Current
Topics
Studies in Vitamin-B Deficiency With Special Reference to Mental and Oral Manifestations By A. G. CLARKE,
b.sc., m.b., d.p.m.
and F. PRESCOTT, \i.sc., ph.D., a.i.c., m.r.c.s. (Abstracted from the British Medical Journal, ii, 23rd October, 1943, p. 503) PSYCHONEUROSIS AND DIETARY DEFICIENCY We have recently seen 17 cases of vitamin-B complex deficiency in patients treated primarily for nervous disorders. This represents 2 per cent of the patients seen by us in the out-patient department of the West End Hospital for Nervous Diseases. Originally they were mostly classified as suffering from functional nervous disorder, and with one exception were women. The parallelism between the manifestations of a deficiency of the vitamin-B complex and those of psychoneurosis is seen from the following list. All are likely to be met with in the psychoneurotic; those in italics may result from a deficiency of the vitaminB complex. General : Fatigue, anorexia, indigestion, constipaytion, diarrhoea, dizziness. Circulatory : Tachycardia, palpitation, shortness of breath. Vasomotor : Pallor, blusfmig, sweating.
THE INDIAN MEDICAL GAZETTE
338
Nervous system : Headache, backache, insomnia, photophobia, hyperacusis, noises in the head, vertigo,' hypercesthesia, parcesthesia. Mental symptoms : Inability to concentrate, selfconsciousness, depression, phobias, anxieties. So close is the parallelism that early cases of pellagra?which is 'a multiple deficiency disease?are often diagnosed as functional' by those unacquainted with the early manifestations.
The Treatment of War Wounds with Penicillin (From the British Medical Journal, ii, 11th December, 1943, p. 755) The following is an account written for us by Prof. L. P. Garrod of a report published by the War Office entitled, 'A Preliminary Report to the War Office and the Medical Research Council on Investigations concerning the Use of Penicillin in War Wounds? carried out under the Direction of Prof. H. W. Florey, F.R?., and Brig. Hugh Cairns, F.R.C?., R.A.M.C.' This report is for official use only, but we are permitted to publish an abstract of its contents. This printed report of 114 pages is in two parts : a general account of the investigation and its results by Florey and Cairns, and 12 detailed descriptions of particular classes of case by individual surgeons, including numerous fairly full case histories. The work described was carried out in North Africa during a period of only 3 months last summer, in order to ascertain as quickly as possible how penicillin can be used to the best advantage in treating battle wounds. The best use of very limited supplies involved discovering how to obtain good results by local treatment only, since this is far more economical than systemic administration. No attempt was made deliberately to compare penicillin treatment with any other?a much more formidable project. Methods of administration Penicillin was applied locally either as a solution in distilled water containing 250 units of calcium penicillin per c.mm., as a powder in which calcium penicillin was diluted with sulphanilamide to give a strength of 500, 2,000, or 5,000 units per g. (in a few cases it was used undiluted), or as a cream in a lanette wax base. Systemic treatment was achieved by intramuscular or intravenous injection of sodium penicillin by continuous drip in glucose saline, the daily dose being usually 120,000 units : owing to impurities in some of the batches used injection by the former route caused pain and by the latter febrile reactions and early venous thrombosis. There were no serious toxic effects. A good plan was to give intramuscular injections for 1 day after operation, then start on intravenous drip, and revert to intramuscular injections later if necessary. Some loss of potency occurred, especially in calcium penicillin, owing to climatic conditions and transport : doses stated are therefore maxima and the probable true dose was up to 30 per cent less. Chronic
wound
sepsis
The first phase of the investigation was the treatment in Algiers by Lieut-Colonel Ian Fraser of a series of septic wounds from 3 weeks to 4 months old. These cases were accommodated in a special 30-bed ward, and full bacteriological control was carried out by Major Thomson. Local treatment with Scott solution, powder, and cream was disappointing : accessible surfaces could be sterilized, but deep-seated infection could be controlled. Systemic not administration was resorted to in 8 cases of septic compound fracture, 4 of which received over 1,000,000 units; this lavish treatment cleared up the infection in 6. It was concluded from this experience that longstanding sepsis with loculated abscesses and poor general condition was a relatively unpromising afield, and that cases should be treated earlier. Almost ideal
[July,
1944
arrangements for this were possible when the campaign in Sicily opened. Lieut.-Colonel Fraser and Major where ?
MacLennan (bacteriologist) proceeded to Sicily, they examined casualties early and gave preliminary or treatment : the men were then evacuated to Tripoli who Sousse, where 10 surgeons in 5 general hospitals took part in the investigation worked in collaboration of with Florey and Cairns. The cases treated were 2 principal classes. Recent
soft-tissue
wounds
Of these there were 171, of which 53 were treated by Lieut.-Colonel J. S. Jeffrey : they were mostly from hours and 22 days), and 3 to 12 days old (extremes 12 ' in fact some were the majority were infected, was purulent and most were clinically dirty. No caseclosed rejected for this reason, and the wounds were before the results of the preliminary bacteriological examination were known'. Large and difficult wounds cases were chosen, including 25 of the buttock : 7 The policy adopted was were amputation stumps.
