Bathing donor-livers in University of Wisconsin solution

Transfer of insulin-dependent diabetes between HLA-identical siblings by bone marrow

Figure: Response to anti-TNF (arrows) In Crohn’s disease PCDAI = paediatric Crohn’s disease activity index; CDAI = Crohn’s disease activity index.

kindly supplied by Centocor, Malvern, USA) 10 mg/kg intravenously over 2 h. The other therapy was unchanged from 2 months before until 3 months after anti-TNF treatment. Immediately after the first dose of anti-TNF, the clinical symptoms improved, body temperature became normal, and the girl started to gain weight (3-2 kg in 10 weeks). Crohn’s disease activity index fell from 311 to 85 (paediatric Crohn’s disease activity index: 77-5 to 10) (figure). Complete endoscopic remission was observed, which lasted for 3 months, after which symptoms recurred. No side-effects were seen. The inflammatory reaction in Crohn’s disease is presumably initiated and propagated by local release of cytokines. During exacerbation of inflammatory bowel disease production of interleukins and TNFcx is increased. 1,2 TNFoc is a potent

SIR—We would support and broaden Lampeter and colleagues’ recommendation (May 15, p 1243) about the risk of adoptive transfer of type 1 diabetes after bone marrow transplantation (BMT) when the HLA identical donor is diabetic. We have reported a similar case1 in which both autoimmune hypothyroidism and type 1 diabetes were transferred into the bone marrow recipient from her HLA-identical sister. The donor was neither diabetic nor hypothyroid at the time of the donation. She later developed hypothyroidism and usual signs of preclinical type 1 diabetes2-ie, high titre islet cell antibody (ICA), anti-GAD antibody, and low acute insulin response to glucose. However, her HLA DR-DQ identical brother has type 1 diabetes and her mother Graves’ disease. Thus, the risk of transfer of diabetes after BMT also exists when both donor and recipient have a genetic background predisposing to the disease. This immunogenetic receptivity is probably a prerequisite since ICA and thyroid antibody positivity seem to be rare after BMT.3 In addition, Lampeter, referring to Sutherland et awl4 concludes that the course of diabetes is longer if diabetogenic lymphoid cells are transferred to an HLA-identical pancreas, as is seen with the transfer of HLA-identical pancreas into a subject with diabetogenic lymphoid cells. In our patient, the time lag between BMT and onset of diabetes was 3 years, which is very close to the 4 years reported by Lampeter. To document the natural history of autoimmune processes, we have followed the time course of anti-organ humoral reactivity and noted that ICA appeared 15 months and thyroid antibodies 7 months after transplantation. This late complication of BMT can be predicted in the recipient by the monitoring of ICA and other antibodies related to diabetes. B

Bert Derkx, Jan Taminiau, Sandra Radema, Arnold Stronkhorst, Cees Wortel, Guido Tytgat, Sander van Deventer Departments of Paediatric Gastroenterology, Nutrition, and Gastroenterology, Academic Medical Centre, 1105 AZ Amsterdam, Netherlands

1

2

3

4

Pullman WE, Elsbury S, Kobayashi M, Hapel AJ, Doe WF. Enhanced mucosal cytokine production in inflammatory bowel disease.

Gastroenterology 1992; 102: 529-37. Brynskov J, Tvede N, Andersen CB, Vilien M. Increased production of interleukin-1&agr;, interleukin-2 and soluble interleukin-2 receptor in endoscopic mucosal biopsy specimens with active inflammatory bowel disease. Gut 1992; 33: 55-58. Murch SH, Lamkin VA, Savage MO, Walker Smith JA, MacDonald TT. Serum concentrations of tumour necrosis factor-&agr; in childhood chronic inflammatory bowel disease. Gut 1991; 32: 913-17. Braegger CP, Nicholls S, Murch SH, Stephens S, MacDonald TT. Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet 1992; 339: 89-91.

