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Radiation induced bowel damage in rats treated under conditions of air or hyperbaric oxygen
C/in. RadioL (1972) 23, 106-109
RADIATION INDUCED BOWEL DAMAGE IN RATS TREATED UNDER CONDITIONS OF AIR OR HYPERBARIC OXYGEN R I C H A R D J. R. JOHNSON,* N A T H A N WISEMAN~ and G E O R G I E R. H O G G ++
From the Lahey Clinic Foundation, Boston, Mass.,* and the Departments of Surgery,~ and Pathology,+ Winnipeg General Hospital. The use of hyperbaric oxygen in radiotherapy will only result in an improved therapeutic ratio if the tumour is hypoxic and normal tissue well oxygenated, since hypoxic normal cells, if present, will also undergo an increased radiation response. When the abdomen is irradiated, acute or chronic bowel damage may occur. If either the normal mucosa or submucosal cells were normally hypoxic, an increased incidence of damage might be expected with hyperbaric oxygen. Some reports of hyperbaric abdominal irradiation in man suggest an increase in incidence of late bowel damage. An experimental model has been designed in which abdominal irradiation has been administered to rats under either conditions of air breathing or hyperbaric oxygen. Mortality at 12 days has been used as an assessment of mucosal damage, and late mortality to assess late bowel injury. No increase in early mortality was shown following hyperbaric irradiation, but late mortality was significantly increased in the hyperbaric group of animals. The significance of these findings and their relevance to the human situation is discussed.
BOWEL may be included in the treatment volume during irradiation of animals or humans under hyperbaric oxygen. An increase in radiation bowel damage would be expected to occur under hyperbaric oxygen if either the mucosal or submucosal coats were normally hypoxic. Hyperbaric oxygen has been shown by Suit (1971), to cause an increased radiation response in mouse skin. Using a strontium plaque, both Van den Brenk (1965), and Johnson (1969), showed that in human skin the erythema produced was increased when the test area was irradiated under hyperbaric conditions. Johnson (1969), in a pilot study of 50 cases of carcinoma of the cervix, showed that in the 25 treated under hyperbaric oxygen the acute bowel reaction was not increased. A five-year follow up suggested that the late bowel complication rate might be increased in the hyperbaric group. In order to examine the possibility that either mucosal or submucosal layers of bowel might be hypoxic under conditions of air breathing, an experiment has been designed to investigate the effect of hyperbaric oxygen on response to abdominal irradiation in rats, using early mortality to assess mucosal injury and late mortality for chronic bowel damage.
METHOD
FIG. 1 Animal hyperbaric chamber showing perspex immobilization tunnels. Cover of cylinder shows perspex windows. Treatment area is defined by lead.
Eighty-one 250 gram White Wistar rats were randomised into two experimental groups. One 106
RADIATION
INDUCED
BOWEL
group of animals was irradiated with 250 KVP x-rays in air, the second group in hyperbaric oxygen. All irradiation was carried out with the rats immobilized in a circular lucite cage (Fig. 1). The immobilization cage consists of 3 rectangular tunnels wedge shaped at the front for the animal's nose with air vents in the 'V' portion. The animal's position was maintained in the tunnel by means of a shutter wtfich fitted into a series of slots. The shutter had a cut-out in its base to fit over the animal's tail. Using this system the animals were unable to move forward or backward and were also unable to turn. The cage size was selected to suit the size of the animals used for the experiment. The cage fitted into a specially designed hyperbaric chamber where they were positioned on a press wood block to produce back scatter. The chamber had a lucite lid permitting direct vision of the animals for set up purposes. The irradiated volume extended from the diaphragm superiorly to the anus inferiorly and covered the full width of the abdomen. The 5 mm long abdominal