1597

controls

seven episodes of rejection were noted while only one episode of rejection was noted (and treated) in those on BT563. (A second patient had a rejection 2 weeks after BT563 treatment was stopped.) 10 of the 18 scheduled biopsies in the BT563 group were histopathologically graded RO; 3 were RO-1, 4 were Rl, and 1 was Rl-2. During the first 10 days of BT563 administration, mean serum antibody levels (murine IgG) were 2-45 (SD 16) mg/ml. During the second 10 days antibody levels fell to 0-30 (0-46) µg/ml due to rising titres of human anti-mouse antibody. Infections were noted in four controls and in three patients on BT563. In the BT563 group pleural and/or abdominal effusions seemed to be more frequent (5 vs 1) and longer lasting than they were in the controls. We conclude that BT563 reduces the risk of early rejection after liver transplantation. Histological pointers to rejection (in 8 biopsy specimens) did not correlate with symptoms. Whether the effusions noted are related to BT563 remains unclear. We are now trying to reduce conventional immunosuppression and to define the best regimen for this monoclonal antibody.

University Surgical Clinic, 6900 Heidelberg, West

Germany

GERD OTTO JOCHEN THIES MARTIN MANNER CHRISTIAN HERFARTH

WALTER J. HOFMANN

Biotest-Pharma GmbH, Dreieich

HELMUT SCHLAG

Department

2 3.

4.

5.

were

Head and Neck Oncology Clinic, Auckland and Green Lane Hospitals, Auckland 3, New Zealand

RANDALL P. MORTON C. S. BENJAMIN

Surveys. Cancer Statistics Registrations, England and Wales. 1978. London: HM Stationery Office, 1982. 2. Warr P, Cook J, Wall T. Scales for the measurement of some work attitudes and aspects of psychological well-being. J Occupat Psych 1979; 52: 129-48.

STEFAN MEUER

Cancer mortality patterns among laboratory workers

Kupiec-Weglinski JW, Diamantstein T, Tilney NL. Interleukin 2 receptor-targeted therapy: rationale and applications in organ transplantation. Transplantation 1987; 46: 785-92. Soulillou JP, Le MauffB, Olive D, et al. Prevention of rejection of kidney transplants by monoclonal antibody directed against interleukin 2. Lancet 1987; ii: 1339-42. Cantarovich D, Le Mauff B, Hourmant M, et al. Anti-IL2 receptor monoclonal antibody (33B3.1) in prophylaxis of early kidney rejection in humans: a randomized trial versus rabbit antithymocyte globulin. Transpl Proc 1989; 21: 1769-71. Cantarovich D, Le Mauff B, Hourmant M, et al. Anti-interleukin 2 receptor monoclonal antibody in the treatment of ongoing acute rejection episodes of human kidney graft: a pilot study. Transplantation 1989; 47: 454-57. Herve P, Wijdenes J, Bergerat JP, Milpied N, Gaud C, Bordigoni P Treatment of acute graft-versus-host disease with monoclonal antibody to IL-2 receptor. Lancet 1988; ii: 1072-73.

Elderly patients with head-and-neck cancer SIR,-Mr Fentiman and colleagues report (April 28, p 1020)

on

elderly patients, which prompted us to record our experience with elderly patients with head-and-neck cancer. Our policy has been to make no distinction on the basis of age,

cancer

did their younger counterparts, and the scores after treatment generally as good as that for the general population (table). This year the theme for the New Zealand "Telethon" is focused on caring for the elderly, a timely reminder that elderly people seek to participate in daily life just as actively as younger people.

as

Applied Immunology,

German Cancer Centre, Heidelberg

1.

patients presenting with head-and-neck cancer had as good scores

1. Office of Population Censuses and

Institute of Pathology, University of Heidelberg

of

PSYCHOLOGICAL WELL-BEING ("LIFE SATISFACTION") SCORES IN PATIENTS WITH HEAD AND NECK CANCER

in

with respect

for head-and-neck cancer. The effects of uncontrolled disease in the head and neck area are so devastating to the patient that we feel that all reasonable attempts to control the local and regional disease should be made. In a recent questionnaire survey of 75 patients about the quality of life in such patients attending our clinic, only those with fungating malignancies that had recurred despite surgery and radiotherapy were concerned about their appearance. Patients who had had major resections of the oral cavity, pharynx, larynx, or neck were remarkably unconcerned about the cosmetic effects of their treatment Although Fentiman and colleagues’ data indicated that about 50% of patients with cancer could be expected to be over age 70, only 32 % of our patients were aged over 70-a figure that is close to overall data for head-and-neck cancer in England and Wales to treatment

