1149

reactively depressed patients respond well to leucotomy. reader is likely to draw the wrong conclusions.-ED. L.

The

APPENDICITIS AND MIMICKING CONDITIONS p.

SI UNITS

SIR,-Perhaps the tragic misunderstanding between a sura pharmacist over the meaning of normal saiine solution, reported in The Times (Nov. 28), which led to the death of a patient will provide the justification to Dr Clark and Dr Sheldon (Nov. 29, p. 1086) for the use of the Systeme International in centres "where the major burden of clinical work is carried out". Use of the appropriate unit for concentration, in this case mol/1, would have prevented this accident. Adoption of SI must surely eliminate the possibilities for misunderstanding which will from time to time arise between physician and pharmacist, chemist, or specialist from an another discipline. geon and

DAVID W. FITZSIMONS

DIAGNOSIS OF HIRSCHSPRUNG’S DISEASE

SIR,-In their article on the value of measuring acetylcholinesterase activity in rectal-biopsy specimens in the diagnosis of Hirschsprung’s disease Mr Boston and his colleagues (Nov. 15, p. 951) give a misleading impression of the difficulty of histological diagnosis in this condition. They state that the initial histological diagnosis is often wrong. Neither of the references they cite supports this statement. One’ claims that an adequate rectal biopsy will always confirm or refute the diagnosis. The other2 records that in 7 of 49 patients no diagnosis could be reached on the first biopsy specimen-not that the diagnosis was incorrect. The criticism that histological examination is subjective may be true in general but it is inappropriate to rectal biopsy in suspected Hirschsprung’s disease where the presence or absence of ganglion cells is the most important diagnostic feature. We agree that histological examination requires experience-just as doing a satisfactory rectal biopsy requires experience-but we would hope that cases of this kind are investigated only in centres where such experience is available. We would like to record our experience with the histological examination in 89 suspected cases of Hirschsprung’s disease in the past five years since suction biopsy was introduced in this hospital. In none of these cases was there an incorrect diagnosis. Early diagnosis of this disease is important, and if there is difficulty in histological diagnosis it is more likely to happen with the newborn. The histological findings in 27 neonates out of the 89 suspected cases were:

The diagnosis of Hirschsprung’s disease was confirmed in all subsequent resection of bowel. The diagnosis of normal (or perhaps more accurately, not Hirschsprung’s disease) has not been questioned on clinical follow-up. In 4 cases, an inadequate specimen was provided, and in 1 of these biopsy was not repeated. We do not consider that an inadequate specimen is a failure on the part of the histological examination. cases at a

Departments of Pathology and Pædiatric Surgery, Royal Hospital for Sick Children, Glasgow G3 8SJ. 1

A. A. M. GIBSON D. G. YOUNG

Nixon, H. H. in Modern Trends in Surgery (edited by W. T. Irvine); p. 16. London, 1966. 2. Aaronson, I., Nixon, H. H. Gut, 1972, 13, 138.

SIR,-In the study by Mr Gilmore and co-workers (Sept. 6, 421) on appendicitis and mimicking conditions, yersiniosis

was not observed or mentioned. In a prospective study’ of 121 consecutive patients admitted with "acute abdomen", and subsequently operated on for appendicitis, we found 15 patients with acute or subacute enteric infection with Yersinia enterocolitica (Y.e.), serotype 3. The diagnosis was established by isolation of Y.e. or by significant titres of agglutinating antibodies. Positive cultures were obtained from faeces and/or the appendix in 9 of these. These results indicate that in a substantial proportion (in our material 12.4%) of patients with acute abdominal symptoms suggestive of appendicitis, infection with Y.e. may be present. In the late ’60s Swedish workers reported a similar occurrence in "acute abdomen", although in somewhat lower in-

cidences, using less selective criteria.23

The distribution of yersiniosis according to the degree of inflammation of the removed appendices was as follows: 4 of 28 patients with a normal appendix were found to have yersinia infection; 8 of 36 patients with a slightly inflamed appendix (i.e., inflammation limited to submucosal and muscular layers); and 3 of 57 patients with a heavily inflamed appendix (i.e., inflammation also involving the serous lining). We operated with the same erroneous diagnosis of appendicitis (28/121=23%) as did Gilmore et at. In conclusion, we advocate that the diagnosis of yersiniosis should be considered in conditions mimicking appendicitis. This would add to our experience and knowledge of the disease

and might help us to reduce the rate of erroneously diagnosed and eventually operated cases of appendicitis-like "acute abdomen". O. B. JEPSEN Department of Clinical Microbiology, Department of Clinical Microbiology,

B. KORNER

Department of Surgical Gastroenterology A,

P. M. CHRISTIANSEN

Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark.

