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Germany: Update on Charité HospitalLast year the East Berlin Charite Hospital attracted

attention because of allegations that critically ill patientswere brought there to serve as organ donors and thatinternationally agreed criteria for brain death had beendisregarded (Lancet Sept 7,1991, p 624). The investigationsinto the alleged goings-on have indicated that themisconduct was not as blatant as claimed.The investigating team pointed out that in East Germany

transplantation medicine was seen in political circles asbeing of considerable prestige for the socialist regime, so itwas heavily supported despite severe shortcomings in otherspecialties. As the numbers of transplantations rose, says thereport, resources for the prompt transfer of organs to the

transplant centres became inadequate. Hence some doctorsrecommended the transfer of potential donors to theCharite. Despite controversy over the proposal, several veryill patients from small, distant hospitals were brought byambulance to the Charite. Reasons given for the transfer-ie, that diagnostic and therapeutic standards were better inthe Charite-did not stand up to scrutiny since there werefacilities nearer than the Charite to those hospitals. Theinvestigating team found that none of these patients becamean organ donor after death. Neither did it find evidence of

premature diagnosis of brain death. Furthermore, there wasno evidence that politicians or members of the secret policeinterfered directly with decisions about patients or secureddonor organs for their own purposes, or that there was tradein organs-only an exchange with Western countries viaEurotransplant as well as with Eastern countries.

Nevertheless the team expressed surprise that some of thedoctors still saw no wrong in unnecessarily transportingcritically ill patients over long distances. These doctors facelegal proceedings and assessment by the Berlin generalmedical council of their fitness to practise.

Annette Tuffs

Australia: IVF under fire

Although Australia has been prominent internationally inin-vitro fertilisation technology, and although our

biomedical companies have successfully exported IVFtechnology to the United States and Asia, research has beenrestricted by legislation in the home state of Victoria. Publiccriticism of IVF has flared again in the past three monthsthrough three diverse sources. First came LivingLaboratories, a book by social psychologist and associateprofessor of women’s studies, Dr Robyn Rowland.Rowland says that when fewer than 10% of women whostart treatment cycle have a child, IVF should be seen as afailure, not a success. She believes IVF is offered too readilyto women who have not tried other methods of encouragingconception or who have not tried for long enough to have achild without assistance. She also says IVF is largelyexperimental, with women as guineapigs to satisfy men’sintellectual curiosity and desire to control reproduction.Next an investigation by the Australian Broadcasting

Corporation’s Four Corners, our most respected televisioncurrent affairs programme, showed that doctors rarelyinform patients about the possibility of prematurity, ovarianhyperstimulation, psychological stress, and the fact that asyet there has been no published study on children bornthrough IVF (although one is in progress).Then recently the newly appointed chair of the Australian

Institute of Health and Welfare, Prof Fiona Stanley,

expressed her concern: "What about the causes of infertility,what about the impact of multiple births and birth defects?"."To introduce [new technologies] without properevaluation is dangerous and very worrying. My majorconcern is that there have been no randomised controlledtrials comparing IVF with either doing nothing or doingother things, for example, surgery for tubal problems."The cost of IVF has also been criticised. It was estimated

in 1987 that it cost A$40 000 per live birth. Rowland puts thecost of IVF in 1991 at A$35 million, with 75 % coming fromgovernment sources. The only defenders of IVF seem to bedoctors and scientists involved in programmes and parentsof healthy, single children born after IVF.

Mark Ragg

Conference

Helicobacter pyloriOf special interest at the fifth European Workshop on

Helicobacter pylori in Dublin were preliminary results fromAdrian Lee of the University of New South Wales

indicating that development of a vaccine is at least a

possibility since a combination of sonicated lifelis and 10 ggof cholera toxin (given five times over 7 weeks) preventedinfection in 95% of specific--pathogen-free mice when theywere rechallenged with IOS Hfelis. More details, though,were given of studies enabling a better understanding of theimmunopathology of H pylori infection and of the action ofproton-pump inhibitors in the treatment of H pyloriinfection.Work from New Orleans, Madrid, and Brussels, with

different in-vitro models, has confirmed the original datafrom Figura and Blaser that showed the existence of theH pylori 120-130 kDa cytotoxin-associated protein. In

addition, workers from New Orleans, where the prevalenceof gastric cancer is high, identified the cytotoxin in H pyloristrains from 89% of patients with chronic atrophic gastritisbut in only 69% without gastric atrophy.1 Neutralisation ofbacterial cytotoxic activity by circulating IgG1 and mucosalIgA antibodies was also reported, the action of the latterbeing associated with recognition of the 120 kDa protein ZAlthough the mucosal IgA response to this protein isassociated with duodenal ulcer and superficial epithelialdegeneration, the relation between antibody response andclinical outcome is not known.What factors are involved in the immunological response?

