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FOOD, TEMPERATURE, AND HEAD GROWTH IN NEONATES
1186
accompanied by release of only small amounts no release of other enzymes (20 minutes’ incubation). Complete release of enterokinase was not seen even with very high protease concentrations. Carboxypeptidase and hyaluronidase did not release any brushactivity
was
of lactase and
border enzymes. The release by bile-salts reported by Hadorn et al.tO was verified. Incubation with 10 (imole bile-salts per ml. (taurocholate and taurodeoxycholate 2/1) released about 35% of the enterokinase activity, but also released other enzymes (such as sucrose) to the same extent. The important finding that the activity of enterokinase is increased 5 times by an optimal concentration of bile-salts was also verified. This activation was seen with both bile-saltsolubilised and protease-solubilised enterokinase. The specificity of the release is in favour of chymotrypsin and trypsin as the physiological release agents. This specificity may reflect a very superficial location of the enterokinase, possibly in the glycocalyx. Unlike the proteases, bile-salts seem to provoke an equivalent release of other brush-border enzymes, and this apparently does not happen in vivo. The fact that trypsinogen must be activated by enterokinase (and chymotrypsinogen by trypsin) before a proteolytic release can occur in vivo is no argument against such a release mechanism, since trypsinogen is partly activated by enterokinase, while this enzyme is still associated with the intestinal wall (unpublished observation). Furthermore, enterokinase is liberated from the mucosa in desquamated cells,7,9 which, after disintegration, will make the enterokinase as accessible as in the isolated brush-borders. The final answer as to which mechanism (or mechanisms) operate in vivo must, however, await experiments using more physiological methods. Research Department 1,
University Hospitals, S-221 85 Lund, Sweden.
C. NORDSTRÖM A. DAHLQVIST.
CHEMOTHERAPY IN INOPERABLE BRONCHIAL CARCINOMA
Sm,-We would accept Professor Israel’s comment (May 8, p. 971) that our present knowledge of the effects of cytotoxic drugs suggests that two or three large doses of not be the most effective method of using chemotherapy to produce regression of a bronchial carcinoma, although his remarks are more correctly applicable to other chemotherapeutic agents whose effects are more dependent upon the proliferative state of cells of tumour and normal tissue Nevertheless, it was a form of drug therapy in common use when our trial (April 10, p. 715)
mustine may
started in 1960, and it was based on the observations of several workers that this kind of treatment was of value in palliation 12-14 and might possibly prolong surviva1.15,16 The evidence Professor Israel cites was not available until some years later, and by this time the results of a less encouraging clinical report were available." We would agree that better results may be obtained by using other cytotoxic drugs given in small doses over a longer period, either singly or in combination, and we are at present investigating the effect of two such regimens compared with a policy of wait11.
12. 13. 14. 15. 16. 17.
Bruce, W. R. in Canadian Cancer Conference; vol. VII, p. 53. Oxford, 1966. Lynch, J. P., Ware, P. F., Gaensler, E. A. Surgery, St. Louis, 1950, 27, 368. Hatch, H. B., Bradford, J. K., Oschner, A. J. Am. med. Ass. 1956, 160, 1129. Levine, B., Weisberger, A. S. Ann. intern. Med. 1955, 42, 1089. Karnofsky, D. A., Abelmann, W. A., Craver, L. Burchenal, J. H. Cancer, 1948, 1, 634. Roswit, B., Kaplan, G. Radiology, 1951, 57, 384. Krant, M. J. (for the Eastern Cooperative in Solid Tumour Chemotherapy). Am. J. Med. 1963, 35, 363.
and-see (treatment of serious symptoms only when they occur) in this disease. Fashions in the dose and time fractionation of cytotoxic therapy are changing, but the type of therapy described in our trial was used for many years and is still used in some centres. Even if it is shown subsequently that there are more effective ways of using drugs in the treatment of bronchial carcinoma, it is difficult to describe our treatment as anything but chemotherapy. K. R. DURRANT Department of Radiotherapy and R. J. BERRY Chest Clinic, J. M. BLACK Churchill Hospital, W. S. HAMILTON. Oxford.
