954 PREVENTION OF CANCER
ally
well tolerated, care being taken to avoid concomitant metal-ion therapy. Bleomycin, as either a single agent or as part of a combination of oncolytic drugs, was given intravenously 1-2 h after the last dose of penicillamine. A similar regimen used in rodents showed considerably enhanced cytotoxicity measured as marrow suppression, but no observable increase in toxic effects. In the patients treated there were no toxic effects such as pneumonitis or nephrotic syndrome. One patient showed a much-depressed leucocyte-count, an effect not normally associated with bleomycin alone. Otherwise the response to the combination was encouraging; assessment is still in progress. These preliminary results tend to confirm the hypothesis that the presence of chelatable copper alters the cytotoxic activity of bleomycin in vivo, and that removing at least some of this copper may have a beneficial effect; and they suggest that the interrelationship of the leucocyte system, copper, and metal-binding agents such as penicillamine and aspirin be investigated further. A. W. PREECE Radiotherapy Centre, P. A. LIGHT Bristol Royal Infirmary, P. A. EVANS Bristol BS2 8ED. M.R.C. Cyclotron Unit, Hammersmith Hospital, London W12
A. D. NUNN
Six,-You cited (March 26,,p. 685) our data to support the contention that cancer is preventable and not determined by heredity. However, in illustrating the point that a prevention programme for one cancer site may increase risk for another you used an example that does not necessarily hold. In the past, populations at low risk of breast cancer have always been at high risk of cervical cancer.’ It is assumed that this is because of an earlier age at first pregnancy, which carries an increased risk of cervical cancer. However, the Mormons, with a lower risk of cervical cancer, also have a significantly lower risk of breast cancer :2 age adjusted rates per 100 000 for the Mormon population compared with those for the Third National Cancer Survey3 (in parentheses) are 62.8 (72-2) for breast cancer and 12.1 (15-5) for invasive cervical cancer. While no specific information is available on age at first pregnancy in Mormons, age at first marriage is a year below that of the U.S. average. A similar result has been observed in the Seventh Day Adventists.4 This implies that cancer of the cervix, while related to early age at first intercourse, is more directly related to other factors associated with intercourse (possibly, an increased susceptibility to viral infection venereally transmitted), and that early age at first pregnancy does not inevitably lead to increased cervical-cancer risk. Department of Family and Community Medicine, University of Utah College of Medicine, Salt Lake City, Utah 84132, U.S.A.
JOSEPH L. LYON
AIR EMBOLISM CAUSED BY FRACTURED CENTRAL-VENOUS CATHETER
SIR,-We would like
to
report
a case
of non-fatal air embo-
during parenteral nutrition via a central venous catheter (’Intra-medicut’, Sherwood Medical) introduced via the internal jugular vein. The patient was a 60-year-old man who was recovering from acute pulmonary insufficiency after receiving multiple inlism
WEIGHT-GAIN INHIBITION BY LACTOSE
SIR,-Dr Mitchell and his colleagues (March 5, p. 500) report inhibition of weight gain in slightly undernourished Aboriginal children both with and without diarrhoea, when they are fed cow’s milk rather than cow’s milk in which the lactose has been hydrolysed. However, there are some aspects of the article on which I should like to comment or seek further information. In the controlled trial there were considerably more children with diarrhoea in the group given normal cow’s milk than in
given lactose-hydrolysed milk (L.H. milk). Was rehydration fully taken into account in these by the method of estimating initial weight (i.e., taking the average of the weights on the first and second day)? The statement that "a negative clinitest result therefore seems to be of little value in excluding lactose intolerance" perhaps needs discussion. Mitchell et al. do not mention the pH of the stools. In some infants with sugar intolerance, especially older infants, the unabsorbed sugar may be completely broken the group
Catheter fractured at hub.
