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ease and stillbirth was the same for the two centres, we find17 survivors out of 27 for the Bristol cases compared withonly 4 out of 12 for the Liverpool cases. Does this mean thatplasmapheresis alone is not as effective as plasmapheresis com-bined with intrauterine transfusion and, if so, was the benefitderived from intrauterine transfusion rather than plasma-pheresis ? The overall survival-rate for the two groups is similarbut, whereas 27 out of 44 of the Bristol cases gave a previoushistory of severe disease or stillbirth, this was only so for 12out of the 52 Liverpool cases. Could the selection of less severecases be the reason that plasmapheresis alone gave relativelygood results?The findings presented warrant the further study of this

method of treatment, but let it be planned in such a way thata valid answer is achieved, and, unless intrauterine transfusionis to be withheld in cases treated by plasmapheresis, any trialmust be designed to simultaneously evaluate intrauterinetransfusion.

W. WALKER

Department of Hæmatology,Royal Victoria Infirmary,Newcastle upon Tyne, NE1 4LP.

THROMBOSIS AND PSORIASIS

J. L. BURTONCYNTHIA N. A. MATTHEWS

Department of Dermatology,Bristol Royal Infirmary,Bristol BS2 8HW.

SiR,—The suggestion by Dr Brustein and his colleagues(Jan. 17, p. 154) that psoriasis may be associated with a tend-ency to thromboembolism may explain the recent observationsthat an episode of vascular thrombosis may occur in psoriaticpatients within a few months of starting therapy with azari-bine.1 The primary effect of this drug is the competitive inhi-bition of the enzyme orotidylic-acid decarboxylase, therebyblocking pyrimidine biosynthesis.3 It has no obvious role inenhancing coagulation, and its use in the treatment of poly-cythaemia vera does not appear to precipitate vascular occlu-sion.4 Of 550 patients with severe psoriasis treated with azari-bine, at least 20 are known to have had an episode of vascularocclusion, including myocardial infarction and axillary-arterythrombosis.’ z It remains to be seen whether the incidence ofthromboembolic episodes is as high in psoriatic patients whohave not received azaribine.

ATTITUDES TO CHILDREN’S ACCIDENTS

SIR,-Child abuse has received a good deal of useful pub-licity in the last few years, but I am wondering whether thependulum has perhaps swung a little too far in one direction.Twenty years ago a mother taking her child to a casualtydepartment with a fractured skull or tibia and a story of a fallfrom a swing would be received with sympathy and reas-surance, and told that the accident was not her fault. Today,such a mother (whose first question may still be, "Will he benormal again?" or, "Will he ever walk?") will be quizzed-often in public-by the receptionist, the nurses, the casualtyofficer, and the ward sister, about the exact circumstances ofthe accident. The staff behave in this way because of a realdread of missing a maltreated child, but the result is that themother is likely to leave hospital feeling that they all think itis her fault-or, worse, that her story is not believed. Whenthe health visitor comes to the house the next day, the mother’sworst fears are confirmed, and gossip spreads through theneighbourhood. The mother and father may each worry thatthe other has been rough, and both will feel very apprehensive

1. Keefer, R. A., Roenigk, H. H., Hawk, W. A. Archs Derm. 1975, 111, 853.2 Crutcher, W. A., Moschella, S. L. Br. J. Derm. 1975, 92, 199.3 Calabrest, P., Turner, R. W. Ann. intern. Med. 1966, 64, 352.4 Deconu, D. C., Calabresi, P. ibid. 1970, 73, 575.

lest another accident should happen, however unavoidable.Even if the mother’s story is proved true, the damage hasalready been done.

Committees investigating potential cases of child abuse onlyfunction by virtue of the common sense and fairness of theirmembers, and their work is overshadowed by a natural fear ofthe newspaper headlines should they make a wrong decision.Many members of such committees become uneasy about theextra-legal basis on which they operate, by their atmosphere ofsecrecy, and by the difficulty of stopping investigations oncethey have begun.We may have missed some maltreated children in the past,

and it is even possible that some deaths could have been pre-vented. But I suspect that the number is small, and that pres-ent methods of investigating possible cases of child-batteringmay produce infinitely more social harm. The severe case ofbattering is usually obvious. Let us try to give the benefit ofthe doubt more often in cases where we are merely suspicious,and remember that accidents do happen.