field was defined by lines engraved on the lid and collimated by means of external lead blocks. The control animals were irradiated with the cage positioned in the hyperbaric chamber in the same way as the hyperbaric treated animals, with the exception that free air circulation was allowed. Animals in the hyperbaric group were compressed to 30 pounds per square inch gauge with 100 per cent oxygen in 5 minutes, maintained for a soaking time of 15 minutes prior to radiation, and decompressed in 3 to 4 minutes. The sources of irradiation were 250 KVP x-rays, 50 cms FSD, HVL 1.9 mm copper. The dose was calculated at the mid-plane of the abdomen. The exposures were calculated from readings obtained from a Victoreen meter with a 225 R chamber, and were identical for both control and hyperbaric groups since the control animals were treated breathing air in the hyperbaric chamber. The animals used were treated with a single dose of 1100, 1200 or 1300 fads. The number of animals in the two treatment groups and the three dose ranges are indicated in Table I. RESULTS Early Mortality Group.--Early and late mortality figures are presented for 81 rats receiving abdominal irradiation (Table I). Early mortality is expressed as the per cent of animals dying on or before the twelfth day following irradiation. The twelfth day was chosen for early mortality since, although the majority of the animals in the early mortality group died in the first 7 days, in some
DAMAGE
IN
107
RATS TABLE 1
ABDOMINAL IRRADIATION MORTALITY (81 animals)
Irradiation dose (rads)
1100 rads
1200 rads
1300 rads
Group (Air, HPO)
AIR HPO ] AIR H P 0
AIR HPO
No. of animals
18
16
Alive on 12th day
10
8
8
1
Alive on 133rd day
[ 12 ~
I
12
11
12
3
2
0
0
0
0
0
0
I
animals diarrhoea and mucus excretion continued until death at 12 days. All animals had persistent watery stools containing blood and mucus for five days following irradiation. The majority of animals at the 1300 rads dosage level died with diarrhoea within 7 days, and all were dead by 12 days. An increase in early mortality observed in the animals irradiated in oxygen at 1100 and 1200 fads was not significant. Late Mortality Group.reLate mortality was defined as a percentage of animals alive at the twelfth post irradiation day who died within 133 days. In the 1200 rads dosage level all animals in both groups were dead by 133 days. The timing of the death for the animals at the 1100 rads level is shown in the survival graph. Of the 10 rats which survived 12 days following a dose of 1100 rads in air, only 2 died in the following (133--13 120) days. On the other hand, 7 of the 8, 12-day survivors following a dose of 1100 rads in hyperbaric oxygen died during this 'late period'. The difference in late mortality for the 1100 rads group (88 per cent in hyperbaric oxygen; 20 per cent in air) was significant (P .005). Animals which died in the late period showed wasting and weakness with diarrhoea for several days prior to death. Death of animals usually occurred at night making autopsies unsatisfactory due to immediate intestinal autolysis. In order to investigate the pathological changes occurring in the animals, two groups of animals irradiated in air or hyperbaric oxygen to an abdominal dose of 1100 rads were sacrificed at 33 and 133 days. Comparison of the histology of viscera of 3 rats irradiated in air and 3 in hyperbaric oxygen sacrificed at 33 days showed no consistent striking differences. Changes common to all in comparison with the normal rat were: 1. A reduction of the lymphocyte population in the lymphoid follicles of the spleen. 2. A decrease in goblet cells in the colon. The viscera of 1 rat sacrificed 133 days after receiving 1100 fads abdominal irradiation in
108
CLINICAL
\
100 90
1100 RADS ABDOMINAl- RADIATION 34 RATS
II
80 70-
2>
RADIOLOGY
60"
HPO . . . . . AIR -
"1 -- - --11
5 5o40-
7 30-
~-7
20-
I
I. . . . . I0. EARL'
10
LATE MORTALITY t
i
i
i
i
i
i
i
i
i
20
30
40
50
60
70
80
90
100
110
"1
120
130
i
140
TIME (DAYS)