174

Vialettes, D Maraninchi

Department of Diabetology and Paoli Calmettes Institute, University of Marseille, 13385 Marseille, France

1

Vialettes B, Maraninchi D, San Marco MP,

2

polyendocrine failure-type 1 (insulin-dependent) diabetes mellitus and hypothyroidism after allogeneic bone marrow transplantation. Diabetologia 1993; 36: 541-46. San Marco M, Vialettes B, Maraninchi D, Bernard D. Auto antibody formation after bone marrow transplantation: a comparison between autologous and allogeneic grafts. Autoimmunity 1991; 11: 7-12. MacLaren NK. How, when and why to predict IDDM. Diabetes 1988;

pro-inflammatory protein, produced by monocytes and activated T cells, which are abundant inflammatory lesions in Crohn’s disease. Serum TNFoc was increased in children with relapse of ulcerative colitis and colonic Crohn’s disease.3 Stool samples show increased TNFcx concentrations that vary with severity of disease.’ TNFcx also activates leucocytes and endothelial cells to express molecules involved in neutrophil adhesion (including 02-integrins and selectins). Because cellular adhesion to vascular epithelium is required for leucocyte diapedesis and entry into the parenchyma, TNFa may have a key role in leucocyte recruitment into the bowel mucosa.

transplantation

3 4

et

al. Autoimmune

37: 1591-94. Sutherland DE, Goetz FC, Sibley RK. Recurrence of disease in pancreas transplantation. Diabetes 1989; 38 (suppl 1): 85-87.

Bathing donor-livers in University of Wisconsin solution SiR-Human donor livers are flushed in-situ with cold University of Wisconson organ preservative (UW). Then, after donor hepatectomy, these livers are usually bathed in UW in plastic bags stored on melting ice. A retrospective analysis of the magnetic relaxation times of 50 isolated human donor livers obtained from various hospitals showed that the relaxation times of the livers were all in the same range. A similar (narrow) range was found for the relaxation times of the bathing fluid. However, one exception was noted in which the bathing fluid had exceptionally long T1 (data not shown) and T2 (figure) relaxation times, closely resembling the relaxation times of saline. Liver parenchyma itself had relaxation times similar to livers that were known to be adequately perfused with UW. The preservation records

logistic regression suggested that the major factor contributing to illness was consumption of cooked food from the market (adjusted odds ratio 3-2, 95% CI 1-6-6-2). This finding was consistent with the age and sex distribution of the cases, since it was mostly adult males who wandered and socialised in the market place, whereas women usually went there only to shop. Environmental factors such as presence of latrine, amount of available water, and source of drinking water tional

identified as risk factors. Furthermore, no association recorded between attack rates in the camp sections and person/latrine ratios in those sections (Spearman’s rank correlation 0-012). Of the 36 stool specimens that were analysed at Kamuzu Central Hospital, Lilongwe, 5 were positive on culture for Shigella dysenteriae type 1 (Sdl). 8 other specimens were analysed at Pasteur Institute, Paris. Polymerase chain reaction was used to detect enterohaemorrhagic toxins VT1 and VT2, and for invasivity gene.2-4 A DNA fragment of 130 nucleotides corresponding to the amplified VT1 toxin gene fragment was obtained in all specimens. No amplification was obtained for VT2 or invasivity genes. These findings suggested the presence of enterohaemorragic E coli and the absence of Sdl in these patients. We now highly suspect E coli 0175:H7 to be the causative agent of the Lisungwi outbreak, although some cases may have been due to Sdl. were not was

Figure: Distribution of T, relaxation times of bathing fluid Arrow=the exception.

did

reveal a cause for the long relaxation times. The recipient had an uneventful recovery from the transplantation and is doing well at present. Our observation suggests that at least one successful transplant has been performed with a UW-perfused donor liver that had been bathed in saline instead of UW. We have been unable to find a published rationale for preferring UW over saline and the bathing fluid. The hepatic capsule tolerates saline well, as is known from general surgery when the abdominal cavity is flushed with saline. Furthermore, bathing donor livers in saline instead of in UW is cost-effective since saline costs less than 1 % of the price of UW ($250 per litre). We feel that the use of UW for bathing purposes should be reconsidered. not

R F Wolf, E H P Deketh Departments of Radiology and Surgery, University Hospital, 9700 RB, Groningen,

This investigation was supported by Medecins Sans Frontieres. We thank Dr Patricia Campbell, ARC, for kindly sharing her clinical data with us.

