CLINDAMYCIN AND PSEUDOMEMBRANOUS COLITIS

878 Certain lipid-containing viruses, particularly arboviruse: and vaccinia, have been shown to produce a hyperlipidxmiz in chick embryos. Work by Grossberg and O’Leary1 indicated that several viruses, inoculated into embryonated hen’s eggs, produced a hyperlipid.Tmia, characterised by high total lipids, with a striking increase in triglycerides and a decrease in phospholipids. In these embryos there was histological evidence of hepatitis. These findings led Grossberg et al. to postulate that the viral-induced lipidasmia resulted from deranged hepatic lipid bio-

synthesis. Virological studies

132 of our renal-transplant recipients during the past 4 years have indicated that virus infections are present in 80% of patients .3,44 The vast majority of these infections have been with herpesviruses, on

particularly cytomegalovirus, which are lipid-containing agents. Virus infection may persist for many months after successful transplantation and may be relatively asymptomatic. It is entirely possible that some of the patients of Dr Casaretto and his colleagues were shedding virus at the time of the lipid analyses. It would be of value to know whether their patients were studied virologically. Because of the frequency of viral infections in renaltransplant recipients, and because of experiments indicating that viruses can produce a hyperlipidaemia with evidence of liver dysfunction, it would be worth pursuing the possibility that the hyperlipideemia observed in successfully transplanted renal allograft recipients may indeed be related

to

virus infections.

University of Minnesota Health Science Center, Minneapolis, Minnesota 55455, U.S.A.

H. H. BALFOUR, JR. R. L. SIMMONS W. A. KRIVIT J. S. NAJARIAN.

LIVER TUMOURS AND STEROID HORMONES

SIR You raised the problem5 whether one should possible development of hepatoma to the previously

add the

of anabolic steroids on the liver. The appearance of a hepatoma has been described in patients with Fanconi’s anxmia who had been treated for many months with anabolic-androgenic steroids. 6-8 Johnson et al.8 reported hepatoma in a patient with postnecrotic cirrhosis-a condition which may favour the occurrence of hepatic carcinoma. Furthermore, Guy and Auslanderreported a patient who, twenty-four years before the onset of liver carcinoma, had received androgen therapy for only four months. We have observed a young girl with hepatoma whose case is relevant to this discussion.

reported effects

At the age of 7 years this girl was seen with a likely diagnosis of Fanconi’s anaemia, on the service of Prof. Jean Bernard (St. Louis Hospital, Paris). She had pancytopenia, retarded growth and pigmentation, syndactyly of the 2nd and 3rd toes, and microcephaly. Later the diagnosis was confirmed by the discovery of unilateral renal atrophy, pubertal failure, and dwarfism and an abnormally high incidence of chromosomal breaks. Splenectomy was performed at 8 years of age. This intervention permitted a longer interval between transfusions, followed by their complete withdrawal. 1. 2. 3.

4. 5. 6. 7. 8.

Grossberg, S. E., O’Leary, W. M. Nature, 1965, 208, 954. Grossberg, S. E., Roch, L. A., Frernan, F. E. Progr. immunobiol. Standard. (in the press). Lopez, C., Simmons, R. L., Mauer, S. M., Najarian, J. S., Good, R. A. Am. J. Med. 1974, 56, 280. Simmons, R. L., Lopez, C., Balfour, H., Uranga, V. M., Mauer, S. M., Najarian, J. S. Unpublished. Lancet, 1973, ii, 1481. Bernstein, M. S., Hunter, R. L., Yachnin, S. New Engl. J. Med. 1971, 284, 1135. Guy, J. T., Auslander, M. D. Lancet, 1973, i, 148. Johnson, F. L., Feagler, J. R., Lerner, K. G., Materus, P. W., Siegel, M., Hartman, J. R. ibid. 1972, ii, 1273.

In 1974, when the patient

was

24 years of age, while the

cause

right hypochondrial pain was being sought a nodular hepatomegaly was found. Peritoneoscopy, scanning with technetium and selenomethionine, and the presence of ct-fetoprotein favoured the diagnosis of hepatoma. This diagnosis was confirmed at of

necropsy. The hepatoma had

developed on a macronodular cirrhosis, hxmochromatosis which was apparently posttransfusional. Au antigen was not found. Careful questionmg of the patient’s family and all the doctors who had treated her indicated that she had never been given any androgen therapy. accompanied by

a

This observation means that a hepatoma may arise during the course of Fanconi’s anaemia, in the absence of androgen therapy. As in Johnson’s case 3, the hepatoma we report developed on a cirrhosis (probably post-necrotic). The high incidence of leukæmia 9,10 and solid turnouts 11 in patients with Fanconi’s anxmia, and in their families,

is well known. The finding of hepatoma may be a new indication of the " malignant potential " of this disease,12 possibly related to chromosome anomalies.13 Créteil University Medical

School, Department of Internal Medicine and Gastroenterology, Nouvel Hôpital, 94-Villeneuve St. Georges, France.