juries in a road-traffic accident. He was being weaned from ventilatory support when his respiration and heart rates rose. Bubbles of air could be seen moving along the lumen of the catheter into the patient’s venous system from a fracture in the hub of the catheter. A second catheter also split. The defect (see figure) developed in the catheter hubs after ten days in the first patient and after eight hours in the second. An additional clinical feature was a blotchy discoloration of the skin overlying both supra-
clavicular regions. The connection between hub and drip set is as a dangerous source of air emboli from disconnection’ and during catheterisation.2Since many catheters have a similar hub design this is clearlv an area for improvement in design. Intensive Care
R. F. ARMSTRONG
Unit, University College Hospital,
J. L. PETERS
London WC1E 6AU
S. L. COHEN
1. Ordway, C. B., Ann. Surg. 1974, 179, 479. 2. Baden, H. Nord. Med. 1964, 590. 3. Levinsky, W. I. J. Am. med. Ass. 1969, 209, 1721.
down to lactic acid, carbon dioxide, and water before the stool is passed. Such stools are usually of an acid pH (6 or below). The group with clinitest-positive stools (declared L.H. group) were much younger (under 6 months) than the two groups in the controlled trial (over 12 months). The young infant with lactose intolerance is the one most likely to produce fluid stools containing more than 0.25g sugar by clinitest. The child over 1 year may retain the stool in the colon for a longer period, giving time for bacteria to convert the sugar to lactic acid and for fluid to be resorbed. Thus the stools are less often of a fluid nature but usually of an acid pH. Although Mitchell et al. recorded the number and quality of stools in each group, they do not give this information in the article. Although I do not find that blood-sugar levels after a lactose 1. Lyon, 2. Lyon,
J. L. in Cancer in Five Continents; vol. III. I.A.R.C., Lyon, 1976. J. L., Klauber, M. R., Gardner, J. W., Smart, C. R. New Engl. J.Med.
1976, 294, 129. Phillips, R. L. Cancer Res. 1975, 35, 3513. 4. Cutler, S. J., Young, J. L. (editors) Third National Cancer Survey: Incidence Data. Natn. CancerInst. Monogr. 1975, 41, 1. 3.
ally
well tolerated, care being taken to avoid concomitant metal-ion therapy. Bleomycin, as either a single agent or as part of a combination of oncolytic drugs, was given intravenously 1-2 h after the last dose of penicillamine. A similar regimen used in rodents showed considerably enhanced cytotoxicity measured as marrow suppression, but no observable increase in toxic effects. In the patients treated there were no toxic effects such as pneumonitis or nephrotic syndrome. One patient showed a much-depressed leucocyte-count, an effect not normally associated with bleomycin alone. Otherwise the response to the combination was encouraging; assessment is still in progress. These preliminary results tend to confirm the hypothesis that the presence of chelatable copper alters the cytotoxic activity of bleomycin in vivo, and that removing at least some of this copper may have a beneficial effect; and they suggest that the interrelationship of the leucocyte system, copper, and metal-binding agents such as penicillamine and aspirin be investigated further. A. W. PREECE Radiotherapy Centre, P. A. LIGHT Bristol Royal Infirmary, P. A. EVANS Bristol BS2 8ED. M.R.C. Cyclotron Unit, Hammersmith Hospital, London W12
A. D. NUNN
Six,-You cited (March 26,,p. 685) our data to support the contention that cancer is preventable and not determined by heredity. However, in illustrating the point that a prevention programme for one cancer site may increase risk for another you used an example that does not necessarily hold. In the past, populations at low risk of breast cancer have always been at high risk of cervical cancer.’ It is assumed that this is because of an earlier age at first pregnancy, which carries an increased risk of cervical cancer. However, the Mormons, with a lower risk of cervical cancer, also have a significantly lower risk of breast cancer :2 age adjusted rates per 100 000 for the Mormon population compared with those for the Third National Cancer Survey3 (in parentheses) are 62.8 (72-2) for breast cancer and 12.1 (15-5) for invasive cervical cancer. While no specific information is available on age at first pregnancy in Mormons, age at first marriage is a year below that of the U.S. average. A similar result has been observed in the Seventh Day Adventists.4 This implies that cancer of the cervix, while related to early age at first intercourse, is more directly related to other factors associated with intercourse (possibly, an increased susceptibility to viral infection venereally transmitted), and that early age at first pregnancy does not inevitably lead to increased cervical-cancer risk. Department of Family and Community Medicine, University of Utah College of Medicine, Salt Lake City, Utah 84132, U.S.A.