C Paquet, W Perea Epicentre, 8

rue

St Sabin, 75011 Paris, France

F Grimont, M Collin Pasteur Institute, Paris

M Guillod Médecins Sans Frontières, Paris

Netherlands

1

Aetiology of haemorrhagic colitis epidemic in

2

Africa 3

SiR-Isaacson and colleagues (April 10, p 961) suggest that of the recent epidemics of haemorrhagic colitis in eastern and southern parts of Africa could be caused by Escherichia coli type 0157. We report a bloody diarrhoea outbreak in a Mozambican refugee camp in Malawi that supports this some

Ministry of Health, Malawi. Bloody diarrhoea situation in the Central Region: report from the Regional Health Office, July, 1992. Lilongwi: MOH, 1992. Pollard DR, Johnson WM, Lior H, et al. Rapid and specific detection of verotoxin genes in Escherichia coli by the polymerase chain reaction. J Clin Microbiol 1990; 28: 540-45. Tyler SD, Johnson WM, Lior H, et al. Identification of verotoxin type 2 variant B subunit genes in Escherichia coli by the polymerase chain reaction and restriction fragment length polymorphism analysis. J Clin Microbiol 1991; 29: 1339-43.

4

Lampel K, Jagow J, Truckess M, Hill W. Polymerase chain reaction for detection of invasive Shigella flexneri in food. Appl Environ Microbiol 1990; 56: 1536-40.

hypothesis. Between Jan 1 and Dec 1, 1992, more than 20 000 cases of bloody diarrhoea were notified in the central and southern regions of Malawi (population 5 million). Case fatality rates changed from 5% to 10% in the districts.1 In the Lisungwi refugee camp (60 000 Mozambicans), 772 cases presented with bloody diarrhoea associated with cramping abdominal pain between July and December, 1992 (attack rate 12-8 per 1000; case fatality rate 4-7%). Fever was uncommon. The duration of illness ranged from 3 days to 4 weeks (mean 8 days) and antibiotics were ineffective. Adults (> 15 years) were 3-7 times more affected than children, and adult males were more affected than females (sex ratio M/F 2-3). These patterns were constant throughout the outbreak. Although attack rates differed widely in sections of the camp, cases did not seem to cluster about water points. To identify risk factors associated with bloody diarrhoea, we conducted a case-control study. 125 cases were matched for age, sex, and section of residence with 125 controls selected at random from the camp population. The questionnaire included demographic and socioeconomic characteristics, environmental factors, and food consumption habits. Condi-

Vitamin E in

proliferating

mitochondrial mitochondria

a

myopathy with

boy with high plasma lactate (10mmol/L, range 7-4-14-0, n=6), was handicapped by a severe myopathy, had never walked independently, and became wheel-chair bound at age 24 months. He had a deficiency of the adenine nucleotide translocator in muscle, which was accentuated by a 2-20-fold increase in other mitochondrial activities. Because complex IV showed the lowest (2-fold) increase in activity, we postulated that the enzyme was inhibited by perixodation of fatty acids in cardiolipinwhich was supported by the observation that the amount of protein in complex IV was about 5 times increased, as assessed by the immunoreactivity of its subunits.1 Although there were no clinical signs of vitamin E deficiency in this normally fed boy, he received orally 500 mg vitamin E (DL ot-tocopherol acetate) twice a day. After 3 weeks, the dose was decreased from 1 0 to 06 g per day. Within 8 weeks, his muscle SIR-A

endurance power increased such that he was no longer severely 175