Veterinary and industrial high pressure injection injuries.
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Accidents, Occupational↗
Biomedical subjects
F Burke
Publications and source records attributed to F Burke.
Cytokines in animal models of cancer.
Cytokines are a complex family of mediators that play a wide role in development, immunity, inflammation and tissue repair. Their use in therapy is still in its infancy and animal models have a key role to play in optimizing doses and schedules. Whilst xenogeneic and syngeneic transplantable systems have traditionally been used to look at the effects of cytokines in tumour models, oncogene transgenic mice prone to develop cancer, may now have a role to play. Moreover, gene therapy has allowed the investigation of ectopically expressed high and continuous levels of cytokines. We will attempt to review the literature on the effect of cytokines and their combinations in these models of cancer.
Animals↗
The role of indoleamine 2,3-dioxygenase in the anti-tumour activity of human interferon-gamma in vivo.
We have studied the relationship between L-tryptophan metabolism and the response to human IFN-gamma in 3 human ovarian cancer xenografts growing in nude mice. During IFN-gamma therapy all 3 tumours showed a profound depletion in L-tryptophan and a corresponding rise in L-kynurenine. The microenvironment surrounding the tumours was also depleted of L-tryptophan. The IFN-gamma-inducible enzyme indoleamine dioxygenase, IDO, was induced in treated tumours. While there was a variability in IDO mRNA expression in the different xenografts tested, in situ hybridization showed that the gene was induced at all levels of the tumour, and not just the periphery. These results show that induction of IDO by IFN-gamma in vivo can metabolize L-tryptophan rapidly enough for it to become depleted, despite a continued supply of L-tryptophan from the host. The IDO mRNA and protein remained induced after the L-tryptophan levels had returned to normal, suggesting that the gene may be post-transcriptionally regulated and/or the IDO co-factor supply may be limited. Another IFN-gamma-inducible gene, tryptophanyl tRNA synthetase, was also induced in the tumour. It is possible that this enzyme, which is responsible for synthesizing tryptophanyl tRNA, acts in a compensatory manner by allowing protein synthesis to continue despite low free L-tryptophan concentrations. There was no correlation of the above parameters with the anti-tumour response to IFN-gamma, suggesting that other mechanisms must play a role. L-tryptophan depletion may be a contributor to a multifactorial growth inhibition of tumour cells following IFN-gamma treatment, but cannot on its own explain their growth inhibition.
Adult↗
Hand surgery coding and classification.
The development of codes for hand surgery as part of the Read Code System is described. A lexicon of clinical terms and surgery has been developed, and will shortly be available from the National Health Service Centre for Coding and Classification in Loughborough, UK.
Forms and Records Control↗
The detection and localization of monocyte chemoattractant protein-1 (MCP-1) in human ovarian cancer.
Chemokines may control the macrophage infiltrate found in many solid tumors. In human ovarian cancer, in situ hybridization detected mRNA for the macrophage chemokine monocyte chemoattractant protein-1 (MCP-1) in 16/17 serous carcinomas, 4/4 mucinous carcinomas, 2/2 endometrioid carcinomas, and 1/3 borderline tumors. In serous tumors, mRNA expression mainly localized to the epithelial areas, as did immunoreactive MCP-1 protein. In the other tumors, both stromal and epithelial expression were seen. All tumors contained variable numbers of cells positive for the macrophage marker CD68. MCP-1 mRNA was also detected in the stroma of 5/5 normal ovaries. RT-PCR demonstrated mRNA for MCP-1 in 7/7 serous carcinomas and 6/6 ovarian cancer cell lines. MCP-1 protein was detected by ELISA in ascites from patients with ovarian cancer (mean 4.28 ng/ml) and was produced primarily by the cancer cells. Human MCP-1 protein was also detected in culture supernatants from cell lines and in ascites from human ovarian tumor xenografts which induce a peritoneal monocytosis in nude mice. We conclude that the macrophage chemoattractant MCP-1 is produced by epithelial ovarian cancer and that the tumor cells themselves are probably a major source. MCP-1 may contribute to the accumulation of tumor-associated macrophages, which may subsequently influence tumor behavior.
Adenocarcinoma↗
The physician-hospital integration sensation.
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Cost-Benefit Analysis↗
Angiolymphoid hyperplasia with eosinophilia in the hand: a case report.
Angiolymphoid hyperplasia is an uncommon condition which may give rise to difficulty in diagnosis. The case described was originally regarded as Kaposi's sarcoma, but H.I.V. testing was negative. Excision of a further lesion established the diagnosis as angiolymphoid hyperplasia.
