16

this position, if there is unilateral dislocation of one hip,one knee will be seen to be higher than the other. Next,the knees are widely abducted. In a normal infant inthis position the hips can be abducted about 80° each.Limitation of abduction in this position is an early andconstant clinical finding in congenital dislocation or

subluxation of the hip (fig. 2) and points to the needfor radiography of the hips.

SECOND TEST

In the newborn the ligaments and muscles may belax, and on full abduction of the flexed hips an audible,visible, and palpable jerk or snap is noticed (Ortolani’s"

sign of the jerk ")-i.e., the femoral head slips over theposterior rim of the acetabulum.

COMMENTS

It should be the aim of all pediatricians, obstetricians,and practitioners to diagnose congenital dislocation of the

Fig. 3-Frejka’s abduction pillow-splint.

hip at the earliest opportunity. These two simple testswill enable them to diagnose all the cases. A few infantswith limitation of abduction of the flexed hips do notgo on to dislocation, but no infant with congenitaldislocation of the hip does not show one of the two

signs.Putti obtained excellent results in 95% of infants

aged less than 1 year. In this country, where most casesare diagnosed at the age of 1 or 2 years, the best resultsdo not approximate 80%, and the older the child theworse is the result.Two of my cases were diagnosed at the age of 3 months :

one by a good general practitioner who knew of theabduction sign, and the other by a nurse who haddifficulty in abducting the baby’s legs to put on a

diaper and therefore called the pædiatrician’s attentionto it.

Treatment in the first few months of life by a Frejka’sabduction pillow-splint (in effect a broad thick diaper)(fig. 3) leads to a high percentage of cures by the time theinfant is ready to walk, thus doing away with manipu-lations and prolonged plaster-of-paris splints when heshould be running about.

If this flexion and abduction test were done on allinfants at the age of 2 or 3 months, many of the ortho-paedic surgeons’ problems on the treatment of thesechildren in later years would be done away with, and ahigher percentage of good results of treatment would beobtained. It is axiomatic that the earlier a congenitalabnormality is discovered and treated the better is thecure.

SONNE DYSENTERY TREATED WITH

TETRACYCLINEA COMPARISON WITH PHTHALYL

SULPHATHIAZOLE AND ORAL STREPTOMYCIN

J. D. ABBOTTM.D. Lond., Dip. Bact.

ASSISTANT BACTERIOLOGIST, PUBLIC HEALTH LABORATORY

(M.R.C.), MANCHESTER

H. E. PARRYM.B. Lond., M.R.C.P., D.C.H.

DEPUTY PHYSICIAN-SUPERINTENDENT, MONSALL HOSPITAL,MANCHESTER

SONNE dysentery is usually mild and short-lasting,.and clinical cure seldom presents any serious difficulty ;.but bacteriological cure is often difficult to obtain.

In the treatment of Sonne infections the sulphon-amides have been widely used, in particular the poorlyabsorbed derivatives sulphaguanidine, succinyl sulpha-thiazole, and phthalyl sulphathiazole. Although it is

generally accepted that there is a clinical response tothese drugs, evidence of their effectiveness in producinga bacteriological cure is less convincing. Hawking andLawrence (1950) have summarised many of the publishedreports of sulphonamide therapy, and Forbes (1953) hasclaimed prompt clinical and bacteriological cure of Sonnedysentery with oral streptomycin. In our experiencetreatment with succinyl sulphathiazole, phthalyl sulpha-thiazole, and oral streptomycin has proved disappointing-because many patients continued to excrete Shigellasonnei after a full course of treatment with these drugs.

Finland et al. (1954) have published the results ofclinical and bacteriological studies with the new anti-biotic tetracycline. This was found to be less toxic andmore active in vitro against Sh. sonnei than either

aureomycin or oxytetracycline (terramycin). We havetreated some cases of Sonne dysentery with tetracycline,others with phthalyl sulphathiazole, and others withoral streptomycin and compared the results. All the

patients were treated as inpatients in the same infectious-diseases hospital.

