- Email: [email protected]
THE MECHANICAL INJECTOR
144
LETTERS TO THE EDITOR
in an interesting comment on this, points out the importance of the " concept that the clinical manifestations termed ’glandular fever’ may represent a common end-
pathway syndrome
activated
by
an
allergic
mechanism."
I wish to thank Mr. J. A. Cholmeley, F.R.C.S., for to record these cases. Institute of Orthopædics, Royal National Orthopædic Hospital,
permission
A. G. TOWERS.
Stanmore.
E.S.R. IN HYPOTHYROIDISM
SiR,—Dr. McAlpine’s paper (July 9) on an increased sedimentation rate in hypothyroidism is of considerable interest as was that of Wilson1 on a similar finding in Simmonds’s disease. The relationship of the increased E.s.R. to the relative increase of serum-globulin was pointed out by Dr. McAlpine. In a paper on the basis of the sedimentation rate, Hardwick and Squire,2 while recognising the importance of elevated plasma-fibrinogen, specially emphasised the importance of raised 1X2- and
y-globulin. It is recognised that cortisone affects protein meta.bolism and y-globulin,3 and I have previously drawn . attention to changes in E.s.R. in some cases of Cushing’s syndrome and of Addison’s disease and to the effects of adrenalectomy and of cortisone.4 These findings were inconstant, and sometimes paradoxical, but nevertheless I regarded them as significant and opening up a new field for an appreciation of the influence of hormones on the E.s.R., and the need to consider the possibility of endocrine disease when the E.s.R. was found to be raised. Since myxcedema may be associated with involution and atrophy of the adrenal cortex,56 the influence of secondary abnormal adrenal function on the E.s.R. in myxcedema, as well as in Simmonds’s disease, becomes relevant. Although thyroid may have a more direct and significant influence, one must also remember that thyroid can favourably influence decreased adrenal function in myxcedema. The potential effect of testosterone may also come into consideration. It now seems unlikely that occult infection can be the sole explanation of a raised sedimentation rate in endocrine disease. The paths opened out warrant further exploration. S. LEONARD SIMPSON. London, W.1. TREACLE FOR CONSTIPATION
theriac contained the entrails of vipers boiled in aniseed and the Exalted or Celestial Treacle of later German pharmacists ran to over 100 ingredients. Nevertheless, despite such precedents, the suggestion by Mr. Lang Stevenson (July 2) that the uncrystallised residue from the refining of sugar contains acetylcholine is arresting, particularly in view of the high temperatures of the process and the instability of the substance. McCance and Widdowson’s Chernical Composition of Foods and Martin and Cooke’s Organic Industrial Chemistry make no mention of acetylcholine in treacle, and it would be interesting to know where the statement occurs. Although Molle in the 17th century decries " these Mountebanks, Triacle Carriers and such other Dogleaches," More refers to the tryacle of holye scripture." No doubt, then, Mr. Lang Stevenson’s method is " the sovran treacle of sound doctrine " (Milton) but its efficacy may have more to do with the laxative hydrophily of concentrated sugar solutions than with its
SiR,—Galen’s treacle
or
"
acetylcholine Whipps Cross
content. Hospital,
London, E.11.
FRANK A. ALLEN Chief Pharmacist.
1. Wilson, L. A. Lancet, 1953, i, 203. 2. Hardwick, J., Squire, J. R. Clin. Sci. 1952, 11, 335. 3. Long, D. A. Int. Arch. Allergy, N.Y. 1955, 6, 337. 4. Proc. R. Soc. Med. 1953, 46, 39, 566. 5. Berkheiser, S. W. J. clin. Endocrin. 1955, 15, 44. 6. Kingsbury, J. W., Emery, S. L., Adams, A. E. Endocrinology, 1955, 56, 299.
THE MECHANICAL INJECTOR
SiR,-Preliminary reports on the use of the painless mechanical injector have already appearedand it seems that the instrument has a place in medical research, Injections, by their very nature, evoke a psychological reaction on the part of the patient,2 and the consistency in the quality of this stimulus is often an important factor in the efficacy of treatment.3 It has been shown, for example, that the variation in response to different doctors administering injections is often greater than the difference in response to an experimental drug and its placebo control.4 Statistically significant differences are thus often masked, and final data may be quite contrary to what is actually the case. A number of modifications for purposes of research have been made in this department on the commercial pattern of the injector gun. One which has universal application is the engraving and calibration of a scale on the skin-shield slide, indicating the depth of penetration in millimetres. This enables a variety of penetration depths to be used in sequence, without the necessity of remeasuring the needle length in the fired position on each occasion, and this will be found par. ticularly useful on the no. 2 model with its preset depth range of 0-50 mm. The manufacturers are at present considering the embodiment of this modification in future models. Meanwhile, the instrument is almost essential in any well. controlled medical investigation involving injections, for the high needle speed and controlled penetration depth combine to produce an efficient, acceptable, and non-varying injection, Winterton Hospital, Stockton-on-Tees.
