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Biomedical subjects

D J Ormrod

Publications and source records attributed to D J Ormrod.

31 records · Page 2Linked to original sources
PubMed1985

Immunopotentiation in infectious disease, II. Effect of bestatin on experimental infection.

A two-stage protocol designed to evaluate putative immunomodulators for use in infectious disease has been proposed. In this report the effect of bestatin on a series of clinically relevant, and sub-lethal infections is described. Pyelonephritis, peritonitis and bacteremia were induced with Escherichia coli, while Klebsiella pneumoniae was used to produce a lung infection. Bestatin had no effect on the course of these infections. In a further experiment we assessed the effect of combined bestatin/antibiotic therapy on the course of renal infection. Again no effect was observed. These findings are consistent with the known immunomodulatory properties of bestatin. This methodology will be used to evaluate selected agents for their potential in infectious disease and should lead to useful clinical protocols.

Adjuvants, Immunologic↗
PubMed1983

Host immune status in uremia. V. Effect of uremia on resistance to bacterial infection.

Infection is a frequent complication and cause of death in renal failure. Although it is widely accepted that uremia has an adverse effect on host resistance to infectious disease, this association has not been proven. In the present experiments, the relationship between uremia and susceptibility to infection has been investigated using an animal model of chronic, severe uremia. Lung infections (using Pseudomonas aeruginosa and Klebsiella pneumoniae), bacteremia, peritonitis and subcutaneous infection (using Escherichia coli) were induced in uremic and normal rats and the course of infection compared. The ability of the uremic host to clear Ps. aeruginosa from the lung was marginally impaired in the first 24 hr after the challenge but was normal in the later stages of the infection. Similarly, in the bacteremia study, secondary invasion of the lungs by several other species of bacteria occurred in 33% of the uremic animals. We found no other evidence of impairment of immunity in uremia in the infections that we studied and, taken overall, the results support arguments that uremia per se is unlikely to be an important factor predisposing patients with renal failure to infection.

Animals↗
PubMed1983

Host immune status in uremia. IV. Phagocytosis and inflammatory response in vivo.

Infection is a frequent complication and cause of death in renal failure, but the association between uremia, depressed immune status, and susceptibility to infection is far from proven. In the present studies, the effect of uremia on the inflammatory response and phagocytic ability was investigated in an animal model. The inflammatory response, as measured by the ability of leukocytes to mobilize into subcutaneous implanted sponges, was impaired at 6 hr but was normal 24 hr after implantation. The peripheral blood response of uremic animals to the leukocytosis promoting protein from Bordetella pertussis was similar to that of control animals. Reticuloendothelial clearance of labelled albumin was unimpaired but catabolism of this substance was reduced significantly in uremic animals. The ability of the uremic host to clear an intravenous challenge of virus was also depressed. Phagocytic and bactericidal capability of polymorphonuclear (PMN) leukocytes, measured in vitro by latex ingestion and phagocytosis and killing of Staphylococcus aureus, was normal. PMN phagocytic function in vivo was determined by the clearance of viable Escherichia coli from subcutaneously implanted sponges and no significant difference between control and uremic groups was found. These studies have further defined the effect of uremia on immune mechanisms and support our contention that uremia per se is not a major factor contributing to the compromised immune status in this host.

Animals↗
PubMed1982

Anti-inflammatory activity in fractionated extracts of the green-lipped mussel.

The New Zealand green-lipped mussel (Perna canaliculus) is the source of a para-pharmaceutical called Seatone. Claims have been made that the preparation may be helpful in the management of inflammatory joint disease but results of clinical studies to date have been contradictory. An earlier experimental study demonstrated anti-inflammatory activity in the crude preparation and further experiments to isolate and characterise the active fraction were indicated. A two-step fractionation procedure resulted in an extract, which although only 16 percent by weight of the parent material, retained anti-inflammatory activity. Experiments involving alternative routes of administration, with heat or enzyme treatment of the active extract and a comparative analysis of fractions from related bivalves, all demonstrated that the anti-inflammatory effect was genuine and did not result from counter-irritancy. The initial results suggest that the active agent is a proteinaceous macromolecule.

Administration, Oral↗
PubMed1982

Synergism between immunosuppressive agents and uremia?

The susceptibility of uremic patients to infectious disease has been widely reported, but the host immune factors associated with the increased incidence of infection have not been clearly defined. In this study, the possibility of synergism between biologically active components that accumulate in uremia and immunosuppressive drugs used in the course of management was investigated. An animal model of chronic stable uremia was used in these experiments to assess the effect of cyclophosphamide, methotrexate, and azathioprine on antibody response in the uremic host. Chronic uremia did not affect the immunosuppressive activity of cyclophosphamide, methotrexate, or azathioprine, and synergism between these agents and uremic components is unlikely to complicate further the immune status of the host in renal failure.

Animals↗
PubMed1981

Evaluation of cefoxitin nephrotoxicity in experimentally induced renal failure.