DRUG TREATMENT IN CROHN’S DISEASE

SIR,-Reports

you

published

were

cautiously

favourable

about the use of both metronidazole4 and dapsone5 in Crohn’s disease. In view of the great difficulties in mounting formal controlled trials in this condition, we have over the past six years run a series of uncontrolled pilot studies in the hope of finding a drug which would merit more detailed study. Assessment was by the usual clinical and laboratory criteria of acti-

vity, including ansemia, folate status, serum-orosomucoid levels, serum-protein pattern, and absorption tests. Other units have probably worked on similar lines, but negative results tend to go unpublished. We first tried two-month courses of tetracycline; the results were unpromising and in at least 1 case diarrhoea was exacerbated. During 1970-71 6 patients were treated with dapsone (25 mg daily) for six months and again we found no convincing evidence of response. Later 6 patients received metronidazole in doses of 600 mg daily for up to three months. 2 patients gradually improved, but 2 others got worse and were treated surgically, and 1 abandoned treatment because of vomiting. Our dose schedules for both these drugs were lower than those recently reported. During the past three years we have used co-trimoxazole as B., Korner, B., Lauritsen, K. B., Hancke, A.-B., Andersen, L., Henrichsen, S., Brenoe, E., Christiansen, P. M., Johansen, Aa. Scand. J. infect. Dis. (in the press). 2. Niléhn, B., Sjöström, B. Acta path. microbiol. scand. 1967, 71, 612. 3. Winblad, S., Niléhn, B., Sternby, N. H. Br. med.J. 1966, ii, 1363. 4. Ursing, B., Kamme, C. Lancet, 1975, i, 775. 5. Ward, M., McManus, J. P. A. ibid. p. 1236. 1. Jepsen, O.

1150

mainstay of medical treatment in some 20 patients. I believe this has been of benefit in some of these cases and that in Crohn’s disease it is more effective than sulphasalazine. Several patients have taken co-trimoxazole continuously for over a year with no side-effects. If any or all of these agents are at all effective, their action may lie in the reduction or alteration of bacterial flora in the small-bowel lumen, thus removing a potentially destructive or antigenic stimulus. If so, it is strange that all these drugs have notable powers of diffusion into the tissues, which suggests the possibility of some more direct action at the site of the lesion.

Department of Health and Social Security, comes first to mind because this office has been proved to be most efficient whilst using the facilities currently available to it. An extension of such an established service seems logical. Should this not be practicable, then the field is open to others to provide this national comprehensive computerised service. The Bath prototype should certainly test the feasibility of such a project.

a

Pharmacy Department,

Royal Lancaster Infirmary,

R. I. COOPER

Lancaster LA1 4RP.

Gastrointestinal Unit,

Birmingham Hospital, Birmingham 139 5ST.

STREPTOZOTOCIN IN THE ZOLLINGER-ELLISON SYNDROME

East

R. DARRAGH MONTGOMERY

SIR,-Dr Sadoff and Dr Franklin describe PREPARATION FOR COLONIC SURGERY

SIR,-Mr Goldring and his colleagues (Nov. 22, p. 997) provide further support for the belief that preparation of the colon with oral antimicrobial agents is associated with a significant reduction in the incidence of septic complications after elective colonic surgery.’ Their results suggest that the combination o kanamycin and metronidazole is especially useful in the suppression of Bacteroides and in the prevention of Bacteroides wound infection. However, preoperative antimicrobial therapy may be of limited value in operations complicated by poor mechanical preparation of the bowel or significant faecal contamination during surgery. We are engaged in a prospective clinical trial of preoperative intestinal preparation with neomycin and metronidazole (versus neomycin alone). The results so far in 25 patients indicate that the problem of abdominal wound infection is largely related to the efficiency of mechanical preparation and the avoidance of faecal contamination during surgery rather than the type of antimicrobial therapy used. Wound infection has occurred in 4 out of 8 cases complicated by one or both of these factors, whereas only 2 of the 17 uncomplicated, well-prepared cases, had wound infection. University Surgical Unit, Royal Infirmary,

