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SEVERE EPISTAXIS
545 2 hours after taking nearly 1000 mg. of amitriptyline. He had been previously admitted with an overdose of trifluoperazine (’ Stelazine ’), and was being treated for depression at another hospital where he was prescribed amitriptyline, 25 mg. three times a day. On admission he was flushed, unconscious, and could not be roused with painful stimuli. Breathing was stertorous, pulse 110 per minute, blood-pressure 150/100 mm. Hg, temperature 97 °F. Neurological examination revealed dilated pupils which did not react to light, and bilateral extensor plantar reflexes. After 4 hours his condition deteriorated, his blood-pressure fell to 90/60, and his temperature to 95°F. A stomach washout was done on admission, and in the next 12 hours he was given 3200 ml. of 10% mannitol anddextrose to force diuresis. The urinary output was 90 ml. during this time; systolic bloodpressure was maintained at 90-100 mm. Hg by metaraminol infusion, and respiration by oxygen through a venturi mask, keeping the oxygen concentration at 28-32%. The treatment was continued, and further forced diuresis resulted in 5120 ml. of urine being passed in the second 24 hours. After 96 hours he regained consciousness, the temperature rose spontaneously to normal levels, and the blood-pressure was maintained without aramine. He continued having hallucinations for the next 3 days.
The severe respiratory depression reported by Dr. Stark and Dr. Bethune was presumably due to the associated barbiturate intake in their case. -
I
am
St.
grateful to Dr. B. A. Young for allowing me to report this case.
Alfege’s Hospital,
London, S.E.10.
T. N. MEHROTRA.
STERILISATION IN GENERAL PRACTICE SIR,-Mr. Hughes’ article and, particularly, the letters on sterilisation by the use of pressure-cookers interest us, for we manufacture devices (’ Diacks ’) to test sterilisers. Dr. Grahame2 suggests that time of exposure be increased if the colour-change indicator does not change colour. This is dangerous, since most colour-change indicators will change in about an hour in boiling water, at a temperature far below sterilisation requirements. Rather than increasing the time, we suggest that the temperature be increased (by increasing the pressure) to 121 °C. The pressure required will vary widely, according to the outside barometric pressure. The temperature can be measured by a thermocouple system, or by a meltingpellet-type steriliser control (which costs about 5 cents). The main problem with any autoclave (including the pressurecooker) is the entrapment of air. By measuring temperature (rather than pressure) air-entrapment can be detected, since it results in lower temperatures for the same pressure. An automobile tyre is at over twenty lb. pressure, but will never sterilise. To adequately remove air from a pressure-cooker, it is nearly essential to have a bottom " blow-off " cock, for air is heavier than steam, and will settle to the bottom or collect in pockets at the centre of bundles. Wrapping articles in aluminium foil is dangerous, since the steam cannot penetrate the foil to drive out the air. Finally, culture of the pack-contents does not tell much about the autoclave, for they may have been nearly sterile when put into it. If culturing is to be done, resistant bacteria should be deliberately placed in the centre of the pack to make sure that sterilisation is occurring. We believe, however, that the best test is of the physical conditions, particularly the temperature. A clean article exposed to saturated (almost moist) steam at 121°C for fifteen minutes will be sterilised, and it makes little difference how the steam is produced. Many pressure-cooker-type autoclaves are successfully used in the United States-in fact the U.S. Army emergency hospitals use such autoclaves. Research Laboratory,
Smith and
Underwood,
Royal Oak,
Michigan. 1. 2.
ROBERT F. SMITH. Hughes, F. A. Lancet, 1965, i, 1161. Grahame, R. ibid. p. 1109.