SIR,—Dr Cordier (May 5, p 1097) reports on excess risk of cancer

laboratory workers. We report similar findings from a retrospective cohort study of cancer risk in the Istituto Superiore di Sanita (ISS). The ISS was founded in the 1930s as a public health institute mainly for the study of malaria; subsequently its field of interest was widened to include food safety, drug control, microbiology (including production of pilot antibiotics), environmental health, and biomedical research. Today, about 1500 people work at ISS. The cohort included all subjects employed from Jan 1, 1960, to June 30, 1989. Records for technical and administrative staff were kept separately; altogether 1797 technical and 345 administrative employees (1269 men and 873 women, 34 354 person-years) were considered. Dates of leaving, mainly because of retirement, were available for subjects who left ISS by June 30, 1989. Vital status was ascertained for 99 1% of the population, and among

causes

of death were established for 98 3% of those who died. The

cause, sex, age, and calendar-time

specific mortality rates were compared with those of the Italian general population. The table shows the observed and expected mortality among technical staff. A relatively low mortality from all causes, all cancers, MORTALITY IN TECHNICAL AND ADMINISTRATIVE STAFF AT ISS BETWEEN JAN, 1960, AND JUNE, 1989

(37%).1 Other data from our survey support the view that the elderly deserve vigorous therapeutic endeavours. Such patients aged over 70 were every bit as active in the community and socially (with 54% and 85%, respectively, belonging to clubs or having physically active or outdoor hobbies), as were those under 70 (52% and 56% respectively). This pattern was maintained after treatment. We also measured psychological well-being, with an abbreviated form of assessment devised by Warr et al2 ("the degree to which a person reports satisfaction with life and life space"). The older

0 = observed. interval-al

E=expected,

SMR=standard

mortality ratio;

Cl=confidence

1598

and

circulatory diseases

was seen

in men; increases in

pancreatic

cancer, brain cancer, and lymphohaematopoietic malignancies were detected. An increased risk of cancer was observed in women,

mainly because of a significant excess of breast cancer. One case of pancreatic cancer and two lymphohaematopoietic neoplasms were detected. Observed and expected mortality did not differ in administrative staff (table). Since the sample size was small, cause-specific mortality is not informative. The observed excess of breast cancer in laboratory workers is consistent with previous reports.! This excess might be explained by these highly educated working women having a different reproductive pattern from that in the general population. Our findings are very similar to those of Cordier. In particular, both studies show an excess of pancreatic and brain cancers. The excess cancer risk was confined to laboratory staff. Cordier did not separate laboratory and administrative personnel, which may explain why many of the SMRs we found were higher than those in the Pasteur study. We thank Prof Rodolfo Saracci of IARC for his helpful criticism and comments; the study is a part of an IARC project supported by the EC "Europe against cancer" programme.

S. BELLI Istituto Superiore di Sanità, 00161, Rome, Italy International

Agency for Research on Cancer

P. COMBA M. DE SANTIS M. GRIGNOLI A.

J. SASCO

J, Li FP, Hoar SH, Mead MW, Fraumeni JF Jr. Causes of death among female chemists. Am J Public Hlth 1985; 75: 883-85.

