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THE TREATMENT OF CEREBRO-SPINAL FEVER IN THE ROYAL NAVY.
909 It is obvious, therefore, that the best conditions Attempts to determine the necessary minimum are shown in Experiment No. 2. The for the experiment have been worked out, but it is pigs were weighed daily by the laboratory assistant, certain that " badmaize does not produce any and we noticed that of 5 pigs in the two groups deleterious results in short periods of a month to which died, from some unknown cause, during the six weeks, even under circumstances most favourfirst 13 days of the experiment 4 pigs weighed able for its action. This throws out of court all the 188 grammes or less. This rather looks as if pigs short experiments so prevalent in the literature in future experiments should be chosen from those about pellagra. which weigh more than 188 grammes. The figures Bibliography.-1. Cencelli, A.: New Theories and Investigations Pellagra, THE LANCET, 1915, vol. i., p. 794. Alessandrini, show that the average weight of these 28 guinea- concerning G.. and Scala, A. : Contribuito Nuovo alla Etiologia e Patogenesi della Tip. naz. Bertero, Rome, 1914. 2. Braddon, W. L.: The pigs exceeded 225 grammes on the first day of the Pellagra, Cause and Prevention of Beri-beri, London, 1907. 3. American experiment. Journal of Tropical Diseases and Preventive Medicine, June,
of cabbage
4. Brit. Med. Jour. (Literary Notes), 1912, vol. ii., 771. 5. The Treatment and Prevention of Pellagra, U.S. Public Reports, Washington, vol. xxix., Oct. 23rd, 1914. 6. Goldberger, J. : The Etiology of Pellagra, U.S. Public Health Reports, Washington, vol. xxix., June 26th, 1914. 7. Report of the Illinois Pellagra Commission, Archives of Internal Medicine, 1912, pp. 123-168 and 219-249. 8. Hopkins, F. G., M.B., F.R.S.: Diseases due to Deficiencies in THE LANCET, 1913, vol. ii., p. 1309, and Proceedings of the Royal Society of Medicine. 9. Journal of Hygiene, 1912-14.
1915,
EXPERIMENT NO. 2. October 1lytlc, 1914, to March 17t7t, 1915, or five months. Twenty guinea-pigs were divided into 5 batches of 4 pigs each :Batch No. 1.-Fed on good maize without any cabbage. All died between 9 and 26 days, with great loss of weight. One had paralysis of the hind legs. Batoh No. 2.-Fed on good maize plus 1 gramme of
p.
p. 1067.
Health
Diet,
’
cabbage. THE Three of these died within 2 months. One was alive at the end of the experiment-i. e., after 5 months-but had lost 100 grammes from its original 625 grammes weight. Batch No. 3.-Fed on good maize plus 2 grammes of
cabbage. Two died within a week. Two lived for nearly 5 months but lost weight. Batch No. 4.-Fed on good maize plus 3 grammes of
cabbage.
TREATMENT OF CEREBRO-SPINAL FEVER IN THE ROYAL NAVY.1
BY TEMP. SURGEON-GENERAL H. D.
ROLLESTON,
M.D., F.R.C.P., R.N., CONSULTANT PHYSICIAN TO THE ROYAL NAVY, ROYAL NAVAL HOSPITAL, HASLAR ; SENIOR PHYSICIAN, ST. GEORGE’S HOSPITAL.
FROM the commencement of the
war
to
July 31st,’
One died after 6 weeks. Three lived for nearly 5 months. 1915, there have been 170 cases of cerebro-spinal, Two were alive at the end of the experiment, one having fever in the Royal Navy. The following summary lost and one having gained weight. of the results of treatment is abstracted from the’ Batch No 5.-Fed on good maize plus 4 grammes of notes of 163 cases, 89, or 54’6 per cent., of which
cabbage.