ORGANISING OUR OPERATING
SIR,-With regard to your editorial (May 15, p. 1002), I would like to take exception to your agreement with the greater part of the joint subcommittee’s recommendations. The idea implicit in the report on operating-theatre staffing -as in the Salmon Report-is that nurses entering training are interested in a career structure in the administrative grades. Girls entering nursing do so to nurse patients; and, when they qualify, the majority wish to go no further than the level of ward or departmental sister. No amount of administration, whether it be lay or nursing, and no amount of reporting up and down the scale can substitute for well-trained nurses in the management of sick patients. In operating-theatres, again, there is no substitute for the well-trained nurse who has taken an interest in this type of work. The first part of the report on the organisation and staffing of operating departments implies that the difficulty is in recruitment, but the fact is that, over the last several years, the policy of the General Nursing Council has been such as to discourage nurses from becoming interested in theatre work. The average time that a student nurse spends in theatre now is about three weeks, and this usually in the second year of full student training. This period is quite insufficient for any girl at this stage to grasp the principles, and certainly insufficient to allow her to do any practical work in the theatre. The older system, where girls in their final year could spend three months in the theatre, allowed them a rather more mature interest in the subject and the possibility of taking part in operations as a scrub nurse. As a result, many girls were interested and applied to return to theatre after they had obtained their qualifications. One hopes that it is not too late to reverse the tendency throughout the administrative world to downgrade the very people who are the backbone of the nursing force. Kettering and District General Hospital Kettering, Northamptonshire.
J. M. S. HAGUE.
FOOD, TEMPERATURE, AND HEAD GROWTH IN NEONATES
SiR—Davies and Davis’ report1 of improved head-size outcome
kept
low-birth-weight infants fed generously and during the neonatal period stimulated us to re-
in
warm
examine measurements of head circumferences obtained in temperature/food/growth trials conducted several years ago.2,33 In each of these separate trials the differences in rates of head growth under warm and slightly cool two
conditions 1. 2.
were not
large enough to inspire confidence, and
Davies, P. A., Davis, J. P. Lancet, 1970, ii, 1216. Glass, L., Silverman, W. A., Sinclair, J. C. Pediatrics, Springfield, 1968, 41, 1033. 3. Glass, L., Silverman, W. A., Sinclair, J. C. Biol. Neonatorum, 1969, 14, 324.
1187 we
dismissed the differences
as
insignificant. We wish
to
point out that the direction of change of the differences was consistent in the
two trials. The median rates were faster in the warm infants fed the same amount of milk (table i), but no differences were observed when cool infants received more calories (table 11). Although the results are far from conclusive, when added to the experience of Davies and Davis they raise an interesting possibility. Growth of the brain of small neonates in the first weeks of life may be more sensitive to minor
TABLE II-INCREASE IN HEAD CIRCUMFERENCE IN INFANTS RAISED IN THE SAME THERMAL ENVIRONMENT BUT RECEIVING DIFFERENT CALORIC INTAKE
(SECOND STUDY)
TABLE I-INCREASE IN HEAD CIRCUMFERENCE IN TWO THERMAL ENVIRONMENTS IN ISOCALORICALLY FED INFANTS
Median head growth during 2 weeks of trial: SH (abdominal skin temperature 350°C; 128 C.{kg.{day) =2,0 cm.; W (abdominal skin temperature 36-5°C; 120 C./kg./day)=2-0 cm. (median intra-pair difference= 0 cm.).
changes in the food/temperature relationship than has been appreciated. In any case, we urge that further studies be undertaken, with special attention paid to long-term effects on the central nervous system. Unfortunately most of our patients were lost to follow-up after discharge from the hospital. New
York, N.Y.
LEONARD GLASS.