immediate closure, relying
on
penicillin applied locally
The principal method of application was through tubes inserted at the operation for suture. Oiie or more 1/8-in. rubber tubes were introduced through stab holes or through the' wound itself, the outer ends projecting beyond the dressing, and through these from 3 to 10 c.cm. of penicillin solution (250 units per c.cm.) were injected twice daily for 4 days. Some cases were also treated by insufflation of powder, either as a preliminary measure in the forward area (which according to Scott Thomson's bacteriological data reduced the frequency of infection with pyogenic cocci on arrival at the forward base from 57 to 26 per cent) or at the base for 3 days before closure was undertaken : powder alone with no irrigation after closure was used in exceptionally clean cases. Complete union was secured in 104 cases, subtotal union?i.e. healing by granulation in some part of the wound?in 60; failures numbered 7. These wounds show little reaction : they may remain dry or disfluid' which turns charge a thin salmon-pink purulent ' Gram-negative pus' green on the dressing?this is containing Ps. vyocyanea, and healing proceeds rapidly in spite of its formation. The results as a whole were such that Jeffrey goes so far as to say : ' With penicillin the obstacle of infection has been practically overcome , and it is estimated that from 3 to 6 weeks in hospital is saved. Causes of failure or subtotal union were : stitching up so tightly in layers that the solution could not penetrate the whole of the wound; placing sutures too near the skin edge; removing sutures too soon; injecting too much solution (3 c.cm. per tube was found better than 10 c.cm.), since this tended to separate the wound surfaces; and relying po when this tends to be before suture ier blood. i8 ,i?naway washed The main difficulty in applyby ing this treatment was caused by unduly drastic wound excision in the forward area; it is very strongly emphasized that this should be conservative, skin especially bemK sPar"'- It is also stated emphatically that suture should not be attempted in the C.C.S., and that at the forward base where it is undertaken the man should remain until healing is complete. to hold infection in check.
_
Recent
fractures
A different method was adopted for compound fractures. 1 here were 36 of these cases, mostly severe comminuted fractures of long bones : they were 5 to 14 days old on arrival at the forward base; 9 had been treated locally with penicillin-sulphanilamide powder and SI with sulphanilamide only. The aim was to convert to a simple fracture by closure and so prevent chronic infection, and systemic treatment was considered necessary : the standard course was 100,000 units daily (by the 3-hourly intramuscular or continuous intravenous route) for 5 days. Only 31 of the wounds was were capable of being sutured : complete union achieved in 16, subtotal in 10, and there were 5 failures. Of the 6 cases not sutured, 5 healed by granulation rapidly without infection and 1 died of fat embolism.
CURRENT TOPICS
July, 1944]
of the femur gave the worst results, and it is advocated that in future systemic treatment for these should be continued for 7 to 10 days. Inadequate and dosage was apparently the main cause of failure, cocci bacteriological studies showed that pyogenic was sometimes persisted after the full course. Closure too ambitious in some of the large wounds, where drainage even for Gram-negative pus would have been Preferable. There were also 2 examples of infection by penicillin-resistant cocci.
Fractures
Miscellaneous infections
Smaller numbers of cases were treated in the followlng categories :? Gas gangrene.?It was not often possible to get these cases to the forward base before they were moribund, but 7 cases were treated, of which complete histories are given. It is pointed out that the treatment should delude full doses of antitoxin to combat the toxaemia, aild the excision of all dead tissue, since penicillin cannot reach this. Systemic administration for 3 to ? .
local application is useless in treatment, although it may be of great value for Prevention. The infection was apparently checked in cases : 3 died from causes apparently outside the control of penicillin. .Head wounds.?Brain wounds 3 to 12 days old, almost a" infected with pyogenic organisms, were excised, c'eaned, and closed : a small tube was passed through a stab hole into the brain cavity, and pus was aspirated solution injected twice daily for 3 to 6 days. Of * cases only 3 died?2 of intracranial infection. These favourably so far as they go, compare very those obtained by other methods. Most nonPenetrating wounds of the skull and scalp were treated y a single application of powder at the time of suture. Undiluted powder and primary suture.?During the r?t 2 days of the Sicilian invasion 13 casualties with involving banes or joints in nearly all cases a0Vnds l!nd averaging 40 hours old were operated on in a ?spital ship ^off-shore. About 1 g. (50,000 units) of ^diluted calcium penicillin powder was applied by 'P??n anj rubbed into all parts of the wound, which as then closed. Results, so far as they are known, ere excellent, but after-histories are not all available. some cases of burns were treated by insufflation with , : hsemo1 ,Per cent penicillin in sulphonamide powder' t~lc streptococcal infection was thus eliminated which res'sted other treatments. One recent and 9 sul v> Phonamide-resistant cases of gonorrhoea were given injections of It-ignore than 12 4-hourly intramuscular units, the effect of which was 'like turning off a no relapse was observed during 2 to 4 weeks' s LaP': gonorrh ^uent observation. (Sulphonamide-resistant French common in N. Africa, possibly because 18 in charge of brothels give small doses of sul?)i/ ??amides to prostitutes as a prophylactic. The .nicillin treatment of gonorrhoea should be restricted Present to highly trained fighting troops, such as n achutists, in forward areas.)
days
is. advocated
a^d results, ^'th
339
employing penicillin. The appointment of a statisis recommended, to supervise accurate record-keeping and a careful follow-up and to assess results. Similar information from an Army- group not using penicillin would be valuable : there is an extreme dearth of accurate information about the frequency and duration of sepsis in battle wounds and the effects of other measures such as sulphonamide treatment. Among other types of case, gas gangrene requires further study, and penetrating wounds of the chest, which have hitherto been excluded, should be studied particularly with a view to discovering whether pyogenic coccal infection can be controlled by the more economical method of local application. 'There can be little doubt that the prevention of infection with pyogenic cocci or its control in war wounds is within reach, and no criticism with its emphasis on difficulties should be allowed to stand in not
tical officer
the way of the attainment of this ideal.'