One died after 3 months. Three alive at end of experiment ; two lost and one gained weight. The average weight of these pigs was 518 grammes on the first day of the experiment.
proved fatal. The prolonged and unsatisfactory cases naturally received more varied treatment than the fulminating cases, some of which died shortly after coming into hospital. As will be seen
This experiment was undertaken in order to determine the minimum amount of green food (cabbage) necessary to sustain life when the diet consisted of good maize. That cabbage is necessary is evident from the results obtained with maize without cabbage, when all the animals died in a very short time. The results indicate that guinea-pigs can survive for five months or more when 3-4 grammes of cabbage are added to their maize diet. It is possible that many guinea-pigs can survive on much less than this-say, 1 gramme ; but the experiment suggests that many would die before they became accommodated to such a low fresh vegetable diet. EXPERIMENT NO. 3.
Begun April 28th, 1915. Seven control guinea-pigs fed on good maize alone :— No. 1 died May 9th. No. 5 died May 18th. 20th. 13th. 22nd. " " All died between 11 and 24 "
71
2 3 4
"
"
" 6 " 7
18th. 20th.
days. Twenty guinea-pigs fed on good maize, plus 1 gramme of cabbage, from April 28th to June 28th. On June 28th only 12 guinea-pigs alive. On June 28th the 12 survivors
No. 1 lot fed
divided into two lots. 1 gramme of cabbage.
were
good maize, plus bad" This feeding on good and bad maize lasted for a month only; since we had no more ’’bad maize " (on account of war difficulties). So far there was absolutely no difference 1 Remarks at a discussion before the Section of Therapeutics and between the good and bad maize. Similar results were Pharmacology of the Royal Society of Medicine on Oct. 19th, being an made to the Medical Director-General and to extract from a No.2 ,,
on
""
obtained with guinea-pigs fed on maize, plus Cabbage. (See Experiment No. 1.)
"
5 grammes of
report
be published in the forthcoming number of the Journal of Naval Medical Service.
the Royal
910
by the tabular statement, various forms and
of intramuscular injections of soamin: (a) when given alone to 21 cases with a mortality of 33’3 per cent., and (b) when combined with intrathecal injection of serum in 18 cases, with a mortality of 61 per cent. It must be recognised that when dealing with small numbers fallacies easily creep in, but merely from these figures the addition of intrathecal injection of serum would appear to have coincided with an increase of mortality in the cases treated with soamin. The high mortality can hardly be explained by the suggestion that it was due to the bad effects of lumbar puncture, for in 13 cases in which lumbar puncture alone was employed there were 9, or 69 per cent., recoveries; and in 91 per cent. of the 163 cases lumbar puncture was performed, and in many cases repeatedly, to relieve symptoms referable to increased intrathecal pressure. Alarming symptoms directly after the intrathecal injection occurred in 2 cases only, thus showing that the gravity method of administration, which was not in vogue in the Royal Navy, is hardly necessary provided due care be taken.
com-
binations of treatment were employed, and the most noticeable point is the failure of the generally approved intrathecal injection of antimeningococcic serum.