SEVERE EPISTAXIS SIR,-Mr. Malcolmson’s letter (Aug. 21) makes it obvious that he has not yet had any cases of epistaxis as severe as the two described in my article, which admits our inability to secure control of hxmorrbage, and was written to point out that such cases can occur. The correspondence I have received lately has endorsed my view that similar cases have caused much worry to other colleagues. He may find the two cases incredible, but I would point out that he was not present. Ear, Nose, and Throat Department, Newcastle General Hospital, IVOR J. C. FREW. Newcastle upon Tyne, 4. FROM MICE TO MEN SIR,-Imbalance between inhibitors and accelerators of cell growth might easily " explain the commonly observed fluctuations in the rate of growth in malignant tumours ", as you wrote last week. Certainly one feels this when studying the mode of death of cancer patients, and there might well be, as you suggest, "profit in turning from mice to men" in the search for evidence. Many years of such clinical study produced a theory of the mechanism of cancer which, however, led back to mice. Using
accepted techniques of cancer transplantation it proved possible demonstrate, in normal human blood, substances which can accelerate growth to twice the control weight, and substances which can inhibit growth to a third of the control weight. (Details will be published elsewhere.) If we accept that there are many carcinogenic agencies, then therapy may lie in understanding the mechanism of cancer growth. Something in that machinery controls the actual rate of increase of a particular tumour, and dictates why similar tumours in different patients grow at different rates and why
to
Such a mechanism as you have discussed. that even if substances were predominant accelerating implies cancer would appear only when cells, acted upon by a carcinogen, were capable of receiving the accelerator. The extracts of human blood which my research colleague, Mr. J. M. Daly, has been preparing for the past ten years contain accelerators or inhibitors according to the method used; our work was at first complicated by our failure to recognise that accelerators might be present under other disease conditions (and even in apparently normal donors), and we finally had to make all our extracts of inhibitor from the red blood-cells of young donors. Others have also found biological inhibitors-Lippman1 in the follicular fluid of pigs, Schmeer and Huala2 in molluscs, and Szent-Gyorgyi3 in extracts of thymus and calf aorta. Some of our experiments support the belief of Szent-Gyorgyi and his team that they are dealing with molecules of low molecular weight. The inhibitor is very labile and its isolation difficult. But in mice consistent inhibition of transplanted tumours can be shown with substances purified from acetone extracts of red blood-cells. The production of accelerators appears to be a self-perpetuating and increasing function of growing cancer cells. This, coupled with a fall in inhibitor, especially as anaemia develops, would explain why some cancers appear to accelerate. But biological processes, especially in mammals, are rarely completely suppressed, and the body will continue to try to preserve its balance. There is therefore always the possibility, as one has seen, of a patient living almost in symbiosis with a cancer, a stationary mass (even a penetrating one) which advances at a very slow rate; and there is the chance of production of enough inhibitor (with or without some medical or surgical intervention) to reverse the process, destroy the cancer, and restore what you describe as the magic words ’biological control ’ ". We can certainly visualise that biological control as arising from a balance of these demonstrable factors in the blood. D. STARK MURRAY. Twickenham, Middlesex. some
regress,
"
1. 2. 3.
Lippman, M. Trans. N.Y. Acad Sci. 1965, 27, 342. Schmeer, M. R., Huala, C. V. Ann. N.Y Acad. Sci. 118, 603. Szent-Gyorgyi, A., Hegyeli, A., McLaughlin, J. A. Science, N.Y. 1963, 140, 1391.
The severe respiratory depression reported by Dr. Stark and Dr. Bethune was presumably due to the associated barbiturate intake in their case. -
I
am
St.
grateful to Dr. B. A. Young for allowing me to report this case.
Alfege’s Hospital,
London, S.E.10.
T. N. MEHROTRA.
STERILISATION IN GENERAL PRACTICE SIR,-Mr. Hughes’ article and, particularly, the letters on sterilisation by the use of pressure-cookers interest us, for we manufacture devices (’ Diacks ’) to test sterilisers. Dr. Grahame2 suggests that time of exposure be increased if the colour-change indicator does not change colour. This is dangerous, since most colour-change indicators will change in about an hour in boiling water, at a temperature far below sterilisation requirements. Rather than increasing the time, we suggest that the temperature be increased (by increasing the pressure) to 121 °C. The pressure required will vary widely, according to the outside barometric pressure. The temperature can be measured by a thermocouple system, or by a meltingpellet-type steriliser control (which costs about 5 cents). The main problem with any autoclave (including the pressurecooker) is the entrapment of air. By measuring temperature (rather than pressure) air-entrapment can be detected, since it results in lower temperatures for the same pressure. An automobile tyre is at over twenty lb. pressure, but will never sterilise. To adequately remove air from a pressure-cooker, it is nearly essential to have a bottom " blow-off " cock, for air is heavier than steam, and will settle to the bottom or collect in pockets at the centre of bundles. Wrapping articles in aluminium foil is dangerous, since the steam cannot penetrate the foil to drive out the air. Finally, culture of the pack-contents does not tell much about the autoclave, for they may have been nearly sterile when put into it. If culturing is to be done, resistant bacteria should be deliberately placed in the centre of the pack to make sure that sterilisation is occurring. We believe, however, that the best test is of the physical conditions, particularly the temperature. A clean article exposed to saturated (almost moist) steam at 121°C for fifteen minutes will be sterilised, and it makes little difference how the steam is produced. Many pressure-cooker-type autoclaves are successfully used in the United States-in fact the U.S. Army emergency hospitals use such autoclaves. Research Laboratory,
Smith and
Underwood,
Royal Oak,
Michigan. 1. 2.
