1991, The British Journal of Radiology, 64, 1075-1077
Correspondence (The Editors do not hold themselves responsible for opinions expressed by correspondents) Nitrous oxide — radiosensitizer or radioprotector? THE EDITOR—SIR,
As part of a wider study of the radiobiological effects of narcotic gas mixtures (Conere, 1989) the possible radiation protection of Chinese hamster ovary cells (CHO) using a 99% nitrous oxide: 1 ± 0.05% oxygen gas mixture has been investigated. This gas mixture was used in the expectation that the narcotic component in the mixture might displace oxygen from sites within the cells where oxygen is required in order to confer oxygen dependent radiosensitivity. 1% was used in the gas mixtures on the basis that further displacement of oxygen in line with the Ebert et al hypothesis (1958) would be readily detectable given the shape of the Alper and Howard-Flanders (1956) hyperbolic response curve relating radiosensitivity to oxygen concentration. This also avoided any artefacts associated with a small degree of oxygen contamination (e.g. from plastic culture vessels) when complete anoxia is attempted. The data were fitted to dose-response curves using the linearquadratic model. There was no significant difference between the survival curves for cells irradiated in air or in 99% nitrous oxide: 1 % oxygen, thus a single curve has been fitted to those data for comparison with the curve for cells irradiated in 99% inert gas: 1 % oxygen (Fig. 1). The two curves are significantly different (alpha 100 q
I
values of 0.223 ± 0.005 and 0.207 ± 0.003 Gy ' and beta values of 0.0356 ± 0.0006 and 0.0226 ± 0.0005 Gy ' for the air/nitrous oxide and inert gas data, respectively). The results indicate no protective effect of using nitrous oxide. This gas appeared to sensitize as much as air. Such sensitization was seen to be additive to that obtained with 99% inert gas: 1 % oxygen. Whilst Ebert and Hornsey (1958) demonstrated major radioprotection using an 80% nitrous oxide: 20% oxygen gas mixture, the present findings indicate that the Ebert et al hypothesis (1958) does not have general application. This may be a consequence of different test systems, biological endpoints used and also irradiation conditions. The present work and that by Roots et al (1982) are, to our knowledge, the only studies that indicate sensitization of mammalian cells in vitro by nitrous oxide. This agreement was obtained using very different experimental procedures with a consensus of 19% sensitization by Roots and 26% by ourselves (at the 0.3% survival level) with respect to nitrogen and 99% nitrogen: 1 % oxygen gassing, respectively. Such findings might balance the present evidence concerning the radiosensitivity of mammalian cells in the presence of nitrous oxide. Ewing et al (1986) found that the amount of sensitization of V79 Chinese hamster cells by oxygen in an oxygen/nitrogen mixture, did not change when the nitrogen was replaced by nitrous oxide. This contrasts with our present results. Michaels et al (1983) did not find any direct evidence of nitrous oxide sensitization of CHO cells. However, in the presence of the OH* radical scavenger 3M DMSO, 20% enhanced sensitization was obtained in nitrous oxide saturated conditions compared with irradiation under nitrogen saturated conditions. In conclusion, the radiation response of mammalian systems to nitrous oxide and even to anaesthetic/narcotic agents in general, has in our opinion yet to be resolved, with possible consequences for present and perhaps future clinical treatment strategies (Conere et al, 1986; Conere, 1987). Acknowledgments We wish to acknowledge the helpful suggestions and comments of Dr O. C. A. Scott, The Richard Dimbleby Department of St Thomas' Hospital and thank Mr John Saunders and his staff from the Medical Physics Department for providing radiation dose calibrations. We also thank Professor W. S. Lowry, Department of Oncology, The Queen's University, Belfast, for his encouragement and the Ulster Cancer Foundation and Friends of Montgomery House for their financial support. Yours, etc.,
1-
0.5-
T. J. CONERE A. BROCK ©-©
0.1-
99 % NITROUS OXIDE :1% OXYGEN
A. H. W. NIAS
Q—Q 99 % INERT GAS: 1% OXYGEN
0.01 5
10
15
Figure 1. Irradiation cell survival curves for Chinese hamster ovary cells whilst exposed to various gas mixtures. Irradiation was with 212 kV X-rays (half value layer = 0.83 mm copper).
