The specific lung-AHH induction, which we previously observed after the inhalation of cigarette smoke, is not due to the route followed by the inhaled smoke, for the same phenomenon occurs after i.p. injection of either cigarette smoke condensate (CSC) or benzo(a)pyrene in low doses. In this respect lung AHH behaves completely differently from the liver and kidney enzyme, in which organs, basal AHH activity (which is low in the foetus) increases rapidly after birth to reach the adult level 2 months later, and is only inducible by CSC and low doses of BP in unweaned rats. In the lung, the basal AHH activity (low in the foetus) increases abruptly at birth, peaks in 5-day-old rats and then decreases slightly. Contrary to enzyme activity in other tissues, lung AHH cannot be induced in unweaned young animals. The enzyme subsequently becomes sensitive to inducing agents and is highly inducible in 90-day-old rats. Similar behaviour occurs in 2 other enzymes linked to cytochrome P1450: ethoxycoumarin deethylase and ethoxyresorufin deethylase. The results could be related to the particular susceptibility of the lung to develop cancer after the inhalation of cigarette smoke.

Despite a decline in mortality rates since about 1931 stomach cancer remains a major cause of death in England and Wales. National death rates from 1916 to 1979 are presented by sex, age and 2 broad social-class groups covering manual and non-manual occupations. In both sexes the decline in rates has been most rapid in the young and has slowed progressively with advancing age. The ratio of male/female rates is currently 1.3 at ages 25-34, increases to a peak of 2.7 at ages 55-64 and then declines again but the pattern was different before 1931. Among both men and married women, rates are consistently higher in manual than in non-manual classes, but the difference is greater among men. Rates for men in non-manual occupations, and for both classes of married women, declined markedly between 1931 and 1951, but for male manual workers the decline was relatively slight until after 1951.

Simultaneous measurement of neutrophil migration, phagocytic activity, candidacidal and bactericidal activity were made during quadruple chemotherapy of advanced Hodgkin's disease (HD). Measurements were also made in normal individuals, hospital patients not on chemotherapy, untreated patients with advanced HD and patients off chemotherapy for over a year. Neutrophil migratory activity was usually normal in untreated HD patients and those on chemotherapy, but less than 20% of all tests showed depressed values, some of which were corrected by plasma. Similar results were found with neutrophil phagocytosis. Abnormalities in these functions were found in both early and late cycles, but there was a tendency for migration to deteriorate during later chemotherapy cycles. Neutrophil candidacidal and bactericidal activity were frequently depressed in patients on treatment and there was deterioration in candidacidal activity during the chemotherapy cycle. These abnormalities of killing activity were frequently corrected in control plasma. Neutrophil function is normal in most patients with advanced HD and in patients in remission. In a minority of patients on treatment there are marked functional defects, especially in killing activity. These defects are partly cell-associated and partly plasma-related. Susceptibility to infection during chemotherapy of HD may be partly due to defective neutrophil function.

The cytotoxic activity of peripheral-blood (PBL), lymph-node (LNC) and tumour-infiltrating lymphocytes (TIL) from 47 patients undergoing surgery for colon carcinoma (Duke's Stage A, 1 patient; B, 24; C, 15 and C with metastases, 7) was examined in short-term 51Cr-release assays, against fresh autologous tumour cells, allogeneic colon cancer cells and the erythroleukaemia cell line, K562. Cytotoxicity against autologous cells was detected in at least one effector population in 23/47 patients (49%), with overall frequencies which did not differ for patients in different Duke's stages of disease. By contrast, lysis of allogeneic tumour cells was infrequent (11%) regardless of the effector population to which they were exposed. Cytotoxicity against K562, cells highly sensitive to NK activity, though variable, was detected in 93% of PBL of normal donors and 83% of patients, and among the latter showed no evidence of significant decline with advancing disease. However, LNC and TIL anti-K562 activity was infrequent (17%) in concordance with previous reports. There was no correlation between the ability of patients' PBL to lyse autologous tumour and K562 cells. The independence of these 2 cytotoxic actions was further explored in studies fractionating lymphocytes: autologous tumour killing was augmented in T-enriched PBL; whereas the greatest anti-K562 activity was found in the corresponding non-T fraction. Lymphocyte cytotoxicity in colonic neoplasia is thus manifest in 2 apparently independent lymphocyte populations; a relatively specific killer T-cell population, detectable in PBL, LNC and TIL, which is preferentially reactive with the autologous cells; and a non-specific killer population, largely limited to PBL, with the properties of NK cells. The activity of neither population reflects the clinical status of patients with this disease.