Antidotes to Arsenic
:
(From the British Medical Journal, ii, 27th November, 1943, p. 681) There has lately been an increase in the number of patients suffering from symptoms of arsenical intoxication as a result of antisyphilitic treatment. The first published work which indicated the mechanism of arsenical poisoning was that of Voegtlin, Dyer, and Leonard in 1923; they showed that the action of arsenic on protoplasm was due to organic sulphur compounds containing the sulphur in the mercaptan or sulphydryl form (?SH). Neoarsphenamine is probably converted in the body into the arsenoxide form, R.As. 0, and Voegtlin and his colleagues showed that =
the action of arsenoxide on trypanosomes, both in the test-tube and in the living rat, was inhibited by adding sulphydryl compounds such as cystein or glutathione. Later the same workers demonstrated th#t the toxic action of arsenoxide for the rat itself was inhibited by the intravenous injection of glutathione in the reduced form. The toxic action was also lessened by feeding rats on a mixture of glutaminic acid and cystine, which are the constituents of glutathione. The conclusion from these observations is that when com-
pounds containing sulphydryl
groups are
administered,
arsenic which is present in the body combines with these sulphydryl groups rather than with the sulphydryl groups of protoplasm. These observations are probably related to the demonstration by Messinger and Hawkins in 1940 that a meat diet is very effective in protecting dogs against the toxic action of arsenic on the liver, and that a fat diet, on the other hand, conduces to toxic effects. For example, one dog eating a high fat diet became toxic and inactive with a high icteric index after the injection of 0.04 g. per kg. arsphenamine. When a protein diet was substituted the icteric index fell and the dog became active. Three more arsphenamine injections were then given, but in spite of these the bilirubinaimia fell ana the dog remained well. It was Future policy then put back on. the fat diet, when the icteric index more arsphenamine. Evidence has been obtained that 'penicillin can make rose from 2 to 21 units without shown to protect the tantial contribution to the health of wounded A protein diet has similarly been solrT? of hospital time'. liver of a dog against chloroform, and it is the sulphurfliers, with saving corresponding p containing amino-acids in the protein which give the use sbould assume that an average of ?50!fuv/or protection; it may be these'amino-acids which protect case is required sodium units of per penicillin for' 8ystemic treatment and of 50,000 units of calcium against arsenic, it should be remembered that casein s?i, For the time being supplies should be contains relatively much cystine. ^In '?rthelocal. A new approach has recently been made by control of the Directorate of Pathology at thp ^ ' Sandground and Hamilton, who were stimulated by the conar be and its should use mainly P?ce> cent. in one theatre of operations'. Surgical and observation of Woods that p-aminobenzoic inhibits the p ,Prated Sieal penicillin officers should be in charge of action of sulphonamides on bacteria. Sandground and p-aminobenzoic acid wbich should be confined to predetermined Hamilton wondered whether tvrf ?f ' case. The most hopeful field is the early would inhibit the action of pentavalent arsenicals such ,s trP on as trypanosomes. They looked for tryparsamide soft-tissue wounds and fractures. Further e^tment ofshould lead to improvements in technique, this action, failed to find it, but discovered that anrfrienee when the acid greatly reduced the toxicity of best methods have been defined 7>-aminobenzoic sho a comparison be made with forms of treatment large doses of tryparsamide, carbarsone, acetarsone, and
f0,
.
trpil0
l^n^
340
THE INDIAN MEDICAL GAZETTE
other pentavalent arsenic compounds. For example, 1.5 g. per kg. carbarsone killed all rats; but if this dose was followed by oral administration of 0.75 g. per kg. p-aminobenzoic acid repeated twice on successive days, all rats survived. Some protective action could be demonstrated with doses so low as 15 mg. per kg. The protection afforded by p-aminobenzoic acid was greatest when it was administered either together with carbarsone or one hour previously; the protection was less if p-aminobenzoic acid was given after the carbarsone. Similarly, p-aminobenzoic acid gave good protection against arsenilic acid if it was given three hours before. "Sandground considers that the protective action is due to p-aminobenzoic acid interfering with the reduction of the pentavalent arsenicals to the arsenoxide form, inasmuch as p-aminobenzoic acid has trivalent veiy little protective action against the arsenical compounds like neoarsphenamine, or against arsenoxides like maphersen. Maphersen, it is interesting to note, is rapidly replacing neoarsphenamine as an antisyphilitic remedy in the United States; probably more than half the cases in the U.S. Army are treated with maphersen. Still further work from another source has now been published. Goldstein, Stolman, and Goldfarb state that methyl chalcone of hesperidin reduces the toxicity of maphersen .for rabbits. These workers were concerned to find a remedy for the encephalopathy which has occurred in 1.3 per cent of patients treated for syphilis with maphersen by the rapid 5-day method. Goldstein and Stevenson observed that maphersen in large doses damaged the brain capillaries of rabbits, and Goldfarb proposed the use of an aqueous extract of whole lemon to prevent arsenical encephalopathy. Lemon was believed to contain the faotor diminishing capillary permeability known as vitamin P. Later a chalcone of hespirid'n (a vegetable dye having vitamin P activity) was isolated from lemon peel, from which Goldstein and his was prepared a methyl chalcone. colleagues have now used this methyl chalcone in conjunction with mepharsen, and state that it gives some protection against the toxic effect of large doses of maphersen. Maphersen in doses of 8 mg. per kg. twice daily for four days killed 13 out of 30 rabbits. If, however, the methyl chalcone was given intravenously daily for 7 days before and for 4 days during the maphersen injections, in doses of from 10 to 30 mg. per kg., then only 3 rabbits out of 30 died. These experiments are, however, still in the preliminary stage. Of the three lines of work described, the first seems the one most likely to have a clinical application, though the second might also be tried. Both compounds, like cystein, containing sulphydryl groups and p-aminobenzoic acid are fairly easy to obtain, and both might be tried, as remedies for arsenical dermatitis or for arsenical jaundice. Let us hope that this is being done.