Vol. 64, No. 767
Richard Dimbleby Department of Cancer Research, United Medical & Dental Schools, St Thomas' Hospital, London SE1 7EH (Received March 1991 and in revised form July 1991) References ALPER, T. & HOWARD-FLANDERS, P., 1956. Role of oxygen in
modifying the radiosensitivity of Ecoli B. Nature, 178,978-979.
1075
Correspondence CONERE, T. J., 1987. Advances in hypoxyradiotherapy. International Journal of Radiation Oncology, Biology, Physics, 13, 1971-1972. CONERE, T. J., 1989. The Radiobiological Effects of Gas Mixtures Under Ambient and Hyperbaric Conditions. PhD Thesis, The Queen's University of Belfast. CONERE, T. J., CHURCH, S. W. & LOWRY, W. S., 1986. The radiopro-
tective role of common anaesthetic and other narcotic agents. Radiotherapy & Oncology, 5, 347-348. EBERT, M. & HORNSEY, S., 1958. Effect of nitrous oxide on the radiosensitivity of mouse Ehrlich Ascites Tumour. Nature, 182, 1240. EBERT, M., HORNSEY, S. & HOWARD, A., 1958. Effect on radiosen-
calcification can be very useful in locating the vessel exactly, and occasionally in avoiding it if the vein is being sought. Some of these differences in our respective techniques may be caused by severity of disease of obesity requiring closer attention to the puncture technique, but I doubt it. Neither do I work in lavish facilities under no time pressure, fiddling with fluoroscopy while real work is waiting to be done. My aim is a clean vessel wall puncture on the first attempt, at a safe level along the common femoral artery, with certain knowledge of the position of the catheter tip, assessment of the flow rate with contrast, and selection of a table movement rate which will show all vessels down to and including the feet without the need for a second run. This cannot be done well without fluoroscopy.
sitivity of inert gases. Nature, 181, 613-616. Yours etc.,
EWING, D., KOVAL, T. M. & WALTON, H. L., 1986. Radiation sen-
sitisation by oxygen of in vitro mammalian cells: is 0, involved? Radiation Research, 106, 356-365. MICHAELS, H. B., PETERSON, E. C. & EPP, E. R., 1983. Effects of
modifiers of the yield of hydroxyl radicals on the radiosensitivity of mammalian cells at ultra-high dose rates. Radiation Research, 95, 620-636. ROOTS, R., CHATTERJEE, A., BLAKELY, E., CHANG, P., SMITH, K. &
TOBIAS, C , 1982. Radiation responses in air, nitrous oxide and nitrogen saturated mammalian cells. Radiation Research, 92, 245-254.
M. J. TOWERS
Department of Radiology, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario M5G 2C4 {Received April 1991) References GRIER, D. & HARTNELL, G., 1991. Percutaneous femoral artery puncture: practice and anatomy. British Journal of Radiology, 64,183. DARCY, M. D., 1991. Lower-extremity arteriography: current approach and techniques. Radiology, 178, 615—621.
