Melanocytic naevi in children having received chemotherapy

114 Influence of cold ischemia time on outcome of human liver transplantation using UW solution. Extended cold ischemia, made possible by the use of UW solution has brought substantial advantages to liver transplantation. In contrast to the results of animal studies using UW solution, there has been very little clinical data on the inverse relationship between cold ischemia time (CIT) and graft function. In a prospective study, the effect of extended cold ischemia on graft function was investigated. Early graft function and subsequent outcome were assessed for 306 consecutive elective liver transplantations according to CIT c I2 h (group A) or 2 I2 h (group B). Initial graft function was better in group A than in group B, as shown by maximum alanine aminotransferase activity (mean 623 f 805 vs 946 + 1I48 III/l - P = 0.02). bile production on days 1-3 (P < 0.05). maximum serum blilirubin by day IO (206 + I66 vs 244 Jt:I63 pmol/I P=O.O4) and frequencies of primary non function (1 f 0.4% versus 4 f 7% - P = 0.006) and hepatocyte necrosis on routine biopsy sample after reperfusion (18% vs 3 1% - P = 0.04). Long-term outcome was also better in group A than group B; graft and patient survival rates were higher and fewer retransplantations were required. These findings suggest that cold ischemia in UW solution for longer than I2 hours is a risk factor for graft function and patient survival. We recommend that the limit of the safe CIT be reconsidered. RAdam(l) HepatoBiliarySurgeryandLiverTransplantResearch Unit HopitalPaulBrousse.Villejuif.France. Hormonal therapy of malignant melanoma Endocrine factors may affect the clinical course and possibly the treatment of malignant melanoma. The presence of estrogen receptors, and occasional responses to anti-estrogen therapy have been reported in the literature. In this randomized study, the administration of dacarbazine (which is the standard chemotherapy) was compared with that of dacarbazine plus tamoxifen in 1I7 patients with metastatic malignant melanoma. The overall objective response rate (complete plus partial remission) was significantly higher and the overall survival was significantly longer in the dacarbazine plus tamoxifen compared to the dacarbazine arm alone. Analysis according to sex showed that both response rate and survival significantly favoured the dacarbazine plus tamoxifen rather than dacarbazine alone treatment in females, while in males differences were smaller and statistically insignificant. Moreover, in the standard treatment arm there was no difference between females and males in response rate of survival whereas in the arm including tamoxifen, both response rate and survival clearly favoured females. This data suggests a (I) Loncet (1992) 30, 1373

favourable influence of endogenous estrogen (plus or minus dacarbazine) on the course of the disease. In post-menopausal women and in males, the unique source of estrogen is the aromatase enzyme which is produced in fat and muscle tissue. This enzyme transforms adrenal androstenedione in estrone. Therefore, the greater the body mass is, the higher the content of endogenous estrogen should be. On this basis, a retrospective analysis of the data was performed in which the median value of an index of body mass (Quelet index) was used to separate post-menopausal women and males having a higher, from those with a lower endogenous estrogen content. This analysis showed that survival was not affected in the dacarbazine alone treatment while, in the dacarbazine plus tamoxifen treatment, survival was significantly longer in patients having a higher Quetelet rather than in those having a lower Quetelet with reference to the median value. The same result was obtained considering males alone. This study demonstrates that, in metastatic malignant melanoma, dacarbazine plus tamoxifen is better than dacarbazine alone, both in response rate and survival. The data suggests that the favourable effects of tamoxifen on survival are conditioned by the estrogen content in the body. Further studies are required to clarify the exact mechanism of action by which the couple (tamoxifen plus estrogens) or the triplet (tamoxif,cn plus estrogens plus dacarbazine) favours a longer survival in advanced malignant melanoma. G Cocconi(2) OspedaleMaggiore, Parrna.Italy Melanocytic naevi in children having received chemotherapy In the past, two publications have reported that children who have recovered from acute leukemia have larger than average numbers of malanocytic naevi. As large numbers of malanocytic naevi are an important risk factor for developing malignant melanoma, this is of potential importance with regard to second malignancies in this population. However, no count had been carried out of naevi in these children prior to either developing their leukemia or to starting therapy. It was therefore possible that the high naevus counts were part of the genetic make-up of these children which was part of their pre-disposition to develop leukemia. For these reasons, we carried out a prospective study of 30 children in Glasgow diagnosed as having acute leukemia prior to and two years after receiving chemotherapy. Our results showed a highly significant increase in naevus counts during the period of chemotherapy. During childhood, numbers of naevi do increase slowly, but the rate in magnitude in the increase of naevi in the children studied was significantly increased over that of a control population. (2)