Fio. 2 Survivalcurvesof animalsreceivinga singledoseof 1100rads of abdominal irradiation in either air or hyperbaric 02 hyperbaric oxygen were examined. There was an increase in lymphocytes, histiocytes and plasma cells in the lamina propria in small and large bowel, with dilatation of gastric m u c o s a l glands and evidence of peritonitis, the cause of which was not established. Other radiation changes were confined to the kidneys, which showed focal glomerulosclerosis with tiny fibrin deposits; in one area the fibrin was present in the arterioles. Four rats sacrificed 133 days after comparable irradiation in air were examined. Inflammatory changes in the bowel were similar to those of the previous group. The renal findings were much less suggestive of radiation effect, being confined to a few foci of lymphocytes in the interstitium and protein casts, changes which were seen in all 4 animals. DISCUSSION The autopsies performed at 133 days on the separately sacrificed group of animals showed inflammatory changes of the bowel compatible with previous radiation. In view of the radiation bowel changes in the animals sacrificed at 133 days and the absence of any severe radiation damage in other organs, death of animals with weight loss and diarrhoea in the late mortality studies was attributed to radiation bowel damage. The only other radiation changes noted in the late survival group were in the kidneys. The hyperbaric treated animal had focal glomerulosclerosis with tiny fibrin deposits, changes which were not present in the 4 animals irradiated in air. The pathological changes in the kidneys of the sacrificed hyperbaric animal were not considered
severe enough to cause renal failure or to contribute to the late mortality rate. These findings are of interest and warrant further study in a larger group of animals at the 1100 rads dose level. The suggested higher incidence of late bowel damage in rats irradiated under hyperbaric conditions does not necessarily infer that similar bowel damage occurs in man, since the physiological effect of hyperbaric oxygen on intestinal blood flow may be different in the two species. The effect of hyperbaric oxygen on the human intestinal circulation has not been assessed, but vasoconstriction has been demonstrated in the retina and detected by indirect methods in the brain, peripheral circulation and in some tumours (Harper (1966), Whalen, et al. 1965, Saltzman, et al., 1965, Johnson 1971) whereas no vasoconstriction has been observed in the mesenteric vessels of rats subjected to hyperbaric oxygen (Johnson et al., unpublished) The possible effect of hyperbaric oxygen on bowel irradiation in man can only be speculative until final results of hyperbaric randomised trials are available. REFERENCES HARPER, A. M. (1966). The effect of hyperbaric oxygen on blood flow through the cerebral cortex. Proceedings of the Third International Conference on Hyperbaric Medicine, Durham, U.S.A.
JOHNSON, R. J. R. (1971). A comparison of the effect of hyperbaric oxygen and oxygen plus 5 per cent COs on tissue circulation and oxygenation. Radiology, 177-181, January. JOUNSON,R. J. R., et al. Unpublished work. JOHNSON,R. J. R. (1969). Hyperbaric O8 and radiotherapy in carcinoma of the cervix Tenth International Cancer Conference, Houston.
RADIATION
INDUCED
BOWEL
JOHNSON,R. J. R. (1969). The use of skin erythema tests as a method of assessing tumour oxygenation procedures. Proceedings o f the Fourth International Conference on Hyperbaric Medicine, Japan. SALTZMAN, H. A., et al. (1965). Retinal vascular response to hyperbaric oxygen J A M A , 191,290-292, January. SUIT, H. D., et aL (1967). Normal Tissue Damage and Tumor Cure Probability for Irradiation Given Under Different Conditions of Tissue Oxygenation in Hybrid Mice. Radiology, 89, 720-726.
DAMAGE
IN RATS
109
VAN DEN BRENK, et al. (1965). Enhancement of radiosensitivity of skin of patients by high pressure oxygen. British Journal Radiology, 38, 857-864. WHALEN,R. E., et aL (1965). Cardiovascular and blood gas response to hyperbaric oxygen. American Journal Cadriology, 15, 638-646. Reprints from Dr. Richard J. R. Johnson, Department of Radiotherapy, Lahey Clinic Foundation, 605 Commonwealth Avenue, Boston, Massachusetts 02215.