Shall Bassini Die ? (From the Lancet, i, 8th
January, 1944,
p.
55)
Misgivings about the results of operation for inguinal hernia have been increased by observations made in examining recruits for the Services. Both in hospital and in private practice the attempted cure of inguinal hernia is one of the commonest surgical procedures; but familiarity has too often bred inattention and the hernia operation has commonly been relegated to the end of the list when it is sometimes performed by assistants and house surgeons without guidance. Even before the war, it was known that the recurrence rate Now Edwards tells of 805 recurrent hernias was high. operated on during six months of 1942 in military hospitals alone, and he estimates that these probably represent only 60 per cent of the number presenting themselves in that short period. The original" operations on these soldiers had been done?mostly Vin^civil life?in all parts of Great Britain and Northern Ireland,
[jULY)
1944
of and were therefore representative of the results British surgery as a whole. Operations on inguinal of our hernias in fit policemen in the wards of one by foremost teaching hospitals have been followed recurrence in as many as 12 to 20 per cent. Faulty technique certainly accounts for a proportion to of failures, and the time has come for surgeons and accept the fact that the operation is difficult worthy of all their skill and patience. But the type of operation may also be at fault. Bassini's operation, a routine, or one of its modifications, is used almost as have and its supremacy may not be justified. Changes lately been discussed in our columns and elsewhere. For example, a modification of the Bassini operation, by known by the name of McArther, is upheld McLaughlin, while Arther has further modified McArther's operation. Arther stitches the conjoint line tendon to Poupart's ligament, and reinforces the the of sutures by el fascial graft, dissected from external oblique but not detached from it. He does safe not believe that simple removal of the sac is under Service conditions where subsequent abstinence from hard manual labour for a long time is impossible. Edwards, on the other hand, is strongly of opinion sac, that, in the normal healthy male, removal of the combined with repair of the tear in the transversals fascia, is all that is needed; indeed he thinks that suture of the internal oblique and the conjoint tendon is destructive and should not be practised in such patients. During 19 months he and Capper perspnally operated on 131 recurrent hernias in men of military age. In 86 of them it was possible with reasonable certainty to?say what was the original method of repair : in 53 this was the Bassini; in 19 the sac only had been excised; in 14 other methods, such as Bloodgood s, had been_ used. In cases treated by the Bassini operation the internal oblique was represented in by a thin sheet of attenuated muscle, pale brown colour. This finding supports the contention that is suture pf the internal oblique to Poupart's- ligament unphysiological, distorts the musculature, and by interfering with its contraction actually weakens the abdominal wall at the inguinal canal. Removal of the sac alone has long been the usual operation in children> where any further repair has been regarded as surgical interference; but dissection of the sac from its coverbe ings must be complete, otherwise the stump will For adults an easy starting point of a fresh hernia. this is recognized as the most important step in the operation; but where there is a gap in the posterior wall, some method of strengthening the inguinal canal must be devised. Discarding the Bassini type of repair) Edwaids proposes a choice of two methods. One is to dissect a flap of the anterior layer of the sheath of rectus abdominis, which is then hinged downwards and attached with interrupted stitches to the upturned edge of Pouparts ligament; this he advises only for the infrequent direct hernia. The other is to darn the gap in the inguinal wall with a Gallie fascial graft. Edwards is less concerned, however, with methods than with results. Hernia can be a grave disability' and working men often pay a heavy price for surgical failure. No one should be burdened through his best years with an unnecessary truss, and to most men radical cure of hernia at 30 is actually more important than radical cure of cancer at 70. The surgeon who takes to care of the gastrectomies but leaves the hernias take care of themselves shows a lack of proportion. It is now evident that ' routine' treatment of hernia cannot be relied on to cure the condition, and Edwards is right in urging that the patient with hernia presents After a problem deserving thought as well as care. operation active treatment is still needed. Three weeks in bed is required, but within a day or two of operato tion the patient should begin graduated exercises restore muscle tone. The custom in the Army is to provide three weeks in bed, three or four weeks in a convalescent home, and finally four to five weeks in a convalescent depot where eventually the soldier is restored to full physical efficiency before he goes back to his unit. _
'
_
REVIEWS
July, 1944]
digitalis
in Cases Showing
Normal Rhythm
By D. M. LYON (Abstracted from the Edinburgh Medical Journal, Vol. L, December 1943, p. 746) with normal a result of digitalization in patients ion
Pu^se slowing
was
produced
in 90 per cent of
trials.
the rate slowing was proportionate to the heart at the time when the drug was begun, the pulse, bven where there is little or no effect on may occur,
a,moun^
uresis bpl fih
and other clinical
seem to fWC]Vld ^ digitalis is only
'n
anC^
severe
improvement the be no justification for effective in cases of auricular cai"diac failure with normal
rhyth Viscose Tubing for Transfusions By H. NAFTULIN A. M. WOLF and S. O. LEVINSON (Abstracted from the Journal oj the American Me ica Association, Vol. CXXIII, 9th October, 1943, p. UD Summary
The cleansing of rubber tubing to be used foi in Ta venous administration of blood or blood protein difficult. Incomplete cleansing of rubber tubing believed to be a major cause of pyrogenic reactions. Heavy walled Viscose tubing is sturdy, pyrogen Ire lrnpermeable to pyrogens, impermeable to bacteria a Quite practical for one time use. In a total of 1,137 blood transfusions given througn Viscose tubing the incidence of pyrogenic reactions was i ,
.
.