a

favourable

effect of

-

-

streptozotocin in a Z.E. patient with liver metastases (Sept. 13, p. 504). In 1968 Murray-Lyon et al.’ described a decrease in gastric-acid secretion and a conversion of gastrin bioassay from positive to negative in a patient with metastatic pancreatic tumour with signs of overproduction of insulin, glucagon, and gastrin, after treatment with streptozotocin. In a later report concerning this patient2 further infusions of streptozotocin did not significantly alter the fasting plasma-gastrin level and the patient died from a perforated duodenal ulcer. Stadil and Rehfeld3 found streptozotocin effective in the treatment of metastatic gastrinoma after administration of this drug via the hepatic

or

In

in

coelic artery.

department streptozotocin had no favourable patients with gastrinoma and liver metastases.

our

two

effect

CASE 1.-In January, 1973, a Billroth-I gastrectomy was performed because of duodenal-ulcer bleeding in a 40-year-old woman. Histological

THOMAS T. IRVIN

Sheffield S6 3DA.

HOW DO DOCTORS LEARN ABOUT DRUGS? SIR,-Dr Padfield and others (Nov. 15, p. 985) and other correspondents rightly stress the importance of the accumulation and dissemination of up-to-date information about drugs. Having seen the Bath prototype computerised system in action, I am convinced that only by using modern techniques can we hope to tackle the problem comprehensively. Most district general hospitals have a drug information service which should be able to deal with 90-95% of queries. The remaining 5-10% are difficult. It would be wasteful to equip all the regional drug information services with computers, in an attempt to store vast quantities of information, because each region would be duplicating the work done by others. The regional services might well develop along the lines of providing useful digests of information, and designing and operating the most effective means of teaching doctors, pharmacists, and nurses about drugs. They could draw upon centrally stored material for this and other purposes. A single national drug information computer service is surely indicated. It would be just as easy to telephone a national centre as a regional one. Such a national service would need to be staffed by pharmaceutically qualified computer operators who would know how to put the right questions to the computer. The site is not crucial. The Martindale Office of the Pharmaceutical Society, backed financially by the

1973 1973

Fig.

I.-Case 1:

,

1974 19T4

serum-gastrin levels during treatment with streptozotocin.

examination of a biopsy specimen from a liver nodule revealed non-&bgr;islet-cell-tumour tissue. The diagnosis of /.1. syndrome was confirmed postoperatively by a high basal gastric acid output (B.A.o. 32.1 meq H+/hr) and elevated serum-gastrin levels (4520 pg/ml). In April, 1973, she underwent total gastrectomy. The decrease in serum-gastrin level (fig. 1) was not accompanied by a reduction in liver tumour mass. Because of progressive extension of liver metastases, associated with fever, weight-loss, and an increase in serum-gastrin levels, treatment with streptozotocin was started in August, 1973. During 9 weeks, wcckty doses of 2 g of streptozotocin were administered intravenoush, without any effect on liver size or symptoms. Treatment was stopped in October, 1973, because of this ineffectiveness and post-mfusion complaints of vomiting and anorexia. In March, 1974, the patient’s condition was further impaired and streptozotocin treatment was re1.

I. M., Eddleston, A L W. F., Williams, R., Brown, M., Hogbin, B. M., Bennet, A., Edwards, J. C., Taylor, K. W. Lancet, 1968, n,

Murray-Lyon, 895.

I. M, Cassar, J., Coulson, R C, Williams, R, Ganguli, P C., Edwards, J. C., Taylor, K. W. Gut, 1971, 12, 717. 3. Stadil, F., Rehfeld, J. F. Personal communication. 2.

1.

Rosenberg, 1. L., Graham, Surg. 1971, 58, 266.

N.

G., de Dombal, F. T., Goligher, J. C. Br. J.

Murray-Lyon,

Letter: Drug treatment in Crohn's disease.

1149 reactively depressed patients respond well to leucotomy. reader is likely to draw the wrong conclusions.-ED. L. The APPENDICITIS AND MIMICKING...
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