BOOK REVIEWS Pathology of Irradiation. Edited by CHARLES C. BERDJIS. 710 pages. Published by Williams and Wilkins, Baltimore, Md., U.S.A. Price £23. Over a quarter of a century ago Shields Warren published in Archives of Pathology a masterly survey of current knowledge related to the effects of ionising radiations on animal tissues. Since that time, the science of Radiology has grown from the foetal stage into adult life: thousands of articles have been written on the pathological effects of radiation from external and internal emitters, and new techniques have demonstrated previously unsuspected changes in cell structures. Radiation accidents and nuclear explosions have confirmed or refuted predictions based on experimental work. Tissues once considered resistant have shown themselves vulnerable and the radiotherapist has developed a belated respect for structures previously disregarded. So many ideas have changed and so much has been added to what we knew before, that Berdjis's decision to survey the field once more is a timely one: it is particularly appropriate and pleasing that Shields Warren should have written the foreword to his book. The contributors have been well chosen and the list of authors reads like a radiobiologist's Almanach de Gotha. Inevitably the style is somewhat uneven, but each contribution stands on its own and there is commendably little overlap or repetition. All books have faults and this one is no exception. There are omissions - one would have expected for example an account of the effect of X-rays on growing bone, which could have been substituted for the chapter on clinical uses of radio-isotopes, which seems out of place. The arrangement of references varies irritatingly and surprisingly from chapter to chapter. It is none the less a very valuable work of reference and should be available to every radiotherapist, radiobiologist and pathologist interested in the ionising radiations. It is hoped they will find it worth every penny of the £23 they will have to pay for it. W. B. DAWSON Radiography of Infants and Children. By DONALD B. DARLING, M.D. Second Edition. Charles C. Thomas, Springfield, Illinois. 1971. This book creates a good impression initially by paying great attention to the need for radiation protection and to methods of effective immobilisation. The author describes various immobilisation devices in detail, and points out that a few extra minutes taken in applying these is often re-paid by an adequate radiograph on the first attempt. He also points out that, as a general rule, parents are better excluded from the X-ray room during immobilisation and radiography.
The remainder of the book is divided into 3 sections dealing with radiography in infants, radiography in children, and finally a section on special studies. The planning of the book in this form has lead to some unnecessary duplication, for example the section on Bronchography in Infants is repeated in a shortened form under the heading Bronchography in Children. The elimination of this sort of duplication would reduce the size of the book, and presumably the price, and one wonders if it would not be better to have a joint section on radiographic procedures, and then to detail the differences between infant and child examinations. The other main criticism of this book, is that the author does not appear to have decided whether he is producing a manual on radiographic procedures, or describing special techniques to the radiologist. The section on special procedures would appear to be too detailed to give the radiographer a necessary insight into the proceedings, and yet is certainly not detailed enough to be a guide to the radiologist wishing to carry out some of these procedures. Various chapters provoke specific comments; for example, the description of barium meal and follow through studies does not lay enough emphasis on the fact that this is essentially a fluoroscopic procedure, and that films are usually taken as dictated by screening findings; there is no mention of the value of the prone oblique view with a little barium in the antrum of the stomach in assessing the pylorus, and it is implied that the procedure is usually carried out by injecting barium through a naso-gastric tube, rather than feeding the baby normally by a bottle. Under the barium enema technique, there is no mention of the value of the delayed film in the assessment of emptying