Clinical Data

From March to August, 1954, 27 patients (26 withsymptoms and 1 without) were treated with tetracycline,and 32 (28 with symptoms and 4 without) with phthalylTABLE I-AGE-DISTRIBUTION OF PATIENTS TREATED WITH

TETRACYCLINE, PHTHALYL SLTLPHATHIAZOLE, AND ORAL

STREPTOMYCIN

sulphathiazole. From June, 1953, to August, 1954, 25patients (23 with symptoms and 2 without) were treatedwith oral streptomycin. The interval between the onsetof symptoms and the beginning of treatment was 1-15days (average 6 days) in the tetracycline group, 1-13

days (average 6 days) in the phthalyl sulphathiazolegroup, and 1-25 days (average 8 days) in the streptomycingroup. The age-distribution is set out in table i.The dosages of tetracycline and phthalyl sulpha-

thiazole are shown in table 11. The tetracycline wasgiven in tablets, which were crushed and suspended withtragacanth for babies and children. The patients treatedwith oral streptomycin were given 0-5 g. twice a dayregardless of age : 19 were treated for 3 days and 6 for5-8 days.

17

Specific therapy was withheld until Sh. sonnei had beenisolated from the stools. Treatment was considered tohave been successful when the first six specimens takenafter the end of treatment were negative for Sh. sonnei,and to have failed when Sh. sonnei was isolated from anyof these specimens. In each group the interval betweenthe end of treatment and the sixth negative specimenaveraged 9 days, with a range of 6-16 days in the tetra-cycline and streptomycin groups and 7-14 days in thephthalyl sulphathiazole group. All the follow-up speci-mens were taken while the patients were still in hospital.

Bacteriological Methods

Fsecal specimens and, occasionally, rectal swabs wereplated on to deoxycholate-citrate agar directly (Hynes1942) and after overnight incubation in selenite broth(Hobbs and Allison 1945). Sh. sonnei was identified bycolonial morphology on deoxycholate-citrate agar andby slide agglutination with S-R Sonne antiserum

(Standards Laboratory).Strains isolated from the tetracycline series were

tested for sensitivity to tetracycline by a doubling-

TABLE II—DOSAGE OF TETRACYCLINE AND PHTHALYL SULPHA-

THIAZOLE

dilution technique in tubes. A stock solution of 2500 µg.per ml. of tetracycline hydrochloride in distilled waterwas prepared each week and kept at 4°C. Furtherdilutions were made in a medium of the followingcomposition :

A series of doubling dilutions of tetracycline in 1 ml.volumes of this medium were prepared, and 0-02 ml. of a1 in 100 dilution of a 24-hour broth-culture of Sh. sonneiwas added to each tube. The sensitivity of the organismwas taken to be the smallest final concentration of tetra-cycline that completely inhibited growth, judged byvisible turbidity after 22-24 hours’ incubation at 37°C.Strains isolated from the series treated with phthalylsulphathiazole were tested for sensitivity to sulpha-thiazole by the disc technique described by Davies (1954).

Results

The results of treatment are summarised in table m.Treatment was successful in 26 of the 27 patients treatedwith tetracycline, in 11 of the 32 treated with phthalylsulphathiazole, and in 9 of the 25 treated with oralstreptomycin.

TABLE III—RESISTS OF TREATMENT WITH TETRACYCLINE,PHTHALYL SULPHATHIAZOLE, AND ORAL STREPTOMYCIN

The strains isolated before treatment in 24 of the 27cases treated with tetracycline were tested for sensitivityto tetracycline. All of them showed a uniform sensitivityto 4—8 u.g. of tetracycline per ml. All the strains isolated

during treatment showed a similar sensitivity. TheOxford staphylococcus was sensitive to 0-5 µg. of tetra-

cycline per ml. A dosage of 0-5 g. of tetracycline 6-hourlyproduced serum-tetracycline levels of 4-5 µg. per ml.(Putnam et al. 1953) and fæces-tetracycline levels as

high as 2230 µg. per g. of wet stool (Maynard et al.1953).