JOSEPH L. LYON
AIR EMBOLISM CAUSED BY FRACTURED CENTRAL-VENOUS CATHETER
SIR,-We would like
to
report
a case
of non-fatal air embo-
during parenteral nutrition via a central venous catheter (’Intra-medicut’, Sherwood Medical) introduced via the internal jugular vein. The patient was a 60-year-old man who was recovering from acute pulmonary insufficiency after receiving multiple inlism
WEIGHT-GAIN INHIBITION BY LACTOSE
SIR,-Dr Mitchell and his colleagues (March 5, p. 500) report inhibition of weight gain in slightly undernourished Aboriginal children both with and without diarrhoea, when they are fed cow’s milk rather than cow’s milk in which the lactose has been hydrolysed. However, there are some aspects of the article on which I should like to comment or seek further information. In the controlled trial there were considerably more children with diarrhoea in the group given normal cow’s milk than in
given lactose-hydrolysed milk (L.H. milk). Was rehydration fully taken into account in these by the method of estimating initial weight (i.e., taking the average of the weights on the first and second day)? The statement that "a negative clinitest result therefore seems to be of little value in excluding lactose intolerance" perhaps needs discussion. Mitchell et al. do not mention the pH of the stools. In some infants with sugar intolerance, especially older infants, the unabsorbed sugar may be completely broken the group
Catheter fractured at hub.
juries in a road-traffic accident. He was being weaned from ventilatory support when his respiration and heart rates rose. Bubbles of air could be seen moving along the lumen of the catheter into the patient’s venous system from a fracture in the hub of the catheter. A second catheter also split. The defect (see figure) developed in the catheter hubs after ten days in the first patient and after eight hours in the second. An additional clinical feature was a blotchy discoloration of the skin overlying both supra-
clavicular regions. The connection between hub and drip set is as a dangerous source of air emboli from disconnection’ and during catheterisation.2Since many catheters have a similar hub design this is clearlv an area for improvement in design. Intensive Care
R. F. ARMSTRONG
Unit, University College Hospital,
J. L. PETERS
London WC1E 6AU
S. L. COHEN
1. Ordway, C. B., Ann. Surg. 1974, 179, 479. 2. Baden, H. Nord. Med. 1964, 590. 3. Levinsky, W. I. J. Am. med. Ass. 1969, 209, 1721.
down to lactic acid, carbon dioxide, and water before the stool is passed. Such stools are usually of an acid pH (6 or below). The group with clinitest-positive stools (declared L.H. group) were much younger (under 6 months) than the two groups in the controlled trial (over 12 months). The young infant with lactose intolerance is the one most likely to produce fluid stools containing more than 0.25g sugar by clinitest. The child over 1 year may retain the stool in the colon for a longer period, giving time for bacteria to convert the sugar to lactic acid and for fluid to be resorbed. Thus the stools are less often of a fluid nature but usually of an acid pH. Although Mitchell et al. recorded the number and quality of stools in each group, they do not give this information in the article. Although I do not find that blood-sugar levels after a lactose 1. Lyon, 2. Lyon,
J. L. in Cancer in Five Continents; vol. III. I.A.R.C., Lyon, 1976. J. L., Klauber, M. R., Gardner, J. W., Smart, C. R. New Engl. J.Med.
1976, 294, 129. Phillips, R. L. Cancer Res. 1975, 35, 3513. 4. Cutler, S. J., Young, J. L. (editors) Third National Cancer Survey: Incidence Data. Natn. CancerInst. Monogr. 1975, 41, 1. 3.
