Biomedical subjects
Publications and source records attributed to H Kelly.
Antimony microelectrodes were used to measure pH in rat seminiferous tubules and epididymides in vivo. Acidification of fluid leaving the testis occurs primarily in the initial segment and to a lesser extent in the intermediate zone.
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Quantitative transplantation assays of a syngeneic murine adenocarcinoma have been used to investigate the effects of stress hormones and tumor take probability. Cortisol, injected intraperitoneally one hour before and 3 hours after tumor cells, caused a dose dependent reduction of TD50 (number of tumor cells required for 50% takes) by factors of from 4 at a total dose 4 microng/g to 68 at 400 microng/g. ACTH, given at 0.2 I.U. daily for 9 days spanning the time of tumor cell injection, reduced the TD50 2.5-fold, indicating that the peak gluco-corticoid level achieved, rather than its duration, was of greater significance. Adrenaline, while much less effective than cortisol, produced an 8-fold reduction in TD50 at its maximum tolerable dose. The effect of cortisol simulated that of whole body irradiation (WBI), and while both these agents depress immune reactivity, evidence is presented to suggest that immunological mechanisms are not responsible for their effect. WBI constitutes a systemic stress, and the demonstration that surgical trauma (laparotomy) could also reduce the TD50 for this tumor suggested that both might act via endogenous glucocorticoids. However, the failure of prior total adrenalectomy of mice to abrogate the effect of either WBI or laparotomy indicated that stress hormones were not essential intermediaries. It is concluded that both stress hormones, especially glucocorticoids, and stressful procedures acting independently of stress hormones, can facilitate tumor transplantation.
Impregnation of the vasculature with ink was used to study microvascular changes induced in rats by liquid (ascites) and solid growth of W256 and Y-P388 tumour cells. Ascites fluid produced by both tumours was heavily blood-stained; the deep red colour of solid tumour deposits was similarly due to the presence of free blood. In both types of tumour growth this free blood was due to diapedesis of erythrocytes through tips of capillary sprouts which grow when neovascularization (angiogenesis) occurs in response to any suitable (non-neoplastic or neoplastic) stimulus. Ascites growth of these tumours induced profuse sprouting from the peritoneal capillaries; this sprouting, together with the "bleeding" it caused, were inhibited by local pre-irradiation of the peritoneal vasculature with X-rays before intraperitoneal inoculation of rats with the tumours. Similar angiogenesis with bleeding did not occur following inoculation with an allogeneic tumour in rats which had been previously immunized against the tumour. LI tumour cells (tumour cells lethally irradiated in vitro to destroy their proliferative integrity, but which remain metabolically active) also induced sprouts to grow in close proximity to the implanted LI cells, but heat-killed tumour cells caused no sprouting. The nature and significance of neovascularization of tumours and their so-called "haemorrhagic" growth are discussed.
The survival and clonogenic growth (measured in terms of colony forming efficiency (CFE) of intravenously injected (i.v.) Walker (W256) tumour cells in the lungs of rats was greatly enhanced by states of topical and systemic stress induced by the intraperitoneal (i.p.) injection of rats with a single dose of 10(-5)-10(-3) mmol g-1 body weight of adrenaline and other beta-adrenergic agonists, inflammatory agents (including local x-irradiation), convulsive seizures, "tumbling" or physical restraint. Lowering of innate resistance of the host to growth of seeded tumour cells induced by states of topical and systemic stress, and by the addition of an excess of lethally irradiated (LI) tumour cells to i.v. injected intact tumour cells, were all potentiated by treatment of rats with aminophylline, an inhibitor of cyclic AMP phosphodiesterase. Enhancement of tumour growth by systemic stress was inhibited by bilateral total or medullary adrenalectomy and is attributed to the release and actions of endogenous adreno-medullary hormones. Alpha-adrenergic and most non-adrenergic agents administered in maximum tolerated doses did not significantly affect host resistance to tumour growth in the lungs. These findings, correlated with measurements of cyclic AMP in the lungs of normal and stressed rats, suggest that changes in the resistance of the host to tumour growth involve changes in cyclic nucleotide metabolism in the target tissues (tumour bed); possible mechanisms of action of cyclic nucleotides in this respect are discussed.