Adult↗
Fractures of the hook of the hamate.
Fractures of the hook of the hamate have been infrequently reported in the literature. A high index of suspicion is required if the correct diagnosis is to be established. We report three cases of fractures of the hook of the hamate and postulate a mechanism of injury in sportsmen. Once established, an excision of the hook is usually necessary to resolve the discomfort.
Adult↗
The cytokine network.
The availability of pure recombinant cytokines and molecular probes for their genes has generated an avalanche of scientific information. These data show that cytokines have a broad and overlapping range of cell regulatory activity both in vitro and in vivo. New factors are added to the cytokine list, and new functions reported for existing cytokines, with such frequency that it is difficult to retain an overall picture. With this problem in mind, a large wallchart was designed and was displayed at the second meeting of the British Cytokine Group* whose members pooled their collective knowledge, to list the known biological activities of these cytokines. This wallchart of cytokine activity, now referenced, is reproduced for Immunology Today. It is not a final list: new information and cytokines are continually reported and space has been left for readers to make their own additions. A neutrophil-activating peptide variously named monocyte-derived neutrophil chemotactic factor (MDNCF), neutrophil-activating factor (NAF), lymphocyte-derived neutrophil-activating peptide (LYNAP), which has been suggested as a candidate for interleukin 8 (IL-8), is included.
Biological Factors↗
Evidence for tumour necrosis factor/cachectin production in cancer.
Labile tumour-necrosis-factor-like (TNF) activity was detected by means of an enzyme-linked immunosorbent assay in 50% of 226 freshly obtained serum samples from cancer patients with active disease. In contrast, only 3% of 32 samples from normal subjects and 18% of 39 samples from cancer patients with no clinically evident disease were positive for this factor, with low levels of activity. Greater proportions of serum samples from patients with ovarian or oat-cell carcinoma were positive (69% and 63%) than those from patients with lymphoma (26%). RNA preparations from peripheral-blood mononuclear cells and solid tumours were probed with TNF complementary DNA; evidence of TNF messenger RNA was found in 8 of 11 samples of peripheral-blood mononuclear cells from cancer patients, but only 1 of 8 normal subjects, and in 2 of 6 colorectal tumours. As yet the inducing stimulus and the clinical significance of TNF production in cancer are not understood.
Adult↗
Surgical treatment of displaced olecranon fractures by tension band wiring technique.
Forty-five displaced olecranon fractures including 14 accompanying dislocated radial heads and seven radial head fractures were treated over a 13-year period by the tension band wiring technique. The use of supplemental internal fixation when necessary allows excellent results with the use of this technique, even in the presence of severe comminution or radial head dislocation. Primary silicone radial head implants fractured in all three patients in which they were used, necessitating repeat surgery in two patients to date. While loss of motion in terminal extension was a common aftermath of displaced olecranon fracture (59%), it was usually minor and functionally insignificant. True Kirschner-wire migration was not a common problem and can probably be eliminated by proper technique. The presence of gaps in the intraarticular surface of the semilunar notch of the ulna produced no ill effects and was compatible with excellent results. If only those cases with isolated olecranon fractures in this series are considered, there were good and excellent results in 29 of 30 cases (97%). Excision of the olecranon fragment(s) should be reserved for those cases when anatomic restoration cannot be achieved with internal fixation.
Adolescent↗
Total and renal sympathetic nervous system activity in alcoholic cirrhosis.
Basal sympathetic nervous system activity was assessed in 8 unmedicated patients with alcoholic cirrhosis using a previously developed radiotracer method for measuring total and renal noradrenaline release to, and clearance from, plasma. Compared to the control group total noradrenaline clearance was significantly increased in the patients with advanced alcoholic cirrhosis (Pugh grade C) [1.89 +/- 0.13 vs 1.51 +/- 0.11 l/min, P less than 0.05) indicating that endogenous plasma noradrenaline levels underestimate total sympathetic nervous system activity in these patients. Renal noradrenaline clearance was similar to controls independent of the severity of the liver disease. Both total and renal noradrenaline release were significantly increased in the patients with cirrhosis. The ratio of renal to total noradrenaline release was similar in cirrhotic (26 +/- 7%) and control (23 +/- 5%) groups. Increased arterial plasma adrenaline levels, indicative of adrenal medullary stimulation, were also evident in the patients with cirrhosis and correlated significantly with total noradrenaline spillover (r = 0.732, P less than 0.05). These results strongly suggest that in patients with cirrhosis, rather than a preferential increase in renal sympathetic tone, the increase is part of a pattern of generalized sympathoadrenomedullary activation. Although renal renin secretion was significantly increased in the cirrhotic group no correlation with renal noradrenaline release was seen (r = 0.199), raising the possibility that in cirrhosis renal sympathetic tone is not a major determinant of renal renin secretion. Finally, renal noradrenaline release did not correlate with renal blood or plasma flow but an influence of the sympathetic nervous system on renal function was suggested by the correlation observed between total noradrenaline spillover and impaired salt (r = -0.683, P less than 0.05) and water excretion (r = -0.702, P less than 0.05) demonstrated in the cirrhotic patients.