R. F. N. DUKEWarwick Hospital,Lakin Road, Warwick.

VITAMIN E. SELENIUM, AND KNEE PROBLEMS

CARL J. REICH

205A Medical Centre,Calgary T2P 1H9,Alberta, Canada.

SIR,-Kienholzl described his personal experience of therelief of knee pain with vitamin E and selenium. He had pre-viously been advised to accept the situation by an orthopaedicsurgeon, who said that it was due to irritation of ligaments onthe anterior and lateral aspects of the knee.

This letter interested me because I have long been

acquainted with the work of Dr R. Outerbridge of New West-minster, B. C., on patellar chondromalacia2 and more recentlybecause my 16-year-old son has developed knee pain and mildswelling that Dr Outerbridge suggested may be an early stageof this syndrome.

I wonder whether a deficiency of selenium may cause faultymaturation or lack of growth of cartilage in this disorder.Outerbridge2 says:

"Just what occurs at the cellular level is still not clear, but it wouldappear that the bonds of the mucopolysaccharides, upon which thetoughness and resilience of the cartilage in large part depend, are splitby enzymes, possibly the protease cathepsin, thus decreasing the elasti-city of the cartilage and allowing stress to produce tissue breakdown.

"Cartilage cells are not inert, however, and have the capacity toform new cells and new matrix and repair at an exceedingly high rate.Thus lesions, certainly in their early stages and possibly even when thedefects are large, are reversible. If the rate of breakdown exceeds therate of svnthesis, enondromalacia begins."

PARENTAL CONSANGUINITY INPYCNODYSOSTOSIS

SIR,-We have seen a child with pycnodysostosis who wasthe offspring of an incestuous mating between a 24-year-oldwoman and her father. These parents had 50% of their genesin common, and their child had a 12-5% risk of inheriting thesame mutant gene from either parent.We have found 45 published pycnodysostosis families with

an adequate family history. Including our own case, parentalconsanguinity was found in 21 families (46%). In 16 familiesthe parents were first-cousins, and in our case the relationshipwas even closer. These figures indicate the highest consan-guinity-rate found in any autosomal recessive disease. Sugiuraet al,3 reported an even higher consanguinity-rate in Japan.

1. Kienholz, E. W. Lancet, 1975, i, 531.2. Outerbridge, R. Clin. Orthop. 1975, 110, 177.3. Sugiura, Y., Yamada, Y., Koh, J. in Skeletal Dysplasias (edited by D.

Bergsma); p. 78. New York, 1974.

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Parental consanguinity was found in 16 (80%) of 20 pycnody-sostosis families, and in 13 of these families the parents werefirst-cousins. The consanguinity-rate in the Japanese popula-tion as a whole is 6%. Sugiura et al. calculate from thesefigures a gene frequency of between 0-0016 and 0.00034.They estimate the incidence of P to be 1-7 7 per 106. If the sameincidence applies to the U.S.A. about 6 cases of pycnodyso-stosis will be born everv vear in this countrv.

MARY WAZIRIHANS ZELLWEGERJOANNA SEIBERT

Department of Pediatrics,University of Iowa,Iowa City, Iowa 52242, U.S.A.

GENTAMICIN RESISTANCE

SiR,—The emergence of resistance to gentamicin duringtherapy has become quite a problem lately. We wish to reportour own experiences in three cases of gentamicin resistanceand results of tests of sensitivity to other aminoglycosides.Case 1A strain of Escherichia coli, isolated from a case of men-

ingitis, was sensitive to chloramphenicol, gentamicin, tobramy-cin, and some other agents. Gentamicin 3 mg/kg 8-hourly wasprescribed, and intrathecal gentamicin in doses between 1.5 5 mgand 4 mg was given on five occasions in the first 14 days. Thepeak serum level was 12.5 fLg/ml (on two occasions). After 15days a small colonial variant was isolated which was resistantto gentamicin and tobramycin by the disc test. Treatment waschanged to chloramphenicol, and the child recovered slowlybut is mentally retarded.Case 2