During the 3rd and 4th weeks of life rats were highly resistant to the toxic effects of alpha-naphthyl thiourea (ANTU) and of thiourea and its derivatives but toxicity developed rapidly during the following 2 weeks. Marked resistance to lung damage by toxic thioureas could be induced in older, mature rats by pretreatment with the toxic agent itself (tachyphylaxis), with other toxic and non-toxic antithyroid drugs or with iodine or iodide--even if the rats were pretreated at an early age before susceptibility to the agent developed. ANTU-tachyphylaxis was dose-dependent. Total thyroidectomy did not affect either lung damage induced by ANTU or the resistance due to tachyphylaxis or to pretreatment with iodide or the antithyroid drugs thiourea, 1-ethyl-1-phenyl thiourea or propyl thiouracil. Neither total nor medullary adrenalectomy affected ANTU toxicity. Marked resistance to ANTU-induced lung damage was induced in rats by pretreatment with either an activator (3-4 benzypyrene) or an inhibitor (SKF 525-A) of drug-metabolizine mixed-function microsomal enzyme systems; the inhibitor, sodium phenobarbitone, had no significant effect on toxicity. The sulphydryl compound, AET, induced marked resistance to ANTU; cysteine was less effective. Neither autonomic blockade with nicotine and atropine nor actinomycin D had significant effects on toxicity to ANTU. The acute pulmonary oedema induced in rats by high pressure oxygen, chemical convulsants, pressor agents and ammonium sulphate differed in many respects from that induced by toxic thioureas; it was typically haemorrhagic in nature, did not result in significant pleural effusion, did not exhibit tachyphylaxis, and was not influenced by pretreatment with iodide or derivatives of thiourea.
A proportion of W-256 tumour cells injected intravenously into a tail vein of the rat are diverted into venous plexuses en route to the lungs; here tumour cells remain trapped, proliferate and form invasive solid tumours in the pelvis and hindquarters, which cause paraplegia, metastases and death. Also, cells trapped in veins produce tumour nodules distributed along the length of the tail; this effect in markedly enhanced by temporarily arresting the outflow of blood from the tail for a few seconds only immediately after cells are injected. Continous monitoring of the radioactive signal over the lungs after W-256 cells labelled with 125IUDR were injected showed that massaging the tail or intravenously injecting isotonic saline into the tail dislodged cells trapped in veins. In heparinized rats, tail trapping was markedly reduced, although not entirely abolished, and venous trapping in vertebral and pravertebral regions was decreased. The anatomical distribution of growth of the trapped cells in rats closely resembled metastases involving dissemination via the "vertebral venous system" produced by certain cancers in man. Labelled tumour cells trapped in the lungs of untreated mature rats commenced dying rapidly in situ wiht 1-2 h after injection; the majority had disappeared within 24 h, and less than 1% of the injected tumour cells survived to form lung colonies. Experimental evidence is presented which indicates that the lungs play a vital role in rapidly eliminating a high proportion of blood-borne cancer cells in the adult individual.