Antimeningococcic
serum
(Burroughs, Wellcome,
and
from various
sources
Co., the Lister Institute,
Mulford (Flexner)) was employed,2 In 105 cases the treatment consisted of lumbar puncture and intrathecal injection of the serum, either alone (62 cases) or with the addition of vaccines, soamin, or hexamine (43 cases). Of these 105 cases 64, or 61 per cent., died; and 41, or 39 per cent., recovered. Of the 62 cases treated by lumbar puncture and intrathecal injection of serum death occurred in 43, or 69.4 per cent., and recovery in 19, or 30’6 per cent.; whereas of 43 cases treated in addition by vaccines, soamin, or hexamine 20, or 46’5 per cent., were fatal, and 23, or 53’5 per cent., recovered. It is therefore obvious that the cases treated solely by the intrathecal injection of serum and lumbar puncture had a higher death-rate than that (54’6B per cent.) of the whole series of 163 cases. Flexner;’ has laid much stress on the importance of injecting
Antimeningococcic serum was given hypodermically in 19 cases, but as in 4 cases only was it the sole form of specific treatment employed,
antimeningococcic serum intrathecally as early as possible in the disease; and in a table dealing with 1211 cases he shows that when the serum is injected within the first three days the mortality rate is
conclusions as to its influence can be drawn. An autogenous vaccine was given in 16 cases, 18 per cent., when between the fourth and seventh mainly by Fleet-Surgeon H. C. Whiteside, R.N., at days 27’2 per cent., and when later than the seventh Plymouth, where the mortality (36’7 per cent.) was day 36’5 per cent. The following tabulation of remarkably low. The cases to which autovaccines 105 cases treated in the Royal Navy has been made were given all received other specific remedies (in 11 cases intrathecal injections of serum), and on the same lines for comparison :showed the very low mortality of 25 per cent. But Deaths. Cases. Recoveries. as the numbers are small this result-though a 42 or 60 per cent.... 28 or 40 per cent. 1st to 3rd day ...... 70 further stimulus to its more extended use-must 4th to 7th day ...... 24 ... 14 58-4 ,, ...10,,41’6 not be insisted on. Later than 7th day ... 11 ... 8 ,, 72.7 ... 3 ,,27.3 As already mentioned, soamin appeared to give results ; its beneficial effect in the septicæmic good The failure of antimeningococcic serum to reduce of the disease was noticed by Staff-Surgeon stage the mortality was therefore not due to its being B. S. Robson, R.N., at Haslar, and has also been given too late, for in 66’7 per cent. of the 105 cases mentioned by others,5 In one case at Portland it was administered within the first three days of as much as 42 gr. of soamin were given. the disease. The serum treatment, which was so Hospital was not noted in any instance. Optic atrophy successful in America (Flexner, Sophian), Belfast Hexamine was given by the mouth in seven cases (Robb), and elsewhere, was given a thorough trial in the hope that, as it is secreted into the cerebroIn very and proved most disappointing. fluid, it would exert a bactericidal- action instances was there the critical improvement spinal on the meningococci, but as it did not appear which is said to occur in about 30 per cent. of the to have any effect clinically it was soon cases that recover (Flexner),4 Possibly the meningoabandoned. " cocci were " fast to the action of the serum Lumbar puncture, which is such an important In consequence of its or were para-meningococci. means of diagnosis, was performed in 149 out of apparent inertness intrathecal injection of serum 163 cases, or in 91’4 per cent. In 38 cases lumbar was in the latter part of the epidemic largely was done once only, but 14 of these cases other methods, puncture or combined with replaced by died soon after they came under observation; 6 such as the intramuscular injection of soamin. other cases, tapped once, died. Of 22 cases, tapped It is true that the mortality naturally diminishes 8 proved fatal, 2 being very acute; 3 tappings twice, towards the end of epidemics; but this does, not were done in 20 cases (9 deaths), 4 in 24 (15 deaths), yet entirely explain why, as shown by the 5 in 15 (9 deaths), 6 in 6 (3 deaths), 7 in 7 (4 tabular statement, the results of intrathecal deaths), 8 in 3 (2 deaths), 9 in 4 (all fatal), 11 in injection of serum compare so badly with 5 (2 deaths), 13 in 1 (fatal), 15 in 1 (fatal), 16 those of almost all the other methods and comin 1 (fatal), and 17 in 2 (both recoveries). Lumbar binations of methods; for up to the end of appears to be a palliative rather February there were 90 cases with a mortality of puncture than a curative remedy and to relieve for a time 52, or 57 per cent., whereas from the beginning of due to increased intrathecal pressure. In March to the end of July there were 80 cases with symptoms 13 cases, of which 4 proved fatal, it was the only a mortality of 38, or 47 per cent. There is, for form of treatment other than the ordinary symexample, a remarkable contrast between the effects ptomatic remedies employed. no
.
...