,
"?64 per cent. This is a material decrease irom faction rate encountered with rubber tubing.
v
341
Topics
Studies in Vitamin-B Deficiency With Special Reference to Mental and Oral Manifestations By A. G. CLARKE,
b.sc., m.b., d.p.m.
and F. PRESCOTT, \i.sc., ph.D., a.i.c., m.r.c.s. (Abstracted from the British Medical Journal, ii, 23rd October, 1943, p. 503) PSYCHONEUROSIS AND DIETARY DEFICIENCY We have recently seen 17 cases of vitamin-B complex deficiency in patients treated primarily for nervous disorders. This represents 2 per cent of the patients seen by us in the out-patient department of the West End Hospital for Nervous Diseases. Originally they were mostly classified as suffering from functional nervous disorder, and with one exception were women. The parallelism between the manifestations of a deficiency of the vitamin-B complex and those of psychoneurosis is seen from the following list. All are likely to be met with in the psychoneurotic; those in italics may result from a deficiency of the vitaminB complex. General : Fatigue, anorexia, indigestion, constipaytion, diarrhoea, dizziness. Circulatory : Tachycardia, palpitation, shortness of breath. Vasomotor : Pallor, blusfmig, sweating.
THE INDIAN MEDICAL GAZETTE
338
Nervous system : Headache, backache, insomnia, photophobia, hyperacusis, noises in the head, vertigo,' hypercesthesia, parcesthesia. Mental symptoms : Inability to concentrate, selfconsciousness, depression, phobias, anxieties. So close is the parallelism that early cases of pellagra?which is 'a multiple deficiency disease?are often diagnosed as functional' by those unacquainted with the early manifestations.
The Treatment of War Wounds with Penicillin (From the British Medical Journal, ii, 11th December, 1943, p. 755) The following is an account written for us by Prof. L. P. Garrod of a report published by the War Office entitled, 'A Preliminary Report to the War Office and the Medical Research Council on Investigations concerning the Use of Penicillin in War Wounds? carried out under the Direction of Prof. H. W. Florey, F.R?., and Brig. Hugh Cairns, F.R.C?., R.A.M.C.' This report is for official use only, but we are permitted to publish an abstract of its contents. This printed report of 114 pages is in two parts : a general account of the investigation and its results by Florey and Cairns, and 12 detailed descriptions of particular classes of case by individual surgeons, including numerous fairly full case histories. The work described was carried out in North Africa during a period of only 3 months last summer, in order to ascertain as quickly as possible how penicillin can be used to the best advantage in treating battle wounds. The best use of very limited supplies involved discovering how to obtain good results by local treatment only, since this is far more economical than systemic administration. No attempt was made deliberately to compare penicillin treatment with any other?a much more formidable project. Methods of administration Penicillin was applied locally either as a solution in distilled water containing 250 units of calcium penicillin per c.mm., as a powder in which calcium penicillin was diluted with sulphanilamide to give a strength of 500, 2,000, or 5,000 units per g. (in a few cases it was used undiluted), or as a cream in a lanette wax base. Systemic treatment was achieved by intramuscular or intravenous injection of sodium penicillin by continuous drip in glucose saline, the daily dose being usually 120,000 units : owing to impurities in some of the batches used injection by the former route caused pain and by the latter febrile reactions and early venous thrombosis. There were no serious toxic effects. A good plan was to give intramuscular injections for 1 day after operation, then start on intravenous drip, and revert to intramuscular injections later if necessary. Some loss of potency occurred, especially in calcium penicillin, owing to climatic conditions and transport : doses stated are therefore maxima and the probable true dose was up to 30 per cent less. Chronic
wound
sepsis
The first phase of the investigation was the treatment in Algiers by Lieut-Colonel Ian Fraser of a series of septic wounds from 3 weeks to 4 months old. These cases were accommodated in a special 30-bed ward, and full bacteriological control was carried out by Major Thomson. Local treatment with Scott solution, powder, and cream was disappointing : accessible surfaces could be sterilized, but deep-seated infection could be controlled. Systemic not administration was resorted to in 8 cases of septic compound fracture, 4 of which received over 1,000,000 units; this lavish treatment cleared up the infection in 6. It was concluded from this experience that longstanding sepsis with loculated abscesses and poor general condition was a relatively unpromising afield, and that cases should be treated earlier. Almost ideal
[July,
1944
arrangements for this were possible when the campaign in Sicily opened. Lieut.-Colonel Fraser and Major where ?
MacLennan (bacteriologist) proceeded to Sicily, they examined casualties early and gave preliminary or treatment : the men were then evacuated to Tripoli who Sousse, where 10 surgeons in 5 general hospitals took part in the investigation worked in collaboration of with Florey and Cairns. The cases treated were 2 principal classes. Recent
soft-tissue
wounds
Of these there were 171, of which 53 were treated by Lieut.-Colonel J. S. Jeffrey : they were mostly from hours and 22 days), and 3 to 12 days old (extremes 12 ' in fact some were the majority were infected, was purulent and most were clinically dirty. No caseclosed rejected for this reason, and the wounds were before the results of the preliminary bacteriological examination were known'. Large and difficult wounds cases were chosen, including 25 of the buttock : 7 The policy adopted was were amputation stumps.