N Engl

J Med

(1992)

327,

516

The biological significance of this increase in naevus counts for these children remains to be established. RM MacKie (1) University of Glasgow, Glasgow G12 8QQ. UK Treatment of gallbladder stones by lithotripsy cholecystectomy: cost effectiveness

and open

There are several common variants of the standard treatment for gallstone disease, open cholecystectomy, such as mini-incision cholecystectomy, and laparoscopic cholecystectomy. All variants share the same approach of removing the gallbladder. An alternative, non-invasive technique is extra-corporeal shock wave lithotripsy in which the stones are shattered by shock waves and the fragments passed out of the gallbladder, possibly with the help of adjuvant bile salts, leaving the gallbladder intact. The comparative effectiveness and costs of lithotripsy and cholecystectomy were unknown until now and we have therefore evaluated them in a randomised controlled trial. Substantial and significant improvements in biliary pain experience, and other common symptoms such as fatty food upset, and also in perceived health status were found with both treatments. Cholecystectomy was a little more cost-effective than lithotripsy in patients with large stone-bulk (over 4cm3 of gallstones), but possibly less cost-effective for patients with small stone bulk. However, the differences were not large, and it was concluded that to some extent, treatment choice could be guided by patient preference. Biologically, the most striking finding was that the improvements in health in the lithotripsy patients were almost immediate and not related to the disappearance of the stones. This suggests that it is not the presence of gallstones per se which gives rise to the symptoms. JP Nicholl(2) University of Sheffield. Sheffield 510 2RX. UK Analysis proteins

of transcriptional

regulation

by Myc and Max

The human c-Myc oncoprotein (Myc) has been shown to be a sequence-specific transcriptional activator whose DNA binding is dependent on dimerisation with its partner Max by using yeast as an in vivo model system. Hetero-dimerisation and DNA-binding require the basic/ helix-loop-helixlleucine zipper (bHLH-Z) domains of Myc and Max, while transactivation is mediated by a distinct amino-terminal domain of Myc. Max can also form homodimers which bind to the same DNA sequence as Myc/Max. However, Max homodimers fail to transactivate and antagonise MyclMax activity. Moreover, the Max HLH-Z domain has a higher affinity (I) EM/ (1992) 305, 799 (2) Lamer ( 1992) 340. 801

for the Myc HLH-Z domain than for itself, suggesting that the heterodimeric Myc/Max activator forms preferentially at equilibrium. These data are consistent with a dual function of Max as an essential partner and suppressor of Myc. The Myc protein is short-lived and its expression is dependent on the presence of growth factors. In contrast, Max has a relatively long half life and appears to be constitutively expressed in resting and cycling cells. Thus, in resting cells Max homodimers may function as inhibitors of proliferation, while upon cell activation the increase in c-Myc levels leads to the preferential formation of active c-Myc/max heterodimers. This mechanism may constitute a powerful switch controlling both entry into and exit from the cell cycle. H Land (3) Imperial Cancer Research Found. London WC2A 3PX. UK HIV-infected

transfusion

recipients

During a review of all cases of HIV infection acquired through blood transfusion in New South Wales, a group of six subjects, who were identified through a single donor were identified. Throughout follow-up (range 6.8 - IO.1 years after infection), five of the recipients and the donor remained clinically free of symptoms, with normal CD4 cell counts and no p24 antigenaemia. HIV was isolated from only one recipient and this isolate did not induce syncytia in vitro. The frequency of progression to AIDS or a CD4+ cell count of less than 0.50 x 109/L was significantly lower among these six subjects (l/6) than among 101 other HIV-infected transfusion recipients, for whom a similar period of followup was available (94/lOl; P < 0.0001). These findings suggest that this group were infected by a less virulent strain of HIV-I and that non-virulent strains of HIV-I may continue to be so in a new host following transmission. These results urge the identification of other similar groups in an effort to investigate the implicated viral strains. B Tindall(4) The University of New South Wales, Sydney, NSW 2010, Australia Pregnancy

and diabetic

relaxin concentrations

Maternal serum concentrations of relaxin, an insulin homologue produced both by the corpus luteum of pregnancy and by the fetoplacental unit. are highest in the first trimester and fall to ther lowest level in the third trimester. We show that maternal serum relaxin concentrations are significantly higher at each stage of preg-

(3) Nature (1992) 359. 423

(4) Lancer (1992) 340. 863