Pseudomonas aeruginosa was isolated from the urine of a3-year-old girl with spina bifida and bilateral hydronephrosis.Blood urea and creatinine levels were normal. The childreceived gentamicin 2 mg/kg twice daily for 11 days, and thecourse was repeated 2 weeks later. 30 days after gentamicintherapy started a gentamicin-resistant variant of Ps. ecruginosabelonging to the same pyocine type was cultured from theurine. The infection responded to colomycin.Case 3E. coli was isolated from the blood of a 9-day-old baby, 4

days after surgery for Hirschsprung’s disease. The strain wassensitive to chloramphenicol, gentamicin, and tobramycin.Gentamicin 3 mg/kg was administered 12-hourly during the

first 24 h and was then increased to 4 mg/kg 8-hourly. Peakserum levels of 11-5 and 11-4 jjLg/ml were detected on the 2ndand 6th days of treatment. 11 days after gentamicin therapybegan, meningitis was suspected clinically, and a small colonialvariant of E. coli resistant to gentamicin and tobramycin wascultured from the c.s.F. The organism was also of interest in

that growth in vitro was enhanced by hamatin. The child wastreated with chloramphenicol and recovered well.

The minimum inhibitory concentrations (M.t.c.) and mini-mum bactericidal concentrations (M.B.c.) of amikacin, gentam-cin, sisomicin, and tobramycin were determined by an agardilution technique on diagnostic sensitivity test agar (Oxoid)covered with a membrane filter and with an inoculum of

approximately 50 000. After incubation at 37°C for 24 h theM.LC. was recorded; the membrane was transferred to an anti-biotic-free plate which was similarly incubated to determinethe M.B.c.The results (see table) showed a 32-fold increase to all four

antibiotics in case 1, with a subsequent fall after withdrawalof gentamicin. In case 2 the decrease in sensitivity was lessstriking but again occurred for all antibiotics tested. The orig.inal isolate from case 3 was not available for testing, but sub-sequent isolates were highly resistant. The M.B.C. was, 2-foldhigher than the M.i.c. in all instances where an end-point forthe M.i.c. had been reached.

These findings differ from those previously reported forPseudomonas in which resistance to amikacin has been lessstriking.1 The difference between the M.I.C. and M.B.C. ofgentamicin in resistant organisms has varied from 2 to 17fold.2-4 In two of our cases the difference was only 2-fold. De-spite adequate serum levels in two of the cases reported here,levels at the site of infection may have been low, favouringresistant mutants. We feel that only a combination of antibi-otics could have hoped to prevent the emergence of resistancein these two cases. The more recently developed aminoglyco-sides are not always active against gentamicin-resistantorganisms.

R. H. GEORGED. E. HEALING

Department of Microbiology,Birmingham Children’s Hospital,Ladywood, Birmingham B16 8ET.

PSEUDO-PSEUDOPODAGRA

SIR,-Huskisson and Balme’ listed some disease processes,including Reiter’s syndrome, in which the big toe can becomeacutely painful and swollen, as in gout. Reiter’s syndrome andgout, however, can coexist, as shown by the following case,which was the only example of such an association among ourpatients, who, in the course of one year, included 98 cases ofgout and 16 cases of Reiter’s syndrome.A 29-year-old man was seen in the emergency room because

of pain and swelling of both big toes for one week. A trace offluid aspirated from the interphalangeal joint of the right bigtoe contained many urate crystals. Oral colchicine resulted incomplete relief of inflammation within thirty-six hours. Fourdays later, however, while the patient was taking colchicine(06 mg three times a day), a large effusion developed in theleft knee. A more detailed history then revealed that, threeyears before, he had had non-gonococcal urethritis followedwithin a month by persistent and fluctuating bilateral heel andforefoot pain. More recently, he had had low back pain. Exam-ination revealed painless shallow ulcers on the oral mucosa,balanitis circinata, and a large knee effusion. The synoviatfluid contained 17 200 white cells/mm3, no crystals, normalcomplement (C;), and many mononuclear cells with one ormore engulfed polymorphs. Radiological examination showedunilateral sacroiliitis, bilateral fluffy plantar spurs, and er0-sions of the interphalangeal and metatarsophalangeal joints ofthe right big toe. A faint overhanging margin was noted in oneof the erosions. HL-A27 was positive. Blood-urate and24-hour-urine urate excretion were normal. Repeated aspira-tion of soft tissue in the great toe yielded an almost solid mas!

1. Hamilton-Miller, J. M. T., Reynolds, A. V., Brumfitt, W. Lancet, 1974,ii,527.

2. Eykyn, S., Phillips, I. ibid. 1975, i, 861.3. Seal, D. V., Strangeways, J. E. M. ibid. 1975, i, 48.4. Barnham, M., Maddocks, A. C., Gaya, H. ibid. 1975, i, 576.5. Huskisson, E. C., Balme, H. W. Lancet, 1972, ii, 269.