immediate closure, relying
on
penicillin applied locally
The principal method of application was through tubes inserted at the operation for suture. Oiie or more 1/8-in. rubber tubes were introduced through stab holes or through the' wound itself, the outer ends projecting beyond the dressing, and through these from 3 to 10 c.cm. of penicillin solution (250 units per c.cm.) were injected twice daily for 4 days. Some cases were also treated by insufflation of powder, either as a preliminary measure in the forward area (which according to Scott Thomson's bacteriological data reduced the frequency of infection with pyogenic cocci on arrival at the forward base from 57 to 26 per cent) or at the base for 3 days before closure was undertaken : powder alone with no irrigation after closure was used in exceptionally clean cases. Complete union was secured in 104 cases, subtotal union?i.e. healing by granulation in some part of the wound?in 60; failures numbered 7. These wounds show little reaction : they may remain dry or disfluid' which turns charge a thin salmon-pink purulent ' Gram-negative pus' green on the dressing?this is containing Ps. vyocyanea, and healing proceeds rapidly in spite of its formation. The results as a whole were such that Jeffrey goes so far as to say : ' With penicillin the obstacle of infection has been practically overcome , and it is estimated that from 3 to 6 weeks in hospital is saved. Causes of failure or subtotal union were : stitching up so tightly in layers that the solution could not penetrate the whole of the wound; placing sutures too near the skin edge; removing sutures too soon; injecting too much solution (3 c.cm. per tube was found better than 10 c.cm.), since this tended to separate the wound surfaces; and relying po when this tends to be before suture ier blood. i8 ,i?naway washed The main difficulty in applyby ing this treatment was caused by unduly drastic wound excision in the forward area; it is very strongly emphasized that this should be conservative, skin especially bemK sPar"'- It is also stated emphatically that suture should not be attempted in the C.C.S., and that at the forward base where it is undertaken the man should remain until healing is complete. to hold infection in check.
_
Recent
fractures
A different method was adopted for compound fractures. 1 here were 36 of these cases, mostly severe comminuted fractures of long bones : they were 5 to 14 days old on arrival at the forward base; 9 had been treated locally with penicillin-sulphanilamide powder and SI with sulphanilamide only. The aim was to convert to a simple fracture by closure and so prevent chronic infection, and systemic treatment was considered necessary : the standard course was 100,000 units daily (by the 3-hourly intramuscular or continuous intravenous route) for 5 days. Only 31 of the wounds was were capable of being sutured : complete union achieved in 16, subtotal in 10, and there were 5 failures. Of the 6 cases not sutured, 5 healed by granulation rapidly without infection and 1 died of fat embolism.
CURRENT TOPICS
July, 1944]
of the femur gave the worst results, and it is advocated that in future systemic treatment for these should be continued for 7 to 10 days. Inadequate and dosage was apparently the main cause of failure, cocci bacteriological studies showed that pyogenic was sometimes persisted after the full course. Closure too ambitious in some of the large wounds, where drainage even for Gram-negative pus would have been Preferable. There were also 2 examples of infection by penicillin-resistant cocci.
Fractures
Miscellaneous infections
Smaller numbers of cases were treated in the followlng categories :? Gas gangrene.?It was not often possible to get these cases to the forward base before they were moribund, but 7 cases were treated, of which complete histories are given. It is pointed out that the treatment should delude full doses of antitoxin to combat the toxaemia, aild the excision of all dead tissue, since penicillin cannot reach this. Systemic administration for 3 to ? .
local application is useless in treatment, although it may be of great value for Prevention. The infection was apparently checked in cases : 3 died from causes apparently outside the control of penicillin. .Head wounds.?Brain wounds 3 to 12 days old, almost a" infected with pyogenic organisms, were excised, c'eaned, and closed : a small tube was passed through a stab hole into the brain cavity, and pus was aspirated solution injected twice daily for 3 to 6 days. Of * cases only 3 died?2 of intracranial infection. These favourably so far as they go, compare very those obtained by other methods. Most nonPenetrating wounds of the skull and scalp were treated y a single application of powder at the time of suture. Undiluted powder and primary suture.?During the r?t 2 days of the Sicilian invasion 13 casualties with involving banes or joints in nearly all cases a0Vnds l!nd averaging 40 hours old were operated on in a ?spital ship ^off-shore. About 1 g. (50,000 units) of ^diluted calcium penicillin powder was applied by 'P??n anj rubbed into all parts of the wound, which as then closed. Results, so far as they are known, ere excellent, but after-histories are not all available. some cases of burns were treated by insufflation with , : hsemo1 ,Per cent penicillin in sulphonamide powder' t~lc streptococcal infection was thus eliminated which res'sted other treatments. One recent and 9 sul v> Phonamide-resistant cases of gonorrhoea were given injections of It-ignore than 12 4-hourly intramuscular units, the effect of which was 'like turning off a no relapse was observed during 2 to 4 weeks' s LaP': gonorrh ^uent observation. (Sulphonamide-resistant French common in N. Africa, possibly because 18 in charge of brothels give small doses of sul?)i/ ??amides to prostitutes as a prophylactic. The .nicillin treatment of gonorrhoea should be restricted Present to highly trained fighting troops, such as n achutists, in forward areas.)
days
is. advocated
a^d results, ^'th
339
employing penicillin. The appointment of a statisis recommended, to supervise accurate record-keeping and a careful follow-up and to assess results. Similar information from an Army- group not using penicillin would be valuable : there is an extreme dearth of accurate information about the frequency and duration of sepsis in battle wounds and the effects of other measures such as sulphonamide treatment. Among other types of case, gas gangrene requires further study, and penetrating wounds of the chest, which have hitherto been excluded, should be studied particularly with a view to discovering whether pyogenic coccal infection can be controlled by the more economical method of local application. 'There can be little doubt that the prevention of infection with pyogenic cocci or its control in war wounds is within reach, and no criticism with its emphasis on difficulties should be allowed to stand in not
tical officer
the way of the attainment of this ideal.'
