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CREATINE KINASE AND BRAIN DAMAGE
558 the kitchen
were examined for carriage of S. typhi. After screening " by the Widal reaction, only those with significant titres were further investigated by stool and bile cultures. Due to a misunderstanding, one of the suspected cooks was also submitted to a blood-culture. Quite unexpectedly it showed rapid growth of a typhoid bacillus belonging to the same biotype and phagotype as the strain that caused the outbreak. Bile and stool cultures were negative. The boy denied even the slightest manifestation that could point to a "
or present enteric fever. Last year we found that intravascular carriers may perhaps also exist for other salmonella serotypes and that they may be of more than academic interest. An African obstetric patient was transfused after an operation. The transfusion had to be interrupted when the patient showed a sudden rise in temperature with chills and incipient shock. The blood of the patient and the transfusion-bottle both grew Salmonella enteritidis. The blood donor was an otherwise perfectly healthy African. He refused a bloodculture, so the final proof of his carrier state could not be established. Department of Bacteriology, J. M. VANDEPITTE Lovanium University Medical School, F. GATTI. Kinshasa xi, Congo.
past
A NEW TEMPERATURE CHART
SIR,-Dr. Bewley’s chart (Sept. 2, p. 513) reads only down to
32°C
(89-6°F).
Most frank
hypothermias
are
below this
at the time of admission, and in this hospital we use a thermometer reading down to 21°C (70°F).1 For this we designed in 1961 a chart reading down to 75°F (24°C) Z; our next edition will read down to 21°C.
These charts are printed for us by the Birmingham (Selly Oak) Group of Hospitals, and incidentally show the continuing need for individual enterprise as against standardised hospital records. IAN A. KELLOCK Summerfield Hospital, ROBERT 18. J. HETHERINGTON. Birmingham, EPITHELIAL CHANGES IN THE UTERINE CERVIX SIR,-Thank you for your reply to my question (Aug. 26, p. 472) about the basement membrane and its relation to uterine cervical malignancy. In it you have, rather disappointingly, done little more than show that there are others too who share your belief that " where the basement membrane has been breached, the malignancy of the lesion is in no doubt". The hope was that you had at last found some real evidence to support this belief, and that your statement was based on something more than the textbook postulate of Novak, for it too, in its turn, is quite unsubstantiated. I believe it right to emphasise that in many cervical (and other) biopsies a basement membrane cannot be convincingly demonstrated, especially in the presence of inflammation, and that the combination of aberrant epithelium and deficient basement membrane does not warrant a diagnosis of cancer. I would go so far as to suggest, in fact, that to most histopathologists the state of the basement membrane has remarkably little relevance to cancer diagnosis. I would not have raised or continued the matter were it not that your large and respectful readership, interested in early cancer diagnosis as are we all, might have been misled by your leading article into thinking that the distinction between non-cancer, superficial cancer, and invasive cancer (with all that this implies for incidence, prevalence, true and apparent curability) was merely a matter of assessing the state of a basement membrane. The appeal of the basement-membrane concept is obvious: it is mechanical and it is simple; it is also unfortunately not valid. University Department of Pathology, Royal Infirmary, Dundee. 1. 2.
Kellock, Kellock,
W. WALLACE PARK.
I. A. Lancet, 1963, i, 336. I. A., Hetherington, R. J. Br. med.
J. 1962, i, 727.
CREATINE KINASE AND BRAIN DAMAGE SIR,-Dr. Langton and his colleagues (Aug. 5, p. 278) measured increases in creatine kinase (C.P.K.) in the peripheral venous blood of patients with several forms of brain damage. Difficulty was experienced in the interpretation of small rises in C.P.K. levels and in excluding that such changes were artefacts due to muscle injury during removal of blood. We have measured C.P.K. levels in the jugular venous blood of adult white Wistar rats, using an A.T.p./phosphoenol pyruvate method coupled to N.A.D.H. (Boehringer und Soehne, Mannheim). Anoxic ischaemic brain injurywas induced in the rats. 0-9-6 m[J. enzyme activity per ml. serum was found in normal animals. Immediately after the completion of the anoxic episode more than fivefold increases in C.P.K. levels were measured. Between 3 and 24 hours later up to ten times normal levels were recorded. Normal values were attained in most test animals four days after injury. Multiple enzyme forms of C.P.K. are known to exist. That occurring predominantly in the brain is more labile than the characteristic muscle form. We have found that when specimens of normal serum were stored at -15°C and C.P.K. activity tested at intervals, reproducible figures were obtained. The high C.P.K. levels found in the fresh serum of rats with anoxic ischsemic brain injury were found to be greatly reduced after 48 hours storage at — 15°C. This is suggestive evidence that tissue-characteristic enzyme forms of C.P.K. may be present in the peripheral blood of brain-injured animals, and analysis of the types of C.P.K. could assist in the interpretation of raised levels of this enzyme in patients with evidence of nervous-system abnormalities. S. L. YAP Departments of Chemistry and Pharmacology, D. C. WATTS Medical School, Guy’s Hospital R. G. SPECTOR. London S.E.1.