"
"
"
few
,
,
,
2 In one case at Deal, 10 c.c. of blood serum from a patient convalescent from the disease was injected intrathecally the day before death. 3 Flexner: Journal of Experimental Medicine, N.Y., 1913, vol. xvii.,
p. 4553.
Quoted by
1913,
p. 282.
Heiman and Feldstein,
Meningococcus Meningitis,
In 14 cases, 10 of which
remedies
only (such
as
proved fatal, symptomatic
morphine
for
pain)
given. Upper Brook-street, 5
W.
Batten : THE
LANCET, 1915, vol. i.,
p. 966.
were
Supplement
to "THE LANCET."
Second
Sixth To illustrate Mr. W. W.
day.
day.
Linington’s
Case of Traumatic Asphyxia.
of cabbage
4. Brit. Med. Jour. (Literary Notes), 1912, vol. ii., 771. 5. The Treatment and Prevention of Pellagra, U.S. Public Reports, Washington, vol. xxix., Oct. 23rd, 1914. 6. Goldberger, J. : The Etiology of Pellagra, U.S. Public Health Reports, Washington, vol. xxix., June 26th, 1914. 7. Report of the Illinois Pellagra Commission, Archives of Internal Medicine, 1912, pp. 123-168 and 219-249. 8. Hopkins, F. G., M.B., F.R.S.: Diseases due to Deficiencies in THE LANCET, 1913, vol. ii., p. 1309, and Proceedings of the Royal Society of Medicine. 9. Journal of Hygiene, 1912-14.
1915,
EXPERIMENT NO. 2. October 1lytlc, 1914, to March 17t7t, 1915, or five months. Twenty guinea-pigs were divided into 5 batches of 4 pigs each :Batch No. 1.-Fed on good maize without any cabbage. All died between 9 and 26 days, with great loss of weight. One had paralysis of the hind legs. Batoh No. 2.-Fed on good maize plus 1 gramme of
p.
p. 1067.
Health
Diet,
’
cabbage. THE Three of these died within 2 months. One was alive at the end of the experiment-i. e., after 5 months-but had lost 100 grammes from its original 625 grammes weight. Batch No. 3.-Fed on good maize plus 2 grammes of
cabbage. Two died within a week. Two lived for nearly 5 months but lost weight. Batch No. 4.-Fed on good maize plus 3 grammes of
cabbage.
TREATMENT OF CEREBRO-SPINAL FEVER IN THE ROYAL NAVY.1
BY TEMP. SURGEON-GENERAL H. D.
ROLLESTON,
M.D., F.R.C.P., R.N., CONSULTANT PHYSICIAN TO THE ROYAL NAVY, ROYAL NAVAL HOSPITAL, HASLAR ; SENIOR PHYSICIAN, ST. GEORGE’S HOSPITAL.
FROM the commencement of the
war
to
July 31st,’
One died after 6 weeks. Three lived for nearly 5 months. 1915, there have been 170 cases of cerebro-spinal, Two were alive at the end of the experiment, one having fever in the Royal Navy. The following summary lost and one having gained weight. of the results of treatment is abstracted from the’ Batch No 5.-Fed on good maize plus 4 grammes of notes of 163 cases, 89, or 54’6 per cent., of which
cabbage.
One died after 3 months. Three alive at end of experiment ; two lost and one gained weight. The average weight of these pigs was 518 grammes on the first day of the experiment.
proved fatal. The prolonged and unsatisfactory cases naturally received more varied treatment than the fulminating cases, some of which died shortly after coming into hospital. As will be seen
This experiment was undertaken in order to determine the minimum amount of green food (cabbage) necessary to sustain life when the diet consisted of good maize. That cabbage is necessary is evident from the results obtained with maize without cabbage, when all the animals died in a very short time. The results indicate that guinea-pigs can survive for five months or more when 3-4 grammes of cabbage are added to their maize diet. It is possible that many guinea-pigs can survive on much less than this-say, 1 gramme ; but the experiment suggests that many would die before they became accommodated to such a low fresh vegetable diet. EXPERIMENT NO. 3.