1. Walrath

Detection by PCR of HHV-6 and EBV DNA in blood and oropharynx of healthy adults and HIV-seropositives SIR,—Initial isolations of human herpesvirus-6 (HHV-6) were from cultures of peripheral blood lymphocytes of patients with lymphoproliferative disorders and HIV infection. Serological studies have shown that HHV-6 infection is very common in healthy adults and that primary infection in infancy is a cause of exanthem subitum (roseola infantum). Dr Levy and his colleagues (May 5, p 1047) isolated HHV-6 from the saliva of more than 80% of healthy adults and immunocompromised patients. We have used the polymerase chain reaction (PCR) to investigate HHV-6 and Epstein-Barr virus (EBV) DNA in oropharyngeal cells and peripheral blood lymphocytes of healthy and HIV-infected adults. DNA was extracted from ’Ficoll-Hypaque’ separated lymphocytes or from cells obtained by low-speed centrifugation of a 10-15 ml saline gargle. HHV-6 DNA was amplified using primers from the sequence of HHV-6 strain U11021 (see legend to figure) and the specificity was confirmed by hybridisation with an internal probe oligonucleotide H6-6/7. EBV DNA was amplified using primers derived from the B95-8 isolate2 and detected with internal probe EBV1/2. After denaturation (94°C for 10 min) all PCR reactions consisted of forty cycles of annealing (65 °C, 1 min), extension (72°C, 2 min), and denaturation (94°C, 1 min) with 1 pmol/1 primers in standard buffer. Under these conditions we can detect less than ten copies of a plasmid containing the HHV-6 target sequence or less than ten IB4 cells (an EBV carrying cell line) in the presence of 105 EBV genome negative cells (data not shown). The figure illustrates typical PCR reactions to detect HHV-6 and EBV DNA in mouthwashings from normal adults. The HHV-6 primers give rise to some non-specific products with human DNA samples in reactions of over thirty cycles, even under stringent conditions, and the internal detection primer is essential to prove specificity. The EBV primers did not give rise to non-specific products but results were confirmed by hybridisation with the internal detection oligonucleotide. Tests on healthy adults (table) showed that about half were positive for HHV-6 and EBV DNA in samples containing DNA from about 105 lymphocytes and that 63% of samples of oropharyngeal cells were positive for HHV-6 and 23% were positive for EBV DNA. Dilution studies showed that DNA from

Gel separations and hybridisation of PCR products of HHV-6 and EBV DNA in oropharyngeal cells from normal adults.

Samples of templates from normal adults (tracks 1, 3-5, 7-9, 11-13) and uninfected JJhan cells (2, 6, and 10) amplified by PCR with HHV-6 primers (panels a, b, and c) or EBV primers (panels d and e). positive controls were ten copies of plasmid pHD5, containing the HHV-6 target DNA sequence (+in panels a, b, and c), or 0001 ml of culture supernatant from the EBV-producer cell line B95-8 (+in panels d and e). Negative controls (-) also used Panels a and d are photographs of ethidium bromide stained gels; panels band e are autoradiographs; panel c is an autoradiograph of labelled HHV-6 probe oligonucleotide bound to Southern blot of gel a p= unincorporated primers, pd=primer-dimer amplification products, 223 bp=HHV-6 product, and 175 bp=EBV product. (Among non-specific products produced by H HV-6 primers is a band close to 223 bp in some umnfected samples which does not hybridise with probe oligonucleotide [eg, tracks 6 and 2] ) Primer and probe sequences were. HHV-6 strain U1102 (primer) H6-6, 5’AAGCTTGCACAATGCCAAAAAACAG, H6-7, 5’CTCGAGTATGCCGAGACCCCTAATC, position 17627-17603 position 17405-17429)

H6-6/7

(probe)

(5’AACTGTCTGACTGGCAAAAACTTTT,

position

17516-17492) EBV B95-8 isolate (primer) EBV-1, 5’AACATGCTGTATGCCTCGCAGCG, position 124935-124957 EBV-2, 5’AATTACTGGCGTGAATTGTGCCCA, position 125109-125086) EBV 1/2 (probe) (5’GCCGTCTGACCGAGAACCTAAGAAA, position 124960-124984)

the equivalent of 104 to 105 cells was normally required for specificc amplification of HHV-6 (ie, to yield about 10 genomes). The large number of oropharyngeal cells necessary to detect HHV-6 DNA suggests, when set beside the virus titre in saliva estimated by Levy et al, that most HHV-6 in the mouth is free virus. The table shows that HHV-6 and EBV DNA within a sample are independent events.

More than 80% of HIV-seronegative individuals were seropositive for HHV-6 and for EBV. The few EBV seronegatives were consistently PCR negative while occasional HHV-6 seronegatives were reproducibly PCR-positive from the mouth with no evidence of seroconversion later. In HIV-infected individuals (table) the prevalence, in lymphocytes, of HHV-6 was much lower than that for EBV, especially in those with symptoms of

Cancer mortality patterns among laboratory workers.

1597 controls seven episodes of rejection were noted while only one episode of rejection was noted (and treated) in those on BT563. (A second patien...
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