ROBERT F. SMITH. Hughes, F. A. Lancet, 1965, i, 1161. Grahame, R. ibid. p. 1109.
SEVERE EPISTAXIS SIR,-Mr. Malcolmson’s letter (Aug. 21) makes it obvious that he has not yet had any cases of epistaxis as severe as the two described in my article, which admits our inability to secure control of hxmorrbage, and was written to point out that such cases can occur. The correspondence I have received lately has endorsed my view that similar cases have caused much worry to other colleagues. He may find the two cases incredible, but I would point out that he was not present. Ear, Nose, and Throat Department, Newcastle General Hospital, IVOR J. C. FREW. Newcastle upon Tyne, 4. FROM MICE TO MEN SIR,-Imbalance between inhibitors and accelerators of cell growth might easily " explain the commonly observed fluctuations in the rate of growth in malignant tumours ", as you wrote last week. Certainly one feels this when studying the mode of death of cancer patients, and there might well be, as you suggest, "profit in turning from mice to men" in the search for evidence. Many years of such clinical study produced a theory of the mechanism of cancer which, however, led back to mice. Using
accepted techniques of cancer transplantation it proved possible demonstrate, in normal human blood, substances which can accelerate growth to twice the control weight, and substances which can inhibit growth to a third of the control weight. (Details will be published elsewhere.) If we accept that there are many carcinogenic agencies, then therapy may lie in understanding the mechanism of cancer growth. Something in that machinery controls the actual rate of increase of a particular tumour, and dictates why similar tumours in different patients grow at different rates and why
to
Such a mechanism as you have discussed. that even if substances were predominant accelerating implies cancer would appear only when cells, acted upon by a carcinogen, were capable of receiving the accelerator. The extracts of human blood which my research colleague, Mr. J. M. Daly, has been preparing for the past ten years contain accelerators or inhibitors according to the method used; our work was at first complicated by our failure to recognise that accelerators might be present under other disease conditions (and even in apparently normal donors), and we finally had to make all our extracts of inhibitor from the red blood-cells of young donors. Others have also found biological inhibitors-Lippman1 in the follicular fluid of pigs, Schmeer and Huala2 in molluscs, and Szent-Gyorgyi3 in extracts of thymus and calf aorta. Some of our experiments support the belief of Szent-Gyorgyi and his team that they are dealing with molecules of low molecular weight. The inhibitor is very labile and its isolation difficult. But in mice consistent inhibition of transplanted tumours can be shown with substances purified from acetone extracts of red blood-cells. The production of accelerators appears to be a self-perpetuating and increasing function of growing cancer cells. This, coupled with a fall in inhibitor, especially as anaemia develops, would explain why some cancers appear to accelerate. But biological processes, especially in mammals, are rarely completely suppressed, and the body will continue to try to preserve its balance. There is therefore always the possibility, as one has seen, of a patient living almost in symbiosis with a cancer, a stationary mass (even a penetrating one) which advances at a very slow rate; and there is the chance of production of enough inhibitor (with or without some medical or surgical intervention) to reverse the process, destroy the cancer, and restore what you describe as the magic words ’biological control ’ ". We can certainly visualise that biological control as arising from a balance of these demonstrable factors in the blood. D. STARK MURRAY. Twickenham, Middlesex. some
regress,
"
1. 2. 3.
Lippman, M. Trans. N.Y. Acad Sci. 1965, 27, 342. Schmeer, M. R., Huala, C. V. Ann. N.Y Acad. Sci. 118, 603. Szent-Gyorgyi, A., Hegyeli, A., McLaughlin, J. A. Science, N.Y. 1963, 140, 1391.