D. CATTAN P. VESIN J. WAUTIER R. KALIFAT S. MEIGNAN.

CLINDAMYCIN AND PSEUDOMEMBRANOUS COLITIS

SIR The report by Dr Scott and his colleagues

11

and

15-18

have drawn attention to the subsequent correspondence association of severe pseudomembranous colitis with treatment with clindamycin. We have recently seen a patient in whom the presentation was somewhat atypical. A 61-year-old woman started clindamycin 150 mg. 6-hourly and cloxacillin 500 mg. 6-hourly on March 7, 1974, for a superficial skin infection. On March 12 a total hip replacement was performed, and the immediate postoperative course was uneventful. On March 23 the patient complained of sudden onset of diarrhoea, nausea, vomiting, right-sided abdominal pain, and pyrexia, which soon settled with conservative treatment. The antibiotics were discontinued. The diarrhoea (about 3 loose stools a day) was adequately controlled with a kaolin preparation until April 8 when the patient became shocked with gross abdominal distension. Laparotomy and total colectomy with ileostomy was

performed. The bowel showed the characteristic naked-eye mucosal pseudomembranous colitis affecting the whole of the dilated colon and rectal stump, the terminal ileum being spared. Histological examination of the membranous plaque appearance of

confirmed the macroscopic diagnosis, and there was partial and full-thickness mucosal necrosis and patchy necrosis of the muscularis propria with intermuscular haemorrhage. There was thrombosis of the submucosal vessels and paracolic veins.

The case is unusual in that, although the diarrhoea started while the patient was receiving clindamycin, the symptoms were not severe and were readily controlled. It was not until 16 days after cessation of antibiotic therapy that the severe acute symptoms appeared. Perhaps in cases with a similar presentation not only should the present 9. Garriga, J., Crosby, N. H. Blood, 1959, 14, 1008. 10. Dosik, H., Hsu, L. Y., Todaroi, G. J., Lee, S. L., Kirschorn, K., Selirio, E. S. ibid. 1970, 36, 341. 11. Swift, M. R. Nature, 1971, 230, 370. 12. Fanconi G. Personal communication. 13. Schroeder, T. M., Anschutz, F., Knopp, A. Humangenetik, 1964 1, 194. 14. Scott, A. J., Nicholson, G. I., Kerr, A. R. Lancet, 1973, ii, 1232. 15. Sissons, J. G. P., Boulton-Jones, J. M., Peters, D. K. ibid. Feb. 2, 1974, p. 172. 16. Stroehlein, J. R., Hoffman, H. N., Sedlack, R. E., Newcomber A. D. ibid. Feb. 9, 1974, p. 221. 17. Temperley, J. M. ibid. 18. Sneddon, J. ibid.

879 PLASMA-ZINC LEVELS

antibiotic therapy be noted but antibiotics given during the

previous

weeks be known.

We thank Mr A. J. Webb for Departments of Medical

permission

to

report this

case.

RICHARD WISE A. J. C. TUDWAY D. E. PELTA.

Microbiology, Histology, and Surgery, Royal Infirmary, Bristol.

PNEUMOCOCCAL ANTIGEN IN SPUTUM SIR Sputum bacteriology is unsatisfactory because sputum is a discontinuous material, the common pathogens may also be present as commensals in the upper respiratory tract, and the patient may be in receipt of antibiotic therapy when the specimen is collected. The relationship between the results of sputum culture and the clinical state of the patient is therefore often difficult to interpret. We were interested in the results obtained by the technique of immunoelectroosmophoresis (I.E.O.P.) of sputum reported by Tugwell and Greenwood. This is clearly a successful procedure where there is a high incidence of pneumococcal pneumonia amongst patients coming to hospital. If the method detects polysaccharide produced in pathological conditions and does not detect that produced by commensal pneumococci it might indeed be a valuable procedure. We

wondered whether i.E.o.p. of sputum would have application in the situation of a busy general hospital in this country and so have applied the method to a small number of routine sputum samples.

