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Biomedical subjects

T C Sorrell

Publications and source records attributed to T C Sorrell.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Endocarditis associated with prosthetic cardiac valves.

Clinical features, microbiology, therapy and outcome of 26 episodes of prosthetic valve endocarditis occurring at Westmead Hospital from 1979 to 1989 were examined retrospectively. Presentation with a new or changed cardiac murmur was associated with early onset infection (within 12 months of prosthetic valve insertion; P = 0.0033). Corynebacteria were the commonest cause of early onset endocarditis (4 of 11 episodes) and Streptococcus viridans of late onset endocarditis (4 of 15 episodes). Nine of 11 episodes responded to antimicrobial therapy and 12 of 15 to medical-surgical therapy. There was a trend towards increased mortality in patients with early onset endocarditis presenting with a new or changed cardiac murmur (4 of 9 v. 1 of 17, P = 0.068), suggesting early surgery should be considered in this group. Analysis of antibiograms and published reports indicated that vancomycin and an aminoglycoside should be recommended as empirical therapy for endocarditis occurring 12 to 18 months after prosthetic valve insertion.

Aminoglycosides↗
PubMed1990

Horizontal transmission of Campylobacter jejuni amongst broiler chicks: experimental studies.

Horizontal transmission of Campylobacter jejuni was investigated in campylobacter-free broiler chicks. One hundred and twenty chicks housed individually, were provided with water containing 10(2)-10(9) c.f.u./ml C. jejuni. Colonization was rapid [47 of 73 (64%) positive cloacal cultures within 3 days and 65 of 73 (89%) within 7 days], dependent on C. jejuni strain and inoculum size but independent of chick age. Groups of 5-24 chicks in isolators were exposed to C. jejuni-contaminated water or colonized seeder chicks. Transmission occurred in 2-7 days concurrent with a gradual increase of C. jejuni in litter, water and feed. Environmental samples were culture-negative within 3 days following removal of colonized chicks. Treatment of 1-day-old chicks with adult caecal microbiota did not affect colonization. Treated and control chicks were all C. jejuni-positive within 3 days of seeder challenge.

Animal Feed↗
PubMed1989

Eicosanoids produced during interactions between Pseudomonas aeruginosa and alveolar macrophages are species-dependent.

Eicosanoid production during phagocytosis of pyogenic bacteria by rabbit alveolar macrophages was studied as a model of early events in the pathogenesis of pneumonia. Adherent alveolar macrophages, prelabelled with [3H]-arachidonic acid (AA), were incubated with live, opsonized Staphylococcus aureus or Pseudomonas aeruginosa (bacteria:macrophage ratio of 50:1) at 37 degrees C for 90 min. Supernatant eicosanoids were extracted and separated by reverse phase high performance liquid chromatography (RP-HPLC). While the amounts of labelled PGE2, TXB2, and PGD2 produced in response to the two organisms were equal, the amount of PGF2 alpha elicited by S. aureus amounted to three times that released during macrophage challenge with P. aeruginosa. Overall, preferential release of cyclooxygenase products occurred during phagocytosis of S. aureus. In contrast, eicosanoids identified presumptively as oxygenated metabolites of AA predominated in cultures challenged with opsonized P. aeruginosa. Live, non-opsonized P. aeruginosa elicited the same profile of eicosanoids, but in reduced amounts. Inhibitor studies indicated that these AA derivatives were not synthesized via the macrophage lipoxygenase pathway. Their production was dependent on the viability of P. aeruginosa. Macrophages challenged with opsonized, heat-killed P. aeruginosa resulted in production of an eicosanoid profile similar to that elicited by S. aureus. Secondary metabolism by P. aeruginosa of eicosanoids released from the macrophage did not contribute to the unique profile produced during the interaction of this organism with labelled macrophages. Our data indicate that during binding to macrophages, the primary human pathogen, P. aeruginosa, specifically modulates the profile of eicosanoids produced. This effect on inflammatory mediators may be of biological significance in the pathogenesis of pneumonia.

Animals↗
PubMed1988

Experimental colonization of broiler chicks with Campylobacter jejuni.

Minimal colonization inocula for two broiler strains of Campylobacter jejuni were determined in broiler chicks aged 2-3 days and 2 weeks. Individually housed chicks were exposed to a single oral or cloacal challenge. Diarrhoeal symptoms were absent in all 380 chicks included in the study. Chick susceptibility to the two C. jejuni strains varied. Colonization was effected by less than 10(2)-10(4) colony forming units (c.f.u.) via cloacal challenge and 10(4)-10(6) c.f.u. via the oral route. Colonization inocula for 2- to 3-day and 2-week-old chicks were similar. Treatment of 1-day-old chicks with fresh adult caecal flora or an anaerobic broth culture of adult caecal flora did not inhibit colonization after challenge with low-dose C. jejuni. Susceptible chicks were colonized rapidly. C. jejuni was detected in 167 of 189 (88%) colonized chicks within 3 days of challenge and persisted during the 2-week monitoring period. Our data suggest that colonization of broiler chicks with C. jejuni is effected more easily by the cloacal than the oral route and is independent of age.

Animals↗
PubMed1987

Extrapulmonary tuberculosis--a continuing problem in Australia.

Extrapulmonary tuberculosis (TB) remains a major health problem in Australia, with 24.3% of all new tuberculosis notifications in 1984 of extrapulmonary origin. We have reviewed our recent experience to assess the epidemiology and clinical features that may allow the earlier recognition and treatment of patients at risk for this disease. From 1980-1985, 51 cases of extrapulmonary TB were identified at Westmead Hospital. Thirty-eight patients were born outside Australia, mainly in South-East Asia and Europe. The commonest sites of disease were the lymph nodes, genitourinary tract, pleura and bone. Tuberculous lymphadenitis occurred predominantly in South-East Asians, whilst genitourinary tract disease was confined to Caucasians. A history of previous exposure to tuberculosis was obtained in 45% of patients. Fever, sweats and weight loss were noted in less than half of the cases. Changes consistent with old pulmonary disease were found on routine chest X-ray in 34% of cases. Laboratory confirmation of TB was made in 88% of cases, with typical histopathology in 90% and isolation of Mycobacterium tuberculosis in 69% of specimens submitted for analysis. Drug resistance was confined to isolates from South-East Asian patients.

Asia, Southeastern↗
PubMed1986

Propionibacterium acnes infection in neurosurgical patients. Experience with high-dose penicillin therapy.

Propionibacterium acnes is an underestimated but significant cause of cerebrospinal fluid (CSF) infection after neurosurgical procedures and in the presence of prosthetic devices. The most effective therapy for such infections has not been defined. We report here our experience with the use of high-dose penicillin in the treatment of six patients with postoperative infection which was caused by P. acnes. All patients received 3-4 million units of penicillin by the intravenous route every four hours, in combination with surgical drainage and removal of prosthetic devices where appropriate. All but one of the patients recovered from their infection. The remaining patient responded to penicillin but died of a massive intraventricular haemorrhage after 12 days. Isolates of P. acnes had minimal inhibitory concentrations to penicillin that ranged from 0.03-0.12 mg/L. No adverse reactions to penicillin were recorded. We conclude that high-dose intravenous penicillin therapy, in combination with surgical drainage and removal of foreign bodies, constitutes appropriate therapy for CSF infections that are due to P. acnes.

Combined Modality Therapy↗