Acute inflammatory reactions were induced in rats by the intravenous injection of cellulose sulphate (CS) or an extract of normal rat lung homogenate (LH), or by intraperitoneal injections of Compound 48/80. These treatments greatly increased survival and clonogenic growth in the lungs of rats of intravenously injected allogeneic W-256 and Y-P388 tumour cells. Increase in the dose of intravenously injected CS caused a logarithmic increase in colony forming efficiency (CFE) of tumour cells in the lungs. CFE was not stimulated by the intravenous injection of rats with pharmacological mediators of inflammation (histamine, 5-hydroxytryptamine, bradykinin and prostaglandins PGE(1) and PGF(2α)) which are released from tissues by agents which induce inflammation. Stimulation of CFE by CS occurred in adrenalectomized rats but was inhibited by treatment of rats with an anti-inflammatory steroid, dexamethasone. CFE was stimulated by CS in tumour immunized rats; the inflammatory state did not prevent the expression of immunity but "rescued" a proportion (approximately 20%) of the injected tumour cells from immunodestruction in the lungs. A higher proportion of tumours grew in the paws of rats when a small number of W-256 cells were injected interdigitally into the acute inflammatory swellings produced by the local injection of paws with LH or CS.CS is a "synthetic heparin" which causes marked prolongation of blood clotting time and also increases fibrinolytic activity of the blood. Anticoagulant treatment of rats with heparin did not affect CFE. Thus, there was no direct correlation between blood clotting time and CFE of blood borne tumour cells in the rat.The mechanisms which may be responsible for the nonspecific growth promoting effects of inflammatory reactions induced by various types of tissue injury on tumour induction and growth are discussed.
Anti-inflammatory corticosteroids administered to rats in high dosages before intravenous injection of allogeneic tumour cells caused 5-10 fold reductions in "take" and clonogenic growth of the cells in lung and kidney and decreased growth and spread of the cells transplanted to leg muscle. Steroid therapy also reduced the effect of local irradiation of lung tissues in increasing tumour colony efficiency (CFE) in the lungs; it also tended to reduce similar effects of sublethal whole body irradiation. A non-steroidal anti-inflammatory drug, phenylbutazone, also reduced CFE in locally irradiated lungs in the rat.The results obtained indicate that corticosteroids do not stimulate the growth of implanted tumour cells by suppressing host immunity but decrease their clonogenic growth by inhibiting local inflammatory reactions to cell arrest, and similarly to local tissue damage caused by x-irradiation; it is asserted that such inflammatory reactions are growth promoting and thereby stimulate regeneration of stroma (repair) and also support survival and early growth of the tumour cell.
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INTRODUCTION: The prevention of pulmonary embolism (PE) is an important component of medical care. AIM: To examine the risk factors for venous thromboembolism in an Irish patient cohort with acute PE, and identify cases that may have been preventable. METHODS: Retrospective review of 60 consecutive cases of computed tomography (CT)-confirmed acute PE. RESULTS: The primary thromboembolic risk factors were elective surgery (27%), medical illness (20%), primary immobility (13%) and isolated distal lower limb fracture (7%). A significant proportion (43%) had been hospitalised within the six weeks prior to PE onset. Some patients had undergone 'low risk' procedures, without prophylaxis, but had other significant thromboembolic risk factors that indicated a requirement for prophylaxis. CONCLUSIONS: Hospital- and ward-based thromboprophylaxis guidelines, based on certain categories of patient or procedure, need to be routinely supplemented by an individual risk factor assessment for each patient, to determine those at particularly high risk for venous thromboembolism.
Sentinel testing for human immunodeficiency virus (HIV) infection aims to monitor the HIV epidemic by testing subgroups of the population, and such testing has been carried out at the Murray Street Clinic in Perth, Western Australia since August 1989. This clinic is part of the State Health Department and is dedicated to the diagnosis, management and control of sexually transmitted diseases (STDs) in Western Australia. Sentinel testing at this clinic is both voluntary and confidential. In the first 6 months of testing at the clinic, 2351 new patients were seen and 3000 HIV antibody tests were performed. The refusal rate for participation was 8%. No patient tested as a sentinel test or because of multiple heterosexual partners was HIV antibody positive. The first 6 months of sentinel testing at the Murray Street Clinic does not indicate a silent HIV infection in the self-selected sexually active group of people using the facilities of the clinic.
Following a burn injury, children can deteriorate very quickly and prompt accurate assessment by the accident and emergency nurse is therefore essential. This article outlines the initial assessment and management of paediatric burns.
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