CARBON DIOXIDE IN THE OXYGEN TENT SIR,-We were interested to read of the improved oxygen tent described by Dr. Wayne and Mr. Chamney (Aug. 12, p. 344), but we were surprised to find no mention of the CO2 levels reached. The carbon-dioxide concentration inside an oxygen tent is, of course, proportional to the oxygen concentration achieved, for any given fresh oxygen flow. On theoretical grounds, assuming an output by the patient of 200 ml. CO2 per minute and a uniform mixing of the gases in the tent, the CO2 concentration in the tent would be approximately 402/4V where A02 is the rise in percentage oxygen concentration and V is the oxygen flow rate in litres per minute. In the tent described, the mean A02 of 26% corresponds to a mean CO2 concentration of slightly less than 1/2% with an oxygen flow rate of 15 litres per min., and of 3/4% for a flow rate of 10 litres per min., reaching 1% when the flow is reduced to 6-5 litres per min. Department of Anæsthesia, D. W. BETHUNE Saint Bartholomew’s Hospital, London E.C.1. J. M. COLLIS. CRACKLES AND WHEEZES SiR,—The point of the experiment with helium which puzzles Mr. Green (Aug. 19, p. 419) is that the pitch of wheezes remains constant when the density of the gas mixture in the lung, and therefore the velocity of sound in the gas, is changed. This observation disproves the widely held view that the pitch of wheezes depends on the length and calibre of the airway generating the sound. It directs attention to the " reed ", which in the lung is represented by airways on the point of closure. The pitch of such an instrument, which resembles the toy trumpet, depends on the mechanical properties of the airway and on the linear velocity of the gas stream flowing through the stenosis. Brook General Hospital, PAUL FORGACS. London, S.E.18. 1.
Levine, S. Am. J. Path. 1960, 36, 1.
were examined for carriage of S. typhi. After screening " by the Widal reaction, only those with significant titres were further investigated by stool and bile cultures. Due to a misunderstanding, one of the suspected cooks was also submitted to a blood-culture. Quite unexpectedly it showed rapid growth of a typhoid bacillus belonging to the same biotype and phagotype as the strain that caused the outbreak. Bile and stool cultures were negative. The boy denied even the slightest manifestation that could point to a "
or present enteric fever. Last year we found that intravascular carriers may perhaps also exist for other salmonella serotypes and that they may be of more than academic interest. An African obstetric patient was transfused after an operation. The transfusion had to be interrupted when the patient showed a sudden rise in temperature with chills and incipient shock. The blood of the patient and the transfusion-bottle both grew Salmonella enteritidis. The blood donor was an otherwise perfectly healthy African. He refused a bloodculture, so the final proof of his carrier state could not be established. Department of Bacteriology, J. M. VANDEPITTE Lovanium University Medical School, F. GATTI. Kinshasa xi, Congo.
past
A NEW TEMPERATURE CHART
SIR,-Dr. Bewley’s chart (Sept. 2, p. 513) reads only down to
32°C
(89-6°F).
Most frank
hypothermias
are
below this
at the time of admission, and in this hospital we use a thermometer reading down to 21°C (70°F).1 For this we designed in 1961 a chart reading down to 75°F (24°C) Z; our next edition will read down to 21°C.