In the phthalyl sulphathiazole group 31 of 32 strainsisolated before treatment were tested for sensitivity;fourteen were sensitive and seventeen resistant tosulphathiazole. Davies (1954) tested strains of 5h. sorirzei.both by the disc technique and by inoeulating about 150viable organisms on to nutrient agar containing5% lysed horse-blood and various concentrations of

sulphathiazole. Strains recorded as sensitive by thedisc technique were completely inhibited by sulpha-thiazole 1 mg. per 100 ml. by the other method ; andstrains resistant by the disc technique were not inhibitedby sulphathiazole 50 mg. per 100 ml.The results of sensitivity tests with streptomycin are

not given, because only a few strains were tested.

Discussion

The number of patients, the age-distribution, and theinterval between the onset of the disease and treatmentwere similar in each group. Although the tetracyclineand the phthalyl sulphathiazole groups were strictlycomparable, the streptomycin series differed slightly inthat many of the patients were treated before March,1954. Successful results were obtained in only a thirdof the patients treated -with phthalyl sulphathiazole orwith oral streptomycin, whereas only 1 failure wasrecorded in the 27 cases treated with tetracycline. Fromthis patient a scanty growth of Sh. sonnei was obtainedfrom a specimen taken on the second day after the endof treatment, but the following six specimens were

negative without further treatment. However, in 1 casetreated with tetracycline where twelve negative specimen swere required before transfer to an institution, a scantygrowth of Sh. sonnei was isolated from the twelfthspecimen, although the preceding eleven were negative.This case has been classed as successfully treated becausethe first six specimens after the end of treatment werenegative. In several of the patients treated with tetra-cycline the faeces were still positive on the 3rd and 4thdays of treatment. We therefore feel that it would beunwise to reduce the duration of treatment to less thanthe 7 days that we have adopted. It is also possible thatbetter results would have been obtained with oral strepto-mycin if the treatment had lasted longer. Most of our

patients were given streptomycin for 3 days becausethis was the length of treatment used hv Forbes

(1953).All the patients were nursed with full harrier technique,

but reinfection may explain some of the failures (Vollumand Wylie 1946). though patients in all three groups wereopen to similar risks.We found no toxic reactions to any of the drugs used.

This confirms the low toxicity of tetracycline reportedby Finland et al. (1954), but the number of cases that wehave treated is small, and no special study of possibletoxic effects was made.

Testing for sulphonamide sensitivity before treatmentproved of little value in predicting the result of treatmentwith phthalyl sulphathiazole.

In 14 patients from whom sensitive strains were

isolated before treatment, there were 5 successes and 9failures, compared with 5 successes and 12 failures in 17 rpatients from whom resistant strains were originallyisolated. In 2 cases resistant strains were recovered after

18

treatment, although a sensitive strain had originally beenisolated. It is uncertain whether this was due to thedevelopment of resistance during sulphonamide therapyor to cross-infection. The results of these sensitivity testsshow that the failure of sulphonamide treatment in manyof these cases cannot be attributed to sulphonamide-resistant strains.

Conclusions and SummaryIn a small trial we have compared the values of

tetracycline, phthalyl sulphathiazole, and oral strepto-mycin in the treatment of Sonne dysentery. Of 84

bacteriologically proved cases 27 i were treated withtetracycline, 32 with phthalyl sulphathiazole, and 25 withoral streptomycin.Treatment was successful in only a third of the patients

who were given phthalyl sulphathiazole or oral strepto-mycin, whereas there was only 1 -failure with tetra-

cycline. Under the conditions of this investigationtetracycline proved superior to phthalyl sulphathiazoleand oral streptomycin in effecting bacteriologicalcure.

All the strains of Sh. sonnei tested were sensitive to4-8 ug. of tetracycline per ml. Sulphonamide-sensitivitytests were of little value in predicting the results oftreatment with phthalyl sulphathiazole.We thank Dr. D. C. Liddle, physician-superintendent,

Monsall Hospital, and Dr. M. T. Parker, director, PublicHealth Laboratory, Manchester, for their help and advice ;and Dr. A. T. Mennie, medical director, Lederle Laboratories,for supplying the tetracycline (‘ Achromycin ’) used in thisinvestigation.