A.$ILVERMAN. SILVERMAN. San Francisco, California, U.S.A. WILLIAM A. JOHN C. SINCLAIR. Hamilton, Ontario, Canada.
FRUSEMIDE AND ACUTE PULMONARY ŒDEMA are that Dr. Tattersfield and Dr. McNicol SIR,-We glad can confirm our observations that intra1, p. 911) (May venous frusemide does not rapidly improve gas exchange in acute pulmonary oedema (March 27, p. 616). At first we also felt that the amount of oedema within the lungs would not fall substantially in the 6 hours after frusemide. However, since we made no hxmodynamic measurements in our patients, we sought guidance from other workers. In 15 patients with mean left-atrial pressures greater than 10 mm. Hg, due to mitral stenosis, the average pulmonaryartery mean pressure fell by 9 mm. Hg, the average directly measured mean left-atrial pressure fell by 4-5 mm. Hg, and cardiac output by 17-4%1 within 45 minutes of 40 mg. parenteral frusemide. From McCredie’s2 studies of the pulmonary extravascular water (P.E.v.), in similar patients, using the double indicator dilution technique, we conclude that these falls in pulmonary vascular pressures would, on average, reduce the measured P.E.v. by 50 ml. per sq. m. body surface. Since this technique probably measures only about 50% of the true P.E.v. in pulmonary oedema,s we expect that this could fall by some 200 ml. within 15-45 Median head growth during 2 weeks of trial (both studies): S (abdominal skin temperature 35.0oC; 120 C./kg./day) = 1.75 cm.; W (abdominal skin temperature 36’5°C; 120 C./kg./day)=2-00 cm. (median intra-pair difference = 0’25 cm.). * Less than 25th percentile, weight for gestational age.
1. 2. 3.
Lal, S., Murtagh, J. G., Pollock, A. M., Fletcher, E., Binnion, P. Br. Heart J. 1969, 31, 711. McCredie, M. Circulation, 1967, 36, 381. Kirk, B. W. J. appl. Physiol. 1969, 27, 607.
F.
accompanied by release of only small amounts no release of other enzymes (20 minutes’ incubation). Complete release of enterokinase was not seen even with very high protease concentrations. Carboxypeptidase and hyaluronidase did not release any brushactivity
was
of lactase and
border enzymes. The release by bile-salts reported by Hadorn et al.tO was verified. Incubation with 10 (imole bile-salts per ml. (taurocholate and taurodeoxycholate 2/1) released about 35% of the enterokinase activity, but also released other enzymes (such as sucrose) to the same extent. The important finding that the activity of enterokinase is increased 5 times by an optimal concentration of bile-salts was also verified. This activation was seen with both bile-saltsolubilised and protease-solubilised enterokinase. The specificity of the release is in favour of chymotrypsin and trypsin as the physiological release agents. This specificity may reflect a very superficial location of the enterokinase, possibly in the glycocalyx. Unlike the proteases, bile-salts seem to provoke an equivalent release of other brush-border enzymes, and this apparently does not happen in vivo. The fact that trypsinogen must be activated by enterokinase (and chymotrypsinogen by trypsin) before a proteolytic release can occur in vivo is no argument against such a release mechanism, since trypsinogen is partly activated by enterokinase, while this enzyme is still associated with the intestinal wall (unpublished observation). Furthermore, enterokinase is liberated from the mucosa in desquamated cells,7,9 which, after disintegration, will make the enterokinase as accessible as in the isolated brush-borders. The final answer as to which mechanism (or mechanisms) operate in vivo must, however, await experiments using more physiological methods. Research Department 1,
University Hospitals, S-221 85 Lund, Sweden.