Begun April 28th, 1915. Seven control guinea-pigs fed on good maize alone :— No. 1 died May 9th. No. 5 died May 18th. 20th. 13th. 22nd. " " All died between 11 and 24 "
71
2 3 4
"
"
" 6 " 7
18th. 20th.
days. Twenty guinea-pigs fed on good maize, plus 1 gramme of cabbage, from April 28th to June 28th. On June 28th only 12 guinea-pigs alive. On June 28th the 12 survivors
No. 1 lot fed
divided into two lots. 1 gramme of cabbage.
were
good maize, plus bad" This feeding on good and bad maize lasted for a month only; since we had no more ’’bad maize " (on account of war difficulties). So far there was absolutely no difference 1 Remarks at a discussion before the Section of Therapeutics and between the good and bad maize. Similar results were Pharmacology of the Royal Society of Medicine on Oct. 19th, being an made to the Medical Director-General and to extract from a No.2 ,,
on
""
obtained with guinea-pigs fed on maize, plus Cabbage. (See Experiment No. 1.)
"
5 grammes of
report
be published in the forthcoming number of the Journal of Naval Medical Service.
the Royal
910
by the tabular statement, various forms and
of intramuscular injections of soamin: (a) when given alone to 21 cases with a mortality of 33’3 per cent., and (b) when combined with intrathecal injection of serum in 18 cases, with a mortality of 61 per cent. It must be recognised that when dealing with small numbers fallacies easily creep in, but merely from these figures the addition of intrathecal injection of serum would appear to have coincided with an increase of mortality in the cases treated with soamin. The high mortality can hardly be explained by the suggestion that it was due to the bad effects of lumbar puncture, for in 13 cases in which lumbar puncture alone was employed there were 9, or 69 per cent., recoveries; and in 91 per cent. of the 163 cases lumbar puncture was performed, and in many cases repeatedly, to relieve symptoms referable to increased intrathecal pressure. Alarming symptoms directly after the intrathecal injection occurred in 2 cases only, thus showing that the gravity method of administration, which was not in vogue in the Royal Navy, is hardly necessary provided due care be taken.
com-
binations of treatment were employed, and the most noticeable point is the failure of the generally approved intrathecal injection of antimeningococcic serum.
Antimeningococcic
serum
(Burroughs, Wellcome,
and
from various
sources
Co., the Lister Institute,
Mulford (Flexner)) was employed,2 In 105 cases the treatment consisted of lumbar puncture and intrathecal injection of the serum, either alone (62 cases) or with the addition of vaccines, soamin, or hexamine (43 cases). Of these 105 cases 64, or 61 per cent., died; and 41, or 39 per cent., recovered. Of the 62 cases treated by lumbar puncture and intrathecal injection of serum death occurred in 43, or 69.4 per cent., and recovery in 19, or 30’6 per cent.; whereas of 43 cases treated in addition by vaccines, soamin, or hexamine 20, or 46’5 per cent., were fatal, and 23, or 53’5 per cent., recovered. It is therefore obvious that the cases treated solely by the intrathecal injection of serum and lumbar puncture had a higher death-rate than that (54’6B per cent.) of the whole series of 163 cases. Flexner;’ has laid much stress on the importance of injecting
Antimeningococcic serum was given hypodermically in 19 cases, but as in 4 cases only was it the sole form of specific treatment employed,
antimeningococcic serum intrathecally as early as possible in the disease; and in a table dealing with 1211 cases he shows that when the serum is injected within the first three days the mortality rate is
