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S Jinks

Publications and source records attributed to S Jinks.

17 recordsLinked to original sources
PubMed1999

Isoflurane can indirectly depress lumbar dorsal horn activity in the goat via action within the brain.

We have examined the response of lumbar dorsal horn cells to a noxious mechanical stimulus during differential delivery of isoflurane to the brain and spinal cord of goats. We hypothesized that isoflurane, acting in the brain, would depress dorsal horn neuronal responses to a noxious mechanical stimulus applied to the hindlimb. Eight goats were anaesthetized with isoflurane and neck dissections performed which allowed cranial bypass. Lumbar laminectomies were performed to allow measurements of single-unit dorsal horn neuronal activity. Isoflurane 1.3% was administered before bypass, and during differential delivery it was administered at each of the following head/torso combinations: 1.3%/1.3%, 0.8%/1.3%, 0.3%/1.3%, 1.3%/0.8%, 0.8%/0.8% and 0.3%/0.8%. When the torso isoflurane concentration was 1.3%, decreasing cranial isoflurane from 1.3% to 0.3% did not significantly affect dorsal horn responses (from mean 325 (SD 262) to 379 (412) impulses min-1; P < 0.05). However, when torso isoflurane was 0.8%, decreasing cranial isoflurane from 1.3% to 0.3% increased mean evoked dorsal horn activity by 42% (388 (359) to 551 (452) impulses min-1; P < 0.05). These data suggest that the major effect of isoflurane on dorsal horn responses to noxious stimuli is direct, but there is an indirect effect occurring via descending projections from supraspinal regions.

Anesthetics, Inhalation↗
PubMed1999

Does the Manchester triage system detect the critically ill?

BACKGROUND: The Manchester triage system (MTS) is now widely used in UK accident and emergency (A&E) departments. No clinical outcome studies have yet been published to validate the system. Safety of triage systems is related to the ability to detect the critically ill, which has to be balanced with resource implications of overtriage. OBJECTIVES: To determine whether the MTS can reliably detect those subsequently needing admission to critical care areas. METHODS: Analysis of emergency admissions to critical care areas and comparison with original A&E triage code by a nurse using the MTS at time of presentation. Retrospective coding of all cases according to the MTS by experts and case analysis to determine whether any non-urgent coding was due to the system or to incorrect coding. RESULTS: Sixty one (67%) of the patients admitted to a critical care area were given triage category 1 or 2 (that is, to be seen within 10 minutes of arrival). Eighteen cases given lower priority were due to incorrect coding by the triage nurse. Six cases were correctly coded by the MTS, of which five deteriorated after arrival in the A&E department. Only one case was critically ill on arrival and yet was coded as able to wait for up to one hour. CONCLUSIONS: The MTS is a sensitive tool for detecting those who subsequently need critical care and are ill on arrival in the A&E department. It did fail to detect some whom deteriorated after arrival in A&E. Most errors were due to training problems rather than the system of triage. Analysis of critically ill patients allows easy audit of sensitivity of the MTS but cannot be used to calculate specificity.

Critical Illness↗
PubMed1986

Comparative studies of total cross-linking, cell survival and cell cycle perturbations in Chinese hamster cells treated with alkylating agents in vitro.

The toxicities of 4-hydroperoxycyclophosphamide (4-OOH CY), phosphoramide mustard (PM), melphalan (MEL) and busulphan (BU) have been compared in Chinese hamster cells, V-79-753B. The initial total amount of cross-linking was a determining factor for the clonogenic survival of cells treated with MEL or PM. Although 4-OOH CY generated cross-links in this cell line, this damage did not account for the toxicity of the compound. There was no evidence for cross-link formation in cells treated with BU, even at a dose of the drug (1000 micrograms/ml) that was too toxic to measure clonogenic survival. Comparison for the four compounds at equitoxic doses showed that both PM and MEL caused the arrest of the cell cycle at G2 which persisted after drug removal. This was accompanied by a decline in the population growth rate and a decrease in total cell count. In contrast, both BU and 4-OOH CY caused a temporary arrest of the cell cycle G2, 24 hr after drug removal. However, the cell cycle distribution returned the control values within 3-4 days after treatment. Both BU and 4-OOH CY showed little effect on the initial growth rate of the cells. It is concluded that the initial amount of cross-links contributes to the toxicity of PM and MEL. However, it is unlikely that the generation of cross-links is of major importance for the toxicity of either 4-OOH CY or BU.