C. NORDSTRÖM A. DAHLQVIST.
CHEMOTHERAPY IN INOPERABLE BRONCHIAL CARCINOMA
Sm,-We would accept Professor Israel’s comment (May 8, p. 971) that our present knowledge of the effects of cytotoxic drugs suggests that two or three large doses of not be the most effective method of using chemotherapy to produce regression of a bronchial carcinoma, although his remarks are more correctly applicable to other chemotherapeutic agents whose effects are more dependent upon the proliferative state of cells of tumour and normal tissue Nevertheless, it was a form of drug therapy in common use when our trial (April 10, p. 715)
mustine may
started in 1960, and it was based on the observations of several workers that this kind of treatment was of value in palliation 12-14 and might possibly prolong surviva1.15,16 The evidence Professor Israel cites was not available until some years later, and by this time the results of a less encouraging clinical report were available." We would agree that better results may be obtained by using other cytotoxic drugs given in small doses over a longer period, either singly or in combination, and we are at present investigating the effect of two such regimens compared with a policy of wait11.
12. 13. 14. 15. 16. 17.
Bruce, W. R. in Canadian Cancer Conference; vol. VII, p. 53. Oxford, 1966. Lynch, J. P., Ware, P. F., Gaensler, E. A. Surgery, St. Louis, 1950, 27, 368. Hatch, H. B., Bradford, J. K., Oschner, A. J. Am. med. Ass. 1956, 160, 1129. Levine, B., Weisberger, A. S. Ann. intern. Med. 1955, 42, 1089. Karnofsky, D. A., Abelmann, W. A., Craver, L. Burchenal, J. H. Cancer, 1948, 1, 634. Roswit, B., Kaplan, G. Radiology, 1951, 57, 384. Krant, M. J. (for the Eastern Cooperative in Solid Tumour Chemotherapy). Am. J. Med. 1963, 35, 363.
and-see (treatment of serious symptoms only when they occur) in this disease. Fashions in the dose and time fractionation of cytotoxic therapy are changing, but the type of therapy described in our trial was used for many years and is still used in some centres. Even if it is shown subsequently that there are more effective ways of using drugs in the treatment of bronchial carcinoma, it is difficult to describe our treatment as anything but chemotherapy. K. R. DURRANT Department of Radiotherapy and R. J. BERRY Chest Clinic, J. M. BLACK Churchill Hospital, W. S. HAMILTON. Oxford.
ORGANISING OUR OPERATING
SIR,-With regard to your editorial (May 15, p. 1002), I would like to take exception to your agreement with the greater part of the joint subcommittee’s recommendations. The idea implicit in the report on operating-theatre staffing -as in the Salmon Report-is that nurses entering training are interested in a career structure in the administrative grades. Girls entering nursing do so to nurse patients; and, when they qualify, the majority wish to go no further than the level of ward or departmental sister. No amount of administration, whether it be lay or nursing, and no amount of reporting up and down the scale can substitute for well-trained nurses in the management of sick patients. In operating-theatres, again, there is no substitute for the well-trained nurse who has taken an interest in this type of work. The first part of the report on the organisation and staffing of operating departments implies that the difficulty is in recruitment, but the fact is that, over the last several years, the policy of the General Nursing Council has been such as to discourage nurses from becoming interested in theatre work. The average time that a student nurse spends in theatre now is about three weeks, and this usually in the second year of full student training. This period is quite insufficient for any girl at this stage to grasp the principles, and certainly insufficient to allow her to do any practical work in the theatre. The older system, where girls in their final year could spend three months in the theatre, allowed them a rather more mature interest in the subject and the possibility of taking part in operations as a scrub nurse. As a result, many girls were interested and applied to return to theatre after they had obtained their qualifications. One hopes that it is not too late to reverse the tendency throughout the administrative world to downgrade the very people who are the backbone of the nursing force. Kettering and District General Hospital Kettering, Northamptonshire.