L. R. C. HAWARD.
LUNG CANCER AND SMOKING
SiR,—May a layman venture to add to the question raised by Mr. Mims in his letter of June 4’1 Has anyone investigated the possible association between the virus of tobacco mosaic disease and lung cancer, particularly in the circumstances of inhaled tobacco fragmentsIt has been claimed that this virus can be transmitted with great ease to other plants merely by the agency of the infected fingers and hand tools of tobacco users. GOODMAN. G. GOODMAN, London, S.W.3. A BARBITURATE ANTAGONIST
SIR,-I -find myself in agreement with nearly all the
which Dr. Wright has raised in his letter of June 25. Especially interesting is his use of paper chromatography ; I feel sure that the use of this important technique will yield further results concerning the barbiturate enigma. I am glad that Dr. Wright agrees that pp-methyl ethyl glutarimide (’Megimide’) and 2-4-diamino-5-phenyl-
points
thiazole (D.A.P.T.) have antagonistic (analeptic) activity towards the short-acting barbiturates. I also agree with him when he says that our results with phenobarbitone have not been as successful. I do not know whether to ascribe this relative lack of response to decreased antagonism or to the fact that the coma due to phenobarbitone is different from that brought about by the mediumacting barbiturates. I disagree with him only when he says that our " safe state " is a state bordering on convulsions." Certainly in our earliest cases the patient did convulse but now that we have learned to appreciate the signs of overdosage this does not occur. Incidentally the convulsions appeared to be harmless. Almost all drugs in therapeutics when used to excess produce undesirable effects. Megimide is no exception ; but I do not agree that when we use it correctly we produce a condition such as Dr. Wright describes. "
Haward, L. R. C. Chem. & Drugg. 1955, 174, 4762 ; Med. World, Lond. 1955, 82, 583. Med. World, Lond. 1953, 79, 126. 2. Haward, L. R. C. 3. Jennison, R. F., Ellis, H. R. Lancet, 1954, ii, 1245. 4. Shapiro, A. P. Psychosom. Med. 1954, 16, 478. 1.
LETTERS TO THE EDITOR
in an interesting comment on this, points out the importance of the " concept that the clinical manifestations termed ’glandular fever’ may represent a common end-
pathway syndrome
activated
by
an
allergic
mechanism."
I wish to thank Mr. J. A. Cholmeley, F.R.C.S., for to record these cases. Institute of Orthopædics, Royal National Orthopædic Hospital,
permission
A. G. TOWERS.
Stanmore.
E.S.R. IN HYPOTHYROIDISM
SiR,—Dr. McAlpine’s paper (July 9) on an increased sedimentation rate in hypothyroidism is of considerable interest as was that of Wilson1 on a similar finding in Simmonds’s disease. The relationship of the increased E.s.R. to the relative increase of serum-globulin was pointed out by Dr. McAlpine. In a paper on the basis of the sedimentation rate, Hardwick and Squire,2 while recognising the importance of elevated plasma-fibrinogen, specially emphasised the importance of raised 1X2- and
y-globulin. It is recognised that cortisone affects protein meta.bolism and y-globulin,3 and I have previously drawn . attention to changes in E.s.R. in some cases of Cushing’s syndrome and of Addison’s disease and to the effects of adrenalectomy and of cortisone.4 These findings were inconstant, and sometimes paradoxical, but nevertheless I regarded them as significant and opening up a new field for an appreciation of the influence of hormones on the E.s.R., and the need to consider the possibility of endocrine disease when the E.s.R. was found to be raised. Since myxcedema may be associated with involution and atrophy of the adrenal cortex,56 the influence of secondary abnormal adrenal function on the E.s.R. in myxcedema, as well as in Simmonds’s disease, becomes relevant. Although thyroid may have a more direct and significant influence, one must also remember that thyroid can favourably influence decreased adrenal function in myxcedema. The potential effect of testosterone may also come into consideration. It now seems unlikely that occult infection can be the sole explanation of a raised sedimentation rate in endocrine disease. The paths opened out warrant further exploration. S. LEONARD SIMPSON. London, W.1. TREACLE FOR CONSTIPATION
theriac contained the entrails of vipers boiled in aniseed and the Exalted or Celestial Treacle of later German pharmacists ran to over 100 ingredients. Nevertheless, despite such precedents, the suggestion by Mr. Lang Stevenson (July 2) that the uncrystallised residue from the refining of sugar contains acetylcholine is arresting, particularly in view of the high temperatures of the process and the instability of the substance. McCance and Widdowson’s Chernical Composition of Foods and Martin and Cooke’s Organic Industrial Chemistry make no mention of acetylcholine in treacle, and it would be interesting to know where the statement occurs. Although Molle in the 17th century decries " these Mountebanks, Triacle Carriers and such other Dogleaches," More refers to the tryacle of holye scripture." No doubt, then, Mr. Lang Stevenson’s method is " the sovran treacle of sound doctrine " (Milton) but its efficacy may have more to do with the laxative hydrophily of concentrated sugar solutions than with its
SiR,—Galen’s treacle
or
"
acetylcholine Whipps Cross
content. Hospital,
London, E.11.