Speakers from Nottingham3 and Bologna4 reported thattissue levels of interleukin 8 (IL-8), but not IL-1, wereraised in H pylori gastritis; the Italians also confirmed earlierreports of increases in mucosal IL-6 in H pylori gastritis.Crabtree et al5 reported that, whilst IL-8 is present innormal gastric mucosa, epithelial expression is upregulatedin patients with H pylori gastritis. In-vitro secretion of IL-8by antral mucosa was increased in patients with activeneutrophilic gastritis. The authors’ finding of mucosal IgAautoantibodies to IL-8 led them to postulate that theseautoantibodies may be important in downregulating andlimiting local mucosal inflammatory responses.

Whatever the mechanisms of tissue damage, evidencefrom London and Brazil of loss of somatostatin-secreting Dcells as the cause ofhypergastrinaemia stimulated by food orgrowth hormone releasing factor was in agreement withAmerican data presented to the American

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Gastroenterological Association 2 months ago. The lack ofsomatostatin inhibition of G cells could allow parietal-cellhyperplasia and thus the changes in acid secretion found inpatients with duodenal ulcers.

Little is known about the interaction between H pylori,urease, gastric acid, and the role of proton-pump inhibitors.Preliminary work suggested that omeprazole alone coulderadicate H pylori but subsequent studies have revealed thatthis drug suppresses the organism only temporarily.Highlighted at the meeting (and confirming our initial

reports) was evidence that the apparent eradication is in factdue to antral clearance of H pylori, which seems to beassociated with increased colonisation of the gastric body.How can we account for these results? In vivo lansoprazole(and to a lesser extent omeprazole) is more active thanbismuth against H pylori. However, both proton-pumpinhibitors are pro-drugs that are inactive at acid pH, sosuppression of infection is most likely due to lack of

hydrogen ions. Neither drug eradicates the infection whengiven alone, although the effectiveness of antimicrobialtherapy can be increased by lowering pH. Several Europeancentres have reported high eradication rates with

omeprazole combined with amoxycillin,’ but UK and Irishgroups have been unable to confirm the results. What are

needed, not only for the specialist but also for the bemusedgeneral gastroenterologist, are large multicentre trials usingreliable methods for assessing eradication.

St Mary’s Hospital,London W2 1NY

Robert P. H. Logan and theParkside Helicobacter Study Group

1. Fox JG, Correa P, Taylor NS, et al. High prevalence and persistence ofcytotoxin positive Helicobacter pylori strains in a population with a highprevalence of atrophic gastritis. Ir J Med Sci 1992; 161 (suppl 10): 50.

2. Armellini D, Crabtree JE, Bugnoli M, Xiang ZY, Figura N.Neutralisation of in-vitro vacuolating activity of Helicobacter pylori bygastric mucosal IgA. Ir J Med Sci 1992; 161 (suppl 10): 22.

3. Atherton JC, Hudson N, Hale TL, Kirk GE, Spiller RC, Hawkey CJ.Interleukin 1 &bgr; and interleukin 8 in gastric biopsy samples: relationshipwith inflammation and epithelial hyperplasia. Ir J Med Sci 1992; 161(suppl 10): 57.

4. Gionchetti P, Varia D, Campieri M, et al. Mucosal levels of interleukin1&bgr;, 6, and 8 in dyspeptic patients. Ir J Med Sci 1992; 161 (suppl 10): 21.

5. Crabtree JE, Peichl P, Wyatt JI, Lindley IJD. Gastric interleukin-8 andanti-interleukin-8 IgA antibodies in Helicobacter pylori infection.

Ir J Med Sci 1992; 161 (suppl 10): 20.6. Logan RPH, Walker MM, Gummett PA, Karim NQ, Baron JH,

Misiewicz JJ. The effect of omeprazole on the dynamics of H pyloriinfection. Ital J Gastroenterol 1991; 23 (suppl 2): 110.