Alkylating Agents↗
PubMed1985

Mesna does not reduce cisplatin induced nephrotoxicity in the rat.

Although mesna afforded protection against the cytotoxicity of cisplatin in Chinese hamster cells, line V-79-753B, in vitro, there was no evidence for protection against nephrotoxicity when this drug combination was examined in the rat. It seems likely that cisplatin-induced nephrotoxicity is mediated by intracellular events in kidney cells which cannot be inhibited by mesna possibly due to its presence within cells in vivo as the stable and unreactive disulphide. On the basis of these data it is unlikely that combinations of mesna and cisplatin will be of therapeutic benefit in man.

Animals↗
PubMed1985

Studies on the relationship between the radiation resistance and glutathione content of human and rodent cells after treatment with dexamethasone in vitro.

A 20 h pre-treatment of human cells from normal (foetal lung) or malignant origin (glioma, lines U118 MG and U251 MG and bladder carcinoma, line EJ) with dexamethasone failed to increase their radiation resistance in vitro despite a 2-fold increase in the GSH content of a glioma cell line, U251 MG, and a small but significant increase in the GSH content of EJ bladder carcinoma cells. In contrast, there was a correlation between an increase in radiation resistance and an elevated GSH content of rodent cells (Chinese hamster lung, line V-79-379A; ovary, line CHO; rat hepatoma, line HTC, and mouse neuroblastoma, line NB413A) after a similar pre-treatment. The results suggest that enhancement of radiation resistance cannot be directly ascribed to an elevated GSH content in steroid-treated cells. On the basis of these data it is unlikely that the efficacy of radiotherapy will be diminished amongst patients receiving concomitant treatment with dexamethasone. However, in vivo testing is required to confirm these findings.

Animals↗
PubMed1985

Polyfunctional radiosensitizers. VII. Radiosensitization by conformationally-restricted isomers of a nitroxyl biradical in vitro.

Bothtrans-N,N'-bis(2,2,6,6-tetramethyl-1-oxyl-4-piperidinyl)-1, 2-diaminocyclopropane[Ro31-2269] and its cis isomer [Ro 31-2778] selectively sensitized hypoxic Chinese hamster cells, line V-79-753B, to radiation by decreasing both the D0 value and extrapolation number, whereas a related dibasic monoradical Ro 31-2655 decreased D0 alone. Although sensitization was maximal after a 1-hr cell-drug contact time, cells continued to accumulate both Ro 31-2269 and Ro 31-2778 when this contact time was increased up to 3 hr. There was no evidence for competition between either biradical and 2,2,6,6-tetramethyl-4-piperidinol-N-oxyl (TMPN) at equimolar concentration or biradical and 0.82 microM oxygen when cells were equilibrated with the biradicals for 3 hr prior to irradiation in the presence of mixtures of either oxygen and biradical, TMPN and biradical, or TMPN alone. Furthermore, when cells were equilibrated with an equimolar radical concentration of the trans isomer Ro 31-2269 and TMPN for 1 hr prior to irradiation in the presence of the mixture, there was no appreciable effect on sensitization of the slope of the hypoxic cell survival curve, but shoulder modification was reduced. When cells were equilibrated with the trans isomer Ro 21-2269 prior to irradiation in combination with 2.92 microM oxygen, cell survival was similar to that seen for cells irradiated with this concentration of oxygen alone. Examination of the plasma membrane from cells equilibrated with the trans biradical Ro 31-2269 showed that the drug accumulated in the membrane when compared with the concentration found in whole cells. Experiments with the conformationally-unrestricted biradical bis(2,2,6,6-tetramethyl-1-oxy-4-piperidinyl) succinate [Ro 03-6061] showed that when cells were equilibrated with the compound for 1 hr prior to irradiation in hypoxia in the presence of a mixture containing an equimolar radical concentration of TMPN, there was an increase in both the slope and the extrapolation number compared with values for hypoxic cells irradiated in the presence of this biradical alone. Furthermore, when cells which had been equilibrated with Ro 03-6061 were washed free of the drug, there was a residual decrease in both the D0 and extrapolation number of the hypoxic cell survival curve for at least 3 hr after removal of the compound. The results are discussed in terms of a model to account for sensitization by these compounds.