in Hirschprungs disease, although the book specifies 5 standard views in the infant with a mega-colon including a post evacuation lateral. The radiographic examination of the hips does not include a mention of the now popular 'Andren' view and there is no note on the radiography of the assessment of ante-version deformity of the femur. Scoliosis studies in the special section recommend an alarming number of views, and only after these have been described is the comment made that the actual number of views should be taken in conjunction with the needs of the Orthopaedic Surgeon. In conclusion, I feel that radiographers working in children's hospital departments or indeed in any department where children are to be radiographed will find much useful information in this book. Many radiologists may find the rather dogmatic and extensive lists of views for procedures which are essentially determined by screening findings to be unnecessary and in danger of advocating excessive radiation. This book could be improved by a selective pruning. R. K. LEVICK
RADIATION INDUCED BOWEL DAMAGE IN RATS TREATED UNDER CONDITIONS OF AIR OR HYPERBARIC OXYGEN R I C H A R D J. R. JOHNSON,* N A T H A N WISEMAN~ and G E O R G I E R. H O G G ++
From the Lahey Clinic Foundation, Boston, Mass.,* and the Departments of Surgery,~ and Pathology,+ Winnipeg General Hospital. The use of hyperbaric oxygen in radiotherapy will only result in an improved therapeutic ratio if the tumour is hypoxic and normal tissue well oxygenated, since hypoxic normal cells, if present, will also undergo an increased radiation response. When the abdomen is irradiated, acute or chronic bowel damage may occur. If either the normal mucosa or submucosal cells were normally hypoxic, an increased incidence of damage might be expected with hyperbaric oxygen. Some reports of hyperbaric abdominal irradiation in man suggest an increase in incidence of late bowel damage. An experimental model has been designed in which abdominal irradiation has been administered to rats under either conditions of air breathing or hyperbaric oxygen. Mortality at 12 days has been used as an assessment of mucosal damage, and late mortality to assess late bowel injury. No increase in early mortality was shown following hyperbaric irradiation, but late mortality was significantly increased in the hyperbaric group of animals. The significance of these findings and their relevance to the human situation is discussed.
BOWEL may be included in the treatment volume during irradiation of animals or humans under hyperbaric oxygen. An increase in radiation bowel damage would be expected to occur under hyperbaric oxygen if either the mucosal or submucosal coats were normally hypoxic. Hyperbaric oxygen has been shown by Suit (1971), to cause an increased radiation response in mouse skin. Using a strontium plaque, both Van den Brenk (1965), and Johnson (1969), showed that in human skin the erythema produced was increased when the test area was irradiated under hyperbaric conditions. Johnson (1969), in a pilot study of 50 cases of carcinoma of the cervix, showed that in the 25 treated under hyperbaric oxygen the acute bowel reaction was not increased. A five-year follow up suggested that the late bowel complication rate might be increased in the hyperbaric group. In order to examine the possibility that either mucosal or submucosal layers of bowel might be hypoxic under conditions of air breathing, an experiment has been designed to investigate the effect of hyperbaric oxygen on response to abdominal irradiation in rats, using early mortality to assess mucosal injury and late mortality for chronic bowel damage.
METHOD
FIG. 1 Animal hyperbaric chamber showing perspex immobilization tunnels. Cover of cylinder shows perspex windows. Treatment area is defined by lead.
Eighty-one 250 gram White Wistar rats were randomised into two experimental groups. One 106
RADIATION
INDUCED
BOWEL