The nephrotoxicity of cefoxitin was studied in a rat model of impaired renal function. Two levels of renal impairment were produced: "moderate," with blood urea concentrations of 100 to 150 mg/100 ml (16.7 to 25.1 mmol/liter) and glomerular filtration rates 25 to 35% of normal, and "severe," with blood urea concentrations greater than 150 mg/100 ml (greater than 25.1 mmol/liter) and glomerular filtration rates 10 to 20% of normal. Sham-operated animals were used as controls. Three dose schedules of cefoxitin were administered to these controls--500, 1,000, and 2,500 mg/kg per day administered as a divided dose for 5 days. Doses given to the moderately and severely uremic animals were adjusted so that serum levels of cefoxitin were similar to those attained in the sham-operated control animals. Concentrations of urea and creatinine in blood, glomerular filtration rates, and the urinary concentrating capacities of the experimental animals were monitored before and after cefoxitin treatment. There was no evidence of nephrotoxicity in even the most challenging experiment, in which blood serum levels of cefoxitin reached 2,000 microgram/ml in animals, with 15% renal function. These findings support available clinical data, suggesting that cefoxitin can be administered safely to patients with compromised renal function.

Animals↗
PubMed1980

Role of complement in chemotaxis: study of a localized infection.

A model of Escherichia coli-induced pyelonephritis was used to study the effect of complement depletion in an organ-specific, nonimmunological inflammatory lesion in rats. In this model of a local infection, which can be considered to be nonspecific inflammatory stimulus, the depletion of complement by the administration of a purified cobra venom factor did not alter the course of the disease. There were minor differences when the results from complement-depleted and normocomplementemic animals were compared, but the composition of the inflammatory infiltrate was not greatly altered. Therefore, the presence of C3 and a functional complement system are relatively unimportant factors in determining the characteristics of the inflammatory response in a localized infection-induced lesion.

Animals↗
PubMed1980

Host immune status in uraemia III. Humoral response to selected antigens in the rat.

The humoral immune status of patients with uraemia is controversial. In the present experiments a carefully defined animal model, in which a chronic state of moderate and severe uraemia was induced, has been used to resolve conflicting views. The capacity of the uraemia host to respond to immunogenic stimulation was assessed by challenging uraemic animals with bacterial, viral, T cell-dependent and T cell-independent antigens. The experiments have shown that the immune responsiveness of animals with chronic severe uraemia, immunized with sheep red blood cells, Escherichia coli 075, keyhole limpet haemocyanin and phi X174 bacteriophage is comparable to those found in sham-operated and control groups. The results strongly suggest that uraemia per se does not affect the ability of the host to respond to a wide range of antigenic stimuli. This conclusion is important in that it provides a basis for assessing further the immune status of the uraemic host. If uraemic patients do have an immune deficit, one possible explanation is that uraemia potentiates the immunosuppressive activity of some drugs used in the clinical management of these patients.

Animals↗
PubMed1978

Complement-mediated immune mechanisms in renal infection.

The belief that the inactivation of complement by renal ammonia enhances the susceptibility of renal tissue to infection has been held for some years. This thesis has been investigated in the present experiments using cultures of renal tissue maintained in vitro under physiological conditions. The experiments have confirmed that exposure of normal serum to renal issue in culture does result in the rapid loss of complement activity, but that the inactivation was not due to renal ammonia. Furthermore, in quantitative experiments, the liver was found to have even greater anti-complementary activity than renal tissue. In experiments where the biological significance of this phenomenon was examined, it was shown that the bactericidal capacity of serum was maintained even after exposure to renal tissue. The results of these investigations suggest that the biological significance of the inactivation of complement by renal tissue in vitro has been over-emphasized and requires further studies in vivo.

Ammonia↗
PubMed1976

Depression of the T-lymphocyte response to phytohaemagglutinin by renal cells.

The lymphocytic infiltrate in the renal parenchyma is a consistent histological feature of pyelonephritis, but the role of the lymphocytes in the immunobiology of pyelonephritis is not known. In this investigation the influence of the local environment on the potential function of T lymphocytes in the kidney was investigated. The experiments have demonstrated that the response of rat lymphocytes to stimulation in vitro with phytohaemagglutinin (PHA) can be entirely ablated by normal kidney cells. Even when the number of kidney cells added to cultures of lymphocytes was less than 2% of the cells present some ablation of T-lymphocyte function could be detected. The biological characteristics of the factor causing ablation of the PHA responsiveness of T lymphocytes were partially characterized and the factor appears to have unique features that differentiate it from lymphocyte chalones and other tissue factors influencing lymphocyte function. The results may explain recent findings where T lymphocytes were found to be the predominant lymphocyte in the inflammatory infiltrate but were not responsive to PHA in vitro.

Animals↗
PubMed1975

Quantitation of immunoglobulin-bearing lymphocytes and the lymphocyte response to PHA in experimental pyelonephritis.

In these experiments the effect of experimental pyelonephritis on the distri-ution of B lymphocytes in the peripheral blood and lymphoid sites in the rat has been determined and the functional capacity of T cells during the course of infection has been investigated. The studies have shown that renal infection affects the distribution of lymphocytes and has a marked effect on the functional capacity of splenic T lymphocytes early in infection. Most of the lymphocytes forming the round cell infiltrate in the kidney have been identified as thymus-derived lymphocytes on their surface labelling characteristics. Evidence is presented to demonstrate the inability of T lymphocytes to function normally in the environment of the kdiney. It is suggested that ablation of cell-mediated immunity may be a factor contributing to the persistence of renal infection.

Animals↗