Animals↗
PubMed1984

Do prostaglandins affect cellular radiosensitivity in vitro?

We have been unable to detect any change in the in vitro radiation response of mouse fibrosarcoma cells, HSDM1C1, which secrete 2 micrograms PGE2/mg cell protein/24 h, in the presence of the prostaglandin biosynthesis inhibitor flurbiprofen. Furthermore, addition of exogenous PGE1 or PGA2 to cultures of Chinese hamster cells was similarly without effect on radiation response. Although a high concentration of PGA2 inhibited the growth of Chinese hamster cells in vitro this effect disappeared upon removal of the prostaglandin. The implications of these results for radiotherapy are discussed.

Animals↗
PubMed1983

In vitro inhibition of misonidazole toxicity and melphalan chemopotentiation by metyrapone.

Overnight exposure of Chinese hamster cells, V-79-753B, to 10(-3)M metyrapone protected them against the hypoxiamediated toxicity of 10(-2)M misonidazole. This protection was accompanied by an increase in radiation resistance. There was no appreciable change in the oxygen-enhancement ratio, nor in the amount of sensitisation produced by 10(-3)M misonidazole. Treatment of cells with metyrapone (10(-3)M) or dexamethasone (1 microgram ml-1 [approximately 2 X 10(-6)M]) prior to exposure first to 5 X 10(-3)M misonidazole in hypoxia and then to melphalan in air, substantially decreased the amount of chemopotentiation produced by the sensitiser, although the toxicity of melphalan alone was not affected in cells treated with either compound. Cells pretreated with either metyrapone or dexamethasone had 2-3 times more glutathione than control cells. This increase in GSH could not explain the change in radiation response, since cells pretreated with 5 X 10(-5)M flurbiprofen, a non-steroidal anti-inflammatory agent, had similarly high GSH levels, but their radiation response is similar to that of untreated cells (Millar et al, 1981). Neither dexamethasone nor flurbiprofen affected cell growth, whilst metyrapone markedly decreased the growth of cells. The results are discussed in terms of possible mechanism(s).

Animals↗
PubMed1983

Polyfunctional Radiosensitizers. VI. Dexamethasone inhibits shoulder modification by uncharged nitroxyl biradicals in mammalian cells irradiated in vitro.

Overnight exposure of Chinese hamster cells (V. 79-753B) in vitro to 1 micrograms/ml dexamethasone increases the radiation resistance of the cells by about 20% both in air and in hypoxia, while having no appreciable effect on the oxygen enhancement ratio (OER). This is accompanied by substantially higher levels of glutathione. When dexamethasone-treated hypoxic cells are irradiated in the presence of nitroxyl biradicals there is no effect on the slope ratio of of the exponential portion of the survival curves. In the case of uncharged biradicals, Ro.03-6061 and RSU-4072. which have been shown to modify the shoulder region of the hypoxic cell survival curve, there is an increase in extrapolation number in dexamethasone-treated cells. When hypoxic cells are exposed to the charged biradical RSU-4073, which does not exhibit shoulder modification, there is no change in extrapolation number. Experiments to examine the effect of concentration of these compounds on radiosensitization show that lower concentrations of both RSU-4072 and RSU-4073 are required to mediate changes in the slope of the hypoxic cell survival curve than to mediate shoulder modification, in the case of RSU-4072. Quantitative ESR data comparing the uptake of RSU-4072 and RSU-4073 with the monoradical TMPN into cells suggest that the cell membrane may act as a barrier to the incorporation of biradicals, and that this is greater for charged than for uncharged compounds. Treatment of cells with dexamethasone does not affect the uptake of the compounds. The data suggest, however, that the cell membrane may be an important site for localization of uncharged biradicals and that this may be important in determining shoulder modification.