Adrenal Medulla↗
Total, and organ-specific, noradrenaline plasma kinetics in essential hypertension.
We have developed radiotracer techniques, based on measurement of the rate of spillover of noradrenaline to plasma, to simultaneously estimate total, and organ-specific, sympathetic nervous activity in humans. In 27 unmedicated subjects without renal or liver disease, or cardiac failure, regional noradrenaline spillover rates were as follows: lungs 33% of total noradrenaline release to plasma, kidneys 22%, skeletal muscle 20%, hepatomesenteric 9%, skin 5%, and heart 3%. These findings have relevance to numerous previous studies on the importance of the sympathetic nervous system in the pathogenesis of human essential hypertension. The indices of overall sympathetic nervous tone which have been used, such as measurements of plasma noradrenaline concentration or total NA release to plasma, are seen to be not sufficiently specific, since the organs and regions thought to be central to hypertension pathogenesis (kidney, heart, splanchnic circulation) are responsible for no more than 35% of all noradrenaline released to plasma. Organ-specific noradrenaline spillover measurements are better suited to the elucidation of any sympathetic nervous system pathophysiology in human hypertension. Early results point to an increase in renal sympathetic tone in young patients with essential hypertension.
Humans↗
The effects of rheumatoid diseases of the hand.
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Arthritis, Rheumatoid↗
Contribution of individual organs to total noradrenaline release in humans.
Plasma noradrenaline measurements are a fallible guide to sympathetic nervous tone, being dependent on noradrenaline plasma clearance. We have developed radiotracer techniques, based on measurement of the rate of spillover of noradrenaline to plasma, to simultaneously estimate total, and organ-specific, sympathetic nervous activity in humans. In 27 unmedicated subjects without renal or liver disease, or cardiac failure, regional noradrenaline spillover rates were as follows: lungs 138 +/- 36 ng/min (mean +/- SE) (33% of total noradrenaline spillover), kidneys 77 +/- 10 ng/min (22% of total), skeletal muscle 64 +/- 11 ng/min (20%), hepatomesenteric 29 +/- 9 ng/min (9%), skin 18 +/- 4 ng/min (5%), and heart 11 +/- 4 ng/min (3%). Organ-specific noradrenaline spillover measurements are well suited to the elucidation of sympathetic nervous system pathophysiology in human diseases. Since the sympathetic nervous system outflow to individual organs is not activated or suppressed uniformly in different disease states, biochemical measures of "overall sympathetic nervous activity" are insufficiently specific for this purpose.
Humans↗
Estimation of 'total' renal, cardiac and splanchnic sympathetic nervous tone in essential hypertension from measurements of noradrenaline release.
The overall rate of release of noradrenaline to plasma was increased in 31 patients with essential hypertension; the median value was 32% (526 pmol/min) higher than in 22 subjects with normal blood pressure. To ascertain the pattern of sympathetic nervous system activation underlying this abnormality, regional sympathetic nervous activity was estimated, from radiotracer-derived estimates of organ-specific noradrenaline release to plasma, in the kidneys, heart and hepatomesenteric circulation. Renal sympathetic nervous tone was preferentially increased in essential hypertension, especially in young patients with hypersecretion of renin. Cardiac noradrenaline release (and possibly cardiac sympathetic tone) was also higher in hypertensive patients; the difficulty in interpretation here arises because left ventricular mass is also increased in essential hypertension. Approximately half of the surfeit in total noradrenaline release to plasma noted in hypertensive patients was accounted for by the increased cardio-renal noradrenaline release. The balance comes from undetermined sites, but not from the splanchnic circulation, in which sympathetic nervous activity was not increased.
Adult↗