7. Labenz J, Gyenes E, Ruhl GH, Borsch G. Amoxycillin and omeprazoletreatment for eradication of Helicobacter pylori. Eur J GastroenterolHepatol 1991; 3 (suppl 1): S10.

Medicine and the Law

Soft tissue sarcoma, aplastic anaemia, andexposure to pesticides

On July 17, 1992, a claim by a former employee ofRentokil Ltd was settled for 90000. A man who hadworked in timber treatment from August, 1978, until May 1,1988, had claimed that while eradicating woodworm andtreating wood for wet and dry rot, often in confined spaces,he had been injured as a consequence of exposure topesticides-namely lindane (y-hexachlorcyclohexane) andpentachlorophenol, in carrier solutions with a solvent base.A hand-held or backpack spray gun was used to create a finemist that settled onto the surface to be treated. He claimedthat his employers should have provided a proper protective

mask fed from an outside air supply and adequately proofedoveralls-and that daily exposure to pesticides via

absorption through the skin or by inhalation had caused thedevelopment of a soft tissue sarcoma (malignant fibroushistiocytoma or MFH).Dr R. A. Cartwright (Leukaemia Research Fund Centre,

Leeds) had reviewed published work and this case in

particular. Malignant histiocytoma is very rare, with anannual incidence of only 6 per 10 million population, and inEngland and Wales the incidence of all soft tissue sarcoma(STS) is only 4 per 100 000. MFH is the rarest subgroup.MFH most often affects limbs, skin, or subcutaneoustissues. The causes have not been systematically researched.Case-reports, in Dr Cartwright’s view, are difficult to assessand could never prove cause but they do suggest aetiologies:"One is the result of physical insult... Thus MFH has beenreported developing in a burn scar, as a result of irradiationto the brain, in a smallpox scar, and in a discoid lupuslesion". The other is chlorophenols.

Cartwright’s review did suggest that "on balance despitethe negative studies there is a real possibility of a linkbetween STS (including MFH) and the chlorophenolgroup of chemicals". The International Agency forResearch on Cancer, in its consensus evaluation, placeschlorophenols in group 2B ("possibly carcinogenic to

humans"). The epidemiological data are "limited" butanimal data for one chemical are "sufficient". Cartwrightalso looked at hexachlorocyclohexanes, one of which islindane. He found some evidence from case-reports thatleukaemia and aplastic anaemia are associated with exposureto lindane. Some short-term test data indicate a potential forcarcinogenicity and the IARC category is also 2B. However,Cartwright stressed that for STS conclusions must betreated with caution because these malignancies are so rareand proper epidemiological studies of timber treatmentworkers had not been done.

During his employment with Rentokil the man had, it wasalleged, used 130 000 litres of woodworm fluid and 42 000litres of pentachlorophenol for dry rot. For 8 years he used aMartindale face mask. In Cartwright’s opinion the MFHwas atypical in respect of site (the abdomen) and age (born1948). There was no evidence that this MFH arose as aresult of other known risk factors. Cartwright concludedthat the balance of evidence in respect of chlorophenols was"gradually tipping towards the conclusion that ... one ormore of the noxious chemicals in that group will prove to bea human carcinogen". It was not possible to make anyconclusion about lindane and STS, he added.Lawyers acting for the plaintiff see the settlement (no

defence was ever served by Rentokil) as a "watershed".However, the settlement, without admission of liability, wasthe instigation of the firm’s insurers (a Lloyds syndicate),despite Rentokil’s firm belief that the claim had "no

justification". Furthermore, Rentokil deplores thesettlement because it may raise "completely unjustifieddoubt" in the minds of its employees. Earlier Rentokil hadsettled for C20 000 by way of compensation a claim inrespect of the death of a boy whose parents’ home had beentreated (by the plaintiff in the other case, as it happened) inMay, 1986. Aplastic anaemia was diagnosed in January,1987. At about the time of that earlier settlement the

Ministry of Agriculture, Fisheries and Food AdvisoryCommittee on Pesticides found that "the weight of evidencesuggests that exposure to Gamma HCH [lindane] does notcause aplastic anaemia in man. If a causal association doesexist it is probably not dose related and is a very rare

idiosyncratic response".