FRANK A. ALLEN Chief Pharmacist.
1. Wilson, L. A. Lancet, 1953, i, 203. 2. Hardwick, J., Squire, J. R. Clin. Sci. 1952, 11, 335. 3. Long, D. A. Int. Arch. Allergy, N.Y. 1955, 6, 337. 4. Proc. R. Soc. Med. 1953, 46, 39, 566. 5. Berkheiser, S. W. J. clin. Endocrin. 1955, 15, 44. 6. Kingsbury, J. W., Emery, S. L., Adams, A. E. Endocrinology, 1955, 56, 299.
THE MECHANICAL INJECTOR
SiR,-Preliminary reports on the use of the painless mechanical injector have already appearedand it seems that the instrument has a place in medical research, Injections, by their very nature, evoke a psychological reaction on the part of the patient,2 and the consistency in the quality of this stimulus is often an important factor in the efficacy of treatment.3 It has been shown, for example, that the variation in response to different doctors administering injections is often greater than the difference in response to an experimental drug and its placebo control.4 Statistically significant differences are thus often masked, and final data may be quite contrary to what is actually the case. A number of modifications for purposes of research have been made in this department on the commercial pattern of the injector gun. One which has universal application is the engraving and calibration of a scale on the skin-shield slide, indicating the depth of penetration in millimetres. This enables a variety of penetration depths to be used in sequence, without the necessity of remeasuring the needle length in the fired position on each occasion, and this will be found par. ticularly useful on the no. 2 model with its preset depth range of 0-50 mm. The manufacturers are at present considering the embodiment of this modification in future models. Meanwhile, the instrument is almost essential in any well. controlled medical investigation involving injections, for the high needle speed and controlled penetration depth combine to produce an efficient, acceptable, and non-varying injection, Winterton Hospital, Stockton-on-Tees.
L. R. C. HAWARD.
LUNG CANCER AND SMOKING
SiR,—May a layman venture to add to the question raised by Mr. Mims in his letter of June 4’1 Has anyone investigated the possible association between the virus of tobacco mosaic disease and lung cancer, particularly in the circumstances of inhaled tobacco fragmentsIt has been claimed that this virus can be transmitted with great ease to other plants merely by the agency of the infected fingers and hand tools of tobacco users. GOODMAN. G. GOODMAN, London, S.W.3. A BARBITURATE ANTAGONIST
SIR,-I -find myself in agreement with nearly all the
which Dr. Wright has raised in his letter of June 25. Especially interesting is his use of paper chromatography ; I feel sure that the use of this important technique will yield further results concerning the barbiturate enigma. I am glad that Dr. Wright agrees that pp-methyl ethyl glutarimide (’Megimide’) and 2-4-diamino-5-phenyl-
points
thiazole (D.A.P.T.) have antagonistic (analeptic) activity towards the short-acting barbiturates. I also agree with him when he says that our results with phenobarbitone have not been as successful. I do not know whether to ascribe this relative lack of response to decreased antagonism or to the fact that the coma due to phenobarbitone is different from that brought about by the mediumacting barbiturates. I disagree with him only when he says that our " safe state " is a state bordering on convulsions." Certainly in our earliest cases the patient did convulse but now that we have learned to appreciate the signs of overdosage this does not occur. Incidentally the convulsions appeared to be harmless. Almost all drugs in therapeutics when used to excess produce undesirable effects. Megimide is no exception ; but I do not agree that when we use it correctly we produce a condition such as Dr. Wright describes. "
Haward, L. R. C. Chem. & Drugg. 1955, 174, 4762 ; Med. World, Lond. 1955, 82, 583. Med. World, Lond. 1953, 79, 126. 2. Haward, L. R. C. 3. Jennison, R. F., Ellis, H. R. Lancet, 1954, ii, 1245. 4. Shapiro, A. P. Psychosom. Med. 1954, 16, 478. 1.