Antidotes to Arsenic
:
(From the British Medical Journal, ii, 27th November, 1943, p. 681) There has lately been an increase in the number of patients suffering from symptoms of arsenical intoxication as a result of antisyphilitic treatment. The first published work which indicated the mechanism of arsenical poisoning was that of Voegtlin, Dyer, and Leonard in 1923; they showed that the action of arsenic on protoplasm was due to organic sulphur compounds containing the sulphur in the mercaptan or sulphydryl form (?SH). Neoarsphenamine is probably converted in the body into the arsenoxide form, R.As. 0, and Voegtlin and his colleagues showed that =
the action of arsenoxide on trypanosomes, both in the test-tube and in the living rat, was inhibited by adding sulphydryl compounds such as cystein or glutathione. Later the same workers demonstrated th#t the toxic action of arsenoxide for the rat itself was inhibited by the intravenous injection of glutathione in the reduced form. The toxic action was also lessened by feeding rats on a mixture of glutaminic acid and cystine, which are the constituents of glutathione. The conclusion from these observations is that when com-
pounds containing sulphydryl
groups are
administered,
arsenic which is present in the body combines with these sulphydryl groups rather than with the sulphydryl groups of protoplasm. These observations are probably related to the demonstration by Messinger and Hawkins in 1940 that a meat diet is very effective in protecting dogs against the toxic action of arsenic on the liver, and that a fat diet, on the other hand, conduces to toxic effects. For example, one dog eating a high fat diet became toxic and inactive with a high icteric index after the injection of 0.04 g. per kg. arsphenamine. When a protein diet was substituted the icteric index fell and the dog became active. Three more arsphenamine injections were then given, but in spite of these the bilirubinaimia fell ana the dog remained well. It was Future policy then put back on. the fat diet, when the icteric index more arsphenamine. Evidence has been obtained that 'penicillin can make rose from 2 to 21 units without shown to protect the tantial contribution to the health of wounded A protein diet has similarly been solrT? of hospital time'. liver of a dog against chloroform, and it is the sulphurfliers, with saving corresponding p containing amino-acids in the protein which give the use sbould assume that an average of ?50!fuv/or protection; it may be these'amino-acids which protect case is required sodium units of per penicillin for' 8ystemic treatment and of 50,000 units of calcium against arsenic, it should be remembered that casein s?i, For the time being supplies should be contains relatively much cystine. ^In '?rthelocal. A new approach has recently been made by control of the Directorate of Pathology at thp ^ ' Sandground and Hamilton, who were stimulated by the conar be and its should use mainly P?ce> cent. in one theatre of operations'. Surgical and observation of Woods that p-aminobenzoic inhibits the p ,Prated Sieal penicillin officers should be in charge of action of sulphonamides on bacteria. Sandground and p-aminobenzoic acid wbich should be confined to predetermined Hamilton wondered whether tvrf ?f ' case. The most hopeful field is the early would inhibit the action of pentavalent arsenicals such ,s trP on as trypanosomes. They looked for tryparsamide soft-tissue wounds and fractures. Further e^tment ofshould lead to improvements in technique, this action, failed to find it, but discovered that anrfrienee when the acid greatly reduced the toxicity of best methods have been defined 7>-aminobenzoic sho a comparison be made with forms of treatment large doses of tryparsamide, carbarsone, acetarsone, and
f0,
.
trpil0
l^n^
340
THE INDIAN MEDICAL GAZETTE
other pentavalent arsenic compounds. For example, 1.5 g. per kg. carbarsone killed all rats; but if this dose was followed by oral administration of 0.75 g. per kg. p-aminobenzoic acid repeated twice on successive days, all rats survived. Some protective action could be demonstrated with doses so low as 15 mg. per kg. The protection afforded by p-aminobenzoic acid was greatest when it was administered either together with carbarsone or one hour previously; the protection was less if p-aminobenzoic acid was given after the carbarsone. Similarly, p-aminobenzoic acid gave good protection against arsenilic acid if it was given three hours before. "Sandground considers that the protective action is due to p-aminobenzoic acid interfering with the reduction of the pentavalent arsenicals to the arsenoxide form, inasmuch as p-aminobenzoic acid has trivalent veiy little protective action against the arsenical compounds like neoarsphenamine, or against arsenoxides like maphersen. Maphersen, it is interesting to note, is rapidly replacing neoarsphenamine as an antisyphilitic remedy in the United States; probably more than half the cases in the U.S. Army are treated with maphersen. Still further work from another source has now been published. Goldstein, Stolman, and Goldfarb state that methyl chalcone of hesperidin reduces the toxicity of maphersen .for rabbits. These workers were concerned to find a remedy for the encephalopathy which has occurred in 1.3 per cent of patients treated for syphilis with maphersen by the rapid 5-day method. Goldstein and Stevenson observed that maphersen in large doses damaged the brain capillaries of rabbits, and Goldfarb proposed the use of an aqueous extract of whole lemon to prevent arsenical encephalopathy. Lemon was believed to contain the faotor diminishing capillary permeability known as vitamin P. Later a chalcone of hespirid'n (a vegetable dye having vitamin P activity) was isolated from lemon peel, from which Goldstein and his was prepared a methyl chalcone. colleagues have now used this methyl chalcone in conjunction with mepharsen, and state that it gives some protection against the toxic effect of large doses of maphersen. Maphersen in doses of 8 mg. per kg. twice daily for four days killed 13 out of 30 rabbits. If, however, the methyl chalcone was given intravenously daily for 7 days before and for 4 days during the maphersen injections, in doses of from 10 to 30 mg. per kg., then only 3 rabbits out of 30 died. These experiments are, however, still in the preliminary stage. Of the three lines of work described, the first seems the one most likely to have a clinical application, though the second might also be tried. Both compounds, like cystein, containing sulphydryl groups and p-aminobenzoic acid are fairly easy to obtain, and both might be tried, as remedies for arsenical dermatitis or for arsenical jaundice. Let us hope that this is being done.