Percutaneous femoral artery puncture: practice and anatomy The EDITOR—SIR,
I read with interest Dr Hartnell's opinion that fluoroscopy is hardly ever warranted in puncturing the femoral artery (Grier & Hartnell, 1991). Perhaps our patient populations are different, but not infrequently I have to puncture a barely palpable, or indeed a nonpalpable artery shown to have flow on non-invasive imaging. My experience is also of thousands of punctures, the majority in severly atherosclerotic vessels. While translumbar, axillary or brachial punctures are then usually indicated, my practice is to attempt a retrograde examination as I have developed faith in the noninvasive assessment that the vessel is open. I do not understand how fluoroscopy slows down the case throughput, as confirmation of catheter tip placement and a contrast injection for timing purposes both require fluoroscopy. Reliance on arterial backflow and depth of placement of the catheter alone is not optimal angiographic technique in 1991 (Darcy, 1991), however widely this is still practised. Dr Hartnell missed my point about the usefulness of checking the fluoroscopy unit by actually using it. I assume nothing when performing invasive procedures, and few radiographers actually check the foot-pedal function. I prefer to know that fluoroscopy is available immediately if required. Has Dr Hartnell never been in a vessel with a good backflow where the guidewire will not advance despite manipulation and the use of a floppy tip guidewire? A contrast injection through the needle under fluoroscopy will often clarify the problem without the need for, and risk of, a second puncture. The detection of vascular calcification is by no means as irrelevant as Dr Hartnell thinks. In difficult punctures tubular or linear
1076
How and why are ultrasonic scanners chosen? The EDITOR—SIR,
What is it that influences the purchase of ultrasound scanners? We recently conducted a postal survey concerned with this. Our objective was to find out how prospective purchasers obtain the information that enables them to select the equipment that they would like to buy. We did not try to discover what features of equipment design, performance and cost are relevant to equipment selection. It is after all reasonable to suppose that purchasers desire ergonimicably designed equipment that produces good images and is competitively priced. We sent a questionnaire to 108 colleagues whom we knew to be actively involved in medical ultrasonic diagnosis; there was a 78% response rate (54 radiologists, 30 others). We were thrilled that so many too the trouble to reply and thank them very much. The questionnaire asked for a score from 0 to 5 to be given for the value of each of a series of possible influences that purchasers might consider, 0 representing least value, 5 the most. These influences included contact with sales people, seeing equipment at commercial exhibitions, taking expert advice and visiting other hospitals to see equipment in use. Detailed presentation of the results is not appropriate in this letter so we have condensed them to produce a league pie chart of those influences thought to be useful by our respondents (Fig. 1). A very striking, but not unexpected, result is that the most valuable influence is a "hands-on" trial of the equipment. Interestingly, none of the respondents mentioned that advertisements, about which we did not specifically enquire, had any impact.
The British Journal of Radiology. November 1991
Correspondence (The Editors do not hold themselves responsible for opinions expressed by correspondents) Nitrous oxide — radiosensitizer or radioprotector? THE EDITOR—SIR,
As part of a wider study of the radiobiological effects of narcotic gas mixtures (Conere, 1989) the possible radiation protection of Chinese hamster ovary cells (CHO) using a 99% nitrous oxide: 1 ± 0.05% oxygen gas mixture has been investigated. This gas mixture was used in the expectation that the narcotic component in the mixture might displace oxygen from sites within the cells where oxygen is required in order to confer oxygen dependent radiosensitivity. 1% was used in the gas mixtures on the basis that further displacement of oxygen in line with the Ebert et al hypothesis (1958) would be readily detectable given the shape of the Alper and Howard-Flanders (1956) hyperbolic response curve relating radiosensitivity to oxygen concentration. This also avoided any artefacts associated with a small degree of oxygen contamination (e.g. from plastic culture vessels) when complete anoxia is attempted. The data were fitted to dose-response curves using the linearquadratic model. There was no significant difference between the survival curves for cells irradiated in air or in 99% nitrous oxide: 1 % oxygen, thus a single curve has been fitted to those data for comparison with the curve for cells irradiated in 99% inert gas: 1 % oxygen (Fig. 1). The two curves are significantly different (alpha 100 q