group of animals was irradiated with 250 KVP x-rays in air, the second group in hyperbaric oxygen. All irradiation was carried out with the rats immobilized in a circular lucite cage (Fig. 1). The immobilization cage consists of 3 rectangular tunnels wedge shaped at the front for the animal's nose with air vents in the 'V' portion. The animal's position was maintained in the tunnel by means of a shutter wtfich fitted into a series of slots. The shutter had a cut-out in its base to fit over the animal's tail. Using this system the animals were unable to move forward or backward and were also unable to turn. The cage size was selected to suit the size of the animals used for the experiment. The cage fitted into a specially designed hyperbaric chamber where they were positioned on a press wood block to produce back scatter. The chamber had a lucite lid permitting direct vision of the animals for set up purposes. The irradiated volume extended from the diaphragm superiorly to the anus inferiorly and covered the full width of the abdomen. The 5 mm long abdominal field was defined by lines engraved on the lid and collimated by means of external lead blocks. The control animals were irradiated with the cage positioned in the hyperbaric chamber in the same way as the hyperbaric treated animals, with the exception that free air circulation was allowed. Animals in the hyperbaric group were compressed to 30 pounds per square inch gauge with 100 per cent oxygen in 5 minutes, maintained for a soaking time of 15 minutes prior to radiation, and decompressed in 3 to 4 minutes. The sources of irradiation were 250 KVP x-rays, 50 cms FSD, HVL 1.9 mm copper. The dose was calculated at the mid-plane of the abdomen. The exposures were calculated from readings obtained from a Victoreen meter with a 225 R chamber, and were identical for both control and hyperbaric groups since the control animals were treated breathing air in the hyperbaric chamber. The animals used were treated with a single dose of 1100, 1200 or 1300 fads. The number of animals in the two treatment groups and the three dose ranges are indicated in Table I. RESULTS Early Mortality Group.--Early and late mortality figures are presented for 81 rats receiving abdominal irradiation (Table I). Early mortality is expressed as the per cent of animals dying on or before the twelfth day following irradiation. The twelfth day was chosen for early mortality since, although the majority of the animals in the early mortality group died in the first 7 days, in some
DAMAGE
IN
107
RATS TABLE 1
ABDOMINAL IRRADIATION MORTALITY (81 animals)
Irradiation dose (rads)
1100 rads
1200 rads
1300 rads
Group (Air, HPO)
AIR HPO ] AIR H P 0
AIR HPO
No. of animals
18
16
Alive on 12th day
10
8
8
1
Alive on 133rd day
[ 12 ~
I
12
11
12
3
2
0
0
0
0
0
0
I
animals diarrhoea and mucus excretion continued until death at 12 days. All animals had persistent watery stools containing blood and mucus for five days following irradiation. The majority of animals at the 1300 rads dosage level died with diarrhoea within 7 days, and all were dead by 12 days. An increase in early mortality observed in the animals irradiated in oxygen at 1100 and 1200 fads was not significant. Late Mortality Group.reLate mortality was defined as a percentage of animals alive at the twelfth post irradiation day who died within 133 days. In the 1200 rads dosage level all animals in both groups were dead by 133 days. The timing of the death for the animals at the 1100 rads level is shown in the survival graph. Of the 10 rats which survived 12 days following a dose of 1100 rads in air, only 2 died in the following (133--13 120) days. On the other hand, 7 of the 8, 12-day survivors following a dose of 1100 rads in hyperbaric oxygen died during this 'late period'. The difference in late mortality for the 1100 rads group (88 per cent in hyperbaric oxygen; 20 per cent in air) was significant (P .005). Animals which died in the late period showed wasting and weakness with diarrhoea for several days prior to death. Death of animals usually occurred at night making autopsies unsatisfactory due to immediate intestinal autolysis. In order to investigate the pathological changes occurring in the animals, two groups of animals irradiated in air or hyperbaric oxygen to an abdominal dose of 1100 rads were sacrificed at 33 and 133 days. Comparison of the histology of viscera of 3 rats irradiated in air and 3 in hyperbaric oxygen sacrificed at 33 days showed no consistent striking differences. Changes common to all in comparison with the normal rat were: 1. A reduction of the lymphocyte population in the lymphoid follicles of the spleen. 2. A decrease in goblet cells in the colon. The viscera of 1 rat sacrificed 133 days after receiving 1100 fads abdominal irradiation in
108
CLINICAL
\
100 90
1100 RADS ABDOMINAl- RADIATION 34 RATS
II
80 70-
2>
RADIOLOGY
60"
HPO . . . . . AIR -
