanin, a phenazine derivative produced by Pseudomonas aeruginosa, in a dose-dependent manner. 1-Hydroxyphenazine (1-OHP), a metabolite of pyocyanin, was not inhibitory under identical conditions. The initial enzymic step in the conversion of LTB4 is catalyzed by an NADPH-dependent cytochrome, P-450. Reduction of the phenazine derivatives by NADPH was measured spectrophotometrically. Pyocyanin was reduced by NADPH in vitro in a pH-dependent manner, while 1-OHP was poorly or negligibly reduced under similar conditions. Formation of NADP+ was 20.3 +/- 1.8 nmol min-1 for pyocyanin (10 microM) at pH 5.5, compared with 0.6 +/- 0.2 nmol min-1 for 1-OHP (10 microM), while at pH 7.5 a value of 2.2 +/- 1.3 nmol min-1 was obtained for pyocyanin, with no detectable activity for 1-OHP. This indicates that inhibition of LTB4 omega-hydroxylase activity by pyocyanin might be achieved by competition for NADPH. Incorporation of exogenous 5-hydroxyeicosatetraenoic acid by PMNL into lipid pools was not affected by either phenazine derivative. The ability of bacterial pyocyanin to limit the omega-oxidation of LTB4 may have important implications for PMNL LTB4 receptor status and chemotaxis in vivo.

Humans↗
PubMed1992

HIV infection of monocytes inhibits the T-lymphocyte proliferative response to recall antigens, via production of eicosanoids.

Human monocytes infected in vitro with human immunodeficiency virus (HIV) soon after adherence to plastic substrate demonstrated a significantly decreased ability to restimulate autologous immune T-lymphocyte proliferation after exposure to soluble (tetanus toxoid) and particulate [herpes simplex virus (HSV)] antigen. Incubation with the cyclo-oxygenase inhibitor, indomethacin (2-5 microM), prevented inhibition of antigen-stimulated lymphocyte proliferation. The inhibitory activity was identified in ultrafiltrates containing the low molecular weight fraction (less than 3000 MW) of supernatants from HIV-infected monocyte cultures. This activity was significantly and markedly reduced in similar ultrafiltrates prepared from indomethacin-treated cultures. Increased concentrations of prostaglandin E2 (PGE2) were detected in ultrafiltrates from HIV-infected monocyte cultures compared with uninfected cultures and cultures preincubated with indomethacin. Ultrafiltrates were inhibitory when added during the presentation of antigen to T lymphocytes but not when removed from monocyte cultures prior to the addition of lymphocytes. In addition, ultrafiltrates inhibited antigen-stimulated lymphocyte proliferation and PHA-induced lymphocyte proliferation to the same extent. These data indicate that cyclo-oxygenase products of arachidonic acid, including PGE2, are produced in excess by HIV-infected monocytes and that PGE2 and perhaps other cyclo-oxygenase products are implicated in the inhibition of antigen-stimulated lymphocyte proliferation via a direct effect on T lymphocytes.

Cell Division↗
PubMed1991

Comparison of human polymorphonuclear leukocytes from peripheral blood and purulent exudates by high resolution 1H MRS.

Human pus samples from various sites, including soft tissue and pleural cavity, as well as sputum from patients with cystic fibrosis have been analyzed by 1H magnetic resonance spectroscopy (MRS) and found to generate high resolution spectra. Assignments have been made for neutral lipid, amino acids, taurine, and lactate. Human peripheral blood polymorphonuclear leukocytes have also been examined and a similar spectrum containing these lipid and metabolite resonances was detected in cells stimulated with lipopolysaccharide. In unstimulated cells, only resonances from taurine and lactate were observed, suggesting that the presence of the lipid and metabolite resonances is an indicator of cellular activation of polymorphonuclear leukocytes. This is the first report of 1H MRS applied to intact human polymorphonuclear leukocytes and extends available documentation as to which types of normal and/or diseased tissue contain MR visible molecules.

Cystic Fibrosis↗
PubMed1991

Infection of vascular prostheses.

Graft infection occurred in 11 of 322 patients (3.4%) who had insertion of a vascular prosthesis for peripheral vascular disease during a 4-year period. The groin was the most common site of infection and multiple resistant Staphylococcus aureus (MRSA) was the most common organism responsible. Six of 7 MRSA infections occurred following a procedure involving a previously placed graft and/or a groin incision. Prophylactic antibiotics effective against MRSA are recommended for patients having a revisional procedure, especially involving the groin.

Bacterial Infections↗
PubMed1991

Production of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by human neutrophils is inhibited by Pseudomonas aeruginosa phenazine derivatives.

Pyocyanin, a phenazine pigment produced by Pseudomonas aeruginosa, and its metabolite 1-hydroxyphenazine inhibited leukotriene B4 and 5-hydroxyeicosatetraenoic acid production by up to 70% in human neutrophils stimulated with the calcium ionophore A23187 (5 microM). This potential anti-inflammatory effect was dose dependent and occurred at low concentrations (10 to 50 microM) that did not inhibit neutrophil viability.

Calcimycin↗