I
values of 0.223 ± 0.005 and 0.207 ± 0.003 Gy ' and beta values of 0.0356 ± 0.0006 and 0.0226 ± 0.0005 Gy ' for the air/nitrous oxide and inert gas data, respectively). The results indicate no protective effect of using nitrous oxide. This gas appeared to sensitize as much as air. Such sensitization was seen to be additive to that obtained with 99% inert gas: 1 % oxygen. Whilst Ebert and Hornsey (1958) demonstrated major radioprotection using an 80% nitrous oxide: 20% oxygen gas mixture, the present findings indicate that the Ebert et al hypothesis (1958) does not have general application. This may be a consequence of different test systems, biological endpoints used and also irradiation conditions. The present work and that by Roots et al (1982) are, to our knowledge, the only studies that indicate sensitization of mammalian cells in vitro by nitrous oxide. This agreement was obtained using very different experimental procedures with a consensus of 19% sensitization by Roots and 26% by ourselves (at the 0.3% survival level) with respect to nitrogen and 99% nitrogen: 1 % oxygen gassing, respectively. Such findings might balance the present evidence concerning the radiosensitivity of mammalian cells in the presence of nitrous oxide. Ewing et al (1986) found that the amount of sensitization of V79 Chinese hamster cells by oxygen in an oxygen/nitrogen mixture, did not change when the nitrogen was replaced by nitrous oxide. This contrasts with our present results. Michaels et al (1983) did not find any direct evidence of nitrous oxide sensitization of CHO cells. However, in the presence of the OH* radical scavenger 3M DMSO, 20% enhanced sensitization was obtained in nitrous oxide saturated conditions compared with irradiation under nitrogen saturated conditions. In conclusion, the radiation response of mammalian systems to nitrous oxide and even to anaesthetic/narcotic agents in general, has in our opinion yet to be resolved, with possible consequences for present and perhaps future clinical treatment strategies (Conere et al, 1986; Conere, 1987). Acknowledgments We wish to acknowledge the helpful suggestions and comments of Dr O. C. A. Scott, The Richard Dimbleby Department of St Thomas' Hospital and thank Mr John Saunders and his staff from the Medical Physics Department for providing radiation dose calibrations. We also thank Professor W. S. Lowry, Department of Oncology, The Queen's University, Belfast, for his encouragement and the Ulster Cancer Foundation and Friends of Montgomery House for their financial support. Yours, etc.,
1-
0.5-
T. J. CONERE A. BROCK ©-©
0.1-
99 % NITROUS OXIDE :1% OXYGEN
A. H. W. NIAS
Q—Q 99 % INERT GAS: 1% OXYGEN
0.01 5
10
15
Figure 1. Irradiation cell survival curves for Chinese hamster ovary cells whilst exposed to various gas mixtures. Irradiation was with 212 kV X-rays (half value layer = 0.83 mm copper).
Vol. 64, No. 767
Richard Dimbleby Department of Cancer Research, United Medical & Dental Schools, St Thomas' Hospital, London SE1 7EH (Received March 1991 and in revised form July 1991) References ALPER, T. & HOWARD-FLANDERS, P., 1956. Role of oxygen in
modifying the radiosensitivity of Ecoli B. Nature, 178,978-979.
1075
Correspondence CONERE, T. J., 1987. Advances in hypoxyradiotherapy. International Journal of Radiation Oncology, Biology, Physics, 13, 1971-1972. CONERE, T. J., 1989. The Radiobiological Effects of Gas Mixtures Under Ambient and Hyperbaric Conditions. PhD Thesis, The Queen's University of Belfast. CONERE, T. J., CHURCH, S. W. & LOWRY, W. S., 1986. The radiopro-
tective role of common anaesthetic and other narcotic agents. Radiotherapy & Oncology, 5, 347-348. EBERT, M. & HORNSEY, S., 1958. Effect of nitrous oxide on the radiosensitivity of mouse Ehrlich Ascites Tumour. Nature, 182, 1240. EBERT, M., HORNSEY, S. & HOWARD, A., 1958. Effect on radiosen-
calcification can be very useful in locating the vessel exactly, and occasionally in avoiding it if the vein is being sought. Some of these differences in our respective techniques may be caused by severity of disease of obesity requiring closer attention to the puncture technique, but I doubt it. Neither do I work in lavish facilities under no time pressure, fiddling with fluoroscopy while real work is waiting to be done. My aim is a clean vessel wall puncture on the first attempt, at a safe level along the common femoral artery, with certain knowledge of the position of the catheter tip, assessment of the flow rate with contrast, and selection of a table movement rate which will show all vessels down to and including the feet without the need for a second run. This cannot be done well without fluoroscopy.