REFERENCES

Davies, J. R. (1954) Mon. Bull. Minist. Hlth Lab. Serv. 13, 114.Finland, M., Purcell, E. M., Wright, S. S., Love, B. D. jun., Mou,

T. W., Kass, E. H. (1954) J. Amer. med. Ass. 154, 561.Forbes, G. B. (1953) Brit. med. J. i, 1139.Hawking, F., Lawrence, J. S. (1950) The Sulphonamides. London ;

p. 204.

Hobbs, B. C., Allison, V. D. (1945) Mon. Bull. Minist. Hlth Lab.Serv. 4, 63.

Hynes, M. (1942) J. Path. Bact. 54, 193.Maynard, A de L., Andriola, J. C., Prigot, A. (1953) Antibiotics

Annual, 1953-54. New York ; p. 102.

Putnam, L. E., Hendricks, F. D., Welch, H. (1953) Ibid, p. 88.Vollum, R. L., Wylie, J. A. H. (1946) Lancet, i, 91.

RELIEF OF PAIN IN INCURABLE CANCER

R. M. MAHERM.D. Lond., B.Sc. Lpool, M.R.C.P.

CONSULTING PHYSICIAN, ROCHDALE HOSPITAL GROUP AND

OLDHAM COUNTY BOROUGH

THE purpose of this article is to describe new andwider applications of intrathecal therapy for relieving thepain of incurable cancer.

Intrathecal therapy aims at selective cell destructionat the posterior root ganglia. Introduced by Dogliotti(1931) for sciatic pain, and developed by Saltzstein (1934)and Stern (1934), it was applied with great success byGreenhill and Schmitz (1935, 1936) and Greenhill (1947)to pelvic carcinoma. They used 0-75 ml. of absolutealcohol, which floated upwards to the ganglia. Completerelief of pain ensued in 60% of group 111 and rv cases,and partial relief in 10%.

Last year it occurred to me that it would be anadvantage to use a heavy " carrying solution," whichcould convey more than one destructive agent, thusincreasing the therapeutic possibilities. lloreov er, a

dense solution would be simpler to control-it is easier tolay a carpet than to paper a ceiling. Phenol and silvernitrate were the agents I employed, with glycerin orpropylene glycol as the vehicle.Injected intrathecally phenol can cause cord destruc-tion. (This was the subject of a recent case in law.)If the phenol is held in glycerin, however, its diffusion is

at a minimum,and when injectedintrathecally i tfalls downwards

(sp. gr. of glycerin,1-25; sp. gr. of

cerebrospinalfluid, 1-007). Withthe patient on hisside (as for lumbarpuncture) it fallsto the posteriorroot ganglia of hislower half (fig. 1).Injected at the

appropriate levelit will usuallycause permanentanaesthesia over

the painful area.

Fig. 2 shows thechief components

Fig. I—Radiograph after injection of* ’Myedil’

(15 parts) and phenol (I part). Resultantanaesthesia over 1st, 2nd, and 3rd ribs, andon inner side of arm, gave complete reliefof pain.

influenced. Motor units are not affected, their cell stationbeing well out of the way in the anterior horn. Further

components affected lie in the posterior root ganglion itself.The aim is to select the group of smaller non-medullatedC units of Erlanger et al. (1926). The large A type ofproprioceptive units must be left intact. This depends onthe concentration of the mixture, the optimum strength ofphenol in glycerin being 1 in 18 to 1 in 20. Such aconcentration appears to give the correct selection,affecting pain and touch fibres only, with loss of cutaneoussensation over the pain area-the only clear indication ofrelief. Cell selection in these circumstances is apparentlyon a size basis.

Agents and Procedure02-03 ml. of heavy cinchocaine hydrochloride (’ Nuper-

caine ’) (the type used in spinal anaesthesia) was employed asa test agent.

1-0—1-7 ml. of 1 part of phenol in 18-20 parts of glycerin,well mixed with 0-1 ml. of sterile water per ml., was theagent used to provide permanent anaesthesia. (If morewater is added the phenol is activated and requires dilutionto half.)

1 ml. of gr. 1/100 silver nitrate in glycerin was occasionallyemployed when phenol proved inadequate.

Largely for psychological reasons, the operation shouldbe carried out at the bedside. For injection, the patient

Fig. 2-Siting of needle.