No. 01 coionies esiaoiisneci on culture piate irom one

01

We selected for examination sputum from which

sputum.

we

had

already isolated pneumococci and some from which no pneumococci were grown. After routine culture the sputum samples were frozen until examined by I.E.O.P. Pneumococcal antiserum (Omni) from Statens Seruminstitut, Copenhagen, was used for this study. Preliminary experiments showed that it was important to homogenise the sputum (pancreatin/trypsin). After homogenisation the sputum was diluted to 1-in-10 for testing, because were often seen if undiluted sputum was tested. We examined 31 sputum specimens: 8 of these were from patients with pneumococcal pneumonia, 20 from patients with bronchitis, and 3 were from patients where the diagnosis was not specified. Pneumococci were isolated from 21 sputum samples and pneumococcal antigen was detected by I.E.O.P. in 14 of these. The sputum from all the patients with pneumonia was positive by i.E.o.p. (see accompanying table), and of 11 patients with bronchitis from whom pneumococci were isolated only 5 had detectable pneumococcal antigen in the sputum. This indicates that the presence of pneumococcal antigen in sputum may be more often associated with pneumonia, as has been suggested. Although the cultures were done on a semi-quantitative basis there seemed to be no direct correlation between the numbers of colonies of pneumococci grown and the presence of detectable antigen. Public Health Laboratory, J. VERHOEF Withington Hospital, D. M. JONES. Manchester M20 8LR.

prozones

1.

Tugwell, P., Greenwood, B.

M.

Lancet, 1974, i, 95.

SIR,—Dr Versieck and his colleagues (April 13, p. 682) draw attention to large discrepancies between control values for plasma-zinc reported by different workers. They rightly emphasise the need to avoid contamination of specimens, but they do not mention other possible sources of smaller discrepancies. Serum yields higher zinc levels than plasma owing to liberation of zinc from disintegrating platelets.’,22 In addition, there is a diurnal variation in plasma-zinc,3,4 with concentrations below the fasting level being observed for 2-3 hours after the ingestion of food.2,5 Thus when zinc is measured in postprandial serum specimens these opposing effects will tend to cancel. Other factors to be considered are the decline in plasma-zinc with age, and the lower levels observed in women than in men.s Zinc determinations should be carried out on samples of unhasmolysed plasma obtained at least three hours after the ingestion of food or drink, preferably from the fasting

subject. Stoke Mandeville

Hospital, Aylesbury,

Bucks HP21 8AL.

R. G. BURR.

CLEFT-PALATE TERATOGENS

SIR,—Dr Szabo and Dr Brent (March 30, p. 565) suggest drugs capable of inducing cleft palate in the mouse may be acting primarily by reducing maternal food and water intake rather than by a direct action of the drug itself that

This does indeed raise the question of on palatogenesis. the usefulness of the mouse for teratogenic screening of drugs suspected of producing cleft palate. It is known that injections of corticosteroids such as cortisoneand corticosterone8 into some strains of pregnant mice will cause a high incidence of cleft palate in the offspring. It has also been shown that stressing pregnant mice may induce cleft palate.9,10 The most sensitive day for the induction of clefts is day 14. We have found that the mouse has very high endogenous levels of corticosterone during the second half of pregnancy, averaging 80 µg. per 100 ml. plasma on day 14, which is around 40 times the non-pregnant resting levels.l’ During stress (24 hours restraint) on day 14 corticosterone levels may rise as high as 800 µg. per 100 ml. plasma and be maintained around 500-600 µg. per 100 ml. for 10-12 hours. These stress levels of corticosterone are similar to those found after subcutaneous injection of 2-5 mg. of corticosterone into the pregnant mouse on day 14, and the incidence of cleft palate in the offspring after each of these two treatments was similar (5%).10 It therefore seems reasonable to conclude that during stress in the pregnant mouse, maternal plasma-corticosterone may reach high enough levels to cause cleft palate in the offspring. It follows that any treatment applied to the pregnant mouse during the critical period for palatal development in 1. 2. 3. 4. 5.

Foley, B., Johnson, S. A., Hackley, B. M., Smith, J. C., Jr., Halsted, J. A. Proc. Soc. exp. Biol., N. Y. 1968, 128, 265. Burr, R. G. J. clin. Path. 1973, 26, 773. Hellwege, H. H. Klin. Wschr. 1970, 48, 1063. Hetland, O., Brugakk, E. Scand. J. clin. Lab. Invest. 1973, 32, 225. Davies I. J. T., Musa, M., Dormandy, T. L. J. clin. Path. 1968, 21, 359.

6. Lindeman, R. D., Clark, M. L., Colmore, J. P. J. Gerontol. 1971, 26, 358. 7. Fraser, F. C., Fainstat, T. D. Pediatrics, Springfield, 1951, 8, 527. 8. Blaustein, F. M., Feller, R., Rosenzweig, S. J. dental. Res. 1971, 50, 609. 9. Rosenzweig, S., Blaustein, F. M. Teratology, 1970, 3, 47. 10. Barlow, S. M., McElhatton, P., Morrison, P. J., Sullivan, F. M. J. Physiol. (in the press). 11. Barlow, S. M., Morrison, P. J., Sullivan, F. M. J. Endocr. 1974, 60, 473.