sitivity of inert gases. Nature, 181, 613-616. Yours etc.,
EWING, D., KOVAL, T. M. & WALTON, H. L., 1986. Radiation sen-
sitisation by oxygen of in vitro mammalian cells: is 0, involved? Radiation Research, 106, 356-365. MICHAELS, H. B., PETERSON, E. C. & EPP, E. R., 1983. Effects of
modifiers of the yield of hydroxyl radicals on the radiosensitivity of mammalian cells at ultra-high dose rates. Radiation Research, 95, 620-636. ROOTS, R., CHATTERJEE, A., BLAKELY, E., CHANG, P., SMITH, K. &
TOBIAS, C , 1982. Radiation responses in air, nitrous oxide and nitrogen saturated mammalian cells. Radiation Research, 92, 245-254.
M. J. TOWERS
Department of Radiology, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario M5G 2C4 {Received April 1991) References GRIER, D. & HARTNELL, G., 1991. Percutaneous femoral artery puncture: practice and anatomy. British Journal of Radiology, 64,183. DARCY, M. D., 1991. Lower-extremity arteriography: current approach and techniques. Radiology, 178, 615—621.
Percutaneous femoral artery puncture: practice and anatomy The EDITOR—SIR,
I read with interest Dr Hartnell's opinion that fluoroscopy is hardly ever warranted in puncturing the femoral artery (Grier & Hartnell, 1991). Perhaps our patient populations are different, but not infrequently I have to puncture a barely palpable, or indeed a nonpalpable artery shown to have flow on non-invasive imaging. My experience is also of thousands of punctures, the majority in severly atherosclerotic vessels. While translumbar, axillary or brachial punctures are then usually indicated, my practice is to attempt a retrograde examination as I have developed faith in the noninvasive assessment that the vessel is open. I do not understand how fluoroscopy slows down the case throughput, as confirmation of catheter tip placement and a contrast injection for timing purposes both require fluoroscopy. Reliance on arterial backflow and depth of placement of the catheter alone is not optimal angiographic technique in 1991 (Darcy, 1991), however widely this is still practised. Dr Hartnell missed my point about the usefulness of checking the fluoroscopy unit by actually using it. I assume nothing when performing invasive procedures, and few radiographers actually check the foot-pedal function. I prefer to know that fluoroscopy is available immediately if required. Has Dr Hartnell never been in a vessel with a good backflow where the guidewire will not advance despite manipulation and the use of a floppy tip guidewire? A contrast injection through the needle under fluoroscopy will often clarify the problem without the need for, and risk of, a second puncture. The detection of vascular calcification is by no means as irrelevant as Dr Hartnell thinks. In difficult punctures tubular or linear
1076
How and why are ultrasonic scanners chosen? The EDITOR—SIR,
What is it that influences the purchase of ultrasound scanners? We recently conducted a postal survey concerned with this. Our objective was to find out how prospective purchasers obtain the information that enables them to select the equipment that they would like to buy. We did not try to discover what features of equipment design, performance and cost are relevant to equipment selection. It is after all reasonable to suppose that purchasers desire ergonimicably designed equipment that produces good images and is competitively priced. We sent a questionnaire to 108 colleagues whom we knew to be actively involved in medical ultrasonic diagnosis; there was a 78% response rate (54 radiologists, 30 others). We were thrilled that so many too the trouble to reply and thank them very much. The questionnaire asked for a score from 0 to 5 to be given for the value of each of a series of possible influences that purchasers might consider, 0 representing least value, 5 the most. These influences included contact with sales people, seeing equipment at commercial exhibitions, taking expert advice and visiting other hospitals to see equipment in use. Detailed presentation of the results is not appropriate in this letter so we have condensed them to produce a league pie chart of those influences thought to be useful by our respondents (Fig. 1). A very striking, but not unexpected, result is that the most valuable influence is a "hands-on" trial of the equipment. Interestingly, none of the respondents mentioned that advertisements, about which we did not specifically enquire, had any impact.
The British Journal of Radiology. November 1991