"1 -- - --11
5 5o40-
7 30-
~-7
20-
I
I. . . . . I0. EARL'
10
LATE MORTALITY t
i
i
i
i
i
i
i
i
i
20
30
40
50
60
70
80
90
100
110
"1
120
130
i
140
TIME (DAYS)
Fio. 2 Survivalcurvesof animalsreceivinga singledoseof 1100rads of abdominal irradiation in either air or hyperbaric 02 hyperbaric oxygen were examined. There was an increase in lymphocytes, histiocytes and plasma cells in the lamina propria in small and large bowel, with dilatation of gastric m u c o s a l glands and evidence of peritonitis, the cause of which was not established. Other radiation changes were confined to the kidneys, which showed focal glomerulosclerosis with tiny fibrin deposits; in one area the fibrin was present in the arterioles. Four rats sacrificed 133 days after comparable irradiation in air were examined. Inflammatory changes in the bowel were similar to those of the previous group. The renal findings were much less suggestive of radiation effect, being confined to a few foci of lymphocytes in the interstitium and protein casts, changes which were seen in all 4 animals. DISCUSSION The autopsies performed at 133 days on the separately sacrificed group of animals showed inflammatory changes of the bowel compatible with previous radiation. In view of the radiation bowel changes in the animals sacrificed at 133 days and the absence of any severe radiation damage in other organs, death of animals with weight loss and diarrhoea in the late mortality studies was attributed to radiation bowel damage. The only other radiation changes noted in the late survival group were in the kidneys. The hyperbaric treated animal had focal glomerulosclerosis with tiny fibrin deposits, changes which were not present in the 4 animals irradiated in air. The pathological changes in the kidneys of the sacrificed hyperbaric animal were not considered
severe enough to cause renal failure or to contribute to the late mortality rate. These findings are of interest and warrant further study in a larger group of animals at the 1100 rads dose level. The suggested higher incidence of late bowel damage in rats irradiated under hyperbaric conditions does not necessarily infer that similar bowel damage occurs in man, since the physiological effect of hyperbaric oxygen on intestinal blood flow may be different in the two species. The effect of hyperbaric oxygen on the human intestinal circulation has not been assessed, but vasoconstriction has been demonstrated in the retina and detected by indirect methods in the brain, peripheral circulation and in some tumours (Harper (1966), Whalen, et al. 1965, Saltzman, et al., 1965, Johnson 1971) whereas no vasoconstriction has been observed in the mesenteric vessels of rats subjected to hyperbaric oxygen (Johnson et al., unpublished) The possible effect of hyperbaric oxygen on bowel irradiation in man can only be speculative until final results of hyperbaric randomised trials are available. REFERENCES HARPER, A. M. (1966). The effect of hyperbaric oxygen on blood flow through the cerebral cortex. Proceedings of the Third International Conference on Hyperbaric Medicine, Durham, U.S.A.
JOHNSON, R. J. R. (1971). A comparison of the effect of hyperbaric oxygen and oxygen plus 5 per cent COs on tissue circulation and oxygenation. Radiology, 177-181, January. JOUNSON,R. J. R., et al. Unpublished work. JOHNSON,R. J. R. (1969). Hyperbaric O8 and radiotherapy in carcinoma of the cervix Tenth International Cancer Conference, Houston.
RADIATION
INDUCED
BOWEL
JOHNSON,R. J. R. (1969). The use of skin erythema tests as a method of assessing tumour oxygenation procedures. Proceedings o f the Fourth International Conference on Hyperbaric Medicine, Japan. SALTZMAN, H. A., et al. (1965). Retinal vascular response to hyperbaric oxygen J A M A , 191,290-292, January. SUIT, H. D., et aL (1967). Normal Tissue Damage and Tumor Cure Probability for Irradiation Given Under Different Conditions of Tissue Oxygenation in Hybrid Mice. Radiology, 89, 720-726.
DAMAGE
IN RATS
109
VAN DEN BRENK, et al. (1965). Enhancement of radiosensitivity of skin of patients by high pressure oxygen. British Journal Radiology, 38, 857-864. WHALEN,R. E., et aL (1965). Cardiovascular and blood gas response to hyperbaric oxygen. American Journal Cadriology, 15, 638-646. Reprints from Dr. Richard J. R. Johnson, Department of Radiotherapy, Lahey Clinic Foundation, 605 Commonwealth Avenue, Boston, Massachusetts 02215.