Shall Bassini Die ? (From the Lancet, i, 8th
January, 1944,
p.
55)
Misgivings about the results of operation for inguinal hernia have been increased by observations made in examining recruits for the Services. Both in hospital and in private practice the attempted cure of inguinal hernia is one of the commonest surgical procedures; but familiarity has too often bred inattention and the hernia operation has commonly been relegated to the end of the list when it is sometimes performed by assistants and house surgeons without guidance. Even before the war, it was known that the recurrence rate Now Edwards tells of 805 recurrent hernias was high. operated on during six months of 1942 in military hospitals alone, and he estimates that these probably represent only 60 per cent of the number presenting themselves in that short period. The original" operations on these soldiers had been done?mostly Vin^civil life?in all parts of Great Britain and Northern Ireland,
[jULY)
1944
of and were therefore representative of the results British surgery as a whole. Operations on inguinal of our hernias in fit policemen in the wards of one by foremost teaching hospitals have been followed recurrence in as many as 12 to 20 per cent. Faulty technique certainly accounts for a proportion to of failures, and the time has come for surgeons and accept the fact that the operation is difficult worthy of all their skill and patience. But the type of operation may also be at fault. Bassini's operation, a routine, or one of its modifications, is used almost as have and its supremacy may not be justified. Changes lately been discussed in our columns and elsewhere. For example, a modification of the Bassini operation, by known by the name of McArther, is upheld McLaughlin, while Arther has further modified McArther's operation. Arther stitches the conjoint line tendon to Poupart's ligament, and reinforces the the of sutures by el fascial graft, dissected from external oblique but not detached from it. He does safe not believe that simple removal of the sac is under Service conditions where subsequent abstinence from hard manual labour for a long time is impossible. Edwards, on the other hand, is strongly of opinion sac, that, in the normal healthy male, removal of the combined with repair of the tear in the transversals fascia, is all that is needed; indeed he thinks that suture of the internal oblique and the conjoint tendon is destructive and should not be practised in such patients. During 19 months he and Capper perspnally operated on 131 recurrent hernias in men of military age. In 86 of them it was possible with reasonable certainty to?say what was the original method of repair : in 53 this was the Bassini; in 19 the sac only had been excised; in 14 other methods, such as Bloodgood s, had been_ used. In cases treated by the Bassini operation the internal oblique was represented in by a thin sheet of attenuated muscle, pale brown colour. This finding supports the contention that is suture pf the internal oblique to Poupart's- ligament unphysiological, distorts the musculature, and by interfering with its contraction actually weakens the abdominal wall at the inguinal canal. Removal of the sac alone has long been the usual operation in children> where any further repair has been regarded as surgical interference; but dissection of the sac from its coverbe ings must be complete, otherwise the stump will For adults an easy starting point of a fresh hernia. this is recognized as the most important step in the operation; but where there is a gap in the posterior wall, some method of strengthening the inguinal canal must be devised. Discarding the Bassini type of repair) Edwaids proposes a choice of two methods. One is to dissect a flap of the anterior layer of the sheath of rectus abdominis, which is then hinged downwards and attached with interrupted stitches to the upturned edge of Pouparts ligament; this he advises only for the infrequent direct hernia. The other is to darn the gap in the inguinal wall with a Gallie fascial graft. Edwards is less concerned, however, with methods than with results. Hernia can be a grave disability' and working men often pay a heavy price for surgical failure. No one should be burdened through his best years with an unnecessary truss, and to most men radical cure of hernia at 30 is actually more important than radical cure of cancer at 70. The surgeon who takes to care of the gastrectomies but leaves the hernias take care of themselves shows a lack of proportion. It is now evident that ' routine' treatment of hernia cannot be relied on to cure the condition, and Edwards is right in urging that the patient with hernia presents After a problem deserving thought as well as care. operation active treatment is still needed. Three weeks in bed is required, but within a day or two of operato tion the patient should begin graduated exercises restore muscle tone. The custom in the Army is to provide three weeks in bed, three or four weeks in a convalescent home, and finally four to five weeks in a convalescent depot where eventually the soldier is restored to full physical efficiency before he goes back to his unit. _
'
_
REVIEWS
July, 1944]
digitalis
in Cases Showing
Normal Rhythm
By D. M. LYON (Abstracted from the Edinburgh Medical Journal, Vol. L, December 1943, p. 746) with normal a result of digitalization in patients ion
Pu^se slowing
was
produced
in 90 per cent of
trials.
the rate slowing was proportionate to the heart at the time when the drug was begun, the pulse, bven where there is little or no effect on may occur,
a,moun^
uresis bpl fih
and other clinical
seem to fWC]Vld ^ digitalis is only
'n
anC^
severe
improvement the be no justification for effective in cases of auricular cai"diac failure with normal
rhyth Viscose Tubing for Transfusions By H. NAFTULIN A. M. WOLF and S. O. LEVINSON (Abstracted from the Journal oj the American Me ica Association, Vol. CXXIII, 9th October, 1943, p. UD Summary
The cleansing of rubber tubing to be used foi in Ta venous administration of blood or blood protein difficult. Incomplete cleansing of rubber tubing believed to be a major cause of pyrogenic reactions. Heavy walled Viscose tubing is sturdy, pyrogen Ire lrnpermeable to pyrogens, impermeable to bacteria a Quite practical for one time use. In a total of 1,137 blood transfusions given througn Viscose tubing the incidence of pyrogenic reactions was i ,
.
.
,
"?64 per cent. This is a material decrease irom faction rate encountered with rubber tubing.
v
341