conclusions as to its influence can be drawn. An autogenous vaccine was given in 16 cases, 18 per cent., when between the fourth and seventh mainly by Fleet-Surgeon H. C. Whiteside, R.N., at days 27’2 per cent., and when later than the seventh Plymouth, where the mortality (36’7 per cent.) was day 36’5 per cent. The following tabulation of remarkably low. The cases to which autovaccines 105 cases treated in the Royal Navy has been made were given all received other specific remedies (in 11 cases intrathecal injections of serum), and on the same lines for comparison :showed the very low mortality of 25 per cent. But Deaths. Cases. Recoveries. as the numbers are small this result-though a 42 or 60 per cent.... 28 or 40 per cent. 1st to 3rd day ...... 70 further stimulus to its more extended use-must 4th to 7th day ...... 24 ... 14 58-4 ,, ...10,,41’6 not be insisted on. Later than 7th day ... 11 ... 8 ,, 72.7 ... 3 ,,27.3 As already mentioned, soamin appeared to give results ; its beneficial effect in the septicæmic good The failure of antimeningococcic serum to reduce of the disease was noticed by Staff-Surgeon stage the mortality was therefore not due to its being B. S. Robson, R.N., at Haslar, and has also been given too late, for in 66’7 per cent. of the 105 cases mentioned by others,5 In one case at Portland it was administered within the first three days of as much as 42 gr. of soamin were given. the disease. The serum treatment, which was so Hospital was not noted in any instance. Optic atrophy successful in America (Flexner, Sophian), Belfast Hexamine was given by the mouth in seven cases (Robb), and elsewhere, was given a thorough trial in the hope that, as it is secreted into the cerebroIn very and proved most disappointing. fluid, it would exert a bactericidal- action instances was there the critical improvement spinal on the meningococci, but as it did not appear which is said to occur in about 30 per cent. of the to have any effect clinically it was soon cases that recover (Flexner),4 Possibly the meningoabandoned. " cocci were " fast to the action of the serum Lumbar puncture, which is such an important In consequence of its or were para-meningococci. means of diagnosis, was performed in 149 out of apparent inertness intrathecal injection of serum 163 cases, or in 91’4 per cent. In 38 cases lumbar was in the latter part of the epidemic largely was done once only, but 14 of these cases other methods, puncture or combined with replaced by died soon after they came under observation; 6 such as the intramuscular injection of soamin. other cases, tapped once, died. Of 22 cases, tapped It is true that the mortality naturally diminishes 8 proved fatal, 2 being very acute; 3 tappings twice, towards the end of epidemics; but this does, not were done in 20 cases (9 deaths), 4 in 24 (15 deaths), yet entirely explain why, as shown by the 5 in 15 (9 deaths), 6 in 6 (3 deaths), 7 in 7 (4 tabular statement, the results of intrathecal deaths), 8 in 3 (2 deaths), 9 in 4 (all fatal), 11 in injection of serum compare so badly with 5 (2 deaths), 13 in 1 (fatal), 15 in 1 (fatal), 16 those of almost all the other methods and comin 1 (fatal), and 17 in 2 (both recoveries). Lumbar binations of methods; for up to the end of appears to be a palliative rather February there were 90 cases with a mortality of puncture than a curative remedy and to relieve for a time 52, or 57 per cent., whereas from the beginning of due to increased intrathecal pressure. In March to the end of July there were 80 cases with symptoms 13 cases, of which 4 proved fatal, it was the only a mortality of 38, or 47 per cent. There is, for form of treatment other than the ordinary symexample, a remarkable contrast between the effects ptomatic remedies employed. no
.
...
"
"
"
few
,
,
,
2 In one case at Deal, 10 c.c. of blood serum from a patient convalescent from the disease was injected intrathecally the day before death. 3 Flexner: Journal of Experimental Medicine, N.Y., 1913, vol. xvii.,
p. 4553.
Quoted by
1913,
p. 282.
Heiman and Feldstein,
Meningococcus Meningitis,
In 14 cases, 10 of which
remedies
only (such
as
proved fatal, symptomatic
morphine
for
pain)
given. Upper Brook-street, 5
W.
Batten : THE
LANCET, 1915, vol. i.,
p. 966.
were
Supplement
to "THE LANCET."
Second
Sixth To illustrate Mr. W. W.
day.
day.
Linington’s
Case of Traumatic Asphyxia.