BOOK REVIEWS Pathology of Irradiation. Edited by CHARLES C. BERDJIS. 710 pages. Published by Williams and Wilkins, Baltimore, Md., U.S.A. Price £23. Over a quarter of a century ago Shields Warren published in Archives of Pathology a masterly survey of current knowledge related to the effects of ionising radiations on animal tissues. Since that time, the science of Radiology has grown from the foetal stage into adult life: thousands of articles have been written on the pathological effects of radiation from external and internal emitters, and new techniques have demonstrated previously unsuspected changes in cell structures. Radiation accidents and nuclear explosions have confirmed or refuted predictions based on experimental work. Tissues once considered resistant have shown themselves vulnerable and the radiotherapist has developed a belated respect for structures previously disregarded. So many ideas have changed and so much has been added to what we knew before, that Berdjis's decision to survey the field once more is a timely one: it is particularly appropriate and pleasing that Shields Warren should have written the foreword to his book. The contributors have been well chosen and the list of authors reads like a radiobiologist's Almanach de Gotha. Inevitably the style is somewhat uneven, but each contribution stands on its own and there is commendably little overlap or repetition. All books have faults and this one is no exception. There are omissions - one would have expected for example an account of the effect of X-rays on growing bone, which could have been substituted for the chapter on clinical uses of radio-isotopes, which seems out of place. The arrangement of references varies irritatingly and surprisingly from chapter to chapter. It is none the less a very valuable work of reference and should be available to every radiotherapist, radiobiologist and pathologist interested in the ionising radiations. It is hoped they will find it worth every penny of the £23 they will have to pay for it. W. B. DAWSON Radiography of Infants and Children. By DONALD B. DARLING, M.D. Second Edition. Charles C. Thomas, Springfield, Illinois. 1971. This book creates a good impression initially by paying great attention to the need for radiation protection and to methods of effective immobilisation. The author describes various immobilisation devices in detail, and points out that a few extra minutes taken in applying these is often re-paid by an adequate radiograph on the first attempt. He also points out that, as a general rule, parents are better excluded from the X-ray room during immobilisation and radiography.
The remainder of the book is divided into 3 sections dealing with radiography in infants, radiography in children, and finally a section on special studies. The planning of the book in this form has lead to some unnecessary duplication, for example the section on Bronchography in Infants is repeated in a shortened form under the heading Bronchography in Children. The elimination of this sort of duplication would reduce the size of the book, and presumably the price, and one wonders if it would not be better to have a joint section on radiographic procedures, and then to detail the differences between infant and child examinations. The other main criticism of this book, is that the author does not appear to have decided whether he is producing a manual on radiographic procedures, or describing special techniques to the radiologist. The section on special procedures would appear to be too detailed to give the radiographer a necessary insight into the proceedings, and yet is certainly not detailed enough to be a guide to the radiologist wishing to carry out some of these procedures. Various chapters provoke specific comments; for example, the description of barium meal and follow through studies does not lay enough emphasis on the fact that this is essentially a fluoroscopic procedure, and that films are usually taken as dictated by screening findings; there is no mention of the value of the prone oblique view with a little barium in the antrum of the stomach in assessing the pylorus, and it is implied that the procedure is usually carried out by injecting barium through a naso-gastric tube, rather than feeding the baby normally by a bottle. Under the barium enema technique, there is no mention of the value of the delayed film in the assessment of emptying in Hirschprungs disease, although the book specifies 5 standard views in the infant with a mega-colon including a post evacuation lateral. The radiographic examination of the hips does not include a mention of the now popular 'Andren' view and there is no note on the radiography of the assessment of ante-version deformity of the femur. Scoliosis studies in the special section recommend an alarming number of views, and only after these have been described is the comment made that the actual number of views should be taken in conjunction with the needs of the Orthopaedic Surgeon. In conclusion, I feel that radiographers working in children's hospital departments or indeed in any department where children are to be radiographed will find much useful information in this book. Many radiologists may find the rather dogmatic and extensive lists of views for procedures which are essentially determined by screening findings to be unnecessary and in danger of advocating excessive radiation. This book could be improved by a selective pruning. R. K. LEVICK