Groups of male and female beagle dogs were given daily doses of 400 mg of various mixtures of naphthylamines for up to 109 months. Survivors were killed at 128 months. A variety of pathological conditions was diagnosed, but the only effect related to treatment was the induction of bladder neoplasms. All dogs which received pure 2-naphthylamine developed transitional-cell carcinomas of the bladder within 34 months. Two of 8 dogs receiving 6% 2-naphthylamine in 1-naphthylamine developed early carcinoma and 2/8 dogs receiving 0.5% 2-naphthylamine in 1-naphthylamine developed haemangioma of the bladder. Some of the dogs receiving 1-naphthylamine (total dose 950 g) and the controls had focal cystitis or hyperplasia, but no neoplasia of the bladder. These results confirm the carcinogenicity of 2-naphthylamine to dogs. No carcinogenic effect of 1-naphthylamine was observed, indicating that it is at least 200 times less potent as a carcinogen than 2-naphthylamine. The incidence of bladder cancer in dogs fed mixtures of both naphthylamines explains why previous experimental and epidemiological studies of impure 1-naphthylamine have revealed carcinogenicity. Images Fig. 1 Fig. 2

The effect of adjuvant immunotherapy with a single neighbourhood injection of 2 mg C. parvum (CP) was investigated in a randomized study involving 43 patients with carcinoma of the cervix uteri, all of whom were treated by radical surgery. All patients had carcinoma confined to the cervix, the upper part of the vagina or the parametrial region. When the malignancy had spread to the parametrial region, additional postoperative radiotherapy was given. 22 patients received immunotherapy 10 days before surgery, whereas the remaining 21 control patients received no immune stimulation. Only minor side effects of CP were encountered. Follow-up shows a relapse rate of 5% in the CP treated group and of 29% in the controls (P less than 0.05). A further 15 patients with more advanced malignancies were added to our studies. In these, CP stimulation had no effect on relapse rates, but the relapse-free intervals were longer after immune stimulation: control 3.5 months (mean) +/- 1.5 (s.d.), CP 13.0 months +/- 7.0 (P less than 0.05). The number of peripheral T cells and the ability to become sensitized to DNCB were increased after CP stimulation. A decrease was found in the number of blood monocytes and the number of monocytes capable of transforming into active macrophages, indicating a possible sequestration of these cells in the tissues.

Twentynine children with non-Hodgkin's lymphomas (NHL) were treated between 1974 and 1977 with a protocol based on those used for childhood ALL. 76% of patients had advanced disease by Ann Arbor criteria. All tumours had Rappaport's diffuse histology. 19 patients (65%) achieved complete remission, 14 (65%) remained alive and disease free beyond 42 months from diagnosis. 10 patients failed to enter complete remission, of whom all died. 7 patients relapsed; 5 died, 2 remain disease free and off treatment at 19 and 29 months. Comparison with a historic group of 20 consecutively treated children shows improved survival (P less than 0.01). 18 controls died. Histology was reviewed using the Kiel classification and staging according to Murphy's criteria. These are compared with the methods used initially. The improved outlook for children with NHL using intensive multiple drug regimes and cranial prophylaxis is confirmed. In staging childhood NHL, Murphy's criteria, which take into account the natural history of the disease, have greater prognosis value. Histology and pattern of outcome of the disease suggest basic differences between primary abdominal and primary mediastinal and nodal disease. This is now being confirmed with immunological typing and will be reflected in the development of future protocols.