Air↗
PubMed1981

Flurbiprofen, a non-steroid anti-inflammatory agent, protects cells against hypoxic cell radiosensitizers in vitro.

Overnight exposure of Chinese hamster cells (V79-753B) to 5 x 10(-5) M flurbiprofen (2-(2-fluoro-4-biphenyl)propionic acid) in vitro reduced the cytotoxic effects of misonidazole, 1-methyl-4-nitro-5-phenoxysulphonylimidazole (NSC 38087) and nitrofurantoin, both in air and in hypoxia at 37 degrees C. Flurbiprofen did not alter the cells' uptake of 14C-misonidazole, nor did it affect the radiosensitivity of aerobic or anaerobic cells, or the degree of hypoxic-cell radiosensitization produced by the sensitizers. When flurbiprofen-treated cells were exposed to melphalan there was no protection against cytotoxicity. These data suggest that flurbiprofen may inhibit the catabolism of radiosensitizers to toxic products and indicate the need to examine whether it will protect against misonidazole-induced toxicity in vivo.

Animals↗
PubMed1981

The effect of dexamethasone on the radiation survival response and misonidazole-induced hypoxic-cell cytotoxicity in Chinese hamster cells V-79-753B in vitro.

Overnight exposure of Chinese hamster cells, V-79-753B, to microgram quantities of the synthetic corticosteroid, dexamethasone, resulted in a decrease in sensitivity towards radiation, both in air and in hypoxia. The effect was dose-modifying and the oxygen enhancement ratio did not change appreciably. Similarly, when dexamethasone-treated hypoxic cells were irradiated in the presence of misonidazole, a hypoxic cell radiosensitizer, there was a decrease in radiation sensitivity compared with untreated hypoxic cells irradiated with misonidazole. The effect of dexamethasone cannot be attributed to classical radioprotection since administration of the drug immediately or 4.5 h before irradiation does not alter the survival response of hypoxic cells with or without misonidazole. Neither can this increased radioresistance be attributed to synchronization to a more resistant phase of the cell cycle since pretreated cells remain more radioresistant for at least 6 h after the removal of the drug. The data suggest that dexamethasone induces metabolic changes in cells which alter their radiosensitivity. Whatever metabolic changes may be occurring there was no effect on the uptake of 14C-misonidazole into dexamethasone-treated or control cells. However, there was a pronounced decrease in hypoxic-cell cytotoxicity induced by misonidazole in cells pretreated with dexamethasone. The implications of these results are discussed.

Animals↗
PubMedDate not supplied

Protection against misonidazole-induced toxicity in vitro by non-steroidal anti-inflammatory agents.

Overnight exposure of Chinese hamster cells, V-79-753B, to certain non-steroidal anti-inflammatory agents (NSAIA) including indomethacin (5 x 10(-5)M), benoxaprofen (5 x 10(-5)M) or aspirin (10(-4)M) protected against misonidazole-induced toxicity both in air and in hypoxia at 37 degrees C. In no instance was the radiosensitivity of cells affected by these treatments nor was there any effect on the amount of acute hypoxic cell radiosensitization produced by 1.0 mM misonidazole. There was no protection against misonidazole-induced toxicity when cells were pretreated with theophylline (10(-3)M). Protection against misonidazole-induced toxicity by benoxaprofen was not reversed by the addition of 1 microgram/ml prostaglandin E1 or F1 alpha. The results are discussed in terms of possible mechanisms.

Animals↗