These charts are printed for us by the Birmingham (Selly Oak) Group of Hospitals, and incidentally show the continuing need for individual enterprise as against standardised hospital records. IAN A. KELLOCK Summerfield Hospital, ROBERT 18. J. HETHERINGTON. Birmingham, EPITHELIAL CHANGES IN THE UTERINE CERVIX SIR,-Thank you for your reply to my question (Aug. 26, p. 472) about the basement membrane and its relation to uterine cervical malignancy. In it you have, rather disappointingly, done little more than show that there are others too who share your belief that " where the basement membrane has been breached, the malignancy of the lesion is in no doubt". The hope was that you had at last found some real evidence to support this belief, and that your statement was based on something more than the textbook postulate of Novak, for it too, in its turn, is quite unsubstantiated. I believe it right to emphasise that in many cervical (and other) biopsies a basement membrane cannot be convincingly demonstrated, especially in the presence of inflammation, and that the combination of aberrant epithelium and deficient basement membrane does not warrant a diagnosis of cancer. I would go so far as to suggest, in fact, that to most histopathologists the state of the basement membrane has remarkably little relevance to cancer diagnosis. I would not have raised or continued the matter were it not that your large and respectful readership, interested in early cancer diagnosis as are we all, might have been misled by your leading article into thinking that the distinction between non-cancer, superficial cancer, and invasive cancer (with all that this implies for incidence, prevalence, true and apparent curability) was merely a matter of assessing the state of a basement membrane. The appeal of the basement-membrane concept is obvious: it is mechanical and it is simple; it is also unfortunately not valid. University Department of Pathology, Royal Infirmary, Dundee. 1. 2.
Kellock, Kellock,
W. WALLACE PARK.
I. A. Lancet, 1963, i, 336. I. A., Hetherington, R. J. Br. med.
J. 1962, i, 727.
CREATINE KINASE AND BRAIN DAMAGE SIR,-Dr. Langton and his colleagues (Aug. 5, p. 278) measured increases in creatine kinase (C.P.K.) in the peripheral venous blood of patients with several forms of brain damage. Difficulty was experienced in the interpretation of small rises in C.P.K. levels and in excluding that such changes were artefacts due to muscle injury during removal of blood. We have measured C.P.K. levels in the jugular venous blood of adult white Wistar rats, using an A.T.p./phosphoenol pyruvate method coupled to N.A.D.H. (Boehringer und Soehne, Mannheim). Anoxic ischaemic brain injurywas induced in the rats. 0-9-6 m[J. enzyme activity per ml. serum was found in normal animals. Immediately after the completion of the anoxic episode more than fivefold increases in C.P.K. levels were measured. Between 3 and 24 hours later up to ten times normal levels were recorded. Normal values were attained in most test animals four days after injury. Multiple enzyme forms of C.P.K. are known to exist. That occurring predominantly in the brain is more labile than the characteristic muscle form. We have found that when specimens of normal serum were stored at -15°C and C.P.K. activity tested at intervals, reproducible figures were obtained. The high C.P.K. levels found in the fresh serum of rats with anoxic ischsemic brain injury were found to be greatly reduced after 48 hours storage at — 15°C. This is suggestive evidence that tissue-characteristic enzyme forms of C.P.K. may be present in the peripheral blood of brain-injured animals, and analysis of the types of C.P.K. could assist in the interpretation of raised levels of this enzyme in patients with evidence of nervous-system abnormalities. S. L. YAP Departments of Chemistry and Pharmacology, D. C. WATTS Medical School, Guy’s Hospital R. G. SPECTOR. London S.E.1.
CARBON DIOXIDE IN THE OXYGEN TENT SIR,-We were interested to read of the improved oxygen tent described by Dr. Wayne and Mr. Chamney (Aug. 12, p. 344), but we were surprised to find no mention of the CO2 levels reached. The carbon-dioxide concentration inside an oxygen tent is, of course, proportional to the oxygen concentration achieved, for any given fresh oxygen flow. On theoretical grounds, assuming an output by the patient of 200 ml. CO2 per minute and a uniform mixing of the gases in the tent, the CO2 concentration in the tent would be approximately 402/4V where A02 is the rise in percentage oxygen concentration and V is the oxygen flow rate in litres per minute. In the tent described, the mean A02 of 26% corresponds to a mean CO2 concentration of slightly less than 1/2% with an oxygen flow rate of 15 litres per min., and of 3/4% for a flow rate of 10 litres per min., reaching 1% when the flow is reduced to 6-5 litres per min. Department of Anæsthesia, D. W. BETHUNE Saint Bartholomew’s Hospital, London E.C.1. J. M. COLLIS. CRACKLES AND WHEEZES SiR,—The point of the experiment with helium which puzzles Mr. Green (Aug. 19, p. 419) is that the pitch of wheezes remains constant when the density of the gas mixture in the lung, and therefore the velocity of sound in the gas, is changed. This observation disproves the widely held view that the pitch of wheezes depends on the length and calibre of the airway generating the sound. It directs attention to the " reed ", which in the lung is represented by airways on the point of closure. The pitch of such an instrument, which resembles the toy trumpet, depends on the mechanical properties of the airway and on the linear velocity of the gas stream flowing through the stenosis. Brook General Hospital, PAUL FORGACS. London, S.E.18. 1.
Levine, S. Am. J. Path. 1960, 36, 1.