J. M. S. HAGUE.
FOOD, TEMPERATURE, AND HEAD GROWTH IN NEONATES
SiR—Davies and Davis’ report1 of improved head-size outcome
kept
low-birth-weight infants fed generously and during the neonatal period stimulated us to re-
in
warm
examine measurements of head circumferences obtained in temperature/food/growth trials conducted several years ago.2,33 In each of these separate trials the differences in rates of head growth under warm and slightly cool two
conditions 1. 2.
were not
large enough to inspire confidence, and
Davies, P. A., Davis, J. P. Lancet, 1970, ii, 1216. Glass, L., Silverman, W. A., Sinclair, J. C. Pediatrics, Springfield, 1968, 41, 1033. 3. Glass, L., Silverman, W. A., Sinclair, J. C. Biol. Neonatorum, 1969, 14, 324.
1187 we
dismissed the differences
as
insignificant. We wish
to
point out that the direction of change of the differences was consistent in the
two trials. The median rates were faster in the warm infants fed the same amount of milk (table i), but no differences were observed when cool infants received more calories (table 11). Although the results are far from conclusive, when added to the experience of Davies and Davis they raise an interesting possibility. Growth of the brain of small neonates in the first weeks of life may be more sensitive to minor
TABLE II-INCREASE IN HEAD CIRCUMFERENCE IN INFANTS RAISED IN THE SAME THERMAL ENVIRONMENT BUT RECEIVING DIFFERENT CALORIC INTAKE
(SECOND STUDY)
TABLE I-INCREASE IN HEAD CIRCUMFERENCE IN TWO THERMAL ENVIRONMENTS IN ISOCALORICALLY FED INFANTS
Median head growth during 2 weeks of trial: SH (abdominal skin temperature 350°C; 128 C.{kg.{day) =2,0 cm.; W (abdominal skin temperature 36-5°C; 120 C./kg./day)=2-0 cm. (median intra-pair difference= 0 cm.).
changes in the food/temperature relationship than has been appreciated. In any case, we urge that further studies be undertaken, with special attention paid to long-term effects on the central nervous system. Unfortunately most of our patients were lost to follow-up after discharge from the hospital. New
York, N.Y.
LEONARD GLASS.
A.$ILVERMAN. SILVERMAN. San Francisco, California, U.S.A. WILLIAM A. JOHN C. SINCLAIR. Hamilton, Ontario, Canada.
FRUSEMIDE AND ACUTE PULMONARY ŒDEMA are that Dr. Tattersfield and Dr. McNicol SIR,-We glad can confirm our observations that intra1, p. 911) (May venous frusemide does not rapidly improve gas exchange in acute pulmonary oedema (March 27, p. 616). At first we also felt that the amount of oedema within the lungs would not fall substantially in the 6 hours after frusemide. However, since we made no hxmodynamic measurements in our patients, we sought guidance from other workers. In 15 patients with mean left-atrial pressures greater than 10 mm. Hg, due to mitral stenosis, the average pulmonaryartery mean pressure fell by 9 mm. Hg, the average directly measured mean left-atrial pressure fell by 4-5 mm. Hg, and cardiac output by 17-4%1 within 45 minutes of 40 mg. parenteral frusemide. From McCredie’s2 studies of the pulmonary extravascular water (P.E.v.), in similar patients, using the double indicator dilution technique, we conclude that these falls in pulmonary vascular pressures would, on average, reduce the measured P.E.v. by 50 ml. per sq. m. body surface. Since this technique probably measures only about 50% of the true P.E.v. in pulmonary oedema,s we expect that this could fall by some 200 ml. within 15-45 Median head growth during 2 weeks of trial (both studies): S (abdominal skin temperature 35.0oC; 120 C./kg./day) = 1.75 cm.; W (abdominal skin temperature 36’5°C; 120 C./kg./day)=2-00 cm. (median intra-pair difference = 0’25 cm.). * Less than 25th percentile, weight for gestational age.
1. 2. 3.
Lal, S., Murtagh, J. G., Pollock, A. M., Fletcher, E., Binnion, P. Br. Heart J. 1969, 31, 711. McCredie, M. Circulation, 1967, 36, 381. Kirk, B. W. J. appl. Physiol. 1969, 27, 607.
F.